ICS - PHARMACOLOGY Flashcards
1
Q
What is pharmacology?
A
The study of the effects of drugs
2
Q
What is pharmacodynamics?
A
How the drug affects the body
3
Q
Pharmacokinetics: How are the majority of drugs broken down and gotten rid of?
A
Hepatically Metabolised and Renal Excreted
4
Q
What is summation?
A
When 2 drugs used at the same time both have the expected effect (1+1=2)
5
Q
What is synergism?
A
When using two drugs together makes both of the drugs more effective
For example, paracetamol and morphine
(1+1>2)
6
Q
What is blockage
A
When one drug blocks the action of another
For example, salbutamol and non-selective beta blockers (1+1=0)
7
Q
What is potentiation?
A
When one drug makes the other more potent, but its potency stays the same (1+1 = 2.5)
8
Q
What is bioavailability?
A
How much of a drug taken is used. IV is always 100% but orally, this figure can change
9
Q
Describe the difference between tolerance and desensitisation
A
- Tolerance - reduction in drug effect over time (continuously repeated high conc)
- Desensitisation - receptors become degraded / uncoupled / internalised
10
Q
What is pharmokinetics?
What are the 4 things?
A
What the body does to the drug. There are 4 things
Absorbtion,
Distribution,
Metabolism
Excretion
ADME
11
Q
Pharmokinetics: Outline what is meant by administration
A
Administration refers to the route/entry to the body.
12
Q
What are the two main rotes of drug administration. What can the first be subdivided into?
A
Systemic and local
Systemic can be split into enteral and par-enteral (GI tract or not GI tract)
13
Q
Give an example of
a) Enteral administration
b) Par-enteral Administration
A
a) Oral, Rectal , Sublingual
b) Intravenous, Intramuscular, Subcutaneous, and at times inhalation and transdermal
14
Q
Give examples types of drug be administered locally
A
Topical
Intranasal
Eye drops
Inhalation (Inh)*
Transdermal*
Inhalation and transderaml can be local of systemic, depending on the drug
15
Q
What are the four main things drugs target?
A
Cellular receptors - main one
Enzymes (ACE inhibitors)
Membrane ion channels (Lidocaine)
Membrane transporters (PPIs)
16
Q
Pharmokinetics: What things does distribution depend on?
A
Blood flow to the area – drug will get to the brain (if can pass through BBB) faster than the skin
Permeability of capillaries – Slits (like in liver) or not (like in brain)
Whether bound to albumin in the blood or not (faster if free from albumin)
Lipophilicity – lipophilic drugs can penetrate the cell membrane easily
17
Q
How does the body metabolise lipid soluable drugs?
A
Liver converts lipid soluble drugs into water soluble drugs so they can be excreted by the kidney
phase 1= make drug hydrophilic (cytochrome p450 catalyses);
phase 2 = if still too lipophilic, add something else to make it polar so the drug can’t be absorbed - e.g. acetylation/adding glutathione)
18
Q
What can happen when drugs influence Cytochrome P450 enzymes?
A
Some drugs induce Cytochrome P450 enzymes ===> so other drugs are metabolised faster - can lead to sub-therapeutic dose
some inhibit CYP450, so other drugs are metabolised more slowly ====>and may reach toxic levels
You can see alcohol abuse, both chronic and acute, can mess up the P450 system
- (chronic alcohol can induce the P450 system, and acute alcohol can inhibit the P450 system)
19
Q
name some drugs that induce the CY P450 enzymes
name some that inhibit it
A
Induce -
Chronic alcoholism
Anti-epileptics: phenytoin, carbamazepine
Smoking
Inhibit
Amiodoarone
Abx: ciproflaxacin, erythromycin
Allopurinol (gout)
SSRIs - fluoxetine, sertraline
20
Q
Rate of elimination - What is meant by
First order elimination?
What is the most common way, first order or zero order?
A
First order = curve
a)
RATE OF METABOLISM DIRECTLY PROPORTIONAL TO THE DRUG CONCENTRATION
so starts off slow as all enzymes are full, when the amount of drug left goes down, the rate can speed up –> Curve )
First order is more common
21
Q
Rate of elimination - what is meant by zero order elimination?
Give examples of some drugs that are eliminated by zero order.
A
b) enzymes saturated by high drug doses, rate of metabolism is constant, e.g. ethanol, phenytoin
Less common than first order
22
Q
How is Paracetamol processed in the liver normally?
