Person centred care: Disease, medicines and patients Flashcards

1
Q

Organisation of the nervous system:

A

Nervous system
into
Central Peripheral
I I
Brain and Somatic
spinal cord autonomic

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2
Q

What’s the 3 protective layers that protect the brain and spinal cord called ?

A

The Meninges

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3
Q

What are the 2 types of matter the spinal cord consists of ?

A

1) Grey matter

2) White matter

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4
Q

Grey matter:

A

cell bodies
and UNmyelinated neurones

makes up outer layer of brain

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5
Q

White matter:

A

Myelinated axons containing ascending (carry sensory info) and descending tracts ( carry motor info).

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6
Q

Function of the Cerebellum ?

A

Voluntary muscle contraction and posture

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7
Q

Whats the Mesencephalon ?

A

Mid brain
helps motor skills
mainly for eyes and ears.

mmmmmmmmmmid

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8
Q

What are the 2 parts that make up the “mesencephalon” ?

A

1) Tectum- 2 pairs of colliculi

Auditory function (inferior) and visual function (anterior).

2) Tegmentum-

Grey matter round

Substantia nigra ( body movement)

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9
Q

What makes up the 2 parts of the Diencephalon ?

A

1) Thalamus

2) Hypothalamus

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10
Q

What is the cerebrum also known as ?

A

The cerebral cortex

2.4 mm thick

contains folds and grooves

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11
Q

What is the function of the limbic system ?

A

Regulation of feeding,fightand flight

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12
Q

What is the function of the basal ganglia ?

A

Connected to substantia nigra

  • controls large automatic movement of the skeletal muscles.
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13
Q

What are the two types of primary motor cortexs ?

A

1) primary motor cortex

2) Primary somatic cortex

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14
Q

Primary motor cortex :

A
  • frontal lobes
  • specialised for control of movement
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15
Q

Primary somatic cortex ?

A
  • posterior lobes
  • specialised for perception.

Receives information such as:
pain
touch pressure
temperature

-Also primary visual and auditory cortex.

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16
Q

What is the function of the association cortex ?

A

Receives info from primary cortex.

  • involved in processing high amount of information.
  • any damage caused to this cortex, such as pain pressure temp and touch or auditory senses.
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17
Q

Small molecule transmitters in the CNS (3) :

A

1) Monoamines

2) Acetylcholine

3) Amino acids

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18
Q

What is the large molecule transmitter in the CNS ?

A

Neuropeptides

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19
Q

Where are nicotinic receptors found (Acetlycholine) ?

A

On muscle fibres

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20
Q

Where are the muscarinic receptors found ( Acetylcholine) ?

A

Found both peripherally, and in the CNS

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21
Q

What are the 3 catecholamines produced from tyrosine ?

A

1) Adrenaline

2) noradrenaline

3) Dopamine

These are all monoanimes

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22
Q

What is the function of noradrenergic receptors ?

A

involved in controlling alertness

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23
Q

What is the function of dopamine ?

A

Movement
Attention
Learning

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24
Q

What are the receptors for dopamine ?

A

D1,D2,D3,D4,D5

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25
Q

What does the degeneration of the dopaminergic neurone of the nigrostrital tract lead to ? ( what disease):

A

Parkinsons

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26
Q

What dopamine receptor has been related to schizophrenia ?

A

D2

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27
Q

What is the the precursor of serotonin ?

A

-Tryptophan

Which helps to make serotonin and melatonin.

melatonin helps regulate sleep cycle

serotonin regulates APPETITE, SLEEP, MOOD AND PAIN.

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28
Q

What are the 3 main amino acid transmitters (in the CNS) ?

A

1) Glutamic acid (glutamate)

2) GABA( Gabba amino butyric acid)

3) Glycine

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29
Q

What are the 3 ionotropic receptors ( Glutamic acid) ?

A

1) NMDA receptors

2) AMPA receptors

3) Kainite

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30
Q

What is synaptic plascity ?

A

The ability of neurones to strengthen their connections

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31
Q

NMDA receptors :

A

Controls a ion channel, ion channel is entry of sodium and ca+ ions

and exit of K+ ions.

  • This ion channel requires glycine as a co-agonist.

ion channel is inhibitied by Mg 2+ ions

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32
Q

Is GABA an inhibitory or excitatory type of amino acid ?

A

inhibitory

important in controlling neural activity, as well as preventing seizures.

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33
Q

What type of ion channel is GABBA associated with ?

A

Cl - ion channel

Divided into 2 different types : Type A and Type B

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34
Q

Type A

(GABBA A receptor)

A
  • When GABBA binds Cl- channel opens.
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35
Q

Type B receptor

(GABBA B receptor)

A
  • Receptor recognises different agonists/ antagonists

bringsabout inhibitory effects via G proteins

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36
Q

Glycine:

A

inhibitory transmitter

  • Also enhances the effects of NMDA receptors.

Located in the spinal cord and lower brain.

  • Similar to GABBA A receptor.
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37
Q

Where does Glycine bind to ?

A

binds allosterically to GLUTAMATE receptors.

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38
Q

Neuropeptides:

A

Around 50 qualify as actual neurotransmitters.

  • most well known are “opiates” in the CNS which bind to receptors in the brain.
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39
Q

What is the blood brain barrier (BBB):

A

A layer of epithelial cells in the brain.

Which has tight junctions between the cells.

Main function is to prevent entry of harmful toxins into the brain.

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40
Q

With regards to Blood brain barrier, what does adding more polar groups to molecules trying to get through the BBB do ?

A

will make it harder for them to pass through the BBB

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40
Q

In drug development and design, is it good or bad if frug enters the brain ?

A

Good if carrying out neurological treatment,

bad if carrying out any other type of treatment,

as to avoid neurological side effects.

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41
Q

What does ABC transporter stand for ?

A

ATP-binding cassette (ABC) transporter.

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42
Q

Whats an example of an ABC transporter ?

(ATP-binding cassette)

A

p-glycoprotein

This transporter can eject a lot of molecules, even before therapeutic concentration is reached.

^ not goog famalam

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43
Q

What are Nociceptors ?

A

Free nerve endings that are receptors for pain, everywhere except the brain.

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44
Q

sharp fast pain:

A

Carried out by A-fibres

0.1 seconds after stimulus

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45
Q

slow pain:

What type of neurones carry this out ?

A

carried out by unmyelinated C fibres.

1 second after stimulus.

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46
Q

What is superficial somatic pain ?

A

pain from nociceptors on the skin.

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47
Q

What is deep somatic pain ?

A

pain in a joint or tendon etc

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48
Q

What’s Visceral pain ?

A

Pain from organ nociceptors.

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49
Q

What are NSAIDs ?

A

Non-steroidal anti-inflammatory drugs.

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49
Q

How do local anaesthetics wot=rk ?

A

They work by reversibly blocking action potential

being carried along nerves.

E.g. by blocking Na+ voltage operated channels.

so nociceptor nerves can’t carry pain signals. Analgesia occurs

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50
Q

On a general basis during action potential generation is there more Na+ or K+ ions outside the cell ?

A

more Na+ ions INSIDE the cell

And more K+ ions OUTSIDE the cell

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51
Q

what are the 3 sequence of events that generally occur during the firing of an action potential ?

A

1) Polarisation ( Na+ ion channel opens, Na+ rushes into the cell)

2) Depolarisation (positive charge distributed)

3) Repolarisation ( K+ ion channel opens, K+ rushes out of cell, more negative potential on the inside).

Hence, the cell is repolarised

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52
Q

What does it mean when we say local anaesthetics are “use dependent” ?

A

This means that the faster the fire rate of a nerve (normally for smaller diameter neurones),

the more efficient the anaesthetic will be at blocking it.

This means they are more likely to enter Na+ VOCs that are open.

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53
Q

What is the general chemical structure of a local anaesthetic ?

A

1) Lipid-soluble hydrophobic AROMATIC group

2) Charged hydrophilic AMIDE group.

The bond between these groups determine whether the drug is a (amide or an ester)

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54
Q

For local anaesthetic what type of bond is stronger ?

A

The amide bond
is stronger than ester linkage

ester linkage can be easily broken.

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55
Q

If an ester linkage is more easily broken than an amide bond, what does this mean ?

A

This means that ester drugs are LESS stable and can’t be stored for as long as amide drugs.

Amide anaesthetics are also more heat stable,

and therefore, they can be “autoclaved” (sterilised by heat).

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55
Q

What has a less chance of causing an allergic reaction esters or amides ?

A

Amides

This is because the metabolism of esters produce PABA, which is associated with allergic reactions.

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56
Q

What does PABA stand for ?

A

Para-aminobenzoic acid

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57
Q

What are the 4 main ways of adminstering local anaesthetics ?

A

1) Surface anaesthesia, by topic application to skin or mucous membrane.

2) Infiltration anaesthesia, by subcutaneous injection.

3) Intracerebral anaesthesia

4) Intravenous anaesthesia

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58
Q

How does “infiltration anaesthesia” work ?

How is it administered

A

By subcutaneous injection,

causing nociceptive nerves to be blocked.

In dentistry “infilatration” is used more.

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59
Q

What is “Epidural” ?

A

Injecting the anaesthetic outside the “spinal dura mater”

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60
Q

What is intrathecal administration ?

A

Spinal injection into cerebrospinal fluid in the subarachnoid space.

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61
Q

What is the most commonly used topical anaesthetic ?

A

Lidocaine.

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62
Q

From what “poppy flower” does opium come from ?

A

Papaver Somniferum

was taken orally for 200 years as “ Tincture of laudanum”.

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63
Q

What actually is an opioid ?

A

Anything with “morphine- like actions”

including endogenous and synthetic agents.

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64
Q

What is a Narcotic ?

A

these drugs are used for opioids.

normally addictive drugs which are illegal.

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65
Q

What are the 3 opioid receptors called ?

A

1) mu

2) delta

3) Kappa

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66
Q

What type of receptors are the 3 opioid receptors classed as .

A

G protein coupled receptors,

which inhibit adenylyl cyclase

reducing the amount of intracellular cAMP (Cyclic AMP).

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67
Q

With regards to opioid receptors, what does “reducing 2nd messenger conc” do ?

A

Affects cell function.

stimulated opioid receptors,

Are able to inhibit the synaptic functions of neurones.

by acting on ion channels.

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68
Q

How do mu and delta opioid receptors, reduce neuronal excitability.

A

They cause K+ ion channel to open

hyperpolarising the nerve

harder to become depolarised

Reduction in neuronal excitability.

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69
Q

How do mu and delta opioid receptors, control potassium ion channels ?

Whatactually causes the K+ ion channel to open ?

A

1) Receptor inactive and unoccupied

2) An opioid agonist binds to the receptor and activates it,

and it’s g-protein diffuses across the membrane.

3) Activated g protein causes K+ channel to to open,

allowing the k+ ions to diffuse out the cells

cell loses positive charge, and hence becomes hyperpolarised.

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70
Q

What is the function of activated k-opioid receptors (kappa) ?

A

inhibits the opening of N-type Ca2+ channels.

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71
Q

How do k-opioid receptors have an affect on neuro transmission ?

A

inhibiting the n-type ca2+ channel,

will mean fewer vesicles will be released

reducing neurotransmission

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72
Q

Which type of the 3 opioid receptor is associated with producing “analgesia” ?

A

mu-opioid receptor.

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73
Q

What are the most common side effects of opioids ?

A

1) Respiratory depression (as respiratory centre becomes less sensitive to co2 in the blood), controlled by mu-receptors in the medulla.

2)Nausea and vomiting

3) Pupillary constriction

4) Constipation

5) Itching, bronchoconstriction, vasodilation, hypotension.

6) Sedation

7) Euphoria, controlled by mu- receptors

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74
Q

What’s the most common lethality from using opioids ?

A

Respiratory arrest.

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75
Q

What are strong opioids used for ?

A

to treat dull, visceral pain.

morphine
diamorphine
fentanyl
pethidine

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76
Q

What are weak opioids used for ?

A

To control mild-moderate pain

codeine (20% the potency of morphine)

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77
Q

What is epimerisation ?

A

Swapping from R to S chiral centres and vice versa.

Not beneficial

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78
Q

SAR of morphine ?

A

Exists as a natural single enantiomer

its unnatural enantiomer has no analgesic effect.

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79
Q

What are 2 other uses of opioids ?

A

1) cough supressing

2) Anti-diarrhoeal preparations.

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80
Q

Whats an example of a drug that acts as an opioid antagonist ?

A

Naloxone

this has affinity for all opioid receptor sub-types.

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81
Q

What are opiod antagonists used for ?

A

To reverse problems

such as respiratory depression etc.

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82
Q

Why might opiod antagonists be bad for opioid users ?

A

In opioid users they may cause unwanted side-effects (dysphoria)

However, in non-opioid users there will be very little effect.

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83
Q

Sigma receptor (for opioids):

A

These receptors are not blocked by naloxone.

not classified as true opioid receptors.

  • non-opioid drugs are also able to bind to sigma receptors (e.g. phencyclidine)

balances euphoric effects, with dysphoric.

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84
Q

What is the definition of “tolerance” ?

A

Tolerance is the increase in dose needed,

to produce a given pharmacological effect.

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85
Q

4 advantages of a tablet ?

A

1) Simple n convenient

2) allows for accurate dosing

3) can be used for both local and systemic treatment

4) cost effective (established manufacturing technologies).

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86
Q

3 Disadvantages of a tablet ?

A

1) may be difficult to administer to very young/elderly patients.

2) slow onset of action

3) Absorption and bioavailability can be difficult.

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87
Q

how to create extended release tablets ?

A

reduce solubility.

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88
Q

Delayed release tablet:

A

Drug is released after a certain period of time (e.g. 4-6hours).

The drug reaches the small intestine,
a change in pH causes the API to be released.

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89
Q

what is the most common type of delayed release tablets ?

A

Enterically coated tablets (EC).

the coating is gastro-resistant, and can withstand acidic conditions.

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90
Q

What 7 things are required for tablet formulation:

A

1) Diluents (fillers): bulk up the API. (e.g.lactose,starch)

2) Binders: Hold particles together (e.g. starch, modified cellulose, sugars)

3) Disintegrants: Break up the tablet into drug particles, to allow dissolution and absorption. (e.g. starch)

4) Glidants: Improve power flowability. (e.g. silicon dioxide)

5) Lubricants: to avoid punch face filming. (e.g. Mg and Ca)

6) Wetting agents: to improve interaction of water molecules with the tablet body and surface during disintegration and dissolution. (e.g. Sodium dodecyl sulphate SDS).

7) Others- ( colouring, sweetener and flavour).

  • Usually for chewable and effervescent tablets.

E.g. Riboflavin (orange) colourant.

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91
Q

Why have “tablet coatings” ?

A
  • increase palitibility by smoothening the surface
  • minimise unpleasant tastes
  • improve visual appearance
  • anti-counterfeiting measures
  • contain highly potent compounds in the body.
  • protect stomach from irritation, to to protect API from acidic stomach environment.
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92
Q

what are the 4 types of tablet coatings ?

A

1) film coating ( water based) 2-5% of tablet’s weight.

2) Sugar coating (20-50% of tablet’s weight)

3) Gelatine

4) Enteric coating

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93
Q

What are 3 factors that affect the rate of bioavailability ?

A

1) Disintegration (tablet breaks up into granules)

2) Deaggregation( granules break up into particles)

3) Dissolution( release of API)

At each stage the SA of the particles increases,

which means rate of dissolution increases.

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93
Q

what are caplets ?

A

Capsule shaped tablets

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94
Q

what makes up a big component of effervescent tablets ?

A

High sodium carbonate/bicarbonate content.

  • not usually formulated with a binder.
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95
Q

what are the most common drugs to treat neuropathic pain ?

A

gabapentin and Pregabalin.

can also be used to treat epilepsy.

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96
Q

What is neuropathic pain ?

A

When nerve fibres become damaged.

they send incorrect nerve signals to other pain receptors.

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97
Q

what do benzodiazepines do ?

A

make the actions of GABA more potent.

binds to regulatory site,
causiing change in shape of the GABAA receptor,

allowing it to bind more efficiently, giving a greater effect.

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98
Q

what do azapirones (buspirone) try to do ?

A

Reduce the release of 5-HT.

to try reduce anxiety.

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99
Q

What is ischaemia ?

A

when blood flow is restricted

causing the concentration of oxygen to be reduced

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100
Q

What does CECS stand for ?

A

Chronic exertional compartment syndrome

Usually during exercise.

lack of muscle control

blood can flow into an area, but can’t drain out

causing discomfort and swelling

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101
Q

what does DOMS stand foor ?

A

Delayed onset muscle soreness

muscle stiffness and muscle tenderness.

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102
Q

What is eccentric exercise ?

A

Exercise where your muscles act as “brakes”

e.g. when you try to slow down whilst running

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103
Q

Do muscles shorten or lengthen during eccentric exercise ?

A

They lengthen

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104
Q

What may cause DOMS what type of exercise might cause DOMS ?

A

Eccentric exercise

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105
Q

what is the normal path of treatment for “mild sport injuries” ?

A

NSAIDs

e.g. ibuprofen

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106
Q

What are “autacoids” ?

A

molecules which can alter the functions of other cells.

NSAIDs work by interfering with autacoids

They inhibit COX

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107
Q

what does Cyclo-oxygenase stand for /

A

COX

it is a derivative of arachidonic acid

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108
Q

What are the 2 isomers of cox ?

A

COX 1 : involved in homeostatic regulation

COX 2: present in low levels normally, but present in high levels during inflammation

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109
Q

what happens during inflammtion ?

A

Blood flows to the affected area

causing increased redness and warmth.

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110
Q

what makes up a group of eicosanoids ?

A

prostaglandalins

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111
Q

how do prostaglandins make histamines more potent ?

A

They increase post capillary venule permeability

causing swelling to be enhanced

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112
Q

what does anti-pyretic mean ?

A

Reduced temperature and fever

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113
Q

what’s an non-selective NSAID ?

A

inhibits both COX-1 and COX-2

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114
Q

What can inhibition of COX-1 lead to ?

A

reduced mucosal protection of the stomach,

And GI ulcers may be formed

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115
Q

What can inhibition of Cox-2 lead to ?

A

Therapeutic effect

Due to reduction in prostanoid synthesis

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116
Q

are NSAIDs OTC/P/POM ?

A

Mainly POM

Some may be OTC

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117
Q

what happens when an NSAID binds to a cox enzyme ?

A

binds reversibly

This binding, renders platelets unable to produce TxA2.

So they are not stimulated
and phospholipase C is not stimulated

So no inositol triphosphate is produced

which means Ca2+ levels does not increase and platelets remain inactive

viscosity of the blood DECREASES

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118
Q

CAn aspirin be used as an “antiplatelet” drug ?

A

yes

but only at low doses for mild to moderate pain

Also aspirin can bind to cox 1 irreversible

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119
Q

If aspirin binds irreversible to cox-1, how can we combat this ?

A

by producing NEW platelets

(takes 7-10 days)

the only way to bring platelet function back to normal

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120
Q

For arterial thrombosis, what is more effective “anti platelet drugs” or “anticoagulants” ?

A

Anti platelet drugs

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121
Q

What are the side effects of NSAIDs ?

A
  • gastric discomfort
  • nausea vomiting
  • indigestion (dyspepsia)
  • skin rashes
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122
Q

what happens if an asthmatic patient takes an NSAID ?

A

Their lung alveoli constricts.

may lead to an asthmatic attack.

NSAIDs must not be supplied to asthmatic patients

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123
Q

How do NSAIDs affect renal function ?

A

They reduce renal function

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124
Q

Why is renal function reduced when taking NSAIDs ?

A

inhibition of prostaglandins,

Causes renal artery to contract

which means blood flow to the kidneys is reduced

This may even lead to renal failure

Therefore NSAIDs are not supplied to patients with kidney injuries (AKI: Acute kidney injury)

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125
Q

What are the 3 main uses of NSAIDs ?

A

1) Analgesic

2) anti-inflammatory

3) anti pyretic

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126
Q

After a sports injury, how long must the patient wait before taking NSAIDs ?

A

48 hours

as first you want the natural healing mechanism from the “inflammatory pathway” to kick start the healing.

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127
Q

why were COX-2 inhibitors developed ?

A

To help remove the unwanted side effects that occurred by “COX-1 inhibition”.

E.g.(negating the effects COX 1 have on the gastrointestinal mucosa lining, allwoing it to be protected)

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128
Q

What is the difference between COX-1 and COX-2 binding sites ?

A

COX-2 has a bigger binding site and contains a “side-pocket”

COX-1 has a narrow binding site

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129
Q

do non-selective NSAIDs bind to COX-1/2 binding sites ?

A

Can bind to both

as they are small enough

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130
Q

How is “clot formation” prevented by cox-1 enzymes ?

A

They produce PGI

which acts against the TxA, that is released by platelets

preventing clot formation

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131
Q

Does administering a COX-2 inhibitor increase/decrease production of PGI ?

