DRUG INTERACTIONS WITH RECEPTORS AND ION CHANNELS Flashcards
Acetyl-beta-methylcholine/methacholine
1 - NACHR agonist.
2 - inactive negative isomer has no affinity.
adenosine
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.
atropine
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)
Bay K 8644
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.
Benzilylcholine mustard
1 - irreversible alkylates the MACHR. sympathomimetic.
2 - an ethylamine
benzocaine
1 - ester local anaesthetic . uncharged so rate and extent of block are independent of pH.
2 - long lasting.
alpha-bungarotoxin
1 - a neurotoxin of the taiwanese banded Krait. irreversibly inhibits the NACHR causing paralysis, respiratory failure and death.
cholera toxin
1 - ADP-ribsoylates Gαs, inhibits GTPase hence prolonged activation.
danazol
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
diazoxide
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.
diltiazem
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,
d-tubocurarine
1 - NACHR antagonist
2 - active ingredient of curare
ethinylestradiol
1 - estrogen (estradiol) agonist.
2 - orally bioactive and used in many combined oral contraceptive pills
fludrocortisone
1 - Mineralocorticoid (aldosterone) agonist.
2 - replace aldosterone in adrenal insufficiency ie addisons and congenital adrenal hyperplasia.
glibenclamide
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.
isoprenaline
1 - β-adrenoceptor agonist
2 - inactive d isomer has affinity
2 - treat bradycardia
lidocaine
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.
lithium
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
mifepristone
1 - Glucocorticoid (cortisol) antagonist
also a progesterone antagonist so used as an abortifacient in first 49 days.
minoxidil
1 - pd gated K channel opener.
2 - vasodilate hence hypertension.
3 - side effect of hirsutism, hence treat alopecia.
muscarine
1 - MACHR agonist
2 - from fly agaric mushroom
nicorandil
1 - pd sensitive K channel opener.
2 - also NO donor.
3 - vasodilate to treat angina (and hypertension).
nicotine
1 - NACHR antagonist
nifedipine
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.