A
95% Converted into nom toxic compounds, conjugated with either sulphate or glucuronide (Phase II metabolism)
5% is converted into N-acetyl-p-benzoquinone imine (NAPQI) by Cytochrome p450 enzymes into highly reactive and toxic which would then be conjugated with glutathione so it can be excreted in the urine
23
Q
What happens in a paracetamol overdose?
A
Too much NAPQI and not enough glutathione, so it accumulates and damages the liver.
24
Q
How do you treat an paracetamol OD?
Either Within an hour of OD, or over an hour since OD
A
If it has been less than 1 hour since OD give activated charcoal
If longer than this give intravenous N-acetylcysteine
25
What is a receptor?
A component of a cell that interacts with a **specific ligand** and initiates a change of biochemical events
They are the principle means by which chemicals communicate
26
What are 3 things that naturally target receptors?
Neurotransmitters e.g., acetylcholine, serotonin
Autoacids (local hormones) e.g., cytokines, histamine
Hormones e.g., testosterone hydrocortisone
27
What are the 4 main different types of receptors?
Ligand-gated ion channels
G protein coupled receptors (most common)
Kinase-linked receptors
All on the cell surface membrane^^^^^
Cytosolic/nuclear receptors
Intracellular^^^
28
What kind of ligands to intracellular receptors recognise?
Hydrophobic ligands eg Steroids, which can diffuse across PL membrane
29
What kind of ligands to cell surface receptors recognise?
Larger ligands that can’t pass through the plasma membrane, or Hydrophyllic ligands
30
Cell surface receptors: What receptors do ligand-gated ion channels have? What happens when this substance binds to them?
**nicotinic ACh receptor:**
* Binding of ACh opens pore and allows an influx of any kind of cation(+ve) or efflux of any kind of anion (-ve).
Typically, cations (Ca2+, Na+, K+) ions passively diffuse into the cell, triggering reactions
31
Cell surface receptors: What is the shape of G-protein coupled receptor, and what is a G protein?
Starts out of the cell, and then wiggles in and out of the cell 7 times (like a snake before ending up inside the cell
G proteins, (guanine nucleotide-binding proteins,) are a family of proteins (35 in humans) involved in transmitting signals from G protien recpetor channels
32
What happens when a ligand binds to a G-protein receptor?
The G protein changes shape, causing GDP to be released, allowing for GTP to bind
...
Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate(GTP) toguanosine diphosphate(GDP)
33
What are the two main types of G protein?
Gq and Gs
34
G protein types: What receptor couples Gq protein? What two molecules does this produce as secondary messengers?
**M3R (muscarinic receptor)** couples with Gq protein =
Leads to **IP3 and DAG** formation, which are its secondary messengers
35
G protein types - what do the secondary messengers of Gq protein coupling go onto do within the cell?
IP3 = opens calcium channels, causing a Ca2+ efflux into the cytoplasm
DAG = activates protein kinase C (PKC),
***Protein Kinase C can go on phosphorylate target proteins**
(The majority of GPCR’s interact with Phospholipase C or adenylyl cyclase)
36
G protein types: What enzyme does Gs protein activate, via what receptor? What two molecules does this produce as secondary messengers?
Binds to Beta 2 adrenoreceptor
Increases amounts of Cyclic AMP, which is its secondary messenger
leads to activation of PKA enzyme (PROTEIN KINASE A)
PKA has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism
37
Cell surface receptors: What happens when ligand binds to a kinase-linked receptor?
Main one is tyrosine kinase
It triggers **phosphorylation of the tyrosine molecules** on the intracellular domain of the receptor.
Phosphorylated tyrosine molecules are involved in many different signalling cascades which are crucial for various processes such as cell division and wound healing.
38
Pharmalogically speaking, why do all medicines cause side effects?
Because in reality no drug is 100% specific. Ligands will not only bind to their target receptors, but also other very similar receptors on/in cells, causing unintended reactions.
39
What are the two types of ion channel, and what do they rely on?
Voltage gated and Ligand Gated
Voltage open or close in response to changes in membrane potential.
Ligand-gated ion channels, open or close in response to the binding of a specific ligand (for example a neurotransmitter) to their extracellular domain.
When they open, they provide a channel through which ions can passively enter the cell.
40
What happens when relevant ligands bind to intracelluar nuclear receptor?
