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MPharm Semester 2 > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What does the autonomic NS consist of?

A

Consists of all the motor outputs from CNS to heart, smooth muscles and glands, apart from skeletal. All about homeostasis.

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2
Q

Where are the ganglionic neurones located?

A

The pre-ganglionic neutron has its cell body in the CNS and synapses in the autonomic ganglion. The post ganglionic neuron has its cell body in the autonomic ganglion and synapses within the effector organ.

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3
Q

What are the sizes of the ganglionic neurons in the sympathetic NS?

A

Short pre-ganglionic, long post-ganglionic

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4
Q

Where do pre-ganglionic sympathetic neurons leave from?

A

The thoracic and lumbar regions of spinal cord (thoracolumbar system)

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5
Q

Where does the synapse occur in the sympathetic NS?

A

At ganglia close to the spinal cord, the sympathetic paravertebral chain.

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6
Q

What does the sympathetic NS innervate?

A

Adrenal medulla releases adrenaline.

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7
Q

What are the sizes of the ganglionic neurones in the parasympathetic NS?

A

Long pre-ganglionic and short post-ganglionic

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8
Q

Where do the pre-ganglionic post sympathetic neurons leave from?

A

The brain stem and the sacral region of the spinal cord (craniosacral system)

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9
Q

Where does the synapse occur in the parasympathetic NS?

A

Synapse at ganglia close to effector organ.

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10
Q

Give an example for the parasympathetic NS?

A

Cranial nerve 10= vagus nerve

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11
Q

Give the main four functions of the autonomic NS:

A
  1. Control of cardiac function
  2. Contraction and relaxation of smooth muscle
  3. Control of exocrine (some endocrine) glands
  4. Regulation of energy metabolism
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12
Q

What are the two major neurotransmitters in the autonomic NS and where do they act?

A

Acetylcholine- parasympathetic

Noradrenaline- sympathetic

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13
Q

What are the two acetylcholine receptors and what type are they?

A

1) Nicotinic- ligand gates ion channels

2) Muscarinic- GPCR

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14
Q

What is the noradrenaline receptor and what type are they?

A

Adrenoreceptors- GPCRs
Subtypes- alpha- adrenoreceptors
- beta- adrenoreceptors

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15
Q

What neurotransmitters are released from the CNS and what receptors do they act on?

A

ACh and act on nicotinic receptors

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16
Q

What is the main function of the kidney? Give three examples:

A

Excrete metabolic products:

1) urea- end of amino acid breakdown
2) uric acid- end of nucleotide breakdown
3) xenobiotics

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17
Q

Give four other functions of the kidney:

A

Regulate body fluid osmolarity and volumes
Electrolyte balance
Acid-base balance, blood 7.4, urine 6- shows getting rid of H+ ions
Endocrine function

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18
Q

Name the eight segments of the nephron in order:

A 
Proximal convoluted 
Proximal straight 
Descending LoH- thin 
Ascending LoH- thin 
Ascending LoH- thick 
Distal convoluted 
Cortical collecting duct
Medullary collecting duct
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19
Q

What is the average amount of glomerular filtrate filtered? How many ml of urine a day?

A

120ml/min and 1.5L

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20
Q

What are the three fundamental processes that account for renal secretion?

A

1) Glomerular filtration
2) Tubular secretion
3) Reabsorption from tubule

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21
Q

How do you calculate the urinary excretion rate?

A

Filtration rate+ secretion rate- reabsorption rate

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22
Q

How much of the glomerular filtrate is filtered?

A

10-20% the rest is passed into the efferent arteriole

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23
Q

What allows a high pressure for filtration?

A

Lumen of the efferent arteriole is more narrow than the afferent arteriole

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24
Q

Which three layers is fluid filtered through?

A

1) The glomerular capillary wall
2) The basement membrane
3) Podocytes in the inner layer of Bowman’s capsule

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25
Q

What type of components can filter through easily?

A

<2000 Daltons easily eg. glucose and amino acids
>50,000 Daltons can’t eg. proteins
Unbound drugs yes but drugs bound to proteins no

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26
Q

What is the glomerular filtration rate regulated by?