And how could this be dangerous ?

A

Decreases production of PGI,

but TxA is still produced by platelet COX-1.

which means the balance has shifted towards TxA,

increasing the risk of developing thrombosis.

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132
Q

What are the different ways NSAIDs have been altered, to limit or control side effects ?

A

1) Enteric coating (protect from stomach ulceration)

2) Soluble preparations- preventing NSAIDs to be concentrated in one area of the stomach.

3) Suppositories: provides an alternative absorption route.

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133
Q

What are the 3 main different types of capsule shell coatings ?

A

1) Gelatine (some can be used as a suppository as they are soft)

2) HMPC (Hydroxypropyl methylcellulose)

3) PVA ( polyvinyl alcohol)

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134
Q

is bioavailability high or low with capsule formations ?

A

High

As capsule shells are designed to dissolve rapidly when it comes in contact with GI fluids.

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135
Q

Why is Gelatine actually used to coat capsules ?

A
  • colourless translucent substance, which is tasteless
  • readily soluble in biological fluids at body temp
  • it is brittle when dry
  • And it is elastic when wet and forms a semi-solid gel.
  • cost-effective to produce
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136
Q

what are the potential disadvantages of using gelatine capsules ?

A
  • very sensitive to heat and moisture

so special packaging and storage may be required.

  • may cause solubility problems with different formulations
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137
Q

what are the components required to create “hard and soft gelatine capsules” ?

A

1) Gelatine

2) water

3) Colourants

4) Preservatives

5) excipients

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138
Q

Advantages of hard gelatine capsules (3):

A

1) can make it easier to administer very low doses (micro doses), due to semi-solid formulation.

2) fewer excipients required

3) better oral bioavailability than tablets

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139
Q

Disadvantages of hard gelatine capsules (4):

A

1) May be difficult to manufacture

2) capsule production used to be slower than tablet production, until “high speed capsule filling equipment was developed.

3) More costly to develop than tablets

4) Not all drugs can be encapsulated.

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140
Q

3 advantages of soft gelatine capsules:

A

1) A good choice for “non-palatable” solutions

2) Great for delivering lipid soluble drugs at low doses

3) Can be immediate, slow or sustained release, also an enteric coat can be added.

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141
Q

4 Disadvantages of soft gelatine capsules:

A

1) Restricts formulation that can be encapsulated

2) Hard to optimise manufacturing process

3) If one capsule breaks during manufacturing or whilst in storage, formulation could leak onto others

this leads to increase waste.

4) moisture sensitive drugs are incompatible with the “moist nature” of the soft gelatine capsules

5) They are temperature sensitive (contents inside should not exceed 35 degrees Celsius).

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142
Q

what’s one example of a hard gelatine capsule related to the musculoskeletal system ?

A

Diclomax SR

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143
Q

what’s one example of a soft gelatine capsule related to the musculoskeletal system ?

A

Nurofen liquid capsules

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144
Q

What is a pharmaceutical powder ?

A

API as crystalline solids that can be made into finely divided solids.

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145
Q

what are pharmaceutical granules ?

A

Like a powder but bigger particle sizes

  • big physical aggregates of powder particles.
  • help to increase “flow” and “compatibility”.
  • easier to handle when exposed to moisture than “powders”.
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146
Q

What are the 2 types of granulation ?

A

1) Dry granulation

2) Wet granulation

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147
Q

What is Dry granulation ?

A

Compaction of powder without water

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148
Q

What is Wet granulation ?

A

Addition of water to powder

followed by mixing and removal of the water.

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149
Q

What are the 2 different types of powders ?

A

1) Bulk powders: Found in large containers

2) Divided powders: Individually packaged pre measured doses.

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150
Q

4 Advantages of powder/granules formulation:

A

1) More chemically stable than liquid formulations

2) Easier to dispense in large doses

3) fast absorption rate

4) Advances in packaging tech, means that it is becoming easier to make divided doses easier to separate.

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151
Q

4 Disadvantages of powder/granules formulation:

A

1) Not as convenient as small containers of tablets

2) more difficult to mask unpleasant taste, to mask taste it has to be converted into “effervescent” form.

3) Hard to administer low doses

4) Can not be used for oral administration

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152
Q

The destruction of “what” causes rheumatoid arthritis ?

A
  • proliferation of synovium

-destruction of cartilage between joints, and also bone by “osteoclasts”.

  • inflammation of cytokines.
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153
Q

why might acute phase proteins, bind to infectious agents ?

A

To function as opsonins

-Enhancing the uptake by macrophages and neutrophils.

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154
Q

What are “autoantibodies” ?

A

Antibodies that react with “self-antigens”

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155
Q

Whats an example of an “autoantibody”

A

Immunoglobulin G

Also known as IgG or IgM

  • found in all Rheumatoid arthritis patients
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156
Q

Does IgG function as an antibody or an antigen ?

A

Actually it can function as BOTH and antigen and an antibody

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157
Q

what are the 2 types of “arthritis” ?

A

RA (autoimmune- body immune system cells attack the joints)

OA (wear and tear)

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158
Q

what are the long term drugs used to treat RA called ?

A

DMARDs

Disease modifying anti-rheumatic drugs

  • causes long term reduced swellings and joint pains
  • causes level of plasma acute phase proteins to decrease.
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159
Q

when do the effects of DMARDs start to kick in ?

A

3 months after

slow onset of action

  • in the mean time NSAIDs may be used to reduce symptoms
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160
Q

What is recommended, when starting a treatment with a DMARD ?

A

“short term bridging treatment” with a corticosteroid

  • to help control symptoms.

whilst waiting for the effects of the DMARD to kick in

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161
Q

Why may long term treatment with corticosteroids, not recommended ?

A

Due to adverse effects that may occur

  • wight gain
  • mood changes
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162
Q

What are the 2 main types of DMARDs ?

A

1) DMARDs that supress rheumatic disease process

2) Cytokine modulators (biologics) derived from antibodies

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163
Q

DMARDs that supress “rheumatic disease process” :

A

They supress or modify immune response

But this can also mean an increase risk of infections

due to interfering with the normal immunological response

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164
Q

How long does it take for the effects of “DMARD methotrexate treatment” to kick in when trying to treat RA ?

A

Takes 1 month

And treatment can then be long term with appropriate monitoring

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165
Q

How many times a week is DMARD methotrexate given ?

A

Once a week ONLY

usually by oral admin

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166
Q

What are the potential side effects of taking more DMARD methotrexate than recommended ?

A
  • nausea
  • stomatitis (inflammation of buccal lining)
  • liver cirrhosis
  • pneumonitis (inflammation of lung tissue)
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167
Q

Why might taking NSAIDs whilst on methotrexate be toxic ?

A

NSAIDs may reduce the rate of renal clearance of methotrexate

leading to increase risk of toxicity

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168
Q

what else might be harmful take, whilst on treatment with DMARD methotrexate ?

A

Trimethoprim

  • if taken together could lead to agranulocytosis or neutropenia

Agranulocytosis- deficiency of granulocytes in the blood, causing an increase in vulnerability to infections.

Neutropenia- low number of white blood cells in the blood

could be fatal

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169
Q

what can be taken to reduce the toxicity of methotrexate treatment ?

A

Folic acid

But should only be taken Once a week ONLY

and should not be taken on the same day as methotrexate.

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170
Q

What is Azathioprine ?

A

It’s a prodrug that acts as an immunosuppressant

by inhibiting the increase of B and T lymphocytes

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171
Q

What is a common use of the immunosuppressant “azathioprine” ?

A

To stop rejection from transplanting organs.

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172
Q

Side effects of Azathioprine ?

A
  • nausea
  • diarrhoea
  • vomiting
  • liver toxicity

-bone marrow suppression

  • increase risk of infections (due to potential over suppression of lymphocytes)
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173
Q

What is bone marrow suppression ?

A

Fewer blood cells being produced in the bone marrow

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174
Q

What is the first symptom of bone marrow suppression ?

A

Sore throat

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175
Q

What are Antimalarials ?

A

Drugs with long half lives

used to treat mild RA

  • not as effective as other DMARDs
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176
Q

When taking antimalarials, what type of examination is required ?

A

Eye examination

as retinopathy could occur (damage of retina) by taking antimalarials

  • patients may be advised to wear sunglasses
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177
Q

What does penicillamine treat ?

A

RA

but can mess up taste buds

and its enantiomer (L-penicillamine) is toxic as it inhibits the action of pyridoxine.

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178
Q

What does Sulfasalazine treat ?

A

A DMARD with fewer side effects than other DMARDs

reduces lymphocyte proliferation and cytokine production.

Treat ulcers and chron’s disease, and inflammation in the bowels.

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179
Q

Whats one way to reduce GI irration ?

A

Enteric coating

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180
Q

What are the 2 main types of corticosteroids ?

A

1) Mineralocorticoids (regulate salt and water balance)

2) Glucocorticoids ( regulate carbs, fats and proteins in response to stress).

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181
Q

What are corticosteroids used for ?

A

Anti inflammatory and immunosuppressant agents

by inhibiting phospholipase A2 and COX-2

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182
Q

What happens during adrenal suppression ?

A

1) Glucocorticoid levels rise in the blood

2) this is detected by the hypothalamus

3) Causes pituitary gland to secrete less adrenocorticotrophic hormone (ACTH).

4) Glucocorticoid synthesis is reduced

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183
Q

What do steroids kinda do ?

A

Kinda decrease the functions of the adrenal gland

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184
Q

What is “Cushing’s syndrome” ?

A

Redistribution of body fat

  • puffy facial cheeks
  • Thin skin- harder to heal from wounds and injuries.
  • Osteoporosis (weak bones)

caused by excess amount of corticosteroid hormones being released

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185
Q

What are “osteoclasts” ?

A

Cells that reabsorb bone by digging “pits”

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186
Q

What are osteo blasts ?

A

Cells that secrete “osteoid” (bone matrix) into the “pits” that osteoclasts dig.

  • The osteoid is then mineralised, resulting in calcium phosphate crystals being made.
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187
Q

What are bones made up of ? ( 3 things)

A

calcium

Phosphate

protein mesh work

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188
Q

What hormone controls the secretion of Ca2+ ions ?

A

Parathyroid hormone (PTH)

PTH is secreted by the parathyroid gland when Ca2+ conc is low.

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189
Q

What stimulates the activation of viatamin D ?

A

The reabsorption of Ca2+ ions by the kidney.

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190
Q

what does the hormone “calcitonin” do ?

A

-Inhibits “calcium mobilisation” (from bone to blood).

-And also decreases reabsorption from the renal tube.

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191
Q

What is “osteopenia” ?

A

Reduction of minerals in the bone

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192
Q

What is “osteoporosis” ?

A

Reduction in actual bone mass

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193
Q

How to treat osteoporosis ?

A

1) Hormone replacement therapy

2) Selective Oestrogen receptor modulators (SERMs): may help to (E.g. Raloxifene)

  • increase osteoblast activity
    -reduce osteoclasts

Raloxifene has a low bioavailability but is well distributed around the body.

3) PTH fragments: Help to increase bone mass by stimulating increase in osteoblast numbers. Given subcutaneously.

They do this by acting on GPCR
activating adenyl cyclase
and raise intracellular CA2+ levels

4) Bisphosphates: Promote apoptosis of osteoclasts, causing bone reabsorption to be inhibited.

  • given orally
  • due to potential GI irritation caused by food (milk). patient is advised to remain upright for 30 mins after taking drug.
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194
Q

What is “rickets” ?

A

condition that causes the softening of bones.

to prevent rickets increase vitamin D intake

  • In adults rickets is known as “osteomalacia”
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195
Q

What to eat to increase vitamin D intake ?

A

Eat oily fish (Salmon and mackerel)

eggs

margarine

cereal

sun light

can be administered as calcitriol (active form of vitamin D)

Or ergocalciferol (inactive form of vitamin D).

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196
Q

what is osteoarthritis (OA) ?

A

joint pain

long term condition

most common type of arthritis in the uk

develops in people over the age 45

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197
Q

Can paracetamol reduce prostaglandin synthesis ?

A

Sometimes it can in some situations

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198
Q

what is the toxic dose range of paracetomal ?

A

Around 10-15 grams

  • no symptoms occur for 24 hours after overdose.
  • but irreversible liver damage reaches peak by 72-96 hours.
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199
Q

How is paracetamol overdose treated ?

A

Ideally N-acetylcysteine should be administered with the first 8-10 hours of overdose.

  • this helps to speed up the replenishment of “glutathione”
  • potential liver transplant if damage too severe.
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200
Q

what is “gout” ?

A

Type of arthritis where crystals of sodium urate form around and inside joints.

  • acute joint pain in hands or feet due to excess uric acid.
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201
Q

Acute drug treatments for gout ?

A

1) Naproxen or NSAID

2) Colchicine - does not cause fluid retention unlike NSAIDs, so can be used in heart patients.

  • also may be toxic at high doses.

3) Corticosteroids: for people who cant tolerate NSAIDs.

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202
Q

Can aspirin be used to treat gout ?

A

No

can inhibit the nephron tubule from uric acid in urine.

causing build up of uric acid

not gooood.

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203
Q

Drug treatments for established gout :

A

Allopurinol

decreases production of uric acid by non- competitive inhibition of xanthine oxidase.

reverses deposition of crystals.

  • not used for for acute treatment.
  • painful as reduction in uric acid, causes crystals to dissolve, which escape into joint cavity and inflame the synovium.
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204
Q

What are the 3 steps to manage “nociceptive pain” created by “WHO” ?

(neurology card made late)

made after finished making cards for musculoskeletal.

A

1) Administer simple analgesics (paracetamol, ibuprofen)

2) Weak opioids

3) Strong opioids

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205
Q

What are the 2 most common drugs used to treat “neuropathic pain” ?

(neurology card made late)

A

1) Gabapentin (used first line)

2) Pregabalin ( used second line)

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206
Q

What’s a fun fact about gabapentin and pregabalin ?

(neurology card made late)

A

As well as being able to treat neuropathic pain

They can also treat “epilepsy”.

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207
Q

What do “benzodiazepines” do to GABA ?

(neurology card made late)

A

Potentiate GABA

by changing the shape of the “GABA type A receptor”, causing it to bind more efficiently to neurotransmitter and give a greater effect.

  • Also causes chloride channel to open, causing more Cl- ions to flow through the channel giving a greater inhibitory effect.
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208
Q

What “clinical effects” does the binding of benzodiazepines to its allosteric site produce ?

(neurology card made late)

A

induce sleep

reduced senses

mild amnesia

reduced muscle tone

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209
Q

What is the function of Azapirones (buspirone) ?

(neurology card made late)

A

To inhibit release of 5-HT

  • well absorbed
  • short half life

nausea and dizziness are common side effects.

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210
Q

What are the 2 types of dopamine receptors ?

(neurology card made late)

A

1) D1 type: D1 and D5 linked to ACTIVATION of adenylyl cyclase

2) D2 type: D2,D3,D4 subtypes
- linked to INHIBITION of adenylyl cyclase
- effective as antipsychotics.

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211
Q

What are the 2 class types for “anti-schizophrenic drugs” ?

(neurology card made late)

A

1) typical: first generation drugs
- chloromazapine, haloperidol

  • binds to D1 and D2 receptors
  • may lead to unwanted side effects

2) atypical: second generation
- Clozapine, risperidone

– more selectivity for D2 receptors
- May reduce unwanted side effects (by blocking 5-HT2A receptors)

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212
Q

What is the “cheese reaction” for MAOI ?

(neurology card made late)

A

A possibility of “hypertension” occurring for people who each cheese whilst taking a MAOI drug.

  • caused by an interaction with “tyramine”.
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213
Q

How is MAOI overdose treated ?

(neurology card made late)

A

To treat the hypertension, “phentolamine” can be given.

To treat hypotension, it is not treated with a drug, due to risk of developing “hypertension”.

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214
Q

How do “Tricyclic antidepressants” (TCAs) work ?

(neurology card made late)

A

Work by competitively inhibiting the reuptake of neurotransmitter from synapses.

  • Which means more NA and 5-HT remain in the synapses
  • Eventually, allowing mood to improve.
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215
Q

How is TCA overdose treated ?

And what are the side effects of TCAs ?

(neurology card made late)

A
  • Dry skin ( cant sweat)
  • Dry mouth
  • blurred vision

To treat administer “activated charcoal”

to prevent further GI absorption.

Seizures can be supressed with “diazepam”

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216
Q

What does SSRIs stand for ?

(Neurology card made late)

A

Selective serotonin reuptake inhibitors

Commonly prescribed as antidepressants

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217
Q

How do SSRIs work ?

(Neurology card made late)

A

-Work by INHIBITING 5-HT reuptake

-Causing increase in 5-HT concentrations

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218
Q

What actually happens when 5-HT is inhibited by SSRIs (acute and chronic treatment) ?

(Neurology card made late)

A

Acute treatment: Initially causes “autotecptors” to be activated
-to inhibit release of 5-HT.

Chronic treatment:
-Causes auto receptors to desensitise.
- causing an increase in the release of 5-HT.

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219
Q

What are the advantages of SSRIs ?

(Neurology card made late)

A
  • reduced antimuscarinic effects
  • safer overdose than an overdose of TCAs
  • don’t cause “cheese reaction” with MAOIs
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220
Q

Disadvantage of SSRIs ?

(Neurology card made late)

A

Only treat moderate depression

TCAs treat more severe depression

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221
Q

Why are SSRIs not recommended for patients under 18 years old ?

(Neurology card made late)

A

It can initially cause to become

Excessively Excited
And even aggressive
And even insomnia

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222
Q

What is the downside of treating with venlafaxine anti depressant) ?

(Neurology card made late)

A

higher risk of withdrawal effects compared to other anti depressants.

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223
Q

is treatment with anti depressants short term or long term ?

(Neurology card made late)

A

Long term

At least 9 months

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224
Q

When changing the anti depressant drug being administered, how long do you have to wait before administering a new SSRI or TCA ?

(Neurology card made late)

A

2-3 weeks following the last MAOI dose.

  • And MAOIs can not be introduced again for 3 weeks following TCA and SSRI therapy (5 weeks after fluoxetine).
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225
Q

What is one anti depressant that does not require a “wash out period” ?

(Neurology card made late)

A

Moclobemide (maoi)

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226
Q

Is overdose risk greater with TCAs MAOIs or SSRIs ?

(Neurology card made late)

A

TCAs

Except for lofepramine.

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227
Q

What plays an important part in “voluntary muscle control” ?

(Neurology card made late)

A

The basal ganglia

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228
Q

What is Parkinsonism a result of ?

(Neurology card made late)

A

Imbalance between excitatory and inhibitory inputs.

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229
Q

What is the most common parkinsonism ?

(Neurology card made late)

A

idiopathic parkinsonism

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230
Q

What causes idiopathic parkinsonism to occur ?

(Neurology card made late)

A

Neurodegeneration( loss of neurones) of the basal ganglia

causing a reduction in dopaminergic cells of the substantia nigra (modulates motor movement).

  • Also a net increase of INHIBITORY GABAergic output occurs.
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231
Q

What percentage of neurones is lost, even before symptoms for parkinsonism develops ?

(Neurology card made late)

A

Over 80%

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232
Q

What is Bradykinesia ?

(Neurology card made late)

A

slowness of movement

symptom of parkinsonism

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233
Q

What is tremor ?

(Neurology card made late)

A

Shaking

Most recognisable symptom of parkinsonism

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234
Q

What is postural instability ?

(Neurology card made late)

A

Affects ability to balance

increases risk of falling

Symptom of parkinsonism

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235
Q

Initially, what is the most effective oral drug to treat PD ?

(Neurology card made late)

A

Co-careldopa

Its a pro drug

A drug which must undergo metabolic processes before becoming pharmacologically acitve.

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236
Q

Can dopamine cross the BBB ?

(Neurology card made late)

A

No its too polar

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237
Q

What’s more polar levodopa or dopamine ?

(Neurology card made late)

A

levodopa

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238
Q

If levodopa is more polar, how can it cross the BBB ?

(Neurology card made late)

A

levodopa is an amino acid

so can take advantage of “protein carrier systems”

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239
Q

What happens to levodopa once it is in the brain after crossing the BBB ?

(Neurology card made late)

A

It is decarboxylated and converted into dopamine.

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240
Q

What enzyme decarboxylates levodopa to dopamine in the brain ?

(Neurology card made late)

A

Dopa decarboxylase.

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241
Q

What is present in co-careldopa, that causes inhibition oof dopa decarboxylase ?

(Neurology card made late)

A

Carbidopa

Carbidopa inhibits dopa decarboxylase

And therefore inhibits transformation of levodopa to dopamine.

  • causing side effects to be reduced.
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242
Q

What causes Alzheimer’s ?

(Neurology card made late)

A

Loss of cholinergic neurones in the hippocampus and frontal cortex.

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243
Q

What is used to treat Alzheimer’s ?

