Autonomic and N.M.J pharmacology

Question 1

what is botulinium toxin and how does it modulate transmission at NMJ

Answer 1

neurotoxic protein produced by the bacterium Clostridium botulinum

ACh is not released as vesicle fusion is blocked. Leads to paralysis

Question 2

how do black widow and joro spider toxins modulate transmission at NMJ

Answer 2

they block calcium channels and so ACh cannot be released

Question 3

hemicholineum

Answer 3

blocks choline transport so ACh cannot be taken back up and resynthesised

Question 4

How do competitive ACh antagonists work?

Answer 4

they bind to nicotinic receptors but don’t open ion channels so ACh cannot bind and no end-plate potential is produced
causes rapid weakening and paralysis of muscles, including those of the respiratory tract, which can lead to respiratory arrest and death.

Question 5

how can you modulate sympathetic transmission at NMJ with drug examples?

Answer 5

introduce a false transmitter like methyldopa
block enzyme that produces adrenaline
block alpha or beta post synaptic receptors (by doxazosin drug or propanol)

Question 6

how can you drugs effect para- sympathetic transmission at NMJ with examples?

Answer 6

muscarinic receptor antagonists- atropine

muscarinic receptor agonists- carbachol, pilocarpine that bind and activate ACh receptors

Question 7

clinical applications of drugs at NMJ

Answer 7

non-depolarising or depolarising blockers used for paralysis during surgical procedures, controlling spasms in tetanus etc

botulinum toxin is used for treating muscle spasm or cosmetic procedures

anti-cholinesterases are used for treating myasthenic syndromes (neuromuscular disease) or countering botulinum posining

Question 8

what are some potential sites of action for drugs at the NMJ?

Answer 8

inhibit choline transporter
block voltage gated Ca2+ channels
block vesicle fusion
use non-depolarising nicotinic receptor blockers
or depolarising nicotinic receptor blockers
prolong the action potential
block acetylcholinesterase

Question 9

example of a depolarising nicotinic receptor blocker

Answer 9

succinylcholine

Question 10

example of a non-depolarising nicotinic receptor blockers

Answer 10

d-tubocurarine

Question 11

how can you stop transmission at the connection between pre and post ganglionic autonomic fibres

Answer 11

so its ACh and nicotinic in both sympathetic and para sympathetic

Inhibit choline transporter (eg hemicholinium)

Block voltage gated Ca2+ channels (eg black widow spider venom)

Block vesicle fusion (eg botulinium toxins)

Block ACh activated channel (eg hexamethoneum)

Non-depolarising nicotinic receptor blockers (eg mecylamine)

Depolarising nicotinic receptor blockers (eg suxamethoneum)

Question 12

why are there no clinical applications with ganglionic transmission?

Answer 12

too many widespread side effects so next to no clinical applications

Question 13

how do drugs affect postganglionic transmission in parasympathetic nerves and their targets

Answer 13

ACh acts on muscarinic receptors here

so either muscarinic receptor agonist ( carbachol, pilocarpine) 
or antagonist (atropine)

Question 14

what will a muscarinic agonist do?

Answer 14

mimic the effect of the parasympathetic system ie slow heart rate, contract smooth muscle in airways and bladder, increase gut motility, constrict pupil)

Question 15

what will a muscarinic antagonist do?

Answer 15

block effects of parasympathetic system so increase heart rate, relax smooth muscle in airways (useful in asthma+anaesthesia) and bladder, reduce gut motility (useful in IBS), pupils dilating- useful in eye examination

Question 16

Glaucoma

Answer 16

muscarinic agonists are used in the treatment of glaucoma
they contract the ciliary muscle supporting the lens and contracts the sphincter muscle of the pupil which should drain fluid out of the eye reducing the intra occular pressure

Question 17

inhibiting post ganglionic sympathetic transmission

potential sites of action

Answer 17

NA and alpha or beta receptors

block enzymes that produce NA (carbidopa)
block transporter that fills up vesicles with NA (reserpine)
introduce a false transmitter (methyldopa)
block alpha or beta postsynaptic receptors

Question 18

which enzyme that produces NA is blocked?

Answer 18

dopa decarboxylase

Question 19

improving postganglionic sympathetic transmission (sympathomimetics)

Answer 19

stimulating NA release by amphetamine

inhibit uptake into neurones (cocaine) or glia (phenoxybenzamine)

activate post-synaptic receptors (salbutamol or phenylephrine)

Question 20

what are sympathomimetics

Answer 20

sympathomimetics- make synapses work better

can be indirect or direct

Question 21

clinical applications of postganglionic sympathetic transmission

Answer 21

alpha 1 agonists-

Question 22

alpha 1 agonists function

Answer 22

decongestants and to dilate the pupil (mydriatics)

Question 23

alpha 2 agonists function

Answer 23

treatment of hypertension (high bp)

by vasodilation not heart

Question 24

beta 2 agonists

Answer 24

mimic the sympathetic response so vasodilation
treatment of asthma
doesn’t affect the heart

Question 25

beta 1 antagonists

Answer 25

treatment of hypertension, angina, cardiac arrhythmias and glaucoma
because it is an antagonist- sympathetic effects are not carried out so there is no increase in heart rate etc

Question 26

which receptor is usually activated in the lungs

Answer 26

beta 2- sym

muscarinic- para sym

Question 27

which receptor is usually activated in the heart in sympathetic system

Answer 27

B1 on pacemaker cells

Question 28

which receptor is usually activated in the eye in sympathetic

Answer 28

Beta 2- ciliary muscle

Alpha 1 - radial muscle

Question 29

which receptor is usually activated in the eye in para sympathetic

Answer 29

muscarinic- on ciliary muscle to focus eye up close

sphincter muscle contracts to make pupil smaller

Question 30

neostigmine

Answer 30

inhibits acetylcholinesterase