Drug Interactions

Question 1

Nicotine

Answer 1

Drug with no receptor
Only affects certain cells via nAChR
Specifically blocked by antagonists that compete with nicotine for its receptor (mecamylamine)
0.2-3.5mg nicotine/cigarette –> plasma conc 100-300nM

Question 2

Ethanol

Answer 2

Drug with no receptor
Similar effects on all cells
No specific antagonists
Many lipophilic compounds have similar effects - physicochemical properties are more important than precise chemical structure
Beer = 1M ethanol –> pint gives plasma conc 10mM

Question 3

d-tubocurarine

Answer 3

Nicotinic antagonist

Question 4

Atropine

Answer 4

Muscarinic antagonist

Question 5

Acetyl-beta-methylcholine

Answer 5

Cholinergic agonist

stereoisomer has no affinity

Question 6

Isoprenaline

Answer 6

beta adrenoceptor agonist

inactive stereoisomer has affinity so acts as an antagonist

Question 7

Pertussis Toxin (PTX)

Answer 7

ADP-ribosylate the alpha-i subunit and prevents activation of Gi in response to receptor stimulation (prevents inhibition of adenylyl cyclase)

Question 8

Cholera Toxin (CTX)

Answer 8

ADP-ribosylate GTPase of alpha-s subunit. Alpha-s not deactivated –> activation of adenylyl cyclase.

Question 9

AlF4-

Answer 9

Mimics the gamma phosphate of GTP so causes persistent activation of G proteins

Question 10

Lithium

Answer 10

Uncompetitively inhibits the phosphatase that converts IP1 to inositol. Can’t uptake inositol from blood as BBB. So stops PLC activation. Treatment of bipolar disorder.

Question 11

Tyrphostins

Answer 11

Tyrosine Kinase Inhibitor

May be of use for controlling neoplastic growth as cell proliferation and differentiation are regulated by RTKs

Question 12

Lidocaine

Answer 12

Local anaesthetic
Fast in fast out so use dependence only at high rates of stimulation
Binds preferentially to inactivated VGSC and stabilises this state - so shifts inactivation curve to hyperpolarised potentials
Most effective in ischaemic tissue
weak base pKa 8-9

Question 13

Procaine

Answer 13

Also a LA

weak base pKa 8-9

Question 14

Benzocaine

Answer 14

LA

pKa 2.6

Question 15

QX-314

Answer 15

Permanently charged derivative of lidocaine

Inactive on VSC if applied to outside, but v effective if perfused to inside

Question 16

Quinidine

Answer 16

Slow in slow out LA
shows use dependence at low frequencies
Used in supraventricular tachycardia SVT

Question 17

Tetrodotoxin

Answer 17

Blocks VGSC
from puffer fish
Bind to outer mouth of pore Glu residues.
Cys in heart confers resistance to action

Question 18

Saxitoxin

Answer 18

Blocks VGSC
Shellfish poisoning
Bind to outer mouth of pore Glu residues.
Cys in heart confers resistance to action

Question 19

Batrachotoxin

Answer 19

Causes VGSC to activate at more -ve potentials

increases excitability and also heart arrhthmias

Question 20

Divalent cations Mn2+ Cd2+

Answer 20

Non-selective block of VGCC

Question 21

Nifedipine

Answer 21

Dihydropiridine
L-type VGCC blocker
Increases probability of Mode 0
Used in hypertension and angina (vascular selectivity)

Question 22

Verapamil

Answer 22

Phenylalkylamine
L-type VGCC blocker
Reduces DHP binding
Antiarrhythmic (cardiac selectivity)

Question 23

Diltiazem

Answer 23

Benzothiazepine
L-type VGCC blocker
Enhances DHP binding
Antiarrhythmic (cardiac selectivity)

Question 24

Bay K 8644

Answer 24

Dihydropyridine
L-type VGCC agonist- ‘calcium agonist’
Increases probability of Mode 2

Question 25

Cromakalim, diazoxide, minoxidil

Answer 25

K+-ATP channel openers in vascular smooth muscle

Question 26

Tolbutamide, glibenclamide

Answer 26

Sulfonylureas
Close KATP channel by actin gon sulphonylurea receptors.
Dep membrane of pancreatic beta cell –> VGCC –> Ca2+ in —> insulin release.
Treat Type II diabetes

Question 27

Metformin

Answer 27

Biguanides

Increase glucose uptake into skeletal muscle and decrease gluconeogenesis.