(Neurology card made late)

A

Acetyl-cholinesterase inhibitors

to increase conc of Ach

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244
Q

What the first choice of drug, to treat kids with epilepsy/seizures ?

(Neurology card made late)

A

valproate

  • increases GABA content
  • effective against both “Grand and Petit Mal seizures”.
  • used in children due to low toxicity
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245
Q

What are 3 examples of AEDs (antiepileptic drugs), used to treat adults with epilepsy/seizures ?

(Neurology card made late)

A

1) Phenytoin: effective for “absence seizures”

2) carbamazepine: Not effective for “absence, atonic or tonic seizures”.

3) Pregabalin and gabapentin

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246
Q

Do bronchioles have cartilage ?

A

Nah

They have “smooth muscle tissue” for contraction and to keep air ways open.

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247
Q

What are the sub types of bronchioles ?

A

Primary Bronchi

Secondary and Tertiary Bronchioles

Terminal bronchioles ( smallest and final branch of bronchioles)

Alveolar sacs

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248
Q

What are alveolar sacs made up of ?

A

Made up of “alveoli”

O2 enters the blood stream through alveolar sacs and Co2 is eliminated.

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249
Q

What type of cells is the respiratory tract lined with * trachea, bronchi, bronchioles) ?

A

pseudostratified ciliated columnar epithelial cells.

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250
Q

What do goblet cells do ?

A

Secrete mucus to trap particles, irritants and any unwanted pathogens.

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251
Q

What is the function of cilia in the respiratory tract ?

A

To waft mucus away from the tract.

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252
Q

When our breathing changes during exercise, what part of our nervous system responds, and how ?

A

Sympathetic nervous system

  • causes an increase in bronchiole calibre (bronchodilation)
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253
Q

if sympathetic nervous system takes care of our breathing during exercise,

what part of our nervous system takes care of our breathing throughout the day, making minor adjustments to bronchiole calibre when needed ?

A

parasympathetic nervous system

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254
Q

What happens during bronchodilation ?

A

1) smooth muscles in the walls of bronchioles RELAX

2) Allowing airways to open up

3) Decreasing air way resistance, and making it easier to breathe.

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255
Q

What is the opposite of bronchodilation ?

A

bronchoconstriction

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256
Q

What is bronchoconstriction ?

A

When bronchiole calibre constrict

Usually during periods of relaxation

to avoid inhaling too many small particulates.

  • Bronchoconstriction, leads to an increase in airway resistance.
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257
Q

What do bronchial smooth muscles cells secrete?

A

Beta2 adrenoreceptors

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258
Q

What are adrenoreceptors ?

A

“Adrenergic receptors”

receptors that respond to adrenaline and noradrenaline

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259
Q

What types of nerves “innervate” the bronchial smooth muscle ?

A

Postganglionic parasympathetic fibres.

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260
Q

Where are M3 (muscarinic receptors) found ? (2 places)

A

1) Bronchial smooth muscle for bronchoconstriction

2) Also found on glands to facilitate the secretion of mucus,

-M3 receptors are the most pharmologically important receptors of the 3 types of muscarinic receptors.

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261
Q

What are the 3 types of muscarinic receptors ?

A

M1, M2, M3

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262
Q

Where are M1 receptors found and what is their function ?

A

Located in the ganglia on postsynaptic cells

  • facilitates nicotinic neurotransmission.
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263
Q

What are M2 receptors and what is their function ?

A

They are “inhibitory auto receptors”

  • They mediate negative feedback on the release of ACh,

from postganglionic parasympathetic fibres.

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264
Q

What do inhibitory auto receptors try to do ?

A

Reduce release of neurotransmitters.

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265
Q

What are auto receptors ?

A

Receptors located in the the membrane of nerve cells.

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266
Q

What is Asthma ?

A

“recurrent reversible obstruction of air flow in the air way,

due to a stimuli which is not considered noxious (harmful),

and would not affect a non-asthmatic patient.

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267
Q

What are some examples of stimuli of asthma ?

A

Allergens
Such as drugs
aspirin
house dust mites
pollen
emotions
cold air
pollutants in the atmosphere
infections

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268
Q

Symptoms of asthma ?

A

Wheezing

coughing

tight chest

Difficulty breathing

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269
Q

What is FEV

A

Forced expiratory volume

in one second.

  • This is lower in asthma patients
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270
Q

What are the 2 main factors in asthma that actually cause reduced airflow ?

A

1) Bronchial hyper responsiveness

2) Inflammation in the airways

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271
Q

What are the stages on an asthma attack ?

A

1) Immediate bronchospasm (Early phase)

2) Bronchiole inflammation (Blood vessels dilate, oedema forms, excess mucus is produced). (known as “late phase”).

  • This is caused by eosinophils releasing inflammatory mediators.

3) Bronchiole smooth muscle contracts, lining of airway become inflamed

4) Leading to reduced airflow.

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272
Q

What is “bronchospasm” ?

A

Bronchoconstriction due to contraction of smooth muscle

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273
Q

What does it mean to be “atopic” ?

A

sensitive to allergens

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274
Q

What actually causes “allergic asthma” ?

A

Activated t cells

with t-helper 2 cells (Th2)

profile of cytokine production in the the bronchial mucosa.

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275
Q

Process that causes allergic asthma” inside the body ?

(Role of T lymphocytes in allergic asthma”)

A

1) APCs present the antigens of the allergen to CD4 T cells, via MHC class II (major histocompatibility complex).

2) These differentiate into Th0 lymphocytes

3) Th1, and clonal expansion of Th2 lymphocytes.

4) Th2 lymphocytes produce various cytokines

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276
Q

What are the cytokines produced by Th2 from “allergic asthma response”.

A

Interleukin 5 Interleukin 4 , Interleukin 13

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277
Q

What does Interleukin 5 do ?

A

Promotes differentiation and activation of eosinophils.

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278
Q

What does interleukin 4 and interleukin 13 do ?

A

Cause B cells and plasma cells to produce and release IgE

And allow the expression of IgE receptors on mast cells and eosinophils.

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279
Q

What does mast cell degranulation cause ?

A

causes the release of spasmogens (mediators of bronchoconstriction)

  • also causes the release of histamines, PGD2, cysLTs (leukotrienes C4 and D4 (LTC4 and LTD4)).

Early phase.

Chemotactic mediators are released in late phase. Late phase is mainly just the progression of inflammatory events from the “early phase”.

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280
Q

can mast cell degranulation happen in non-topic asthma patients ?

A

Yes

Can also happen in patients with normal levels of IgE.

can be triggered by respiratory tract infections.

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281
Q

Are anti histamines effective or not very effective against treating asthma ?

A

Not very effective.

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282
Q

How can EARLY PHASE bronchospasm be “reversed” ?

A

By treating with:

  • Beta2 adrenoreceptor agonists
  • CysLT receptor antagonists
  • Theophylline.
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283
Q

How can LATE PHASE bronchospasm be “reversed” ?

A

Inhibited by Glucocorticoids.

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284
Q

What can cross linking of over expressed IgE on mast cells lead to ?

A

Mast cell degranulation

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285
Q

General process of Early phase asthma ?

A

1) Allergic trigger or non specific trigger

2) Mast cells

3) Bronchoconstrictors and chemotactic mediators (Histamine, cysLT, PGD2)

4) Bronchospasm

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286
Q

General process for late phase asthma ?

A

1) Infiltration of Th2 cells and their cytokines they produced, and activation of eosinophils

2) mediators of inflammatory response
(CysLTs, adenosine, neuropeptides)

AND toxic proteins AND growth factors (smooth muscle cell hypertrophy, hyperplasia)

3) Airway inflammation/ air way hyper-reactivity (if epithelial is damaged)

4) Bronchospasm, coughing and wheezing.

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287
Q

What is smooth muscle hypertrophy ?

A

Increased size of smooth muscle cells and thickening of smooth muscle around airways.

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288
Q

What is hyperplasia ?

A

increased size of tissue or organ

due to excessive cell production

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289
Q

If epithelial is damaged what is likely to happen to the airways ?

A

Airway hyper reactivity

airways become very sensitive

-leads to a “steeper slope on the dose response curve”

-and also a greater “maximal response “ to the agonist.

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290
Q

What are the 2 types of drugs used to treat asthma ?

A

1) Bronchodilators- help to reverse bronchospasm

2) Anti inflammatory agents- help to prevent or inhibit the inflammatory components and causes of asthma.

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291
Q

Can some bronchodilators also have “anti inflammatory actions” ?

A

Yes

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292
Q

What type of receptors are b2-adenoreceptors ?

A

G protein coupled receptors

They need the help of a “g protein” to go between it and its target.

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293
Q

In what location do B2-adenoreceptors, need to form a “second messenger” ?

A

in bronchial smooth muscle

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294
Q

Process of how B2-adenoreceptors agonists cause “relaxation of bronchial smooth muscle”

A

1) Salbutamol/adrenaline bind to activated b2-adenoreceptor

2) This causes the G protein to activate.

3) The G protein then diffuses across the cell membrane, and comes into contact with “adenyl cyclase”

4) Adenyl cyclase then converts ATP into cAMP (Secondary messenger).

5) cAMP then diffuses into the cell and comes into contact with Protein kinase A (PKA), and activates it.

6) Activated PKA causes phosphorylation of the myosin-light chain kinase (MLCK).

7) This causes smooth muscle contraction of bronchi to be inhibited. Relaxation of smooth muscle.

8) Results in bronchodilation. Reducing asthmatic symptoms.

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295
Q

As well as smooth muscle relaxation, what other positives can B2-adenoreceptor agonists induce ?

A

Increased mucus clearance by an action on cilia in the airway.

  • inhibit mediators being released from “mast cells”
  • inhibits release of tissue necrosis factor-alpha.
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296
Q

What happens if too much salbutamol is being administered and how might this affect other areas of the body negatively ?

A

Too much salbutamol

means B2-adenoreceptor occupancy in airways is high

so any excess salbutamol will start to bind to other receptors

could bind to receptors in the heart
- which could cause palpitations or tachycardia. (by binding to B1-adenoreceptors)

could bind to receptors in the skeletal muscle by binding to b2-adenoreceptors. This may cause muscle tremor.

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297
Q

How is salbutamol synthesised from aspirin ?

A

1) “Fries rearrangement” of aspirin, causes a ketoacid to be produced

2) The keto acid is then esterified.

3) Bromination of the ketone allows for the introduction of an amino group by nucleophilic substitution.

4) Methyl ester and ketone then undergo reduction, and the N-benzyl group is removed.

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298
Q

What can be changed to the chemical strucutre of salbutamol, to increase the duration the drug acts for ?

A

Replacing the tert-butyl group with large alkyl groups

This lead to the production of the drug “Salmeterol”

  • twice as potent as salbutamol, and has an extended action of 12 hours. usually given twice a day.

Another long duration of action drug is “indacaterol”. Usually only given once a day.

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299
Q

What is the function of a muscarinic antagonist drug ?

A

To relax bronchiole constrictions

mainly used for treating COPD

by antagonising M3-muscarinic receptors on bronchial smooth muscle cells to cause relaxation.

  • may also have inhibitory effects on mucus secretion in asthmatic
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300
Q

Whats an example of a muscarinic antagonist drug ?

A

Ipratropium

  • Administered by inhalation.
  • max effect occurs after 30 mins
  • lasts for 3-5 hours
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301
Q

What happens if too high dose of ipratropium is being administered ?

A

May go rogue

may not be able to differentiate between muscarinic receptor subtypes.

E.g. May bind to M2 instead of M3-muscarinic receptors
- causing more Ach to be released
- causing more vagally-mediated bronchoconstriction.

  • This may cause a reduction in M3 antagonism at high doses of ipratropium.
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302
Q

What an example of a long lasting muscarinic antagonist drug ?

A

Tiotropium

lasts for at least 24 hours

time to increase FEV1 ( forced expiratory volume in one second) = 30 mins

time to increase to PEAK FEV1 (max effect) = 1.5-3 hours

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303
Q

How does parasympathetic innervation, cause bronchoconstriction ? (process)

A

1) Acetylcholine released from postganglionic parasympathetic nerves
and binds to M3 recepetors on bronchial smooth muscle cells

2) Sub unit of the g protein activates phospholipase C, which hydrolyses phosphatidylinositol 4,5-bisphosphate(PIP2) into diacylglycerol(DAG) and inositol 1,4,5-triphosphate (IP3)

3) IP3 binds to IP3 receptor located on he endoplasmic reticulum (ER)

4) Ca2+ released from intracellular stores of the ER

5) Ca2+ binds to calmodulin to activate myosin light chain kinase (MLCK)

6) Smooth muscle contracts when myosin light chain undergoes phosphorylation.

  • DAG may also stimulate entry of Ca2+ ions.
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304
Q

What part of ipratropium’s structure, makes it unable to cross the blood brain barrier ?

A

It’s quaternary nitrogen”

  • Ipratropium also has low systemic absorbance.
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305
Q

What is an epoxide functional group ?

A

Three membered ring containing oxygen.

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306
Q

What functional group does tiotropium contain ?

A

Epoxide group

  • very reactive
  • but hard for nucleophiles to enter “inside” the ring. Not enough space
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307
Q

What happens if intracellular levels of cAMP increase ?

A

Bronchodilation

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308
Q

What are the 3 proposed mechanisms of therapeutic actions of methylxanthines ?

A

1) Inhibits PDE (phosphodiesterase).
- levels of cAMP increase
- causes bronchodilation

2) Competitive antagonism at adenosine receptors (A1 and A2 receptors)

3) Activation of histone deacetylase
- An enzyme that inhibits the acetylation of core histones, that are required for the transcription of inflammatory genes.

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309
Q

What does the enzyme “histone deacetylase” do ?

A

Inhibits acetylation of core histones, required for transcription of inflammatory genes.

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310
Q

What are some unwanted effects of methylxanthines ?

A

1) interfere with sleep patterns

2) vasoconstrict blood vessels but will vasodilate most other vessels

3) GI irritation

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311
Q

What are some additional positive effects of methylxanthines ?

A

1) Increase renal blood flow, therefore increase glomerular filtration rate

2) Cause increased alertness

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312
Q

What is the recommended therapeutic window for methylxanthines ?

A

30-100 micromol

> 110micromol can cause adverse effects

> 200 micromol can be lethal

can cause serious CNS and cardiovascular effects, and even seizures.

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313
Q

How are methylxanthines normally administered ?

A

Either orally

or sustained release

or IV injection, followed by IV infusion

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314
Q

What type of drugs reduce the plasma conc of methylxanthines ?

A

Drugs which ACTIVATE P450 enzymes

such as

Carbamazepine, phenytoin and rifampicin.

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315
Q

What type of drugs increase the plasma conc of methylxanthines ?

A

Drugs which INHIBIT p450 enzymes

such as

Erythromycin, ciprofloxacin, diltiazem, fluconazole.

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316
Q

What acid is “leukotriene” produced from ?

A

Arachidonic acid

  • Leukotriene is a major inflammatory mediators

More specifically LTD4 and LTC4 (major mediators of bronchoconstriction)

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317
Q

What is the chemical structure of arachidonic acid ?

A

20 carbon

with 4 C=C bonds.

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318
Q

Why might aspirin be dangerous for asthmatic patients ?

A

Less than 10% of asthma patients

are very sensitive to aspirin

which means leukotrienes can not bind to their receptors.

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319
Q

When are leukotriene antagonists usually given ?

A

As a 3rd line drug along with inhaled corticosteroids and beta2 agonists

  • less effective at bronchodilation than salbutamol.
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320
Q

What are 2 examples of leukotriene antagonists ?

A

1) montelukast

2) Zafirlukast

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321
Q

What is a general rule of thumb for drug types used to treat early phase bronchospasm ?

A

Bronchodilators help to reverse early phase of bronchospasm

Whereas,

Glucocorticoids inhibit the inflammatory effects that occur during both phases.

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322
Q

Are glucorticoids high or low in lipid solubility ?

A

High

so crosses the plasma memmbrane easily

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323
Q

Mechanism of action of glucocorticoids ?

A

1) Cross plasma membrane

2) binds to intracellular receptors which “dimerise”

3) move towards the nucleus and interact with DNA

4) This causes transcription of genes to be modified

5) This induces synthesis of some proteins,
but may also inhibit the synthesis of other proteins.

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324
Q

3 main ways glucocorticoids induce anti-inflammatory actions:

A

1) enhance expression of lipocortin
- suppressing phospholipase A2
- Reducing formation of arachidonic acid and therefore leukotrienes.

  • limited evidence of annexin-1 (lipocortin) having therapeutic use in treating asthma.

2) Decrease the formation of Th2 cytokines
Inhibits:
- Activation of eosinophils
- clonal expansion of b cells dividing into plasma cells to produce IgE.

3) Reduce the synthesis of cytokines
- supressing early phase response to allergens.

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325
Q

Unwanted effects of Glucocorticoids ?

A

1) Metabolic effects
hyperglycaemia (high blood sugar)
- thinning of skin- easily bruised. Purple/red stretch marks.
- fat redistribution (onto neck shoulders and face)

2) Osteoporosis

3) Reduced growth in kids

4) Reduced ability to heal wounds

5) More susceptible to infection

  • It’s anti-inflammatory function may supress features of immune response.
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326
Q

What may happen if glucocorticoids are given over long periods of time ?

A

Cushing’s syndrome

  • too much of the hormone cortisol in the body

-fat on chest,tummy, neck or shoulders

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327
Q

How do glucocorticoids actually help when treating asthma ?

A

Simply by reducing or preventing inflammatory effects.

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328
Q

How are glucocorticoids given in clinical use ?

A
  • patients who require regular bronchodilators, are also considered to take “beclomethasone” along with it (glucocorticoid).
  • patient with acute asthma may require IV hydrocortisone and oral prednisolone (glucocorticoid)
  • If severity of clinical condition is deteriorating, a “rescue course” of prednisolone may be administered.
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329
Q

What are patients who inhale steroids advised to do, to avoid developing oral thrush ?

A
  • to gargle after inhaling
  • to use “spacers” in their inhalation device.
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330
Q

What is the benefit of using a “spacer” in an inhalation device ?

A

1) slows down aerosolid particles, increasing the amount of fine particles being deposited into the lungs.

2) Helps patients with reduced manual dexterity. Helps patients who find it hard to activate the pMDI by pressing down on the canister.

3) Reduces deposition of larger particles into the mouth and back of the throat.

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331
Q

What are the two most common agents used in a combination inhaler ?

A

1) LABA

2) Glucocorticoid

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332
Q

Do all combination inhalers only use 2 ingredients ?

A

No

Some use 3 agents (trim bow)

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333
Q

Do patients with combination inhalers need to still take theri “reliver inhaler” ?

A

Yes they do

The combination inhaler is just used prevention treatment.

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334
Q

Reasons why a combination inhaler might be prescribed ?

A
  • might be better at controlling symptoms
  • lower doses of inhaled corticosteroids needed: minimising risk of adverse effects.
  • More convenient for the patient
  • May be more cost effective
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335
Q

2 disadvantages of patients using combination inhalers ?

A

1) Possible lack of dose flexibility

2) may use inhaler to relieve bronchospasm, which means patient may inhale a much larger amount of steroid than intended.

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336
Q

What is the first line of treatment for asthma ?

A

salbutamol

for both acute and chronic asthma

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337
Q

What are the potential side effects of salbutamol ?

A
  • tremor in hands
  • nervous tension
  • headache

-cramps, palpitations

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338
Q

What 2 diseases is COPD a combination of ?

A

1) Emphysema (alveoli)

2) Bronchitis (bronchi)

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339
Q

What is the most common cause of COPD ?

A

Smoking

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340
Q

Except smoking what other things may cause COPD ?

A
  • Dust
  • exposure to chemicals
  • environmental exposures (second hand smoke).
  • Genetic (deficienccy of alpha-antitypsin)
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341
Q

What is the common age of COPD patients ?

A

50-80

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342
Q

What percentage of COPD pateitns have alpha 1-antitrypsin deficiency ?

A

1-2 %

its rare

lung function decline is faster for these type of patients than smokers.

As there is not enough antitrypsin to inhibit certain enzymes that cause lung damage.

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343
Q

Symptoms of COPD ?

A
  • Breathlessness
  • Chronic cough
  • Regular phlegm production 9may require antibacterial treatment).
  • Bronchitis in the winter
  • wheezing
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344
Q

What is winter bronchitis

A

When COPD patient gets a cold or flu in the winter. May cause winter bronchitis.

  • cant maintain normal oxygenation of blood
  • lips and tongue may be visibly blue
  • may lead to pulmonary hypertension
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345
Q

Clinical treatment of COPD ?

A
  • Bronchodilator therapy
  • as well as treatment usiing a nebuliser
  • Administering oxygen if needed.
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346
Q

When treating COPD, what can be given as an alternative to nebulisers ?

A

Aminophylline via IV administration.

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347
Q

For COPD patients how is continuous breathlessness usually treated ?