Forms a ligand-receptor complex, which will then bind to DNA in the nucleus and directly affect gene transcription and protein synthesis.
41
Name diseases that are due to an imbalance of chemicals/ligands in signalling.
allergy; increased histamine
Parkinson’s; reduced dopamine
42
Name diseases that are due to an imbalance of receptors in signalling.
myasthenia gravis; loss of ACh receptors
mastocytosis; increased c-kit receptor
43
Define ligand
a molecule that binds to another (usually larger) molecule.
44
Define Agonist
a compound that binds to a receptor and activates it
45
Define antagonist
a compound that reduces the effect of an agonist
46
Define Efficacy
Describes how well a ligand activates the receptor
47
Does antagonists have efficacy?
No they Have affinity but zero efficacy
48
What receptors do G protein coupled receptors have?
M3R (muscarinic receptor)
Beta-2-adrenoreceptor. Produces second messenger cyclic-AMP
49
What are kinase-linked receptors targets for?
Growth factors
50
Give the pharmalogical definition of Affinity.
How strongly a medication binds to its receptor (determined by the strength of the chemical bond between the two)
51
What are cytosolic receptors targets for?
Steroids
52
Where would you find intracellular (nuclear) receptors? What tends to bind to them?
In the cell cytoplasm and nucleus,
Small, hydrophobic (i.e. lipid-soluble) molecules, which can diffuse across the plasma membrane by themselves tend to bind to them.
53
Give the pharmalogical definition of Potency
Amount of medication need to elicit an effect. (higher the affinity of a drug, the higher the potency)
54
What is intrinsic activity?
Emax of partial agonist/Emax of full agonist
Basically, how well a drug works against something that fully works
eg Emax of partial agonist (substance X) gives a 68% response
We know that a full agonist would give 100% response, so 68/100= 0.68
Therefore substance X has an intrinsic activity of 0.68
55
How do competitive antagonism work? What will it do to the drug sigmoidal curve?
The reverse the effects of agonists by competing with them to bind with receptors.
This therefore prevents agonists from having as strong of an effect
They shift the curve to the right meaning more agonist is required for the same response
DECREASE POTENCY. AS MORE OF THE FURG IS THEREFORE NEEDED TO ILLICT THE SAME RESPONSE - BUT EFFICACY STAYS THE SAME
(Like competitive inhibitor?)
56
How does non-competitive antagonism work? What will it do to the drug sigmoidal curve?
It shifts the curve right and down meaning even more agonist is required to illicit the same response
This is because an non-
competitive antagonist binds near the receptor and prevents activation of it but does not bind directly to it so the agonist is still
able to bind but just not activate the receptor
(like allosteric site inhibitors)
done up to 19
57
What do kinase receptors do?
Transfer phosphate groups between proteins,
58
What is tolerance?
The reduction in drug potency over time
Seen with continuous, repeated high concentration of drug over time
59
Define Emax
maximum value of efficacy that a drug could possibly have (maximum response)
60
define EC50
value of 50% of sigmoid (half the maximal response of a drug)
61
What do competitive antagonists do to a drug? What effect does this have on the sigmoid curve?
- reverses the effects of agonists, by competing with them to bind to the receptors
- So stops the agonists from having as strong an effect
- SHIFTS CURVE TO THE RIGHT
DECREASE THE POTENCY OF THE DRUG, AS MORE IS NEEDED TO ILLICIT THE SAME RESPONSE
62
What do non-competitive antagonists do to a drug? What effect does this have on the sigmoid curve?
Decrease potency - as more drug is needed to elicit the same response - **curve goes the the right**
competitive antagonists bind away from the ligand that the receptor would bind to - so the ligand will still bind to this receptor still but no response will be elicited **(decrease efficacy, as no activation)** - ***curve goes down***
63
What are cholinergic receptors? What are the two types?
receptors on the surface of cells that bind the neurotransmitter Acetycholine (Ach)
There are two types of cholinergic receptors: nicotinic and muscarinic receptors
64
In the sympathetic nervous system, what do preganglionic neurons release? What does this bind to on the cell body of the postganglionic neuron cell bodies?
neurotransmitter Ach, which binds to nicotinic receptors on the cell membrane of postganglionic neuron cell bodies
Preganglionic - always nicotinic !!!!!
