DRUGS

Question 1

TTX

Answer 1

Na+ channel inactivation

Question 2

TEA

Answer 2

K+ channel inactivation, but non selective so it can target Ca2+ channels and also target the nAChRs

Question 3

Cocaine

Answer 3

Agonist of NA+ channels in use dependent competitive manner - 3% actually binds to Na+ channels O’Leary 2010 - joyous feelings arise from the indirect agonist of dopamine reuptake receptors (DAT)

Question 4

Derivatives of cocaine used because

Answer 4

Coke takes ages to unbind from Na+ receptors - and hence the effects cannot be appropriately mediated - 8x slower - Crumb and Clarkson 1990

Question 5

3 major discoveries of the synapse

Answer 5

1936 Loewi and Dale NP - demonstrated that transmission was chemical
Loewi - placed two frog hearts in a bath and slowed the first - the second slowed two and determined the substance was Vagustoff
Dale then determined this was ACh with experiments on leech muscle

Vesicles - then from the coloured with histochemical staining then electron microscopy - Koelle et Al - 1949

Fatt and Katz - 1954 - determined the vesicular and quantal nature of ACh release - mEPPs - determined too big to be of just one ACh molecule and that they were uniform in size

Question 6

Turbocuraine

Answer 6

NMJ - Non depolarising competitive antagonist of nAChRs - long duration paralytic

Question 7

Suxamethonium

Answer 7

Depolarising direct cholinergic agonist - intermediate fasiculation

Question 8

Sarin nerve gas

Answer 8

Inhibits by competitive binding AChE - seizures and resp arrest

Question 9

Organophosphates

Answer 9

AChE inhibitors also excess muscarinic and nicotinic action

Question 10

Botulinum toxin

Answer 10

Cleaves SNAP 25 - no partial fusion so no vesicular release

Question 11

Myaesthenia Gravis

Answer 11

IgG autoantibodies - bind to and increase the rate at which the receptor itself is degraded - treated with AChEs

Question 12

Atropine

Answer 12

Anticholinergic muscarinic competitive antagonist - acts on M2 (inhibits an inhibitory) - at vagus nerve junction

Question 13

Pirenzepine

Answer 13

Muscarinic M2 receptor antagonist - inhibits gastric acid secretion

Question 14

Gallamine

Answer 14

M2 competitive antagonist - muscle relaxation in general anaesthetic

Question 15

Darifenacin

Answer 15

M3 agonist located in smooth muscle (bladder)

Question 16

Hess experiment

Answer 16

1920s - invented interrupted DC and paced it through a cats brain - could induce higher HR and a generalised stress state - termed the region the arcuate nucleus of the hypothalamus

Question 17

Alpha 1 both

Answer 17

Gq
Agonist - phenylephrine - activation of α1-adrenoceptors in the arterioles of the nasal mucosa. This causes vasoconstriction, which leads to decreased edema and increased drainage of the sinus cavities.

Antagonist - prazosin - relaxed muscle, including blood vessels and therefore lowers blood pressure

Question 18

Alpha 2 both

Answer 18

Gi
Agonists - methyldopa antihypertensive - all normally oppose the effects of the sympathetic nervous system to produce sedation, analgesia, and euphoric effects and partially block acute withdrawal symptoms in chronic opioid users

Antagonist - mirtazapine - dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonising the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors and increase sympathetic action

Question 19

Beta 1 both

Answer 19

Gs
Agonist - dobutamine - inotropic effect increases contractility, leading to decreased end-systolic volume and, therefore, increased stroke volume

Antagonist - metoprolol - cardiac output by negative inotropic and chronotropic effects and decreases sympathetic activity

Question 20

Beta 2 both

Answer 20

Gs
Agonist - albuterol - relaxes the bronchial smooth muscle. It also inhibits the release of immediate hypersensitivity mediators from cells, especially mast cells to treat/ prevent bronchospasm

No selective beta 2 antagonists

Question 21

M3

Answer 21

Agonist - Pilocarpine - By directly stimulating these receptors, pilocarpine causes smooth muscles, such as the iris sphincter muscle and ciliary muscle, to contract

Antagonist - tiotropium - bronchodilation by relaxing and opening the air passages to the lungs to make breathing easier

Question 22

M1

Answer 22

Agonist - sabcomeline - though in spite of important cognitive enhancing effects, most trials have been discontinued due to considerable side-effects

Antagonist - scopolamine - central nervous system (CNS) to create a calming effect on the muscles in the stomach and bowels (gut) post anaesthesia anti-nausea