A

Short course of oral corticosteroid, such as prednisolone 30mg for 1-2weeks

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348
Q

First line of treatment for COPD ?

A

Short acting beta agonist/short acting antimuscarinic agent.

Salbutamol is an example of a short acting beta agonist.

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349
Q

Are glucocorticoids effective at treating COPD

A

NO

As in smokers HDAC activity is inhibited

explaining the lack of effect glucocorticoids have

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350
Q

Additional treatments for COPD patients ?

A

1) Immunised against influenza

2) Antibacterial treatments

3) Oxygen administration
- However be cautious for potential co2 retention

  • only 24% o2 is administered

4) Administration of mucolytic drugs ro reduce plegm production

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351
Q

What type of nerve stimulation, leads to sneezing and itching ?

A

Afferent nerve stimulation.

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352
Q

What are the 4 types of histamine receptors ?

A

H1,H2,H3,H4

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353
Q

Function of H1 receptor

A

involved in the defensive actions of histamine

  • coupled to Gq, inositol phospholipid metabolism, Ca2+ intracellular signalling pathways
  • Regulate intracellular Ca2+
  • some may be located in the CNS, and help with learning and memory.
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354
Q

Function of H2 receptor

A

Mediate gastric acid secretion

-generates cAMP as a secondary messenger

  • involved in cardiac function
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355
Q

Function of H3 receptor

A
  • Involved in cognition and appetite
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356
Q

Function of H4 receptor

A

Located on eosinophils and basophils and mast cells.

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357
Q

What histamine receptor is involved with allergic reaction ?

A

H1

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358
Q

What else does H1 receptor activation effect ?

A

causes blood vessels to dilate

which leads to vasodilation

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359
Q

What may happen when histamine is injected “intra-dermally” ?

A

Reddening (vasodilation)

  • increased permeability of post-capillary venules
  • stimulation of sensory fibres leading to CGRP (sometimes referred to as triple response).
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360
Q

What are antihistamines classed as ?

A

Inverse agonists

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361
Q

What di antihistamines do ?

A

reduce the level of activity at h1 receptors

and block the effects of histamine.

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362
Q

What is ephedrine

what does it do

A

Ephedrine is a a1-adenoreceptor agonist

produces local vasoconstriction

causes the opening of the nasal pathway

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363
Q

Where is ephedrine found in ?

A

Topical nasal decongestants

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364
Q

What may prolonged use of ephedrine lead to ?

A

Impaired activity of ciliary in the nasal mucosa

  • therefore can not be used for more than 7 days
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365
Q

How many generations of antihistamines are there ?

A

3

first,second,third

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366
Q

What generation of antihistamines is chlorphenamine ?

A

First

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367
Q

Properties of first gen antihistamines ?

A

1) lipophilic, can cross the BBB

2) may cause drowsiness and psychomotor impairment

3) Produce anti-muscarinic side effects, such as dry mouth, blurred vision, urinary retention, GI irritation.

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368
Q

What are some examples of 2nd gen antihistamines ?

A

Cetirizine and loratadine

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369
Q

Properties of 2ndd gen antihistamines ?

A

(non-sedating)

  • more hydrophilic/more ionised at certain pH.
  • Can not pass through BBB easily
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370
Q

What are 3rd gen antihistamines ?

A

Active metabolites of second gen antihistamines.

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371
Q

What is an example of a 3rd gen antihistamine ?

A

Desloratadine

  • its an active metabolite of loratadine.
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372
Q

What is the pharmacokinetics of 1st and 2nd gen antihistamines ?

A

1st gen are absorbed slowly

whereas as 2nd gen are absorbed fast from the gut

  • 1st gen undergo considerable first pass metabolism into inactive compounds
  • 2nd gen metabolised in the liver into active compounds
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373
Q

Half life of 1st gen antihistamines ?

A

10-20 hrs

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374
Q

Half life of 2nd gen antihistamines ?

A

2-20hrs

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375
Q

What are the 2 types of antihistamines ?

A

New and Old antihistamines

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376
Q

What are old antihistamines ?

A
  • cross the BBB and cause drowsiness and sedation.
  • can have antimuscarinic side effects
  • despite being old, they are still useful )e.g. to treat people who cant fall asleep due to hay fever, or to treat motion sickness).
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377
Q

What are new antihistamines ?

A
  • does not cross BBB
  • affects muscarinic receptors
  • produces fewer side effects
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378
Q

In regards to drug deposition into the lungs, where does the drug need to pass through to be effective ?

A

The oropharynx

just behind the oral cavity

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379
Q

According to the different locations of receptors scattered around the respiratory system,

where does:

1) Ipratropium bromide need to go

2) Salbutamol need to go?

A

1) trachea and bronchi )lower respiratory tract)

2) to bronchiole and alveolar region

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380
Q

What’s the difference in drug deposition between fine aerosols and large aerosol particles ?

A

Fine aerosols distributed on peripheral airways, but deposit less drug per unit surface area.

  • larger particle aerosols deposit more drug per unit surface area, but on the larger more central airways.
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381
Q

What are the most therapeutically effective types of aerosols ?

A

Heterodisperse aerosols

containing a wide range of particle sizes.

382
Q

What are the 3 different mechanisms of drug deposition depending on particle size in the lungs ?

A

1) Impaction:
-occurs in UPPER respiratory tract.
-particles with a diameter greater than 10um.
- large particles are swallowed, but this has no therapeutic effect

2)Gravitational sedimentation:
- particles with diameter less than 10um
- deposited in the LOWER respiratory tract.

3) Gravitational diffusion:
- occurs in particles below 0.5um.
- any not deposited, are exhaled during exhalation (sometimes even 80% exhaled).

383
Q

What is the general rule of thumb for where drug particles are deposited in the lungs, based on particle size ?

A

1) Diameter of 5-10um = deposited in UPPER respiratory tract

2) Diameter of 1-5 um = Deposited in the LOWER respiratory tract and alveoli.

384
Q

what are the 3 different types of inhalation devices ?

A

1) nebuliser

2) dry powder inhaler

3) meter dose inhaler

385
Q

what are the 2 types of nebulisers ?

A

1) Jet nebuliser- gas

2) ultra sonic nebuliser- liquid
(higher freq = smaller size of droplets produced)

386
Q

Advantages of nebulisers:

A
  • provide large doses with very little patient co-ordination or skill.
  • disposable nebulisers are cost effective
387
Q

Disadvantages of nebulisers:

A
  • consuming and inefficient
  • Drug wastage (50%)
  • however, the actual compressors supplying the air in a nebuliser are not low cost.
  • most of the drug tends to never reach the lungs (most of it either stays in the nebuliser or is released into the environment when breathing out).
  • only 10% makes it to the lungs on average.
388
Q

With regards to pmdi’s, what is the drug initially prepared as ?

A

suspension/solution in a select propellent

389
Q

Process of aerosol delivery from a pmdi ?

A

1) Small volume of drug is homogenously dispersed in a high vapour pressure propellant.

2) metering chamber is opened through an actuator nozzle (this is achieved by a meter valve)

3) Once open to the atmosphere, the high pressure contents of the metering valve, equilibrate with atmospheric pressure.

  • Contents are propelled rapidly through the nozzle, causing shear and droplet formation.
390
Q

Through the process a pmdi is active, what 3 things are happening to the propellent ?

A

1) evaporating

2) propelling

3) shearing

Ultimately, to reduce the size of droplets produced

391
Q

What percentage of drug from a pmdi tends to be deposited into the lungs ?

A

Only 10-20%

50-80% goes to the oropharyngeal region

392
Q

Increase in IFR (inspiratory flow rate), means what with regards to drug deposition into the lungs ?

A

Means a lower drug deposition into the lungs.

(Higher IFR=lower drug deposition

393
Q

how does fast inhalation effect drug deposition ?

A

Less deposition of drug into alveoli

  • as aerosol is more readily deposited by impaction in the bronchiole and oropharyngeal region.
394
Q

What is the cold freon effect ?

A

When freezing spray temperature, causes patient to stop inhaling the drug.

395
Q

Why is breath actuated pmdi better than regular pmdi ?

A
  • helps to reduce co-ordination difficulties
  • increased drug deposition into the lungs from 7.2% to 20.8%.
  • however, they dont improve lung deposition in patients who already have good pmdi technique.
396
Q

How have dpi’s been developed further to reduce the amount of effort the patient puts in whilst in inhaling ?

A

By adding a battery-driven propeller

  • which helps in the dispersion of the powder. without out too much effort inhaling.
397
Q

what things may effect the performance of nebulisers ?

A

1) susceptibility to hydrolysis

2) Light and heat

3) Presence of complex agents might affect solubility

4) conc near the “solubility limit” may cause precipitation.

398
Q

why must nebulisers be prepared as sterile products ?

A

Due to degradation of drugs and potential microbial growth.

399
Q

What happens if pH is too low in a nebuliser /

A

May induce bronchoconstriction

and coughing and irritation of the lung mucosa

400
Q

How does high drug concentration effect nebulisers ?

A

May cause drug output to decrease by producing foams

this is more common in ultra sonic nebulisers.

401
Q

What are the 4 things needed to create a pmdi ?

A

1) propellent (inert, quite unreactive, hydrophobic).

2) drugs

3) co-solvents (e.g. ethanol) (semi polar) (sensitive to moisture uptake)

4) surfactants- reduces its surface tension, thereby increasing its spreading and wetting properties

402
Q

What 3 things can vapour pressure dictate in a pmdi ?

A

1) force of emission of droplets

2) droplet size

3) where in the lung the drug deposits

403
Q

What determines the “force of emission of droplets” in a pmdi ?

A

The difference in vapour pressure and atmospheric pressure.

404
Q

What is the function of surfactants in pmdi’s ?

A

To disperse respirable particles in a suspension.

405
Q

What is the only excipient used in pmdi’s ?

A

Oleic acid.

406
Q

What is the purpose of “co-solvents” in pmdi’s ?

A

To bring the drug into solution

  • to achieve a homogenous distribution in the propellent.
407
Q

How are dpi’s initially prepared ?

A

From a pure drug substance

  • sometimes blends with lactose are prepared
408
Q

Why is lactose added in dpi’s ?

A

-To act as a diluent

  • to help disperse the drug and act as a fluidising agent to assist dispersion.
  • improves flow properties of the formulation.
409
Q

What is the definition of “respirable fraction” ?

A

Amount of drug that reaches the alveolar region

410
Q

How is the delivery efficiency of dpi’s increased ?

A

By increasing the surface roughness of lactose particles.

  • this increases the emitted dose as the lactose can carry more drug particles.
411
Q

What is the difference between salbutamol and salmeterol ?

A

1) salbutamol is SABA (max effect within 30 mins, duration of 4-6 hours), salmeterol is LABA (duration of 12-24 hours)

2) Salbutamol has faster onset of action than salmeterol.

3) Salbutamol has a smaller chain with no ether bond, whereas salmeterol has a longer chain with an ether bond.

412
Q

antibiotic defintion ?

A

Substance produced by microorganism or by chemical synthesis,

that kills or inhibits the growth of other microorganism

413
Q

Whats a bacillus ?

A

Rod-shaped bacteria

414
Q

Bacteriostatic def ?

A

Agents that INHIBIT growth of bacteria

415
Q

Whats a coccus ?

A

Spherical shaped bacteria

416
Q

Dermatophyte def ?

A

A fungal pathogen that causes skin, hair, nails and mucus membranes infections

417
Q

what is mycosis ?

A

infection caused by a fungus

418
Q

Vaccine def ?

A

Preparation of anti-genetic material that can be used to stimulate the development of antibiotics and therefore cause active immunity against a disease or specific number of diseases.

419
Q

Chemotherapy def

A

Treatment of disease using chemical substances

420
Q

Antimicrobal chemprophylaxis

A

Treatment of infection with chemical substances

421
Q

What are some examples of antibiotics that inhibit bacterial NUCLEIC ACID SYNTHESIS ? (6 examples)

A

1) trimethoprim

2) sulfonamides

3) quinolones

4) rifamycins

5) nitroimidazes

6) nitrofurantoin

422
Q

What is the biochemical pathway for the bacterial production of nucleic acids?

A

Pteridine + (PABA)P-aminobenzoic acid
Diphosphate
I

                         Dihydropteroic acid

                             I
                      Dihydrofolic acid
                              I
                       Tetrahydrofolic acid
                              I
                      Nucleic acid bases
  • between PABA and pteridine diphosphate, and dihydropteroic acid

1) enzyme: dihydropteroate synthetase
2) Drug inhibitor: sulphonamides

  • between dihydrofolic acid and nucleic acid bases

1) enzyme: dihydrofolate reductase
2) drug inhibitor: trimethoprim (inhibits it’s “1)”)

423
Q

What is co-trimoxazole usually used for ?

A

To treat a specific type of pneumonia infection that HIV and cancer patients are susceptible to.

424
Q

What is trimethoprim usually used for ?

A

Used to treat UTI’s

425
Q

How do quinolones work ?

A

Inhibit DNA gyrase

  • they also prevent “re-sealing” of DNA strands, so the DNA becomes damaged
  • classed as bacterialcidal
426
Q

How the chemical structure of fluoroquinolone’s better ? (3 reasons)

A

1) fluorine atom (only one): increase activity and cellular uptake

2) basic amine group (piperidine): forms a zwitterion with COOH,
Which helps pharmacokinetic aspects (e.g cellular uptake)

3) Cyclopropyl group: increases broad spectrum activity.

427
Q

What’s the most common used fluroquinolone in pharmacy

A

Ciprofloxacin

428
Q

What is the most commonly used nitroimidazole ?

A

Metronidazole

Effective for anaerobic infections

Commonly used in dental, skin,GI and GU infections

  • common side effect of these types of drugs is GI irritation/disturbance.
429
Q

What advice is given for patients on metronidazole ?

A

Avoid alcohol

430
Q

What is disulfiram for ?

And how does it work

A

-Used in the treatment of alcohol dependence

Works by inhibiting acetaldehyde dehydrogenase,
which makes it so the toxic by-product acetaldehyde accumulates more and more

431
Q

What drug has been associated with inducing disulfiram like reactions ?

A

Metronidazole ( a type of nitroimadazole)

432
Q

What is the most commonly used rifamycin ?

A

Rifampicin

433
Q

How do rifamycins work ?

A

Prevents RNA transcription by inhibiting RNA polymerase.

434
Q

What are rifamycins usually used to treat ?

A

Turberculosis (TB)

435
Q

Why is the nitro group for both nitroimadazoles and nitrofuratoins both important ?

A

The nitro group is reduced when the drug enters the bacterial cell wall.

  • this leads to the formation of a reactive species which destroys the DNA.
436
Q

What is daptomycin ?

A

A cyclic lipopeptide, that is only active against gram positive bacteria.

437
Q

How does daptomycin work ?

A

-Binds to bacterial membranes of growing and stationary phase cells

  • this causes depolarisation to occur
  • leading to rapid inhibition of protein,DNA and RNA synthesis.
438
Q

What are the available formulation types for daptomycin ?

A

Only available as

powder or

solution for injection or

Infusion

439
Q

What is endocarditis ?

A

Inflammation of the inner lining of the hearts chambers and valves

440
Q

How do daptomycin formulations need to be stored ?

A

In the fridge

441
Q

What are some What are some examples of antibiotics that inhibit bacterial CELL WALL synthesis ? (4 examples)

A

1) B-lactam antibiotics (penacillin,cephlasporin,carbapenems, monobactams).

2) Glycopeptides

3) Fosfomycin

4) Polymyxins

442
Q

what are bacterial cell walls made up of ?

A

Long peptidoglycan chains

that are cross-linked via pentaglycine bridges.

443
Q

what do penicillin/cephalosporin drugs do to bacterial cell walls ?

A

Make them weaker

  • This is because the shape of these drugs closely resembles the shape of some bonds that are formed in the cell wall.
  • also prevents pentaglycine links from forming in bacterial cell walls.
444
Q

What does the B-lactam ring structure for penicillin and cephalosporins determine ?

A

Drug activity

  • By making sure the drug molecules are the correct size/shape
445
Q

What are the 4 different types of penicillin ?

A

1) Natural

2) aminopenicillin

3) Anti-staphylococcal

4) Anti pseudomonal penicillin

446
Q

What is the general mechanism of action of penicillin ?

A
  • Inhibits transpeptidase
  • Therefore inhibits the final step in the synthesis of cell wall
  • Inhibits crosslinking of peptidoglycan.
447
Q

How does B-lactamase destroy penicillin ?

A

Hydrolyses the peptide bond of the beta-lactam ring.

  • causing the antibiotic to become ineffective.
448
Q

Natural penicillin:

A

Benzylpenicillin (penicillin G)
and
phenoxymethylpenicillin (penicillin V)

directly purified from penicillium mold.

449
Q

What type of gram bacteria is natural penicillin mainly active against ?

A

Gram positive

  • and they are vulnerable to B-lactamases.
450
Q

Is pencillin G sesitive to acid ?

if so how is it administered ?

A

Yes

  • it can react with water under acidic conditions
  • causing the beta lactam ring to break down in a hydrolysis reaction
  • stomach acid is not good for this
  • hence the drug is administered via parenteral administration (injection or infusion.
451
Q

Aminopenicillins:

A

Examples : Amoxicillin and ampicillin

  • Contain an amino group to improve physiochemical properties.
  • Vulnerable to B-lactamase
  • So are usually combined with a beta-lactamse inhibitor (amoxicillin or clauvulanic acid known as co amoxiclav)
452
Q

What type of gram bacteria is aminopenicillin mainly active against ?

A

Broad spectrum of activity

  • Gram positive and gram negative
453
Q

Out of amoxicillin and ampicillin, what is more commonly used and why ?

A

Amoxicillin as it has better absorption.

454
Q

Anti-staphylococcal penicillin:

A

Also known as penicillinase-resistant penicillin

E.g. flucloxacillin and temocillin analogues which have big R group side chains.

455
Q

What is the function of the big R group side chains of anti-staphylococcal penicillin ?

A

To prevent binding of staphylococcal B lactameses

  • Allowing them to be at least initially effective against staphyloccoccus.
  • But resistance to this has developed.
456
Q

Anti-pseudomonal penicillin:

A

Also known as extended spectrum penicillins

examples: Piperacillin and ticarcillin (a carboxypenicillin)

  • Broad spectrum and are only available with beta lactamase inhibitors (e.g. ticarcillin/clavulonic acid and pipercillin/tazobactam)
457
Q

Whats an example of a pro drug penicillin ?

A

Pivmecillinam

458
Q

What are the 2 most common cephalosporins ?

A

1) Cefalexin

2) Cefuroxime

459
Q

How many generations of cephalosporins are there

And what does their generation depend on ?

A
  • 3 generations
    first,second,third
  • depends on their spectrum of activity.
460
Q

which generation of cephalosporins penetrate and don’t penetrate the CNS and cerebrospinal fluid ?

A

2nd gen don’t penetrate CNS

3rd gen penetrate the cerebrospinal fluid when the meninges are inflamed

therefore 3rd gen cephalosporins are used to treat CNS infections, such as meningitis.

461
Q

What are some additional examples of beta lactam antibiotics ?

A

1) carbapenems- low bioavailability

2) Monobactams

  • Only used to treat resistant infections
  • when other drugs are no longer effective
  • or just to overall avoid resistance
462
Q

Why were additional beta lactam antibiotics developed ?

A

To deal with B-lactamase

and prevent them from producing gram-negative organisms that may be resistant to penicillin.

463
Q

What is the monobactam “aztreonam” only active against ?

A

Gram negative aerobic bacilli

  • due to an unsual spectrum of activity
464
Q

Why is cross reactivity noticeable between penicillin and cephlasporins ?

A

Due to similar side chains

therefore patients who are allergic to penicillin may also be allergic to cephalosporins.

465
Q

What’s the safest antibiotic to give to a patient with penicillin allergy ?

A

Aztreonam

As it is less immunogenic

due to many differences in their structure

466
Q

What is the most commonly used glycopeptide ?

A

Vancomycin

467
Q

What does vancomycin do ?

A

Effects cell wall synthesis

  • by inhibiting peptidoglycan formation
468
Q

Disadvantages of vancomycin ?

A

Can sometimes cause nephrotoxicity(toxicity in the kidney)

and ototoxicity( trouble hearing or balancing).

469
Q

What is the structure of vancomycin ?

A

Complex and rigid structure

  • aromatic rings unable to rotate.
470
Q

Why are aromatic rings unable to rotate in vancomycin good ?

A

Allows for very specific targeting of bacterial cell walls.

471
Q

explain the general chemical structure of vancomycin ?

A

1) peptide backbone is held by 5 hydrogen bonds with the cell wall peptide.

2) Dimerisation of vancomycin, to give a highly stable dimer, which acts as a steric shield

3) Access to transglycoside and transpeptidase enzymes is blocked.

472
Q

How did resistance against vancomycin develop ?