65
In the sympathetic nervous system, what do postganglionic neurons release? What does this bind to on the cell body of the postganglionic neuron cell bodies?
adrenaline (epinephrine) and noradrenaline (norepinephrine), collectively called catecholamines. These catecholamines bind to adrenergic receptors on the plasma membrane of the target organ cells.
66
In the parasympathetic nervous system, what do preganglionic neurons release? What does this bind to on the cell body of the postganglionic neuron cell bodies?
Ach, which binds to nictotinic receptors on the postganglionic cell bodies
Same as sympathetic preganglion!
67
In the parasympathetic nervous system, what do postganglionic neurons release? What does this bind to on the cell body of the postganglionic neuron cell bodies?
postganglionic neurons release ACh, but in this case it binds to the muscarinic receptors on the target organ cells.
*Remember - Muscarinic receptors - a type of Cholinergic receptor*
68
Somatic Nervous system: How many neurons between CNS and what it innervates?
Single Neuron between CNS and skeletal muscle
Innervates Skeletal muscle
Leads to muscle excitation, not inhibition
69
Autonomic nervous system - How many neurons?
Unlike the somatic system, the ANS has two neurons separated by the autonomic ganglion - *pre and post ganglionic neurones*
70
How are the two neurons arranged in
a) Sympathetic Nervous system
b) Parasympathetic nervous system
In the sympathetic system, the **ganglion is within a chain adjacent** to the spinal cord
In the parasympathetic system, the **ganglion is within or very close to the effector organ**
The sympathetic and parasympathetic systems are also different in their use of neurotransmitters
71
Exception - what do
a) sweat glands
b) blood vessels
release at **postganglionic** termini within the **sympathetic** nervous system?
At both these places, what does sympathetic action lead to?
a) acetylcholine (sweat)
b) Dopamine (Vasodilation)
72
Where would you find M1 receptors?
Where would you find M2?
M1 Brain
M2 - Heart (found in the SA node)
73
Where would you find M3 receptors?
Where would you find M4 and M5?
M3: All organs with parasympathetic innervation - eyes, lungs, gut, skin
M4: Mainly CNS
M5: Mainly CNS
74
What does activation of M2 do? (parasympathetic)
Activation of M2 on heart SA node
Decreases heart rate
Activation of M2 on heart AV node
Decrease conduction velocity
Induces AV node block (increases PR interval)
75
What does activation of M3 receptors do, in lungs, GI tract and skin?
Stimulation in the Respiratory System
Produces mucus (airways and nasopharynx)
Induces smooth muscle contraction (bronchoconstriction)
GI tract
Increase saliva production
Increases gut motility
Stimulates biliary secretion
Skin
Only place where Sympathetic system releases ACh
Stimulation of M3 causes sweating
76
What does activation of M3 receptors do, in urinary system and eye?
Both parasympathetic
Urinary System - Contraction of detrusor muscle, relaxation of Internal urethral sphincter
Eye - secretion of tears, MYOSIS, PUPIL CONSTRICTION -
77
What are Cholinergic agonists?
What are the two types?
Cholinergic agonists are drugs that mimic or enhance the action of ACh at the neuromuscular junction.
They can either be direct acting agents or indirect acting agents
78
What are some kind of things that cholinergic receptors do
(Increases GI and GU tone, increases bronchial tone and respiratory secretions. Enhances parasympathetic NS activity)
79
What is the basic pathophysiology for myasthenia gravis?
Antibodies bind to receptors blocking Ach from binding, leading to skeletal muscle weakness
Treatment includes anti-cholinesterase (pyridostigmine) to increase ACh availability at neuromuscular junction
80
How does Direct acting Cholinergic agonists work? Give an example
They Mimic ACh and bind to ACh receptors
eg Carbachol (constrict pupil)
81
How does indirect-acting Cholinergic agonists work? Give an example
Inhibit enzyme AChE, increasing the concentration of ACh available at the synapse
eg Neostigmine, Pyridostigmine (myasthenia gravis, reverse anesthesia)
82
How do nicotinic anatagonists work? When would they be used?
Compete with ACh for binding to the nicotinic receptor
eg Curare, Pancuronium (relax skeletal muscles during surgery) -
**STOP SYMPATHETIC**
83
How do Muscarinic anatagonists work? When would they be used?
