DRUG INTERACTIONS WITH RECEPTORS AND ION CHANNELS

Question 1

Acetyl-beta-methylcholine/methacholine

Answer 1

1 - NACHR agonist.

2 - inactive negative isomer has no affinity.

Question 2

adenosine

Answer 2

1 - Targets the A1 receptor linked to the Kach channel by inhibiting adenylyl cyclase and hence increasing K efflux.
2 - slows HR
3 - can terminate some dysrhythmias
3 - inhibits renin release via A1R.

Question 3

atropine

Answer 3

1 - MACHR anatagonist nonselective
2 - sympathomimetic effects as it inhibits parasympathetics
3 - tertiary ammonium
4 - from deadly nightshade
5 - mydriasis (dilates pupils)
6 - prolonged action (1 hr ish)

Question 4

Bay K 8644

Answer 4

1 - Dihydropyridine (DHP) calcium agonist.
2 - highly lipid soluble - aromatic.
3 - accesses Ca channel via lipid phase of the membrane.
4 - favours mode 2 channel gating - prolonged opening.
5 - opens L type Ca channels.

Question 5

Benzilylcholine mustard

Answer 5

1 - irreversible alkylates the MACHR. sympathomimetic.

2 - an ethylamine

Question 6

benzocaine

Answer 6

1 - ester local anaesthetic . uncharged so rate and extent of block are independent of pH.
2 - long lasting.

Question 7

alpha-bungarotoxin

Answer 7

1 - a neurotoxin of the taiwanese banded Krait. irreversibly inhibits the NACHR causing paralysis, respiratory failure and death.

Question 8

cholera toxin

Answer 8

1 - ADP-ribsoylates Gαs, inhibits GTPase hence prolonged activation.

Question 9

danazol

Answer 9

1 - Progestagen (progesterone) antagonist
2 - modified derivative of testosterone.
3 - initially used to treat endometriosis (cells from the lining of the uterus (endometrium) appear and flourish outside the uterine cavity, most commonly on the peritoneum which lines the abdominal cavity)
4 - causes decreased secretion of estradiol

Question 10

diazoxide

Answer 10

1 - opens pd sensitive K channel
2 - inhibits insulin release so not only used to treat hypertension (but only in a hypertensive emergency) but also hypoglycaemia as a result of an insulinoma.

Question 11

diltiazem

Answer 11

1 - blocks L type Ca channel but distinct site to DHP. enhances their binding.
2 - greater use dependence and more prolonged than DHPs.
3 - preferential to cardiac hence antidysrhytmic (type 4), Acts preferentially at the nodes where the AP depends upon the L and T type current hence slowing conduction.
4 - a benzothiazepine.
5 - more effect on S.M. than verapamil.
6 - well absorbed by GI, extensively metabolised.
7 - side effects - flushing and headache,

Question 12

d-tubocurarine

Answer 12

1 - NACHR antagonist

2 - active ingredient of curare

Question 13

ethinylestradiol

Answer 13

1 - estrogen (estradiol) agonist.

2 - orally bioactive and used in many combined oral contraceptive pills

Question 14

fludrocortisone

Answer 14

1 - Mineralocorticoid (aldosterone) agonist.

2 - replace aldosterone in adrenal insufficiency ie addisons and congenital adrenal hyperplasia.

Question 15

glibenclamide

Answer 15

1 - closes Katp channel via sulphylurea receptor.
2 - orally acting hypoglycaemic used to treat T2D.
3 - weight gain side effect. well absorbed. excreted so action enhanced in elderly.

Question 16

isoprenaline

Answer 16

1 - β-adrenoceptor agonist
2 - inactive d isomer has affinity
2 - treat bradycardia

Question 17

lidocaine

Answer 17

1 - local anaesthetic, pd gated Na channels.
2 - pKa 8-9
3 - stabilises inactivated state by blocking channel
4 - an amineester
5 - neutral crosses membrane, protonated form blocks.
6 - inhibits C and Aδ fibres first
7 - use dependent for high rates of stimulation. class 1b antidysrhythmic w/ v.fast association/dissociation.
8 - neuropathic pain.
9 - amides metabolised in the liver.
10 - increases proportion of inactive channels at any pd.

