Drug Interactions Flashcards
Nicotine
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
Ethanol
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
d-tubocurarine
Nicotinic antagonist
Atropine
Muscarinic antagonist
Acetyl-beta-methylcholine
Cholinergic agonist
stereoisomer has no affinity
Isoprenaline
beta adrenoceptor agonist
inactive stereoisomer has affinity so acts as an antagonist
Pertussis Toxin (PTX)
ADP-ribosylate the alpha-i subunit and prevents activation of Gi in response to receptor stimulation (prevents inhibition of adenylyl cyclase)
Cholera Toxin (CTX)
ADP-ribosylate GTPase of alpha-s subunit. Alpha-s not deactivated –> activation of adenylyl cyclase.
AlF4-
Mimics the gamma phosphate of GTP so causes persistent activation of G proteins
Lithium
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.
Tyrphostins
Tyrosine Kinase Inhibitor
May be of use for controlling neoplastic growth as cell proliferation and differentiation are regulated by RTKs
Lidocaine
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
Procaine
Also a LA
weak base pKa 8-9
Benzocaine
LA
pKa 2.6
QX-314
Permanently charged derivative of lidocaine
Inactive on VSC if applied to outside, but v effective if perfused to inside
Quinidine
Slow in slow out LA
shows use dependence at low frequencies
Used in supraventricular tachycardia SVT
Tetrodotoxin
Blocks VGSC
from puffer fish
Bind to outer mouth of pore Glu residues.
Cys in heart confers resistance to action
Saxitoxin
Blocks VGSC
Shellfish poisoning
Bind to outer mouth of pore Glu residues.
Cys in heart confers resistance to action
Batrachotoxin
Causes VGSC to activate at more -ve potentials
increases excitability and also heart arrhthmias
Divalent cations Mn2+ Cd2+
Non-selective block of VGCC
Nifedipine
Dihydropiridine
L-type VGCC blocker
Increases probability of Mode 0
Used in hypertension and angina (vascular selectivity)
Verapamil
Phenylalkylamine
L-type VGCC blocker
Reduces DHP binding
Antiarrhythmic (cardiac selectivity)
Diltiazem
Benzothiazepine
L-type VGCC blocker
Enhances DHP binding
Antiarrhythmic (cardiac selectivity)
Bay K 8644
Dihydropyridine
L-type VGCC agonist- ‘calcium agonist’
Increases probability of Mode 2
Cromakalim, diazoxide, minoxidil
K+-ATP channel openers in vascular smooth muscle
Tolbutamide, glibenclamide
Sulfonylureas
Close KATP channel by actin gon sulphonylurea receptors.
Dep membrane of pancreatic beta cell –> VGCC –> Ca2+ in —> insulin release.
Treat Type II diabetes
Metformin
Biguanides
Increase glucose uptake into skeletal muscle and decrease gluconeogenesis.