Compete with ACh for binding to the muscarinic receptor, TO STOP PARASYMPATHTIC ACTIVITY AT THE POST GANGLOINIC NMJ
eg iprotropium, a Short acting Muscarinic antagonist, (SAMA) used in Asthma management
84
Adrenergic Pharmacology: what
a) Alpha 1
b) Alpha 2
receptor do
Both G coupled
a1- Vasoconstriction, increased BP, Increased closure of internal sphincter of the bladder, pupil dilation
a2 - Inhibits NA release, and inhibits Ach release. Also inhibits Insulin release
85
Adrenergic Pharamcology: what
a) Beta 1
b) Beta 2
c) Beta 3
receptor do?
All G coupled, sympathetic (obvs)
a) Chronotropic and inotropic effects on heart *(tachycardia and increased contractility)*
b) Relaxes smooth muscle (seen in labour/asthma) **bronchodilation**, inhibits labour, **causes insulin and glucagon** to be secreted)
c) Enhances lipolysis relaxes bladder detrusor (urine retention)
86
Outline the MOA of Dobutamine
**Dobutamine is a β1-agonist that acts as a positive inotrope** that
increases heart muscle contractility and tries to increase cardiac
output
87
Adrenergic Pharmacology: What would Alpha 1 blockers do?
Lower blood pressure e.g. doxazosin (generally less frequently used than modern antihypertensives
88
Adrenergic Pharmacology what would Beta 1 Blockers do?
Beta (1) blockers will therefore
Reduce heart rate
Reduce stroke volume
Reduce myocardial oxygen demand and help remodelling in heart failure or post-myocardial infarction
E.g. carvedilol, bisoprolol, atenolol…
Caution in Asthma
89
Broncho constriction/dilation - what is Parasympathetic and what is sympathetic?
Bronchodilation is SYMPATHETIC Bronchoconstriction is PARASYMPATHETIC
90
Salbutamol is an agonist drug for Beta 2. Why is this useful in treating asthma?
it acts on beta 2, which will lead to bronchodilation. (sympathetic)
91
What is the bioavailability of morphine taken orally
50%
92
10mg of morphine is taken orally. What is the equivalent dose if given parenterally?
5mg
93
Give 5 side effects of opioid use
1. Respiratory depression.
2. Sedation.
3. Nausea.
4. Vomiting.
5. Constipation
94
Describe the dose-response curve for morphine.
As dose increases response increases. This association is initially rapidly and then the graph plateaus. It is not sigmoidal!
95
What it do you give to reverese a morphine overdose?
Naloxone - its an antagonist to morphine
96
What drug to you give to manage an opioid addiction? How does it work?
methadone
It functions as a **long-acting agonist on the mu-receptors,** providing a controlled, steady release of the drug, which helps to reduce cravings and withdrawal symptoms without precipitating the euphoria commonly associated with opioid misuse.
97
Briefly outline how opioids work.
1. Inhibit the release of pain transmitters in spinal cord and midbrain
2. Modulate pain perception at higher centres, creating euphoria
98
What is the main opioid receptor, that all the drugs we currently use act on?
The main opioid receptor is the mμ receptors-opioid receptor (MOR).
99
Name other receptors that morphine been found to bind to. Agonism of what receptor has been known to cause mental depression instead of euphoria?
after delta (DOP) and kappa (KOP) receptors.
Kappa agonists cause mental depression instead of euphoria
100
Where may you finD μ receptors (MOP) in the body?
* Midbrain
* Spine
* GI tract - can get constipated with opioid use
* Breathing centre - it communicates using opioid receptors, opioid use
can cause respiratory depression
101
Why can giving Buprenorophine be safer than morphine?
Because it is only a partial agonist, so only reaches up to 50% response.
102
Outline the potentsies of Diamorphine and pethidine, relative to morphine.
Relative potencies:
- Diamorphine (Heroin)- 5mg (twice as potent as morphine)
- Morphine - 10mg
- Pethidine - 100mg (10 times weaker than morphine)
Diamorphine - Heroin:
- More potent and faster acting (crosses blood-brain barrier quickly)
103
Would a drug with a lower EC50 have a lower or greater potency?
Greater potency.
104
Would an antagonist shift a dose-response curve to the left or right?
The antagonist would shift the dose-response curve to the RHS. The drug therefore becomes less potent.
105
Describe allosteric modulation.
An allosteric modulator binds to a different site on a receptor and influences the role of an agonist.
106
What is inverse agonism?
Where an agonist has a negative effect at a receptor.