Question 18

lithium

Answer 18

1 - noncompetitively inhibits phosphatase for IP1 to inositol and hence blocks inositol recycling. imp in brain as no uptake of I through BBB
2 - used to treat manic depression

Question 19

mifepristone

Answer 19

1 - Glucocorticoid (cortisol) antagonist

also a progesterone antagonist so used as an abortifacient in first 49 days.

Question 20

minoxidil

Answer 20

1 - pd gated K channel opener.
2 - vasodilate hence hypertension.
3 - side effect of hirsutism, hence treat alopecia.

Question 21

muscarine

Answer 21

1 - MACHR agonist

2 - from fly agaric mushroom

Question 22

nicorandil

Answer 22

1 - pd sensitive K channel opener.
2 - also NO donor.
3 - vasodilate to treat angina (and hypertension).

Question 23

nicotine

Answer 23

1 - NACHR antagonist

Question 24

nifedipine

Answer 24

1 - DHP L type antagonist.
2 - aromatic, highly lipid soluble, accesses channel via lipid phase.
3 - favours mode 0, closed.
4 - Causes peripheral and coronary vasodilation hence treats hypertension and angina.
5 - causes reflex tachycardia.
6 - more active on vascular Ca channels as inactive channels dominate due to the less negative resting pd.
7 - usually combined with a β blocker to combat reflex tachycardia.

Question 25

norethisterone

Answer 25

1 - progestagen (progesterone) agonist.

2 - some contraceptives. to treat painful/irregular/heavy periods

Question 26

pertussis toxin

Answer 26

ADP-ribosylates Gαi inhibiting its action.

Question 27

prednisolone

Answer 27

1 - Glucocorticoid (cortisol) agonist
2 - to treat a wide range of inflammatory and autoimmune diseases by modulate transcription for various genes inc reducing COX-2 cytokines, iNOS and cell adhesion molecules.

Question 28

procaine

Answer 28

1 - ester local anaesthetic pKa 8-9
2 - broken down by BuChE
3 - inhibit C and Aδ fibres first

Question 29

quinidine

Answer 29

1 - intermediate rate of association/ dissociation. 
2 - stereoisomer of quinine. 
3 - class 1a antidysrhythmic (first group classified hence nomenclature), increases AP duration.

Question 30

QX 314

Answer 30

1 - quaternary amine local anaesthetic. pd gated Na channel blocker.
2 - charged so cant cross membrane.
3 - amides metabolised in liver.

Question 31

spironolactone

Answer 31

Mineralocorticoid (aldosterone) competitive antagonist. also antiandrogenic.
2 - primary use as a potassium sparing diuretic.

Question 32

tamoxifen

Answer 32

1 - estrogen (estradiol) antagonist.

2 - treat braest cancer

Question 33

tetrodotoxin

Answer 33

1 - toxin with guanidinium groups. blocks pd gated Na channels from the outside.
2 - no use dependence.
3 - from japanese pufferfish.
4 - works exclusively from the extracellular side.

Question 34

tolbutamine

Answer 34

1 - closes Katp via sulphonylurea R.

2 - orally acting. depolarises pancreatic beta cell, opens pd gated Ca channel, Ca in causes exocytosis.

Question 35

tyrphostins

Answer 35

1 - inhibit tyrosine kinases, interest in controlling neoplasic growth.
ie imatinib for chronic myelogenous leukaemia.

Question 36

verapamil

Answer 36

1 - blocks L type channels. a Phenylalkylamine.
2 - binds distinct site to DHPs and reduces their binding.
3 - D600 is its derivative.
greater use dependence and longer action than DHPs
4 - preferentially blocks cardiac over vascular hence a class 4 antidysrhythmic. Acts preferentially at the nodes where the AP depends upon the L and T type current hence slowing conduction.
5 - slows HR.
6 - constipation side effect