A

Autonomic NS

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27
Q

How much fluid passes through the peritubular capillary in the proximal tubule?

A

80-90%

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28
Q

What are the two transporters in the proximal tubule?

A

Organic Anion Transporters (OAT)

Organic Cation Transporters (OCT)

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29
Q

How much of: Water are absorbed?
Na+ ions
Glucose
Urea

A

99%
99.5%
100%
44%

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30
Q

Where does water move in the proximal tubular function?

A

Tight junctions

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31
Q

How is glucose reabsorbed in the blood?

A

Co- transporters with Na+ then with a carrier protein to the peritubular capillary

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32
Q

Why is the ascending loop impermeable to water?

A

Its tight junctions are tight

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33
Q

Why is the descending loops permeable to water?

A

Lots of aquaporins

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34
Q

Is the distal tubule permeable or impermeable to water?

A

Highly impermeable to water

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35
Q

What happens in the collecting duct?

A

ADH increases the number of aquaporins so more permeable to water so increases reabsorption.
Aldosterone increases Na+ channels so more reabsorption of Na+ and thus increasing blood volume.

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36
Q

Is the inside or the outside of a cell more negative?

A

Inside

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37
Q

What secondary structure is a transmembrane domain?

A

a- helices

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38
Q

What is a voltage sensor on a voltage gated ion channel?

A

Detects electrical charge and rotation and opens the channel pore.

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39
Q

How many transmembrane domains are in Na+ voltage gated channels?

A

24, 6x4 homologous repeats

40
Q

What is a P-loop on a voltage-gated ion?

A

Selectivity filter, determines which ions can pass through

41
Q

On which transmembrane domain is the voltage sensor located on and why?

A

Has an overall positive charge, on the fourth one

42
Q

What subunits does the Na+ voltage gated ion channel associate with?

A

Accessory (auxiliary) B- subunits

43
Q

How many varieties of Na+ voltage gated ion channels are there?

A

Nine a- subunits

From Nav1.1 - Nav1.9

44
Q

Where are the N and C termini associated cellularly in a Na+ voltage gated ion channel?

A

Intracellular

45
Q

What are the main properties of the Ca2+ voltage- gated channel structure?

A

Very similar to the Na+ voltage gated ion channel

However its auxiliary subunits are; B, γ and a2- δ subunit

46
Q

What do auxiliary subunits do?

A

Help get the a1 subunit get to the membrane and regulate ion channel properties

47
Q

How many varieties of Ca2+ voltage gated ion channels are there?

A

Ten a1 subunits

Cav 1, 2 and 3

48
Q

How are Na+ voltage gated ion channels activated?

A

At resting membrane potential (-70mV) Na v are closed
Na v open above the threshold (-55mV) sensed by the S4 domain and opens the activation gate
Rapid depolarisation occurs and no longer active by the inactivation gate

49
Q

How would you measure ion channels?

A

Tight seal between glass micro electrode and plasma membrane, by providing light suction
Pulling this ion channel away can cause a circuit

50
Q

Name the four type of cell responses to ligands and how fast do they act:

A

Nuclear receptors- hours
Enzymes- minutes
Receptors- Seconds
Ion channels- milliseconds

51
Q

What is the relationship of free energy of hydration going down group 1?

A

Decreases

52
Q

What is the potassium selectivity filter compromised of?

A

Two protein loops

53
Q

How does the potassium ion channel work?

A

Four amino acids provide four carbonyl groups for binding of the cation
Passage of the ion occurs by a bullard ball mechanism in which one cation forces the second further down the channel
In the selectivity filter, the K+ binds to the outer binding side held by 4 carbonyls
Then moves to the second binding site, when 2 K+ are in, they repel each other so the first moves through the ion channel

54
Q

How does a K+ ion exist in solution?

A

A hydrated ion, around 6 H2O

55
Q

How does a K+ ion move through a K+ channel in solution?

A

When the K+ ion enters the channel it must lose 4 of its water molecules and the peptide carbonyl groups provide the hydration
Energy is needed for the cation to lose its solvation and released as it binds into the channel
The cation is more stable within the channel

56
Q

Why can’t Na+ ion move up a K+ ion channel?