107
How many litres of water are there in the following body compartments:
a) Plasma.
b) Interstitial space.
c) Intracellular space.
a) 3L.
b) 11L.
c) 28L.
108
What compound do many lipid soluble drugs combine with to increase their hydrophilicity?
Glucuronic acid.
109
Write an equation for the volume of distribution (Vd).
Vd = amount of drug administered/concentration of drug in plasma.
110
If a drug had a high Vd what would that tell us about the drug?
This would indicate that the drug was **highly lipid soluble** and that most of the drug had moved into the **intracellular space**, ***less was in the plasma***.
111
What is the relationship between plasma concentration and Vd?
Plasma concentration is inversely proportional to Vd.
112
Give an advantage of a drug having a low Vd
Drugs with Low VD - high amount of drug in the plasma
It is **easy to reach steady state** and ***plasma concentration is ‘responsive’ to dose rate.***
113
Briefly describe catecholamine synthesis.
Tyrosine -> L-DOPA -> Dopamine -> Noradrenaline -> Adrenaline.
114
Where does the conversion from Dopamine to Noradrenaline happen?
In a vesicle in the pre-synpatic neurone
115
What is an adverse drug reaction?
A response to a drug which is noxious (harmful) and unintended
116
How do we classify adverse drugs reactions? How many categories are there?
There are 5, ABCDE (Rawlins-Thompson)
Augmented
Bizarre
Chronic
Delayed
End of Use
117
Outline a type A Augmented drug reaction.
Its the most common, an EXTENSION OF THE CLINICAL EFFECT (Drug works too well)
DOSE RELATED -
Examples:
- Diuretic causing dehydration
- Anticoagulant causing bleeding
- Drug for hypertension causing hypotension
So any EXPECTED OR KNOWN SIDE EFFECTS
118
Outline a type B Bizarre drug reaction.
A reaction that is seemingly Unrelated to dosage and **not expected from what the what the drug is known to do** (pharmacological action)
Mostly immunological mechanisms, eg Hypersensitivity
Those with predisposing factors such as; history of allergy,
asthmatics and some family history are at greater risk, can be genetically linked
Can be seen in drugs that inhibit certain metabolic pathways
119
Outline a type C Chronic drug reaction.
Occurs AFTER LONG TERM therapy, so might not be obvious with new medicines
eg Steroids predispose to hypoglycaemia - may result in diabetes
120
Outline a type D Delayed drug reaction.
Also occurs after a long period of time after treatment - many years eg 20-30
eg
- Teratogenesis (congenital malformations in foetus) after taking
thalidomide
- Neoplasia
121
Outline a type E End of use drug reaction
Relatively long term use (days/weeks)
* Withdrawal reactions
* Serious complication of stopping related to clinical effect
AKA WITHDRAWAL
*Tertiary adrenal insufficeny, due to stopping long term steroids, HPA axis hasn’t woken up to making own steroids again.*
122
What would you ask your self if you were suspicious of
a) Type A Augmented Drug reaction
b) Type B Bizarre Drug reaction
c) Type C Chronic drug reaction
Is it predictable from the mechanism of action? Does it seem
dose-related? - Type A (Augmented)
Is there a history of allergy? - Type B (Bizarre)
- Has the patient been using the medication for a long time? - Type
C (Chronic)
123
What would you ask yourself if you were suspicious of a
Type D Delayed drug reaction
Type E End of Use drug reaction
- Has the patient uses a drug in the past that could be causing a
problem now? - Type D (Delayed)
- Is the patient withdrawing from a medicine? - Type E (End of
Use)
124
Give some factors that can increase susceptibility for ADRs (Adverse drug reactions)
Age - elderly
- Gender - more common in females
negative effect on baby etc.
- Disease - liver or renal in particular
- Drug interactions
- Diet or alcohol intake changes
- Genetics
125
If you suspect/see a ADR, what should you do?
Report it by the MHRA YELLOW CARD SCHEME
MHRA = Medicines and Healthcare products Regulatory Agency - Regulatory body in UK that makes sure drugs are safe
126
Other Receptors: What would a GABA agonist do? What would it bind to? In what drugs/condition would you see this?