A

-Due to modification of the cell wall precursors,

-D alanine became replaced with D-lactic acid.

  • the loss of NH and therfore the hydrogen bond between vancomycin and the peptide weakens the binding
  • causing the antibiotic to become inactive
473
Q

What’s another example of a glycopeptide antibacterial ?

A

Teicoplanin

  • has similar structures to vancomycin
  • does not dimerise
474
Q

How does teicoplanin work ?

A

Its alkyl side chain anchors itself to the cell membrane allowing it to interact with the building blocks for cell wall synthesis.

475
Q

When is teicoplanin used ?

A

For serious infections caused by gram positive bacteria.

476
Q

Fosfomycin:

(glycopeptide)

A
  • inhibits first stage of intracellular bacterial cell wall synthesis

by blocking peptidoglycan synthesis

– Used in the treatment of UTI’s

477
Q

Polymyxins:

(glycopeptide)

A
  • Affect the cell wall
  • commonly used via nebuliser
  • polymyxin B is used in a combo with other meds in ear and eye preparations.
478
Q

Examples of antibiotics that work via inhibition of PROTEIN SYNTHESIS ?

A

1) tetracyclines

2) Aminoglycosides

3) Chloramphenicol

4) Macrolides

5) Oxazolidinones

6) sodium fusidate/fusidic acid.

479
Q

Via what site do tRNA mmolecules enter the ribosome ?

A

Via the A site

480
Q

What is the p site on a ribosome ?

A

Where the growing peptide chain is bound to tRNA

481
Q

What “ribosomal subunit”, do tetracyclines bind to ?

Once bound, what is their function ?

A

30S

  • And block tRNA molecules from entering the A site
  • Stopping the peptide chain from growing any longer.
482
Q

What’s one thing to note about administering tetracyclines orally ?

A

Must not be given with food that contains divalent cations (e.g. Ca2+,Mg2+, Fe2+)

This is because, this may cause insoluble complexes to form by chelation in the gut

  • reducing how efficiently the drug is absorbed
483
Q

What type of patients must tetracycline not be given to ?

A

1) Pregnant/lactating

2) children 12 and under

484
Q

Why should pregnant/children patients, not take tetracylines ?

A

1) Children: Tetracyclines will chelate with Ca2+ ions in bones and teeth, staining teeth yellow

2) Pregnant: Affects skeletal development in the foetus.

485
Q

how do aminoglycosides work ?

A

Cause the misreading of mRNA

  • coding for a non-functional peptide
486
Q

What is the most commonly used aminoglycoside ?

A

Gentamicin

487
Q

Is vancomycin a aminoglycoside ?

A

Nah

  • its a glycopeptide antibiotic
488
Q

What conditions to aminoglycosides work best in ?

A

Slightly alkaline conditions

e.g. pH 7.4

489
Q

Mechanism of aminoglycosides ?

A

1) Ionic interaction between cell membrane and aminoglycosides results in rearrangement.

2) This produces pores, which the drug can pass through.

3) Drug trapped inside cell and it accumulates

4) Leads to selectivity.

490
Q

What 3 aminoglycosides is gentamycin made up of ?

A

1) pupurosamine

2) garosamine

3) 2-deoxystreptamine

491
Q

Chloramphenicol:

A
  • Mainly used for formulating eye drops
  • Inhibits transpeptidation ( stops peptide bonds form forming between peptide chain and arriving amino acids).
492
Q

Side effects of chloramphenicol ?

A

bone marrow aplasia ( cant produce enough blood cells)

suppression of white and red blood cells

encephalopathy

optic neuritis: swelling, damages optic nerve.

493
Q

What “subunit” does chloramphenicol bind to on rRNA ?

A

23S (Found in the peptidyl transferase centre in the ribosome).

on 50S RIBOSOME

494
Q

How does chloramphenicol inhibit peptide bond formation ?

A
  • inhibits peptide bond formation

by interfering with positioning of the aminoacyl of tRNA in the A site.

495
Q

examples of macrolides ?

A

Erythromycin, azithromycin, clarithromycin

496
Q

Mechanism of macrolides ?

A
  • inhibit ribosome translocation, stopping peptide synthesis from synthesising any further.
  • may also inhibit cytochrome p450 enzymes
497
Q

side effects of macrolides ?

A

Nausea/ vomiting

498
Q

What’s better clarithromycin or erythromycin ?

A

Clarithromycin as it is more stable to acid and has better oral absorption

499
Q

What ribomal subunit do macrolides bind to ?

A

50S

just like chloramphenicol
so they should not be administered together

otherwise they will compete and be less effective.

500
Q

Whats the only lincosamide available ?

A

Clindamycin

501
Q

What ribosomal subunit does clindamycin bind to ?

A

50S

502
Q

What may clindamycin be used for also ?

A

bone and joint infections

such as osteomyelitis (inflammation of bone marrow).

503
Q

Mechanism of mupirocin:

A

Inhibits bacterial protein synthesis

  • by reversibly binding to isoleucyl tRNA synthase.
504
Q

What is mupirocin commonly used to treat ?

A

To eradicate MRSA from the nose

  • usually available in topical formulations.
505
Q

WHAT IS FUSIDIC ACID USED TO TREAT MAINLY ?

A

Staphylococcal infections

  • resistance is common
    so course length is normally short

usually given in combo with other antibiotics

506
Q

What is fusidic acid commonly used for ?

A

Skin infections

treated via topical route of administration

507
Q

What is the tablet formulation of fusidic acid known as ?

A

Sodium fusidate

508
Q

What is the mechanism of oxazolidinones ?

A

Its functional group ( oxazolidinone ring system) binds to 50S ribosome

  • preventing protein synthesis from occurring.
509
Q

What’s the only oxazolidinone available ?

A

Linezolid

  • only used under special supervision

serious side effects: diarrhoea, dizziness, fainting, fever, rash.

510
Q

What are the 4 main ways antibiotic resistance can occur ?

A

1) Production of inactivating enzymes (e.g. beta lactamases)

2) Decreased accumulation of drug

3) Ribosomal alternations: Ribosomal sites become modified so they have no affinity for drugs.

4) Development of alternative metabolic pathways

e.g. Sulfonamide and trimethoprim resistance occurs:

when modified dihydropteroate synthetase and dihydrofolate reductase enzymes are produced,

which have no affinity for drugs.

511
Q

What are the 2 ways large populations of resistant bacteria develop ?

A

1) Selection:
-In a population there may be resistant bacteria

  • drug kills all non-resistant bacteria
  • Resistant bacteria that remains can multiply and colonise the area.

2) Transferred resistance:

-Genes that encode for resistance can be transferred and distributed throughout the population.

  • Resistance genes are carried on plasmids, which are transferred during bacterial conjugation.

or the genetic material can be transferred through bacteriophages (which distribute plasmid DNA)

512
Q

What is bacterial conjugation ?

A

When bacteria transfer genetic material to one another through direct contact.

513
Q

is fungi eukaryotic or prokaryotic ?

A

Eukaryotic

514
Q

What things cause fungi to actually be pathogenic ?

A

1) mycotoxin production

2) Allergens

3) Inflammation

4) Tissue invasion

515
Q

What are the 3 types of fungi ?

A

1) True yeasts

2) Yeast like fungi

3) Moulds

516
Q

True yeasts (1/3 types of fungi) ?

A

example: cryptococcus neoformans

which causes pulmonary infections and “cryptococcal meningitis”.

cryptococcal means spreading from lungs to brain.

517
Q

Yeast like fungi (1/3 types of fungi) ?

A

example: candida albicans

cause oral thrush

and septicaemia (blood poisoning)

518
Q

Moulds (1/3 types of fungi) ?

A

Dermatophytes

  • digest keratin (athletes foot, ringworm)
  • Aspergillus fumigatus: grows freely on airway lesions, causing pulmonary aspergillosis (mould forming in the lungs).
519
Q

How can antifungal drugs work to achieve selective toxicity?

A

By selectively targeting the “ergosterol” that fungi produce.

520
Q

Disadvantage of antifungal drugs ?

A

Some may be toxic

521
Q

What are some examples of antifungals which belong to the “Polyenes” group ?

A

Amphotericin and nystatin

  • interact with ergosterol in fungal cell membranes forming open pores.
  • cell contents are then uncontrollably lost through these pores.
  • fatally damaging the cell (fungicidal)
522
Q

What is the general route of administration for amphotericin ?

A

intravenous infusion.

523
Q

What is renal tubular acidosis ?

A

When the kidneys ca no longer move acid, from the blood into the urine.

524
Q

What is nephrocalcnosis ?

A

deposition of calcium salts into the kidney

525
Q

What is azotaemia ?

A

Build up of nitrogen, creatine and other waste products in the blood /

526
Q

As amphotericin has a high possibility of anaphylaxis (severe allergic reaction), what precaution should be taken first ?

A

1) Take a test dose

2) Carefully observe for signs of anaphylaxis for at least 30 mins.

527
Q

Why is amphotericin described as a “tunnelling molecule” ?

A

This is because,

it interacts with lipids and sterols of fungal cell membranes to create holes

  • allowing the cell contents to empty
    resulting in cell death
528
Q

What properties of amphotericin allows it to create pores ?

A

Its hydrophobic/hydrophilic nature

  • allowing a cluster of molecules to come together to create pores.
  • tunnel is lined with polar OH groups, which helps the polar contents of the cell to drain way.
529
Q

Can nyastatin be used parenterally ?

A

Nah too toxic

530
Q

can nyastatin be absorbed orally ?

A

Nah

531
Q

What is nyastin normally formulated into ?

A

Oral suspension

that is held in the mouth for as long as possible.

  • provides local action to treat oral mycoses
532
Q

Examples of antifungals that belong to the “IMIDAZOLES group ?

A

1) Miconazole (powder/spray/oromucosal gel)
2) Clotrimazole( used as pessary)
3) ketoconazole (greatest systemic absorption)
4) Econazole
5) tioconazole

  • the last 2 are less common in practice.
533
Q

Mechanism of imidazoles ?

A

inhibit synthesis of ergosterol
- disrupting the structure of the fungal membrane.

  • cellular constituents then leak out into the extracellular environment.
534
Q

How are imidazolse normally administered ?

A

Topical administration

due to low oral absortipon

535
Q

is miconazole a CP450 inhibitor ?

A

Yes

536
Q

Although sytemic absorption is low for miconazole, what may happen ?

A

Some of the drug may still be absorbed from the Gi tract and even buccal absorption.

537
Q

What the only imidazole that has great oral absoprtion ?

A

ketoconazole

  • therefore is used to treat systemic mycoses
538
Q

Disadvantage of ketoconazole ?

A

There is a risk of hepatotoxicity when used orally.

  • could cause adrenal insufficiency
  • Ketoconazole no longer has an MA to provided orally.
539
Q

Examples of antifungals which belong to the “TRIAZOLES group”

A

1) Fluconazole
2) Itraconazole
3) Posaconazole
4) Voriconazole

  • can be administered orally
  • less chance of causing adrenal sufficiency than ketoconazole (an imidazole).
  • but can still cause hepatoxicity
540
Q

Itraconazole:

A

Toxic in pregnant women

  • may cause heart/liver related problems.
541
Q

What kind of environment does itraconazole require ?

A

An acidic environment in the stomach.

542
Q

What caution label does itraconazole have ?

A

Label 5: “Do not take indigestion remidies 2 hours before or after you take this medicine”

543
Q

Why does itraconazole have cautionary label 5 ?

A

indigestion remedies may decrease gastric acid, decreasing the absorption of itraconazole.

544
Q

What weird tip is given for patients with low gastric acidity taking itraconazole capsules ?

A

Take it with a carbonated drink

e.g. non-diet cola

to increase bioavailability in patients with low amounts of gastric acid ( which may be due to either disease or medication they take).

  • can only be used with capsule formulation.
545
Q

what’s the most commonly used triazole in practice, as an oral antifungal ?

A

Fluconazole

  • no Cl group so not toxic
546
Q

What triazoles are used to treat severe infections ?

A

Posaconazole and voriconazole

  • or used if other treatments don’t work.
  • these are rarely seen in practice.
547
Q

What are examples of antifungals which belong to the “ECHINOCANDIN antifungals” group ?

A

Caspofungin

micafungin

Anidulafungin

548
Q

How do echinocandin antifungals work ?

A

They work by inhibiting 1,2-beta-d-glucan synthase

  • which is an enzyme essential for production of cell walls in some fungi.
549
Q

What type of diseases do echinocandins work against ?

A

Aspergillus and candida

550
Q

How are echinocandin antifungals administered ?

A

Only administered parenterally

due to their large molecular size, and extensive tissue protein binding

not effective against CNS infections
-CNS penetration is low

551
Q

Whats the most commonly used echinocandin antifungal ?

A

Caspofungin

  • used for severe cases
552
Q

Flucytosine antifungal:

A

it is converted into 5-fluororacil

which inhibits DNA synthesis

side effects (2): Hepatoxicity and bone marrow suppression.

  • Only used to treat severe infections.
  • not used alone due to high probability of resistance.
553
Q

is griseofulvin still used as an antifungal in practice ?

A

Nah

554
Q

For skin/nail infections what is the first antifungal of choice ?

A

Terbinafine.

555
Q

What is amorolfine ?

A

Available as a “nail lacquer” (nail polish) for fungal nail infections.

556
Q

What is a virus in simple terms ?

A

Organisms that infect other microorganisms

  • rely on hosts for replication
  • may be either single/double stranded DNA/RNA
  • surrounded by a protein coat (capsule/plasmid).
557
Q

What is may the capsid of a virus surrounded by ?

A

May have a lipoprotein envelope derived from host’s plasma. Membrane

  • which may also contain some viral glycoprotein.
558
Q

What is a virus known as when it is OUTISIDE of the host ?

A

A virion

559
Q

What is the general mechanism of a virus replicating ? (6)

A

1) Attach themselves onto host cells by using binding sites on their capsid or envelope protein, to bind to receptors.

2) Once attached, endocytosis then occurs and brings the virus receptor complex into the cell.

3) It is then uncoated by the host’s lysosomal enzymes.
- Allowing viral genes to use the host’s cellular structure to produce copies of itself.

4) The mRNA produced is then translated into peptides by host cells.
- these peptides can then produce enzymes.

5) RNA polymerase then produces copies of viral RNA. Other enzymes synthesise copies of viral structural proteins.

  • All this leads to the creation of copies being created of the original virus.
560
Q

How are viral protein coats produced ? (3)

A

1) RNA retrovirus contains a reverse transcriptase enzyme

2) once inside the host cell, they will synthesise DNA from their RNA template.

3) Newly synthesised DNA is then inserted into a hosts DNA,
where it undergoes transcription, to form viral RNA and viral protein coats.

561
Q

What happens once viral DNA, gets into the host’s cell ? (2)

A

1) Viral DNA gets transcribed into mRNA, via the host’s RNA polymerase, leading to the production of viral specific proteins

2) Once viral DNA and protein coats have been produced,
- virions will then be released either by lysis of the host cell or budding.

562
Q

What are the 2 types of specific immunological response ?

A

1) Humoral immune response (antibody mediated immunity)

2) Cellular immune response (cell-mediated immunity).

563
Q

What is the function of memory cells ?

A

Recognise the same antigens on subsequent exposures.

  • resulting in a more rapid response, as plasma cells are formed quicker
564
Q

what happens on initial contact with an antigen ?

A

1) They will proliferate to produce memory cells and cytotoxic t lymphocytes ( CD8/killer t cells), T helper cells(CD4), natural killer t cells(NK) and suppressor t cells.

2) infected cells will present the viral peptides on their surface (APC’s). This is complexed with MHC molecules, which are recognised by t lymphocytes.

565
Q

How might viruses make themselves undetectable ?

A

By inhibiting the presenting of MHC peptide complexes.

  • However, some natural killer t cells, may still attack cells with abnormal MHC expression.
566
Q

How might a virus be able to avoid NK cells ?

A

By inducing expression of a MHC class I homologue,

which is very similar to the host’s MHC.

567
Q

Can virus inhibit cytokines ?

A

Yes

  • which causes interference with immune responses.
568
Q

What is the function of antiviral drugs ? (4)

A

1) inhibiting viral penetration of host cells

2) inhibiting nucleic acid synthesis

3) inhibiting proteolytic enzymes (enzymes that break down proteins)

4) inhibiting viral exit of cells.

569
Q

What are examples of antiviral drugs that stop host cell penetration and inhibit viral exiting ?

A

Oseltamivir and zanamivir

  • they are neuraminidase inhibitors.
  • inhibit influenza virus neuraminidase enzymes, which are glycoproteins found on the surface of virions.
  • can prevent/reduce symptoms of influenza (if administered within 48 hours of the first signs of infection).
  • still used to treat influenza, but are normally saved to treat more high risk patients.
570
Q

What are examples of antiviral drugs that inhibit nucleic acid synthesis ?

A

DNA polymerase inhibitors

NRTIS’s (nucleoside reverse transcriptase inhibitors)

NNRTI’s (nucleoside non reversible transcriptase inhibitors)

Protease inhibitors (PI’s)

571
Q

What is the most commonly used DNA polymerase inhibitor ?

A

Aciclovir

572
Q

What are DNA polymerase inhibitors,

and why is their structure helpful ?

A
  • Guanosine analogues.
  • Allows it to bind to DNA polymerase and inhibit it. This is due to its structure being so similar to guanosine.
573
Q

How can aciclovir act as a chain terminator ?

A

As it lacks the OH group normally present in DNA bases on the 3’ carbon position of the sugar ring.

574
Q

What is the actual mechanism of aciclovir ?

A

Its a pro drug

-So it is converted into it’s aciclovir monophosphate by thymidine kinase.

  • The host cell then converts aciclovir monophosphate into aciclovir tri phosphate
  • inhibiting DNA polymerase and viral DNA synthesis.
575
Q

How can aciclovir be administered ?

A

Orally (even though absorption is low) (Valganciclovir)

IV ( Side effects most common with IV administration). (Ganciclovir)

Topically (skin/eye)

576
Q

What are side effects of aciclovir ?

A

Nausea, headache, rash, nephrotoxicity (caused by drug crystallisation in the kidney).

577
Q

What type of aciclovir has higher solubility ?

A

The one with more polar functional groups

which is famciclovir

  • it undergoes ester hydrolysis, to reveal the alcohol group, which is then phosphorylated. Also the purine ring under goes oxidation.
578
Q

Why might some viruses be immune to these drugs ? (Acyclovir)

A

Low/ lack of enzyme thymidine kinase.

579
Q

What are some examples of NRTI’s ?

A

Zidovudine

Abacavir (similar to guanosine)

Didanosine (Similar to adenosine)

Emtricitabine

Lamivudine (Similar to cytosine)

Stavudine (similar to thymidine)

Tenofovir Disoproxil

  • Used in the treatment of HIV.
580
Q

Zidovudine:

A

NRTI

Undergoes phosphorylation into its triphosphate.

  • This then competes with thymidine triphosphatase as a substrate for reverse transcriptase enzymes.
581
Q

How many times a day can zidovudine be administered orally ?

A

Twice a day

582
Q

Why might some patients not be able to tolerate side effects of taking zidovudine ?

A

May be partly caused DNA polymerase.

Side effects: Nausea,headaches,anaemia, neutropenia.

583
Q

What is the mechanism of zidovudine ?

A

Its function is to inhibit the nucleoside reverse transcriptase, which is unique to HIV.

  • Zidovudine lacks 3’ OH group, so once it is incorporated into a DNA chain,
  • the chain is terminated as no other nucleotide can go on to form a new 3’-5’ phosphodiester bond.
584
Q

Examples of NNRTI’s:

A
  • Efavirenz
  • Etravirine
  • Nevirapine

-Rilpivirine

  • Also used to treat HIV
  • orally administered, and have long plasma half lives). Around 50 hours. So is given once a day
585
Q

HOw do NNRTI’s work ?

A

Drugs that bind to the active site of reverse transcriptase enzymes and denature them.

  • These drugs are metabolised by the liver
  • They also induce cytochrome P450 enzymes.
586
Q

Side effects of NNRTI’s ?

A

Rash, nausea, vomiting, abdominal pain, diarrhoea, headache, fatigue, hepatoxicity.

587
Q

Examples of viral protease inhibitors ?

A

Atazanavir

Darunavir

Lopinavir (available along with ritonavir)

Ritonavir

Saquinavir

Tipranavir.

  • Also used to treat HIV
588
Q

How does HIV actually induce viral potency ?

A
  • mRNA is translated into polyproteins that are initially inert.
  • virus specific proteases then convert these poly proteins into viral proteins.
  • which cleave the poly proteins at certain points.
589
Q

Integrase inhibitors:

A

Drugs that inhibit the enzyme integrase

Makes it so viral dna can not be injected into hosts dna

  • used in combination with other HIV drugs.
590
Q

Whats one example of an integrase inhibitor ?