A

The same process for Na+ as K+ when in solution, but for Na+ its harder to lose the four water molecules as more disolvation energy is needed
It is also not as stabilised in the channel so won’t move through it

57
Q

Describe why some metal ions can and can’t move through the K+ ion channel:

A

The size of the cation is important
K+ can form four ideal bond lengths with the peptide
Na+ and Li+ are too small to form four good interactions so less stable
Selenium ions are too large and therefore rejected
Rubidium is transported through the K+ channel but is not present in the body in large quantities so no competition

58
Q

What size is the Na+ ion channel pore restricted to?

A

Å radius

59
Q

What molecules does the sodium ion channel allow to pass through?

A

Sodium and one water molecule

Lithium and some organic cations but NOT K+

60
Q

What does it mean by Ca2+ is a divalent cation?

A

Divalent cations are transported 3x the rate if monovalent cations by a Ca2+ channel

61
Q

What makes the calcium ion channel selective for Ca2+ rather than Na+?

A

Negatively charged side chains of four glutamate residues are crucial
If a mutation to lysine, reverses the selectivity for that of Na+

62
Q

What is the main neurotransmitter in the sympathetic NS and what does it do?

A

Noradrenaline

Involved in fight or flight

63
Q

What is the rate limiting step in noradrenaline synthesis?

A

Tyrosine hydroxylase

64
Q

What is VMAT and what does it do?

A

Vesicular Monoamine Transporter
Powered by transvesicular proton gradient
Lots of protons in vesicles

65
Q

Describe Ca2+ medicated exocytosis:

A

The action potential in the presynaptic nerve causes the termination button to depolarise
This depolarisation opens calcium voltage gated Ca2+ channels in the terminal
Ca2+ flows down its electrochemical gradient and enters the presynaptic terminal

66
Q

What is uptake 1, termination of the adrenergic signal?

A

Noradrenaline uptake
Terminates signal in periphery using noradrenaline transporter
75% repacked into vesicles by VMAT

67
Q

What is uptake 2, termination of the adrenergic signal?

A

Noradrenaline mechanism
Remaining 25% is uptaken by non- neuronal cells
By extraneuronal monamine transport (EMT)

68
Q

Which enzymes metabolise noradrenaline?

A 
By two intracellular enzymes 
Monoamine oxidase (MAO) which is bound to the surface of mitochondria 
Catechol- O- methyl transferase (COMT)
69
Q

Name the five types of adrenergic receptors:

A

a adrenergic:
a1 and a2
B adrenergic:
B1, B2, B3

70
Q

Where is the a1 adrenergic receptor found and what does it do?

A

Found in the smooth muscle and it a Gq G- protein

It increases PLC, IP3 and increases the intracellular Ca2+ conc and therefore increases contraction

71
Q

Where is the a2 adrenergic receptor found and what does it do?

A

Found in the presynaptic and its a Gi G-protein

It decreases the activation of adenylate cyclase and decreases in cAMP

72
Q

Where is the B1 adrenergic receptor found and what does it do?

A

Found in the heart and is a Gs G- protein

Increases inactivation of adenylate cyclase and increases in cAMP and increases intracellular signalling pathway

73
Q

Where is the B2 adrenergic receptor found and what does it do?

A

Found in the smooth muscle and is a Gs G- protein

Increases inactivation of adenylate cyclase and increases in cAMP and increases intracellular signalling pathway

74
Q

Where is the B3 adrenergic receptor found and what does it do?

A

Found in the fat tissue and is a Gs G- protein

Increases inactivation of adenylate cyclase and increases in cAMP and increases intracellular signalling pathway

75
Q

Which adrenergic receptors work on the blood vessels and what effect do they have?

A

a1, a2 and B2
a= constriction
B2= dilation

76
Q

Which adrenergic receptors work on the heart and what effect do they have?

A

B1, they increase contraction

77
Q

Which adrenergic receptors work on the bronchi and what effect do they have?

A 
a1= increase in contraction
B2= relaxation
78
Q

Which adrenergic receptors work on the kidneys and what effect do they have?