Drugs that bind to BENZODIAZEPINE RECEPTORS, lead to the enhanced inhibitory effect of GABA - so used to treat anxiety/sleep disorders/alcohol withdrawal
eg Lorazepam and Diazepam
127
Other Receptors: What is the effect of histamine binding to H1 receptors?
histamine elicits the contraction of smooth muscle of the respiratory tract, increases vascular permeability, and induces the production of prostacyclin and platelet activating factor by activating H1r
128
Other allergies: When could excessive and uncesscary binding of Histamine to H1 receptors be bad? What would you do to treat this/give example of a drug?
Seen in allergies/hypersensitive/ anaphylaxis, so in this case, GIVE H1 ANATAGONIST, EG LORATIDINE to counteract
129
Other Receptors: What is the effect of histamine binding to H2 receptors? Where are H2 receptors found
H2 receptors are found on the acid-secreting gastric parietal cells.
This initiates a cascade that eventually increases the intracellular cyclic adenosine monophosphate (cAMP). ==> Cyclic AMP activates the hydrogen-potassium pump, causing secretion of hydrogen ions.
==> Increased Secretion of Gastric Acid!
130
Other recpetors - what would an anatagonist of H2 receptors lead to? It what pathology would this be used? Name a common H2 anatagonist.
Used as a Second line treatment for GORD/too much Gastric Acid, after PPI.
eg Ranitidine, Cimetidine
131
Antiplatelets: How does Aspirin work as an antiplatelet?
Aspirin works by irreversibly inhibiting the enzyme cyclo-oxygenase (COX-1) which reduces thromboxane synthesis.
Thromboxane is required to facilitate platelet aggregation and to stimulate further platelet activation.
132
Antiplatelets: How does Clopidogrel work as an antiplatelet?
It inhibts the binding ADP to its platelet receptor, so indirectly inhibits platelet aggregation.
By inhibiting platelet aggregation, blood flows more freely around the body.
Clopidogrel belongs to the class of medicines known as adenosine diphosphate (ADP) receptor antagonists (also called P2Y12 inhibitors). It is also a type of antiplatelet medicine
133
Breifly outline morphine metabolism
Morphine is metabolised in the liver to morphine 6 glucuronide (10%) and morphine 3 glucuronide (90%)
134
How do loop diuretics work? Give an example
act at the ascending limb of the loop of Henle
**Reversibly inhibit the Na/K/Cl cotransporter**, inhibiting the reabsorption of filtered sodium and chloride ions.
Ergo hypertonicity of the renal medulla, thus inhibiting water reabsorption by the collecting ducts.
eg Furosemide, Torsemide
135
Normal physiology - What does Aldosterone do? Where does it act? What inhibits it?
Aldosterone acts on the principle cells of the collecting duct, =
Leading to more Na+ and Cl- reabsorption and water retention , and more K+ secretion into the urine
*(bring in Na+ and water at the expense of kicking out K+)*
**inhibited by ANP**
136
How do thiazide diuretics work? Where do they act and give an example
Work on the distal convoluted tubule
inhibit reabsorption of sodium and chloride ions, by **blocking the thiazide-sensitive Na-Cl symporter**.
Inhibits the reabsorption of water, reabsorption of water is also inhibited, as water follows sodium.
Examples include clorothiazide and Bendroflumethiazide.
137
How do aldosterone antagonist diuretics work? Give an example
binds competitively to the aldosterone receptor (AR) at the **aldosterone-dependent sodium-potassium exchange site.**
This promotes sodium and water excretion and potassium retention
138
What are some side effects of spirinolactone?
Common side effects include drowsiness, dizziness, nausea, vomiting. More severe side effects include hyperkalaemia and anti-androgen effects, e.g. gynaecomastia, loss of libido, erectile dysfunction
139
What are some side effects of thiazide diuretics?
include alkalosis Sexual dysfunction hypochloraemic; diarrhoea; hyperglycaemia and hyperuricaemia to name a few.
140
What are some side effects of loop duiretics?
Common side effects include dizziness, electrolyte imbalance, fatigue and headache.
141
G protein types - what do the secondary messengers of Gq protein coupling go onto do within the cell?
IP3 = opens calcium channels, causing a Ca2+ efflux into the cytoplasm
DAG = activates protein kinase C (PKC),
***Protein Kinase C can go on phosphorylate target proteins**
(The majority of GPCR’s interact with Phospholipase C or adenylyl cyclase)
142
Outline the MOA of Dobutamine
**Dobutamine is a β1-agonist that acts as a positive inotrope** that
increases heart muscle contractility and tries to increase cardiac
output
