LS1- Receptors and Ion Channels

Question 0

Isoprenaline

Answer 0

β-adrenoreceptor agonist. The D-isomer is inactive but has affinity so acts as a competitive antagonist with the L-isomer.

Question 1

Acetyl-β-Methylcholine

Answer 1

AChR Agonist. Its isomer is inactive and has no affinity.

Question 2

Nicotine

Answer 2

NAChR Agonist

Question 3

Atropine

Answer 3

MAChR Antagonist

Question 4

Muscarine

Answer 4

MAChR Agonist

Question 5

D-Tubocurarine

Answer 5

NAChR Antagonist

Question 6

Benzilylcholine

Answer 6

Irreversible MAChR antagonist. Causes alkylation of the receptor. Demonstrates the spare receptor principle, as maximal responses can still be achieved in the initial period after application.

Question 7

Cholera Toxin

Answer 7

Causes ADP ribosylation of αs subunit, which inhibits it’s intrinsic GTPase activity. Results in sustained activation of adenylyl cyclase.

Question 8

Pertussis Toxin

Answer 8

ADP ribosolation of αi prevents activation of Gi in response to receptor stimulation, therefore preventing inhibition of adenylyl cyclase activity.

Question 9

Lithium

Answer 9

Uncompetitive inhibitor of phosphatase that converts IP1 to inositol. Blocks IP3 recycling pathway, affects the brain particularly since blood cannot provide an alternative source of IP3 as it does not cross the BBB. Used to treat manic depression.

Question 10

Tyrphostins

Answer 10

Inhibitors of tyrosine kinases. Have potential uses if the treatment of neoplastic growth.

Question 11

Prednisolone

Answer 11

Glucocorticoid Receptor Agonist. May have anti-inflammatory or immunosuppressive effects.

Question 12

Mifepristone

Answer 12

Glucocorticoid R Antagonist. Also a partial progestagen R agonist. It has abortifacients effects.

Question 13

Fludrocortisone

Answer 13

Mineralocorticoid R agonist. Used in replacement therapy to treat Addison’s disease.

Question 14

Spironolactone

Answer 14

Mineralocorticoid R antagonist. Diuretic effects

Question 15

Ethinylestradiol

Answer 15

Estrogen receptor agonist, used in HRT and for contraceptive purposes.

Question 16

Tamoxifen

Answer 16

Estrogen R antagonist used in the treatment of breast cancer

Question 17

Norethisterone

Answer 17

Progestagen receptor agonist used in contraception

Question 18

Danazol

Answer 18

Progestagen R antagonist. Used in the treatment of endometriosis and menorrhagia. In men, it can be used to treat gynomastia

Question 19

Lidocaine

Answer 19

V-gated Na+ channel blocker. LA. Use-dependent, so has a mild selectivity for rapidly firing pain fibres. Shifts the inactivation curve of the channel to the left, such that at any given membrane potential, a greater proportion of the channels are inactivated. It is a weak base (pKa 8-9) so exists in both forms at the physiological pH. It needs to cross the CSM in the unprotonated form, but is a more potent blocker in its charged, protonated form. It binds preferentially to the I form of the channel, so is most effects in ischaemic tissue. Used to treat ventricular dysthymia, and has fast association/dissociation properties.

Question 20

Procaine

Answer 20

V-gated Na* channel blocker. LA. A weak base (pKa 8-9) so exists in both forms at physiological pH. Most potent in the protonated form, but needs to cross CSM unprotonated.

Question 21

QX314

Answer 21

A quaternary LA which is a permanently charged form of lidocaine. It is inactive when applied externally, but potent when infused.

Question 22

Benzocaine

Answer 22

V-gated Na+ channel blocker that acts as a LA. It is always uncharged (pKa 2.6) so it only enters via the hydrophobic pathway, showing no use dependence. It is not affected by pH changes in the physiological range, as shown in the Hille experiments.

Question 23

Quinidine

Answer 23

V-gated Na+ channel blocker, LA. Slow association/dissociation properties means it shows use dependence at low rates of stimulation only. It is used to treat supraventricular tachycardia.

Question 24

Tetradotoxin

Answer 24

Na* channel blocker. Possesses a guanidinium. Blocks the channels from the outside, showing no use dependence.

Question 25

Bay K 1844

Answer 25

L-Type Ca2+ channel agonist

Question 26

Nifedipine

Answer 26

L-type Ca2+ antagonist. It is a dihydropyridine, which preferentially binds to the inactivated form of the channel, so has a selectivity for vascular tissue (which undergoes prolonged periods of depolarization.) Used to treat hypertension and angina pectoral as it can cause both coronary and peripheral vasodilation.

Question 27

Verapamil

Answer 27

L-type Ca2+ channel antagonist. It is a phenylalkamine that binds to a different site from the DHP, but decreases the affinity of DHP binding. It shows greater use dependence and a more prolonged block than produced by the DHPs. Anti-dysrhythmic uses.

Question 28

Diltiazem

Answer 28

L-type Ca2+ antagonist. A benzothiazepine that binds to a site different to the DHP, but increases the affinity of DHP binding. Produces a more use dependent and prolonged block than the DHP.

Question 29

Diazoxide, Minoxidil, Nicorandil.

Answer 29

K+ channel openers that acts on K+ATP channels. The increased K* effluent leads to hyperpolarisation which results in smooth muscle relaxation. Potential clinical applications in the treatment of IBS, asthma and male alopecia. They are useful in the treatment of hypertension, however their action on insulin release leads to decreased glucose tolerance and hyperglycemia.

Question 30

Tolbutamide and Glibenclamide

Answer 30

Orally acting anti-hyperglycemic agents. Sulphonylureas bind to sulphonylurea Rs on sites associated with the K+ATP channel. This results in β islet cell depolarization, Ca2+ influx and insulin release . Used in the treatment of NIDDM.