A

Raltegravir

591
Q

Active immunisation:

A

Vaccines

  • catching a cold then recovering.
  • injecting a killed/modified microbe.
    It is harmless, but still antigenic.
  • Toxin can also be administered (A toxoid)
  • If host comes into contact with antigens again, then antibodies are rapidly produced.

may take anywhere from a few days to a few weeks to be effective.

  • booster injections required in order to maintain immunity.
592
Q

What are 3 specific examples of active immunisation ?

A

1) Live attenuated: live but weakened organisms that express antigens.

2) Inactivated vaccine: Heat-killed / chemically inactivated pathogens.

3) Absorbed vaccines: Inactivated vaccines,
absorbed onto aluminium hydroxide,
releasing antigenic material slowly, more antibodies produced.

593
Q

Passive immunisation:

A

Administering antibodies harvested from immune human/animal donors, or using in vitro engineering and cloning techniques.

594
Q

When does passive immunity end ?

A

Once adminstered antibodies have degraded naturally.

  • immunity lasts for around 2 weeks
  • can be used in emergency situations.
595
Q

What are the 2 types of glands ?

A

1) Exocrine glands

2) Endocrine glands ( slow to start response and have a long duration of response)

596
Q

What do exocrine glands do ?

A

Secrete hormones onto epithelial surfaces via ducts.

597
Q

What do endocrine glands do ?

A

Secrete hormones directly into the circulatory system.

598
Q

Where are the hormones stored in endocrine glands prior to release ?

A

In intracellular vacuoles or granules.

599
Q

what are paracrine and autocrine

A

Paracrine are hormones that act on a different target cell

autocrine are hormones that act on the same cell.

600
Q

What are the 5 main stages of hormone regulation and secretion ?

( example: production of thyroid hormones)

A

stage 1: low/high level of “thyroid hormones” is detected by the hypothalamus.

stage 2: hypothalamus synthesises thyrotropin releasing hormone (TRH), which then passes onto the anterior pituitary

stage 3: TRH stimulates the anterior pituitary to release thyroid stimulating hormone (TSH) into the blood.

  • This is detected by thyroid epithelial cells
  • production of T3 and T4 increases. - - This is also regulated by TSH.

stage 4: Thyroid levels in the blood increase

stage 5: Hypothalamus detects increasing levels of thyroid hormones in the blood. production of TRH decreases, thyroid hormone production is reduced.

601
Q

How is T3 and T4 actually produced ?

A

The enzyme “thyroperoxidase” allows for the incorporation of iodide onto tyrosine residues of thyroglobulin

  • producing T3 and T4 within the lumen of the thyroid.
  • this is then endocytosed back into the follicle cell, and secreted into the blood plasma.
602
Q

What is there more of T3 or T4 ?

A

T4

603
Q

What has a faster turn over rate T3 or T4 ?

A

T3

604
Q

Where is T4 mainly found (thyroxine) ?

A

in the circulation

605
Q

Where is T3 mainly found (tri-iodothyronine) ?

A

mainly found intracellularly.

606
Q

With regards to T4, what happens to it once it is within the target cell ?

A

It is converted into T3

which then interacts with a nuclear receptor,

to regulate transcription of genes.

607
Q

What is the effects of T3 and T4 ?

A
  • stimulating metabolism
  • increased oxygen consumption
  • increased regulation of growth and development
608
Q

What converts T4 into T3 ?

A

D2 ( 2-deiodinase)
- which is found on the ER

609
Q

What thyroid receptor does T3 bind to ?

A

RXR-TR heterodimer

(TYPE OF THYROID RECEPTOR)

610
Q

What is hyperthyroidism ?

A

Over reactive thyroid

611
Q

What are the symptoms of hyperthyroidism ?
(thyrotoxicosis)

A
  • high metabolic rate
  • high temperature
  • sweating
  • tremor
  • tachycardia
  • weight loss
  • increase in appetite
612
Q

What is Radio-iodine ( treatment for hyperthyroidism)

A

When radioactive iodine is injected and taken up by the thyroid.

  • the radioactive decay then damages the cells
  • eventually leading to hypothyroidism.

radio-iodine is normally used when the other drugs don’t work.

613
Q

What drug can treat hyperthyroidism ?

A

Carbimazole

614
Q

How does carbimazole treat hyperthyroidism ?

A
  • reduces iodination of thyroglobulin
  • therefore decreasing synthesis of thyroid hormones.
  • works by inhibiting thyroperoxidase
615
Q

what is propylthiouracil ?

(hyperthyroidism treatment)

A

A thyroperoxidase inhibitor

  • given when carbimazole is not effective.
616
Q

How does giving “iodine” treat hyperthyroidism ?

A

Works by decreasing vascularity,
of the thyroid gland.

  • also reduces hormone secretion.
  • not used as long term treatment.
  • normally given 10-14 days prior to “thyroidectomy”
617
Q

what 2 beta blockers are used to treat graves disease ?

A

Propranolol

Atenolol

  • used to treat symptoms.
618
Q

What is graves disease ?

A

Type of auto-immune disease.

  • more immunoglobulins directed at TSH receptor
  • leading to an increase in thyroxine secretion.
  • common sign/symptom protruding eye balls.
619
Q

What is hypothyroidism ?
(myxoedema)

A

Either an auto-immune

or drug induced condition.

620
Q

What are the symptoms of hypothyroidism ?

A
  • low metabolic rate
  • slow speech
  • lethargic
    -bradycardia
  • sensitivity to cold
  • thick skin
621
Q

What is Hashimoto’s thyroiditis ?

A

Thyroid hormone deficiency since birth

  • leads to slow growth
622
Q

What is normally given to treat Hashimoto’s thyroiditis ?

A

Levothyroxine
(T4)

  • given orally
  • mechanism of action: mimics the effects of endogenous hormones.
623
Q

What is given to treat Hashimoto’s thyroiditis in emergencies ?

A

Liothyronine (T3)

as an injection

  • quicker onset by doesn’t last as long as T4.
624
Q

What are the 2 endocrine organs the two adrenal glands are made up of ?

A

1) Adrenal cortex- outer layer.

2) Adrenal medulla- inner layer.

625
Q

What are adrenal cortex hormones known as ?

A

Adrenocorticosteroids.

626
Q

What are the 2 classes of activity of adrenocorticosteroids ?

A

1) Glucocorticoid activity- zona fasciculata

2) Mineralocorticoid activity- zona glomerulosa

627
Q

What do the “glucocorticoid activity” adrenocorticosteroids do ?

A
  • they have an effect of the metabolism of carbs and protein.
  • also have strong anti-inflammatory effects.
628
Q

What do the “Mineralocorticoid activity” adrenocorticosteroids do ?

A
  • Affect water and electrolyte balance.
629
Q

What’s an example of glucocorticoids and mineralocorticoids ?

A

1) Gluco - Hydrocortisone (cortisol)

2) Mineralo- Aldosterone.

630
Q

How are active steroids synthesised from cholesterol ?

A

Cholesterol
I
Pregnenolone
I

Aldosterone, Hydrocortisone, Testosterone
Oestradiol.

631
Q

Where is CRF released from ?

A

Corticotrophin releasing factor

  • released from the hypothalamus.
632
Q

What is the purpose of CRF ?

(HPA)

A

To stimulate the anterior pituitary

  • to release ACTH(Adrenocorticotrophic hormone).
  • which them stimulates,

glucocorticoid production in the adrenal cortex.

633
Q

What is HPA ?

A

hypothalamo-pituitary-adrenal axis.

  • process of regulating levels of steroids.
634
Q

How are levels of mineralocorticoids regulated ?

A

by the

renin-angiotensin system.

635
Q

How can sudden withdrawal from long term prednisolone treatment cause acute adrenal crisis ?

A

not enough cortisol being produced

to combat sudden stop of prednisolone.

636
Q

What is there more of in the pancreas exocrine or endocrine tissue ?

A

Exocrine

637
Q

What is the exocrine tissue of the pancreas for ?

A

For the production of digestive enzymes.

638
Q

What is the endocrine tissue in the pancreas for ?

A

Synthesising and secreting hormones.

  • islets of Langerhans.
639
Q

What are the 4 main cell types islets of Langerhans are composed of ?

A

1) Alpha cells- secrete glucagon

2) Beta cells- secrete insulin
- also secretes amylin

3) Delta cells- secrete somatostatin

4) PP cells- Secrete pancreatic polypeptide.

640
Q

Function of glucagon ?

( released when blood glucose is low)

A

increase blood glucose

Break down glycogen into glucose

641
Q

Function of insulin ?

(released when blood glucose is high)

A

Decrease blood glucose

  • by increasing uptake of glucose into tissues.
  • Promotes synthesis of glycogen to glucose.
642
Q

Function of somatostatin ?

A

Inhibits secretion of glucagon and insulin.

643
Q

Function of amylin ?

A

Amyloid peptide

  • delays gastric emptying (fart)
  • stimulates the break down of glycogen in striated muscle.
    ^ as a means to increase blood glucose
644
Q

what are incretins

A

protein hormones

645
Q

What is the main function of incretins ?

A

To modulate glucose metabolism

by stimulating the release of insulin

and also inhibiting the release of pancreatic glucagon from alpha cells.

also slows down the rate of absorption of digested food (by decreasing gastric emptying).

646
Q

with regards to insulin what can parasympathetic nerves do ?

A

Can act on muscarinic receptors to stimulate secretion of insulin.

647
Q

with regards to insulin what can sympathetic nerves do ?

A

Can act on alpha2 adrenoreceptors to inhibit secretion of insulin.

648
Q

What is the mechanism for the secretion of insulin from pancreatic beta cells.

A

Following an increase in blood glucose:

1) Glucose enters pancreatic beta cells by the glucose transporter (GLUT2).

2) Glucokinase then phosphorylates glucose into glucose-6-phoshphate,
- which is then metabolised by glycolysis and the TCA cycle.
-causing an increase in ATP and decrease in ADP.

3) increase in ratio of ATP:ADP, causes the inhibition of ATP sensitive K+ channel.
- causes K+ to accumulate within the cell. Slightly increasing the positive charge of the cell.
- This leads to partial membrane depolarisation , causing voltage gated Ca2+ channel to open.

4) Ca2+ then moves into the pancreatic beta cells.
- an increase in intracellular levels of Ca2+, stimulates EXOCYTOSIS of secretory granules containing insulin via vesicles.

649
Q

What is the overall consequence of insulin being secreted ?

A

Ultimately, results in movement of nutrients from the blood into tissues.

  • To meet energy demands for physical movement etc.
650
Q

What are some examples of “short term” cellular events triggered by activation of inuslin receptors ?

A
  • immediate metabolic effects
  • recruiting glucose transporters (GLUT4)
    to the plasma membrane, so glucose can move into the cell.
  • Activation of the enzyme “glycogen synthase” to promote synthesis of glycogen.
  • gluconeogenesis and break down of glycogen is inhibited.
651
Q

What is GLUT 4 ?

A

An insulin sensitive glucose transporter present in muscle and fat cells.

652
Q

What are the short term immediate metabolic effects from insulin activation regulated by ?

A

Kinase and phospholipase enzymes.

653
Q

What is an example of “long term” cellular events triggered by activation of insulin receptors ?

A

promotes gene expression

  • synthesis of enzymes involved in the regulation of blood glucose, cell growth and cell division.
654
Q

What are the events and effects that occur after insulin has binded to a insulin sensitive receptor.

A

1) Insulin binds to it’s receptor on the target cell

2) insulin receptor consists of 2alpha and 2 beta sub units.
- the beta sub units have intrinsic tyrosine kinase activity.

3) Insulin binds to alpha sub units on the extracellularly on the membrane
- promoting auto phosphorylation of tyrosine residues on the intracellularly.

4) tyrosine phosphorylation of adaptor proteins occurs
- examples of adaptor proteins: IRS-1 (insulin receptor substrate) which contains 22 tyrosine residues.

5) Phosphorylated tyrosine residues act as a docking sites for signalling proteins which contain SH2 domains ( such as PI3 kinase).
- proteins which contain SH2 domains bind to phospho-tyrosine stuff.

6) - occupied insulin receptors aggregate into clusters, which are then internalised into vesicles. This results in down regulation of the receptor at the membrane.
These receptors are then recycled back into the plasma membrane.

655
Q

What does PI3 kinase do ?

A

phosphorylates PIP2 into PIP3.

656
Q

What does PIP3 do ?

A

Recruits protein kinase B

so it can mediate 2 signalling response mechanisms:

  • maintenance of blood glucose homeostasis - immediate metabolic effects of insulin
657
Q

What are the 2 signalling response mechanisms that protein kinase B regulates ?

A

1) PKB signalling: to promote movement of GLUT 4 vesicles to the plasma membrane.

2) PKB phosphorylates: deactivates glycogen synthase kinase (GSK-3).
- which leads to the activation of the enzyme glycogen synthase and the synthesis of glycogen.

658
Q

What is type 1 diabetes mellitus caused by ?

A

T-cell mediated autoimmune response causes,

  • the destruction of the pancreatic beta cells that produce insulin.
659
Q

for t1dm patients, what causes the “increased urine vol” ?

A

Osmotic diuresis

660
Q

What is osmotic diuresis ?

A
  • increased urination due to the presence of certain substances (urinary glucose and ketone bodies) in the fluid filtered by the kidney
  • this fluid then becomes urine
  • The actual osmosis process causes more water to come into the urine

therefore leading to an increase in urine volume.

661
Q

what are ketone bodies ?

A

Product of metabolism of fats.

  • they are toxic
662
Q

what are the symptoms of t1dm ?

A
  • weight loss
  • premature growth in kids.
  • low insulin levels
663
Q

How are low insulin levels treated for t1dm patients ?

A

Insulin replacement

664
Q

Why are type 1 diabetes mellitus patients treated with insulin replacement ?

A

To avoid ketosis
- which could lead to coma or be fatal

if untreated

  • to control maintenance of blood glucose to prevent or delay onset of long term symptoms.
665
Q

Why is insulin only administered parenterally ?

A

This is because it is a “peptide”

and is therefore quickly destroyed in the GI tract.

666
Q

What is the half life of inuslin once absorbed ?

A

around 10 mins

to break down/ avoid toxic levels accumulating:

  • as enzymes inactivate it in the liver and kidney.
  • Also 10% of it is secreted in urine.
667
Q

How does “renal impairment” affect dosage requirements of insulin ?

A

Reduces it.

  • insulin clearance decreases due to renal impairment.
668
Q

After how many hours would insulin return to basal level following a meal ?

A

2-4 hours.

Note: This is for insulin therapy

669
Q

What are 4 types of classes of insulin therapy ?

A

1) Rapid acting

2) Short acting

3) Intermediate acting

4) long acting

670
Q

What is rapid acting insulin therapy ?

A
  • Insulin Aspart (novorapid) and insulin lispro (humalog)
  • onset of action is 15 mins
  • duration of action: 2-5- hrs
  • mimics the effects of insulin to cope with a meal.
  • administered before or after a meal.
671
Q

What is short acting insulin:

A
  • soluble insulin (Actrapid)
  • Onset of action is 30-60 mins
  • duration: up to 8 hrs
  • Administered 15-30 mins before a meal via injection.
672
Q

What is intermediate acting insulin:

A
  • isophane insulin (insulatard, humalin I)
  • Suspension of insulin with protamine
  • onset of action: 1-2 hrs,

max effects: 4-12 hrs

Duration: 16-35 hours

injected once or twice daily.

673
Q

What is long acting insulin:

A
  • Insulin zinc suspension: Insulin Glargine (Lanctus) (Injected once a day).

Insulin Detemir (Levemir) (Injected twice a day).

  • Finely divided solids which are injected as a suspension, which insulin is slowly absorbed.
  • reaches a steady level after 2-4 days.
674
Q

Why might protamine zinc and insulin not be used ?

A

Rarely used

  • as it may bind with soluble insulin when mixed in the same syringe.
675
Q

What is Biphasic insulin:

A

Either rapid or short acting

mixed with intermediate acting insulin

Example: NovoMix
( 30% insulin aspart, 70% insulin aspart protamine).

676
Q

What are the 5 factors to consider for formulation of insulin ?

A
  • Sterility
  • stability ( of API in water)
  • Isotonicity ( API/excipient concentration).
  • pH ( if pH isn’t right may cause changes at the site of administration such as irritation.
  • Local effects: May cause “local effects” at the site of injection.
677
Q

What happens if stability of API in water isn’t great for insulin ?

A

often if solubility isn’t great it is overcome using other solvents,

to formulate the product as a powder for reconstitution prior to admin.

678
Q

For insulin lispro, what analogues are switched ?

A

Lys and pro

are switched

  • allowing it to act rapidly, but for a shorter time than natural insulin.
679
Q

For insulin glargine how are analogies modified ?

A

Asparagine is substituted with a glycine on the A chain.

  • to provide a constant basal supply off insulin.
680
Q

For insulin aspart (Novorapid) how are the analogues modified ?

A

Substitution of Pro 28 to Asp.

Reduces it’s tendency to form hexamers, giving it a higher rate of absorption.

681
Q

What is associated with type 2 diabetes ?

A

Insulin resistance

and impaired insulin secretion

682
Q

What 2 things cause tissues to become unresponsive to insulin ?

A

1) Down regulation: loss of insulin receptors from the cell surface.

2) Impaired signalling mechanisms: which recruit GLUT-4 (impaired signalling to glut-4)
so glucose can not bind to it and enter cells.

683
Q

Process of how impaired insulin secretion happens ? (5)

A

1) high sugar and carbs, causes high levels of insulin.

2) Tissues become unresponsive to insulin due to 2 things: Down regulation and impaired signalling mechanisms.

3) insulin sensitive tissues become unresponsive and resistant to insulin.

4) Pancreatic Beta cells produce more insulin in attempt to increase glucose uptake into cells, resulting in “hyperinsulinemia”

5) Eventually, pancreatic beta cells become depleted of insulin causing impaired insulin secretion.

684
Q

What is IGT ?

A

impaired glucose tolerance

Pre diabetic state of hyperglycaemia.

Above normal levels of both blood glucose and insulin after a glucose test.

685
Q

What is a glucose test ?

A

large quantity of glucose given as an oral solution to drink.

  • level normally observed after 2 hours.
686
Q

What type of drug class is metformin (type 2 diabetes) ?

A

Biguanide

687
Q

Pharmacodynamics of metformin ?

A
  • reduces hepatic glucose production (gluconeogenesis).
  • also increases uptake of glucose and utilisation in skeletal muscle.
  • reduces absorption of carbohydrates
  • reduces levels of LDL and VLDL.

low density lipo protein

very low density lipo protein

688
Q

What are the side-effects of metformin ?

A

1) Anorexia

2) Diarrhoea

3) Nausea

4) GI-related effects

689
Q

What is the most serious side effect of metformin ?

A

Lactic acidosis

  • more likely in patients with reduced drug elimination
690
Q

Except for treating type 2 diabetes, where else might metformin be used ?

A

Heart patients

691
Q

Pharmacodynamics of sulphonylureas ?

A
  • stimulating insulin secretion, reducing plasma glucose.
  • action on the pancreatic beta cells
  • so it is only effective if there are functional beta cells available.
  • not used in t1dm
    or late type 2
692
Q

where are sulfonylureas receptors present ?

A

SUR1 receptors

present on the ATP sensitive potassium channel in the pancreas.

  • sulfonylureas block the output of potassium channels.
  • which results in partial membrane depolarisation, triggering the activation of Ca2+ channels.

^ entry of Ca2+ and exocytosis of secretory granules containing insulin.

693
Q

Pharmacokinetics of sufonyureas ?

A
  • well tolerated
  • most common side effect is hypoglycaemia
    ( dependedn ton the specific one given)
694
Q

Why are long acting sulphonylureas avoided in elderly patients ?

A

Due to their reduced renal function

this also applies to patients with renal impairment.

695
Q

What are the 3 main sulfonylureas ?

A

1) Tolbutamide - lowest potency and duration (6-12hrs)

2) Glipizide- medium potency and duration (16-24hrs)

3) Glibenclamide- highest potency and duration (18-24hrs)

696
Q

What are the 2 main thiazolidinediones (glitazones) used ?

A

1) Pioglitazone- however, associated with increased risk in heart failure so not to be used in heaert patients.

2) Rosiglitazone: the MA for this has been withdrawn.

697
Q

Pharmacodynamics of glitazones ?

A
  • bind to the nuclear receptor PPAR ( proliferator activated receptor)
  • After ligand binding, PPARs form heterodimers with retinoid X receptor alpha (RXR-a).
  • Then undergo a conformational change,

which facilitates binding to “peroxisome proliferative response element (PPRE) in the enhancer regions of target genes.

698
Q

What are some of the pharmacodynamic effects of glitazones ?

(4)

A

1) reduce insulin resistance in inuslin sensitive tissue: by increasing transcription of GLUT-4 glucose transporters, therefore ccausing uptake of gluccose to increase.