A

a1 and a2= vasoconstriction

B1 and B2= renin release

79
Q

Which adrenergic receptors work on the adipocytes and what effect do they have?

A 
a2= inhibition of lipolysis 
B= lipolysis
80
Q

How is the a1 receptor involved in smooth muscle constriction?

A

Noradrenaline binding leads to activation of Phospholipase , which catalyses PIP2 to form DAG AND IP3. IP3 opens Ca2+ channels on sarcoplasmic reticulum and therefore increases cytoplasmic concentration of Ca2+ ions

81
Q

How is the a2 receptor involved in the negative feedback loop?

A

Noradrenaline binding to Gi which inactivates adenylate cyclase, this decreases CAMP levels and activates protein kinase A
Location is important for consequence

82
Q

How is B1 receptor in the cardiac muscle involved in cardiac contraction?

A

Increases cytoplasmic Ca2+ concetration

83
Q

How is B2 receptors stimulate bronchodilation?

A

Inactivation of myosin light chain kinase, which switches off myosin and decrease in force being produced so relaxed

84
Q

Give five classes of drugs that were/ are used to inhibit an adrenergic synapse and therefore noradrenaline:

A
  1. Noradrenaline synthesis inhibitors
  2. vMAT inhibitors
  3. Noradrenaline release inhibitors
  4. Inhibition of noradrenaline uptake
  5. Inhibition of noradrenaline metabolism
85
Q

Give an example of noradrenaline synthesis inhibitors and how are they used?

A

Metyrosine
Inhibits tyrosine hydroxylase
Originally used to treat hypertension but not specific

86
Q

Give an example of vMAT inhibitors and how are they used?

A

Reserpine

Originally used to treat hypertension but non specific, acted on all noradrenaline

87
Q

Give an example of noradrenaline release inhibitors and how are they used?

A

Guanethidine
Internalised during uptake stage with noradrenaline
Concentrated in transmitter vesicles
Decrease in noradrenaline content in vesicles
Non specific

88
Q

How do inhibitors of noradrenaline uptake work?

A

Bind and block reuptake transporter

89
Q

Give an example of noradrenaline metabolism inhibitors and how are they used?

A

Pheneizine and iproniazid
Irreversible MAO inhibitors
Used to treat depression

90
Q

What is a diuretic?

A

Anything that promotes the formation of urine by the kidney

e.g caffeine, alcohol

91
Q

How do diuretics work?

A

In the kidney by inhibiting the reabsorption of ions (mainly Na+) which gives a higher osmolarity in the kidney tubule and hence more excretion of water

92
Q

Give five classes of diuretics and an example of each:

A
  1. Thiazides e.g bendroflumethiazide
  2. Loop diuretics e.g. furosemide
  3. Potassium sparing diuretics e.g. amiloride, aldosterone antagonists
  4. Carbonic anhydrase inhibitors- no longer used
  5. Osmotic diuretics e.g mannitol but not used in the treatment of hypertension
93
Q

What occurs in the proximal tubule?

A

Reabsorption of most of the solutes and water occurs there
60-70% of water and Na+ reabsorbed here, 98% of glucose
Na+ is reabsorbed via the Na+-H+ exchanger so H+ ions are excreted
Bicarbonate ions are absorbed to regulate pH
Carbonic anyhdrase inhibitors act here to have their diuretic effect by providing the H+ ions

94
Q

What occurs in the loop of Henle?

A

Water is reabsorbed in the descending loop
Na+ and Cl- is reabsorbed in the ascending loop
Loop diuretics act at the ascending loop of Henle. by inhibiting the Na+, K+, Cl- (NKCC2) co-transporter
The inner medulla has high osmolarity which allows Na+ in so K+ and Cl- up its gradient

95
Q

What occurs in the distal tubule?

A

Na+ and Cl- is reabsorbed
Thiazide diuretics act at the distal tubule
Inhibit the Na+, Cl- co transporter

96
Q

What occurs in the collecting ducts?

A

Water is reabsorbed under the control of hormones, ADH (antidiretic hormone vasopressin) and aldosterone
Potassium sparing diuretics act here

MPharm Semester 2 (9 decks)

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