2) Reduce hepatic glucose output

3) Reduction of fatty acid as an energy source: increases utilisation of glucose.

4) Reduction in small dense LDL

  • Slow onset of effect
    maximal effect is around 1-2 months after treatment.
699
Q

How do thiazolidinediones cause reduction in fatty acids as an energy source ?

A

Acts on PPAR in adipocytes, promoting adipogenesis.

700
Q

What are some common unwanted side effects of glitazones ?

(2)

A

-Due to enhanced expression of genes that regulate fat metabolism, and fluid volume

unwanted side effects:

1) Weight gain- due to differentiation of adipocytes and increase in lipogenesis.

2) Fluid retention- due to reabsorption of NA+ in the renal collecting ducts. causing plasma vol to increase up to 500ml, and also a reduction in haemoglobin conc.

701
Q

What is adipogenesis ?

A

fat laden cells accumulate as adipose tissue

702
Q

What is lipogenesis ?

A

Metabolic formation of fat from glucose.

703
Q

What do glucosidase inhibitors inhibit ?

A

Inhibits the enzyme glycoside hydrolase (glucosidase).

  • leading to delay in absorption of carbs
  • reducing the increase in blood glucose after a meal.
704
Q

Example of glucosidase inihbitor ?

A

Acarbose

705
Q

What are the sideeffects of acrbose ?

A
  • loose stool
  • fart
  • diarrhoea
  • abdominal pain/bloat
706
Q

What do incretin mimetics do ?

A

Example: exenatide

incretins are peptides that stimulate pancreatic beta cells to secrete insulin.

  • incretins also inhibit pancreatic glucagon secretion from alpha cells.
  • They also slow the rate of absorption of digested foods, by decreasing gastric emptying.

administered via injection just like insulin, as it is a peptide

707
Q

What are incretin mimetics referred to as ?

A

GLP-1 receptor agonists

Glucagon-like peptide-1

  • also used for management of weight gain.

the drug recommended for this is semaglutide

708
Q

What are the 4 ways glucagon like peptide 1 agonists lower blood glucose ?

A

1) Enhancing glucose dependent insulin release from pancreatic B cells

2) inhibiting glucagon from pancreatic alpha cells

3) Slowing gastric emptyinng, delaying absorption of carbs after a meal and metabolism

4) Acting as a appetite suppressant, reducing consumption of carbs.

709
Q

Why might GLP-1 receptor agonists have a lower risk of causing hypoglycaemia than sulfonyylureas ?

A

As they are glucose dependent, so insulin only releases when levels of glucose is high, and less when levels are normal.

710
Q

What are gliptins ?

A

Dipeptidylpeptidase-4 inhibitors (DDP4)

They are added as agents to orally active drugs

and are well tolerated and don’t affect weight much.

711
Q

What do gliptins do ?

A

Potentiate incretins by competitively inhibiting an enzyme that breaks down incretins.

712
Q

What does SGLT-2 inhibitor stand for ?

A

Sodium glucose transporter 2 inhibitor.

713
Q

How do SgLT-2 inhibitors work ?

A

Inhibits SGLT-2 in the proximal convoluted tubule of the kidney,

preventing reabsorption of glucose and also helping it’s excretion of glucose in urine.

Glucose is excreted, causing plasma level to decrease.

714
Q

Why does SGLT-2 not affect pancreatic beta cells ?

A

This is because their mode of action relies upon normal glomerular-tubular function.

715
Q

In what type of patients is SGLT-2 inhibitor efficacy reduced ?

A

In patients with renal impairment.

716
Q

What is diabetic ketoacidosis ?

A

Sever lack of insulin levels.

  • cant use glucose as an energy source
  • so fat stores are used instead.
  • Also causing ketones to be released.
717
Q

What is the mechanism of action of SGLT-2 inhibitors ? (5)

A

1) Na+/K+ ATPase pump removes Na+ from S1 segment renal proximal tubule.

2) SGLT-2 causes Na+ to move down it’s concentration, causing glucose to move into S1 segment renal proximal tubule.

3) Glucose is then reabsorbed into the blood via GLUT-2.

4) SGLT-2 inhibitors then inhibit SGLT-2 in the proximal convoluted tubule of the kidney, to prevent reabsorption of glucose and facilitate excretion of glucose in urine.

5) As glucose is excreted in urine, levels of plasma glucose decreases.

718
Q

What are the 2 main female steroid hormones which regulate the reproductive system ?

A

1) Oestrogen

2) Progesterone

719
Q

How do the female steroidal hormones work generally ?

A
  • They passively diffuse into the cell and bind to their cognate receptors either in the cytoplasm or nucleus.
720
Q

What 2 specific receptors does oestrogen bind to ?

A

1) ER alpha

2) ER beta

  • they have different tissue distributions.
721
Q

What are the 2 specific receptors that progesterone binds to ?

A

1) PR-A

2) PR-B

722
Q

Mechanism of action of oestrogen and progesterone ?

A
  • interacts with nuclear receptors
  • upon ligand binding, receptors dimerize and translocate to the nucleus, causing transcription of target genes.
  • also non genomic actions.
723
Q

What does the HPG axis stand for ?

A

Hypothalamic-pituitary-gonadal-axis.

724
Q

What is menstruation ?

A

When the superficial layer of the endometrium is shed.

725
Q

how long does menstruation last ?

A

3-6 days

726
Q

What are the 4 phases of menstruation ?

A

1) Menstruation

2) Follicular phase

3) Proliferative phase

4) Luteal phase

727
Q

Follicular phase:

A
  • endometrium regenerates after menstrual flow stops.
  • Gonadotrophin releasing hormone (GnRH) is secreted from the hypothalamus, which stimulates the anterior pituitary to release follicle stimulating hormone (FSH) and luteinising hormone (LH).
  • FSH and LH then act upon ovaries, causing a small group of follicles to form (each contain an ovum (egg)) .
  • One follicle develops faster than the rest, this is known as the “graafian follicle” (GF)
  • which then secretes oestrogen.
728
Q

Proliferative phase:

A
  • Oestrogen help regenerate the endometrial ( from day5/6 - mid cycle).
  • thickness and vascularity of the endometrium then increases.
  • at peak oestrogen levels, there is a cervical secretion of mucus (which contains high amounts of proteins and carbs, facilitating entry of sperm into ovum).
  • high secretion of oestrogen just before mid-cycle, then stimulates the release of LH.
  • causing rapid swelling and rupture of graafian follicle, causing ovulation.
  • if fertilisation occurs at this stage, then the fertilised ovum passes down the fallopian tube to the uterus.
729
Q

What actually causes ovulation ?

A

Swelling and rupture of graafian follicle.

due to release of oestrogen and LH

730
Q

Luteal phase:

A
  • The ruptured graafian follicle proliferates and develops into the corpus luteum, which then secretes progesterone.
  • Progesterone then acts on oestrogen primed endometrium, allowing it to become suitable for implantation of fertilised ovum. Cervical mucus thickens to hinder sperm.
  • Progesterone then exerts negative feed back on the hypothalamus and pituitary, causing release of LH to decrease.
731
Q

What happens if fertilisation and implantation does not occur in the luteal phase ?

A

Progesterone secretion stops at the end of the cycle, triggering menstruation.

  • Also the corpus luteum keeps on secreting progesterone

causing negative feed back: preventing further ovulation.

732
Q

What does oral contraceptive contain ?
And how does it work

A

combo of synthetic oestrogen with synthetic or natural progesterone.

  • high levels of synthetic oestrogen and progesterone, prevent the exact cycle of hormonal events of the menstrual cycle occurring.
733
Q

What does COCP stand for ?

A

Combined oral contraceptive pill

734
Q

What’s the difference between 1st and 2nd gen oral combined hormonal contraceptive pills ?

A
  • 2nd gen has lower oestrogen count than the 1st gen.
735
Q

What is different about the 3rd gen oral combined hormonal contraceptive pill ?

A

They contain modified progestogens ( which have less adrenergic activity).

examples: desogestrel, gestodene

736
Q

What is safer 2nd or 3rd gen oral combined hormonal contraceptive pill

A

2nd gen safer

as 3rd gen has a greater risk of thromboembolism than 2nd gen.

  • which is a blood clot forming in a vein.
737
Q

how often and how long for is COCP taken ?

A

for 21 days in a row ( out of 28 days)

  • then pill free until the 28th day ( to enable withdrawal menstrual bleed).
738
Q

What is the “ED version of COCP”

A

When there are placebo pills to be taken from day 22-28

739
Q

What is the mechanism of action of the COCP ?

A

Oestrogen Inhibits the release of FSH

Progesterone inhibits the release of LH.

  • Lack of follicle development, causes cervical mucus to become inhospitable to sperm.
740
Q

What are the side effects of COCP ?

A

Weight gain

nausea

  • reversible hypertension- due to an increase in plasma renin due to oestrogen production.
  • blood pressure monitoring is advised.
  • Thromboembolism (3rd gen pill)
741
Q

Advantages of COCP ?

A
  • decrease chance of irregular periods
    and inter-menstrual bleeding.
  • reduces heavy menstrual bleeding and pain.
742
Q

What is the POP pill

A

Progesterone only pill

  • Makes cervical mucus thicker and more hostile to sperm.
  • also development of endometrium
743
Q

How is COCP different to POP

A

POP taken every day with no break.

744
Q

What is more risky POP or COCP ?

A

POP

as it is less reliable at low doses.

  • Also irregular bleeding is more common
745
Q

Why might POP be given instead of COCP ?

A

When they can develop risk of hypertension, cardiac related problems, thromboembolism.

746
Q

Pharmacokinetics of synthetic oestrogen/progesterone drugs ?

A
  • metabolised slower than natural oestrogen/ progesterone
  • have a longer half life
  • greater bioavailability
  • they are also less susceptible to first-pass metabolism.
747
Q

What enzymes metabolise COCP and POP ?

A

Cytochrome p450

748
Q

What is enterohepatic circulation ?

A

movement of bile acid from liver to small intestine and then back to the liver.

749
Q

What is the main concern with drug clearance of COCP and POP

A

It is ideal to minismise the dose of oestrogen ( to avoid thromboembolism)

  • HOwever increase in clearnace of COCP or POP may lead to contraception fail.
  • symptoms of increased clearance of COCP/POP : vomitting, diarrhoea
750
Q

What can an increase in metabolism of COCP and POP ?

A
  • reduced efficacy
    and also contraceptive fail
751
Q

What types of drugs are avoided to be given along with COCP/POP ?

A
  • anti-convulsant
  • anti-retroviral
  • antibiotics

This is because they increase they are “enzyme inducing drugs”,

that increase the potency of cytochrome p450 enzymes, and therefore the clearance of COCP/POP.

752
Q

What is menopause ?

A

No longer suitable to bear a child,

  • generally occurs when there is no period bleeding for a year.
753
Q

What is perimenopause ?

A

Process of change that leads to menopause.

754
Q

What is a symptom of menopause/perimenopause ?

A

low levels of oestrogen due to depletion of ovarian follicles.

  • progesterone levels also decrease if ovulation does not occur.
755
Q

What are symsptoms of meno pause ?

A
  • hot flushes
  • night sweats
  • osteoperosis
756
Q

What drug is given to prevent post-menopausal symptoms ?

A

Tibolone

  • also prevents osteroperosis and bone loss.
  • but can cause menstrual bleeding
  • so not used within 12 months of last period.
757
Q

What is Tibolone ?

A

Synthetic compound with weakly oestrogenic and androgenic properties.

758
Q

What is a SERM

A

Selective oestrogen receptor modulator

759
Q

What is an example of a SERM ?

A

Raloxifene

induces anti-oestrogenic effects on breast tissue and uterus

  • but is pro-oestrogenic on the bone and lipid metabolism.
  • helps to prevent osteoporosis.
760
Q

What is HRT

A

Hormonal replacement therapy

  • involves continuous administration of low doses of one or more oestrogens, with/without a progesterone
  • progesterone prevents endometrial associated risks as well as ovarian cancer.
  • helps treat the vasomotor symptoms associated with meno pause(sweating, hot flushes)
  • however does not reduce risk of coronary heart disease or abnormalities in cognitive function.
761
Q

What does HRY increase risk of ?

A

Stroke

thromboembolism (venous)

Endometrial cancer ( that can be treated with progesterone)
breast cancer, ovarian cancer

  • increased risk of coronary heart disease if HRT is started 10 years after menopause
762
Q

What are the 3 KNDy neurons ?

A

kisspeptin

neurokinin B (NKB)

Dynorphin

  • interact to affect pulsatile release of GnRH
763
Q

What is GnRH ?

A

Stimulates the release of FSH and LH

764
Q

How does ovarian failure affect KNDy neurons ?

A

can cause an increase in the neuronal size of kisspeptin

and gene expression

and hypertrophy of arcuate nucleus

also increase in NKB expression in post menopausal peeps.

765
Q

What is hypertrophy ?

A

increase in number and size of muscle cells

766
Q

How does less oestrogen affect KNDy neurons ?

A

less negative feed back from osestrogen,

causes

increased kisspeptin and NKB signalling

  • resulting in hypersecretion of GnRH.
767
Q

How does KNDy neurones affect body temp ?

A
  • KNDy neurons project axons to the MnPO (median preoptic area of hypothalamus)
  • Then receiving and projection of input is directed to the thermoregulatory pathway via the MnPO nucleus.
768
Q

What is the MnPO nucleus ?

A

A hub for thermoregulation

receiving input and projecting input to thermoregulatory pathway.

  • Also expresses the primary receptor for NKB
769
Q

What is the primary receptor for NKB ?

A

NK3R mRNA

770
Q

What’s an example of a drug used to treat hot flushes during menopause ?

A

Fezolinetant (Veozah)

given once daily as a non-hormonal pill

771
Q

Mechanism of action of fezolinetant ?

A

Antagonises NKB at neurokinin-3 receptors

772
Q

What is the general function of the GI system ?

A

To process food and water and extract nutrients and get rid of waste

773
Q

oral liquid dosage formulation def ?

A

API in a liquid vehicle for oral administration

774
Q

5 advantages of liquid oral dose formulation ?

A

1) Great patient compliance

2) Great absorption

3) Less GI irritation

4) No “drying step” required in the manufacturing process (lower cost)

5) Solutions do not undergo phase separation.

775
Q

Disadvantages of Oral liquid dosage form ?

A

1) Doesn’t mask taste well

2) susceptible to microbial contamination

3) Dose uniformity issues (emulsions, suspensions)

4) Hydrolysis of API

5) Not as convenient as tablets or capsules

6) Hard to transport large bottles of liquid
- and hard to pack glass bottles (risk of breaking)

776
Q

Pharmaceutical solution def ?

A

A solution is a homogenous mixture that usually contains one or more solutes, dissolved in a suitable solvent ( such as water).

777
Q

What is one reason to develop a solution rather than a tablet/capsule ?

A

This is because solutions do not have to undergo disintegration and dissolution

whereas tablets have to

778
Q

What are the components required to formulate a solution ? (7)

A

1) API

2) vehicle

3) Co-solvent ( to improve solubility)

4) Buffer ( form maintaining optimum temperature

5) Sweeteners, colours, taste masking and flavouring agents

6) Preservatives

7) Anti-oxidants

779
Q

Syrup definition ?

A

Aqueous solutions

which contain high quantity of sugar/ sweetner

780
Q

Ideally what percentage of sugar should syrups contain ?

A

85% or more

781
Q

Advantage of syrups ( regarding sterility and contamination) ?

A

Resistant to microorganism due to low water content.

782
Q

Formulation considerations for syrups ?

A
  • Preservatives are kept to a minimum due to osmotic effects or high sugar conc. And reduce crystallisation
  • polyhydric alcohols may be used to maintain solubility acting as co-solvents.
783
Q

In low sugary syrups, what is used to maintain a high osmotic gradient ? ( 3 things)

A

1) Sorbitol

2) Glycerol

3) Propylene glycol

784
Q

Why might preservatives be used in syrups ?

A

This is to avoid microorganism growth.

785
Q

Why might crystallisation be bad for syrups ?

A

Crystallisation can form around the cap

  • this can form a solid plug stopping the syrup from flowing .
  • To minimise crystallisation of syrups:
  • polyhydric alcohols are used as well as invert syrup (glucose fructose mixture)
786
Q

What is an elixir ?

A

A sweetened solution of API in a mixture of water and ethanol ( 12-15%).

787
Q

Difference between syrups and elixirs ?

A

Elixirs have a lower conc of sugar than syrups.

They are also less viscous

  • however less able to mask taste.
788
Q

What are tinctures ?

A

Alcholic or hydroalcoholic solutions containing API or extracts from plant materials.

Alcohol content is roughly 15-80%

  • They are flammable
  • also avoid high temps
789
Q

Disadvantage of oil-based solutions ?

A
  • often used when API is hydrophobic, when API is unstable in aqueous solution.
  • unpleasant taste and feel in mouth
  • However oil based solutions help prolong drug release
790
Q

Why are solutions susceptible to degradation ?

A

Due to high mobility

Decreased potency of drugs as well as chance of less toxicity.

791
Q

What is a suspension ?

A

A dispersion of solid within a liquid of gas

used for low soluble drugs

792
Q

What are the 2 types of classes of suspension ?

A

1) Course suspension (particles greater than 1um)

2) colloidal dispersion (Particles lower than 1 um).

793
Q

What 8 components are suspensions made out of ?

A

1) API

2) Wetting agent

3) Suspending agents

4) Flocculating agents

5) Preservatives

6) Sweeteners

7) Flavours

8) Colourants

794
Q

What do wetting agents do ?

A

Form a coating around the API

and act to reduce surface tension and facilitate wetting

and therefore dispersion/ dissolution.

This is because drugs with hydrophobic surfaces are difficult to disperse in aqueous medium

795
Q

What do suspending agents do ?

A

INcrease viscosity of the medium and slow down sedimentation.

usually gums, cellulose derivatives.

796
Q

What do flocculating agents do ?

A

prevent flocculation and neutralise the high charge density of certain particles

797
Q

Why are suspensions unstable ?

A

Due to large surface area of dispersed particles

798
Q

Flocculation def:

A

When particles of a liquid suspension form relatively weak bonds to create loose, light fluffy flocs, held together by weak van der waal forces of attraction.

  • overtime these vdw forces of attraction will thicken to form a thick layer of sediment.
799
Q

Aggregation def:

A

When particles of a liquid suspension are held together by strong inter-particle forces and aggregate

  • Aggregation leads to crystallisation, forming a thin solid layer of precipitate (cake/caking)
800
Q

What type of suspension is hard to resuspend ?

A

The ones that aggreagete

  • the ones that floc are cool tho
801
Q

3 advantages of emulsions ?

A

1) Increase API bioavailability

2) Increased drug stability compared to aqueous solutions

3) Prolonged drug action:

Oil reserve acts as a reservoir, where API slowly partitions into aqueous phase for absorption.

802
Q

2 disadvantages of emulsions ?

A

1) Thermodynamically unstable, leading to possible flocculation, coalescence or breaking

2) more complex to formulate than other solutions

803
Q

how is energy added during emulsification process ?

A

in a pharmacy

energy is added via trituration (mixing and grinding components)

In manufacturer this is done by a homogeniser (mixer)

804
Q

What are the 3 different types of emulsions ?

A

1) oil in water emulsion

2) Water in oil emulsion

3) Multiple emulsions:
Water in oil in water
oil in water in oil

805
Q

Emulsion def

A

An emulsion is a system, that consists of two immiscible liquids (where one phase is polar and one phase is non polar),

where on liquid is dispersed within the other liquid as small globules, and usually stabilised by an emulsifier.

806
Q

3advantages of emulsions

A

1) Ability to formulate hydrophobic API into a liquid.

2) more stable than solutions

3) Prolonged drug action- as api slowly partitions into the aqueous phase.

807
Q

2 Disadvantages of emulsions

A

1) Thermodynamically unstable

2) Harder to formulate than formulating a solution.

808
Q

What is an emulsifier ?

A

An agent added to an emulsion to stabilise it

809
Q

What are the 4 big no no that unstable emulsions could cause ?

A

1) coalescence

2) Flocculation

3) Creaming

4) Breaking (cracking)

810
Q

What is coalescence ?

A

Dispersed droplets merge together to form large particles.

irreversible process

and leads to breaking

811
Q

What is flocculation ?

A

Dispersed particles form weak interactions with each other, forming flocs within the continuous phase.

812
Q

What is creaming ?

A

Upwards movement of dispersed droplets, leading to phase separation.

reversible by gentle mixing.

813
Q

why is mixing not ideal for emulsions ?

A

Could cause an increase in coalescence

814
Q

What is breaking ?

A

complete separation of an emulsion into its component phases.

815
Q

bmi equation

A

Weight / height ^2

816
Q

What is the most common type of enteral feeding given for short term treatment ?

A

Nasogastric administration

or if not possible than either oesophageal surgery

or a peg or pej

817
Q

What is parenteral nutrition ?

A

Iv administration of a nutritionally balanced and physiochemically stable and sterile combination of the six main groups of nutrients with water

(fatty acids, amino acids, glucose, vitamins and electrolytes, trace elements).

818
Q

how is PN administered ?

A

IV admin via a central vein

allowing the nutrients to be delivered into the superior vena cava or the right atrium.

819
Q

2 advantages of PN route of admin ?

A

1) Passes directly into systemic circulation.

2) Bypasses the GI tract and avoids first pass metabolism by the liver.

820
Q

When might PN not be ideal ?

A

1) when there is intestinal failure

2) patients with fever

3) underweight infants

821
Q

What are the 3 main types of lipids ?

A

1) Triglyceride

2) Sterols

3) phospholipids

822
Q

What are the fat soluble viatamins ?

A

A,D,E,K

water soluble vitamins: C,B

823
Q

what makes rectal suppositories able to be systemically absorbed ?

A
  • large blood supply
  • haemorrhoidal veins drain into the inferior vena cava, avoiding first pass metabolism.
824
Q

What happens to the suppository upon administration ?

A

it melts at body temp

dissolution of suppository base in surrounding fluids

dispersion of suppository base in surrounding fluids.

825
Q

3 advantages of suppositories ?

A

1) Systemic absorption

2) Can be used in unconscious patients, or patients nil by mouth

3) no GI irritation, and first pass metabolism.

826
Q

2 disadvantages of suppositories ?

A

1) Unacceptable to some patients, or they may refuse

2) Difficult to administer to certain types of patients, such as elderly

827
Q

What are the 2 types of bases that can be used to make a suppository ?

A

1) Fatty hydrophobic bases

2) Water- soluble hydrophilic bases.

828
Q

What are some formulation requirements for suppositories ?

A

1) Must melt at body temp

2) able to dissolve in rectal fluid

3) should have a narrow melting point

4) must be chemically and physically stable

5) should be compatible with api

829
Q

What are the types of additives added to a suppository ?

A

1) Viscosity enhancer

2) Surfactants

830
Q

What is an evacuant enema ?

A

An enma used to stimulate bowels to treat constipation

  • vol reaches up to 2 litres
  • should be warmed to body temp b4 admin
831
Q

What is a retention enema ?

A

An dosage formed retained in the rectum, for to either provide treatment locally or systemically.

  • vol not higher than 100ml
832
Q

Gastric acid production mechanism introduction

A

1) Parietal cells secrete HCl into the lumen of the stomach.

2) H+/K+ ATPase pump, pumps H+ ions into the stomach lumen. This proton pump is regulated by ACh, gastrin and histamine

833
Q

gastric acid production mechanism ?

A

1) Vagus nerve releases ACh, stimulating m1 muscarinic receptors on parietal cells

2) Food enters stomach, and proteins in the stomach wall trigger the release of gastrin from G cells.

3) Gastrin stimulates its receptors on parietal cells,

4) This causes an increase in intracellular concentration of Ca2+ ions, causing H+/K+ ATPase pump to activate.

5) Stimulation of muscarinic and gastrin receptors on paracrine cells cause the release of histamine.

6) This stimulates h2-histamine receptors on parietal cells, increasing the intracellular concentration of cyclic AMP.

834
Q

Dyspepsia

A

Hyperacidity, indigestion, bloating, heart burn

835
Q

How can dyspepsia cause heart burn ?

A
  • When lower oesophageal sphincter does not close properly
  • HCl could affect the linin of the oesophagus, causing a burning sensation.

usually treated using antacids

836
Q

How do antacids work ?

A

Neutralise gastric acid in the stomach lumen

causing pH to increase.

  • also less gastric production, could cause more gastric acid to be produced. (acid rebound)
837
Q

What are the 3 types of antacids ?

A

1) Sodium bicarbonate:

2) Magnesium hydroxide

3) Aluminium hydroxide

838
Q

Sodium bicarbonate as an antacid ?

A
  • rapid action
  • CO2 it prooduces, stimulates the relase of gastrin.
  • NaHCO3 can cause sytemic alkalosis, and is not receommended for patients trying to cut down on sodium intake.
839
Q

Magnesium hydroxide as an antacid ?

A
  • insoluble in water unlike sodium bicarbonate
  • rapid reacts with hcl
  • low chance of alkalosis
  • can produce a laxative effect
840
Q

Aluminium hydroxide as an antacid ?

A
  • not well absorbed from the intestines
  • tendency to cause constipation
  • slowly reacts with hcl
841
Q

What 2 antacids are often combined together ?

A

Magnesium hydroxide and aluminium hydroxide

842
Q

what do alginates do when combined with antacids ?

A
  • increases mucus viscosity
  • increasing it’s adherence to intestines mucosa

-

843
Q

How are peptic ulcers treated ?

A

Proton pump inhibitor

Histamine h2 antagonist (cimetidine and ranitdine)

844
Q

side effects of histamine h2 antagonists ?

A
  • dizziness
  • diarrhoea
  • rashes
845
Q

examples of PPI’s

A

lansoprazole

omeprazole

they are pro drugs
that activate are low ph

846
Q

histamine h2 antagonists mechanism of action ?

A

-Reversibly bind to histamine h2 receptors on gastric parietal cells

-inhibiting activity of histamine

-reducing gastric acid secretion.

847
Q

Proton pump inhibitor mechanism of action ?

A

-Irreversibly bind to proton pumps

-inhibiting proton pumps on parietal cells

-precenting gastric acid secretion,

848
Q

how do lansoprazole and omeprazole generally work ?

A
  • once it enters acid environment the drug becomes protonated
  • This protonation triggers an acid catalysed conversion, which activates the drug.
  • then binds irreversibly to cysteine residues.
    Blocking pump, preventing release of HCl, to stop PPI’s from being further activated.
849
Q

How does H-pylori survive in stomach acid ?

A

Attaches to a sugar molecule in stomach and uses mucus layer as protection.

850
Q

What are the 3 types of ways h-pylori survives in the stomach ?

A

1) Uses flagella to migrate through alkaline mucus.

2) settles in antrum of stomach, where there is no parietal cells.

3) produces urease, breaking down urea, to produce ammonia.
Ammonia then neutralises HCl.

851
Q

How does h pylori cause ulcers to form ?

A

by producing inflammatory toxins, that break down the gastric mucosal barrier

  • causing a greater chance of pepsin and gastric acid to come into contact,

causing stomach wall damage.

852
Q

what does “triple therapy treatment” ?

A

Proton pump inhibitor

along with 2 antibiotics

for one week

853
Q

why are mucosal protectants given on an empty stomach

A

if not given on an empty stomach

they would react with dietary proteins and will not function effectively

854
Q

side effects of the mucosal protectant bismuth

A

1) blacken teeth

2) blacken tongue

3) blacken faeces

4) nausea, vomiting

855
Q

Misoprostol side effects (mucosal protectant)

A
  • diarrhoea
  • abdominal cramps
  • uterine contractions.
856
Q

What do mucosal protectants drugs do ?

A

Form protective barrier over an ulcer, preventing it from being damaged by gastric acid.

857
Q

What are the 4 types of laxatives ?

A

1) Bulk forming laxatives: bulks out intestinal contents with polysacchrides, inducing peristaltic movement.

2) Osmotic laxatives: bulk out intestinal contents with water, helps soften stool. Keep hydration levels up with this

3) Stimulant laxatives: Stimulate mucosa to produce intestinal movements.
side effects: intestinal cramps/damage

4) Faecal softeners: soften faeces

858
Q

What actually happens with diarrhoea ?

A

As an attempt to flush out microbes,

more fluid and electrolytes are being lost than they are absorbed.

  • leading to dehydration, and electrolyte imbalance.
859
Q

main anti-diarrhoeal treatment

A

oral rehydration therapy

860
Q

What does oral rehydration therapy involve ?

A

Oral solutions of glucose and electrolytes are administered

  • Works by absorbing na+ ions and glucose, and water follows these absorbed ions by osmosis.
861
Q

characteristics of loperamide ?

A
  • lipophilic
  • slowly absorbed
  • prone to me
  • can not cross BBB
862
Q

Whats an examp,e of an adsorbent drug that treats diarrhoea ?

A

kaolin

  • adsorbs microbes and toxins
  • and coat and protect intestinal mucosa
  • or adsorb excessive fluid in the bowel, to reduce diarrhoeal symptoms.
863
Q

How is kaolin adminstered ?

A

As an oral suspension

or as a mixture with other drugs like morphine.

864
Q

how do lipase inhibitors drug works ?

A

Orlistat

inhibits lipids and fat from being digested

reduces lipid absoprtion
reducing calorie intake.

865
Q

side effect of orlistat ?

A

Increase excretion of fat in faeces.

abdominal cramps
bloating

866
Q

What is nausea ?

A

feel like gonna vomit

867
Q

What is the CTZ

A

Chemoreceptor trigger zone

868
Q

What is the function of CTZ

A

Detects stimulus of by communicating with the “vomit centre” vomit
and monitors chemical composition of blood

  • also receives signals from eyes and ears
869
Q

Where does vomit centre receive signals from ?

A

1) Limbic cortex

2) nucleus solitarius: involved with gag reflex

3) Spinal cord: involved with nausea due to physical injury.

870
Q

vomit centre to abdominal muscles, process of events ?

A

1) Reversal of peristalsis in small intestine, intestinal contents and bile enters stomach

2) glottis closes

3) Breath held

4) Oesophagus and gastric sphincter relax

5) Contraction of abdominal muscle to eject stomach contents.

871
Q

What are antiemetic drugs ?

A

Drugs given to prevent vomit

These include:
1) Antimuscarinic
2) H1-histamine receptor antagonists
3)Dopamine d2 receptor antagonists
4)5-hydrroxytryptamine receptor antagonists
5) Cannabinoids
6) Substance P antagonists
7) Glucorticoids

872
Q

What drug given for morning sickness ?

A

No drugs given

to prevent harm to foetus

873
Q

how do antimuscarnincs work (treating vomit) ?

A

Antagonises muscarine receptors on the vomiting centre.

  • prevent/reduce motion sickness

example: Hyoscine (scopolamine)

874
Q

how do h1 antagonists treat vomit ?

A

Cyclizine (promethazine) antagonises h1 receptors on the vomit centre.

  • treat nausea and vomit and motion sickness.
875
Q

How do dopamine d2 receptor antagonists treat vomit ?

A

Phenothiazines (prochlorperazine, metoclopramide, domperidone).

  • block dopamine d2 receptors on the CTZ.
  • and antagonise muscarinic and histamine receptors.
876
Q

Does metoclopramide cross the BBB

A

Yes

  • so could cause centrally mediated side-effects.
877
Q

Does domperidone cross BBB

A

No

878
Q

side effects of cannabinoids ?

A

reduces cytoxic induced vomiting

  • drowsiness
    -hypotension
879
Q

symptoms of Irritable bowel syndrome (IBS) ?

A

1) Abdominal pain and cramping

2) Change in bowel habits: constipation, diarrhoea

3) bloating

4) flautulence

5) incomplete bowel emptying.

880
Q

What are the types of IBS ?

A

1) Chron’s disease: affects GI tract

2) Ulcerative colitis: affects large bowel (rectum and colon)

881
Q

treatment for chron’s disease ?

A
  • diarrhoeal symptoms treated with anti-diarrhoeas.
  • and advised to eat low fat diet
  • glucocorticoids used to induce remission.
882
Q

For treatment for chron’s disease, what is used if glucorticoids don’t give response ?

A
  • 5- aminosalicylate (e.g. sulfasalazine).
  • if no response to this, then immosupressants
    (methotrexate, azathioprine).
883
Q

Treatment for ulcerative colitis ?

A
  • treated with amino salicylate.
  • steroids can be administered in combo with amino salicylates.
884
Q

What does “rescue therapy” for ulcerative colitis involve ?

A

involves IV admin of hydrocortisone and ciclosporin.

885
Q

For proctitis type ullcerative colitis, what rectal formulation is used

A

suppository

886
Q

For proctosigmoiditis, what rectal formulation is used ?

A

Foam

887
Q

For left sided colitis , what rectal formulation is used ?

A

Enema

888
Q

Atheroma:

A

Arterial disease

where arteriosclerotic plaque develops in luminal walls.

889
Q

Atherosclerosis pathway ?

A

1) Endothelial cell is damaged, monocytes form macrophages in arterial walls.

2) This causes free radicals to be produced, these free radicals oxidise LDL.

3) macrophages take up this oxidised LDL forming foam cells, which causes the release of inflammatory cytokines.

4) Foam cells form fatty streaks releasing growth factors.

5) Causes smooth muscle to develop, forming plaque.

6) Rupture of plaque causes thrombosis.

890
Q

statins inhibit what enzyme

A

Hmg CoA reductase

891
Q

Hmg CoA pathway (statins) ?

A

Hmg Co A - > mevalonic acid -> farnesol -> cholesterol
Hmg CoA reductase

892
Q

examples of statins

A

atorvastatin
lovastatin
simvastatin

  • lower cholesterol
893
Q

mechanism of action of statins ?

A

Inhibits hmg co a reductase prevents substrate from binding, inhibiting the conversion of HMG Co A reductase to mevalonic acid, preventing synthesis of cholesterol

894
Q

side effects of statins

A

Headache
Dizziness
Nausea
Muscle pain
Rashes

895
Q

When are statins usually administered ?

A

usually at night to reduce peak cholesterol synthesis during the day

896
Q

What do fibrates do ?

A

Reduce LDL and increase HDL

Stimulating lipase, reducing triglyceride content o VLDL’s.

897
Q

Examples of fibrate

A

Clofibrate

898
Q

Side effects of fibrates

A

Nauase

Upset stomach

Diarrhoea

899
Q

Example of bile sequestrant

A

Colestipol (divided powders)

900
Q

Mechanism of action of bile sequestrant

A

1) bind to bile, preventing reabsorption

2) cholesterol, causes more bile acid to be produced

3) increases demand of cholesterol, increases hepatic LDL receptor expression

4) causes increase in LDL cholesterol clearance

901
Q

Side effects of bile sequestrant (colestipol)

A
  • interfere with absorption of fat soluble viatamins
  • GI irritation
902
Q

Example of a selective cholesterol absorpption inhibitor

A

Ezetimibe

903
Q

Ezetimibe mechanism of action

A

Reduces delivery of cholesterol to the liver
Promoting synthesis of LDL receptors with low levels of LDL-C.

904
Q

Side effects of Ezetimibe

A

Stomach pain
Diarrhoea
Muscle pain
Joint pain

905
Q

What is arteriosclerosis

A

Thickening of ,muscle layer of arterial walls, narrowing arteries

906
Q

What is atherosclerosis

A

Build up fat cholesterol and plaque in arterial walls, narrowing arteries.

907
Q

Treatment pathway for hypertension (under/over 55).

A

Under 55: ACE inhibitor Over 55: calcium channel blocker

Then A + C

Then A,C +D

Then: thiazide like diuretic or alpha/beta blocker.

908
Q

What could combining beta blockers and diuretics do

A

Could cause diabetes

909
Q

How do A,C and alpha 1-blockers generally work ?

A

Lower BP vasodilation

910
Q

Examples of ACE inhibitors (angiotensisin converting enzyme)

A

Anything ending in @opril@

  • captopril
  • perindopril
911
Q

ACE inhibitor moa

A

Prevents formation of angiotensin’s 2

  • preventing blood vessels from being narrowed
  • lowering bp
912
Q

Side effects of ace inhibitors

A
  • dry cough
  • hyperkaelaemmia
  • dizziness
  • headache
913
Q

How do ace inhibitors cause dry cough ?

A

As ace inhibitors inhibit break down of bradykinin
Causing it to accumulate in lungs

Causing dry cough.

  • so ARBs may be given instead
914
Q

Examples of arbs

A

Losartan
Valsartan

915
Q

Advantage of arbs over ace

A

Does not inhibit breakdown of bradykinin

916
Q

Arbs moa

A

Blocks action of angiotensin 2
Lowering bp

917
Q

Side effects of arbs

A

Hyper kaelaemia
Dizziness
Diarrhoea
Headache
Cough

918
Q

Examples of calcium channel blockers

A

Amlodipine
Diltiazem

919
Q

Calcium channel blockers moa

A

Blocks calcium channel

Decreasing vascular force

Less calcium to react with cal modules

Peripheral resistance decreases

Lower bp

920
Q

Side effects of calcium channel blockers

A

Headache
Dizziness
Arrythmia
Nausea
Chest pain
Constipation

921
Q

D type CCBs moa

A
  • slows down sa and increases av node contraction
  • slowing heart rate
922
Q

Why is verampril avoided with diltazem

A

To avoid Brady cardia and hypotension

923
Q

Examples of alpha 1 blockers

A

Doxazosin
Prazosin

924
Q

Alpha 1 blockers moa

A

Blocks alpha 1 receptors so norepinephrine can not bind to them.

Causing vasodilation

Lowering bp

925
Q

Alpha 1 blockers moa

A

Blocks alpha 1 receptors so norepinephrine can not bind to them.

Causing vasodilation

Lowering bp

926
Q

Side effects of alpha 1 blockers

A

Dizziness
Headache
Postural hypotension- due to impaired arteriolar vasoconstriction when standing up.

927
Q

When other treatments don’t work to treat HT

A

Minoxidil, hydralazine

Vasodilator
Side effects: tachycardia

928
Q

What’s last resort to treat HT

A

Beta blockers

929
Q

What’s last resort to treat HT

A

Beta blockers

930
Q

Formula for CO

A

Co = Hr x sv

931
Q

Two types of beta blockers

A

Non selective: propranolol: blocks b1,b2

Selective: atenolol, bisoprol: blocks b1

932
Q

Beta blockers moa

A

Block adrenaline and noradrenaline

Reducing peripheral resistance

933
Q

Side effects of beta blockers ?

A

Dizziness
Cold hands/ feet
Nausea

934
Q

Example of a hybrid of beta and alpha blocker

A

Carvedilol

  • avoided for diabetes patients, as may affect carbs metabolism
  • amide group- increases water solubility
935
Q

Side effects of carvedilol

A
  • bronchospasm
  • bradycardia
  • ## fatigue
936
Q

What is used to treat pregnancy hypertension

A

Methyldopa

937
Q

How do diuretics work

A

Increase urine of vol produced
More water excreted
Circulatory volume decreases

938
Q

Examples of thiazide diuretics HT

A

Indapamide
Chlorthalidone

939
Q

What is an oedema

A

Large vol of blood in veins

940
Q

What time of day are thiazide diuretics administered, and why

A

Morning

To avoid sleep disturbance

941
Q

Side effects of thiazide diuretics

A
  • increased cholesterol levels
  • impaired glucose tolerance
942
Q

What do loop dieuretics do

A

Inhibit salt absorption in the thick ascending limb of loop of henle

943
Q

Loop dieurtics examples

A

Furosemide
- reduces oedema

944
Q

Side effects of loop dieuretics

A

Low k+- hypokaelamia
High ca2+- hypercaelaecim

945
Q

How do potassium sparing dieuretics work ?

A

Blocks Na+ channel
- reducing an+ absorption, preventing hypokaelamia

946
Q

Examples of potassium sparing dieuretics ?

A

Amiloride
Triamterene

  • ACE and Arbs not used with these
  • as it reduces aldosterone levels
  • leading to adrenal insufficiency
947
Q

2 types of aging

A

Stable and unstable angina

948
Q

What is angina ?

A

Less blood flow to myocardium
Low supply of o2 to cardiac muscle

949
Q

What is angina ?

A

Less blood flow to myocardium
Low supply of o2 to cardiac muscle

950
Q

Stable angina

A

Predictable
Stable levels of coronary blood supply during rest
Unstable levels during exercise

  • supply of blood does not meet demand, causing ischaemia
951
Q

Unstable angina

A

Acute coronary syndrome (ACS)

  • rapid onset
  • pain occurs at rest
  • longer duration and more severe sysmptoms

Caused by atherosclerosis plaque, leads to thrombosis.

952
Q

Side effects of stable angina

A

Chest pain

953
Q

Symptoms of unstable angina

A

Chest pain
Tight chest
Shortness of breath
Sweating

954
Q

Treatment for angina

A

Nitrates: nitroglycerin

Glyceral trinitrate (GTN): to treat chest pain
Sublingual tablet/spray- duration 30 mins

955
Q

How do nitrates treat angina ?

A

Nitrates cause venodialtion

  • less venous return
  • reduced cardiac pressure loading, work load on heart and o2 demand.
956
Q

What is venodilation

A

Venous pooling of blood

957
Q

Mechanism of action of nitrates

A

1) nitrates convert into nitrous oxides

2) guanylyl cyclise converts GTP into cGMP

3) causes Ca2+ ions to be taken up into sacroplasmic reticulum.

958
Q

How is GTN packed for air, moisture, heat and light

A

Air: air tight containers

Heat: not put in trousers

Moisture: packaged with a desiccant

Light: amber glass bottles.