ANS drugs Flashcards
What is acetylcholine degraded to? (By acetylcholine esterase)
Choline and acetate
How is acetyl choline synthesised? Where?
Choline acetyltransferase (CAT) catalyses the reaction of choline and acetyl CoA In the cytoplasm of cholinergic terminals
At which type of cholinergic synapse is the activity of acetyl cholinesterase the highest at?
Fast (nicotinic) cholinergic synapses
How is noradrenaline synthesised?
Within the nerve terminal
Tyrosine ➡️ dopa (tyrosine hydroxylase) (rate limiting step)
Dopa ➡️ dopamine
In synaptic vesicles
Dopamine ➡️ noradrenaline (dopamine β-hydroxylase)
Why can noradrenaline be recycled?
The vesicular transporter recognises noradrenaline as well as dopamine.
How is the intra-vesicular concentration of noradrenaline kept high?
H+-ATPase generates a cytoplasm-vesicle H+ gradient to move catecholamines against their concentration gradient.
What is cytoplasmic noradrenaline broken down by?
Monoamine oxidase
What removes noradrenaline from the synaptic cleft?
High affinity reuptake system - uptake 1
What are the major drug classes acting on cholinergic nerve terminals?
Nicotinic cholinoceptor antagonists
Muscarinic cholinoceptor agonists and antagonists
Cholinesterase inhibitors
Example of a nicotinic cholinoceptor antagonist and its action?
Tubocurarine
Muscle paralysis during anaesthesia
Example of a muscarinic cholinoceptor antagonist? Action?
Ipratropium bromide
Treat bronchoconstriction in asthmatics
Example of a cholinesterase inhibitor and its action?
Endrophonium
Treatment of glaucoma or myasthenia gravis
Classes of drugs acting on adrenergic receptors?
Selective β1, β2 and α1 agonists
Selective α1 and α2 antagonists
β antagonists (blockers)
Example of a selective β1 agonists and its action?
Dobutamine
Positive inotropic/chronotropic effects in the heart
Example of selective β2 agonist and its effect?
Salbutamol
Bronchodilation
Example of a selective α1 agonist and its action?
Adrenaline
Vasoconstriction to retard dissipation of anaesthetic
Selective α2 agonist and its action?
Clonidine
Anti hypertension
Acts on presynaptic receptors to reduce NA release
Example of an α-antagonist and its effect?
Phentolamine
Peripheral vasodilation to treat peripheral vascular disease
Example of an α1 antagonist and its effect?
Prazosin
Hypertension
Example of a β antagonist and its effect?
Propranolol Hypertension MI Angina Unwanted side effect: bronchoconstriction
What does α-methyl-tyrosine do?
Competitively inhibits tyrosine hydroxylase and therefore blocks de novo synthesis of noradrenaline. Used to inhibits NA synthesis in pheochromocytoma
What does α-methyl-DOPA do?
Taken up by neurones and converted to α-methyl-noradrenaline. Is it poorly metabolised and therefore accumulates in synaptic vesicles of noradrenergic terminals.
When released by Ca mediated exocytosis, it preferentially activates pre-synaptic α2 receptors.
The βγ subunit of the α2 receptor inhibits the VOCC, reducing Ca mediated neurotransmitter release.
What does carbiDOPA do?
Inhibits DOPA decarboxylase in the periphery but not in the CNS as it cannot cross the BBB. Used in combination of L-DOPA in treatment of Parkinson’s disease.
Effect of adrenergic blocking drugs?
Local anaesthetic by reducing impulse conduction, calcium mediated exocytosis and repletion of NA from synaptic vesicles
What do indirectly-acting sympathomimetic agents do?
Recognised and transported into the adrenergic terminal by uptake 1
Taken into synaptic vesicles
NA is displaces and leaks into synaptic cleft without calcium
Extent to which NA leaks out can be enhanced by inhibition of MAO
What class of drugs are tricyclic antidepressants?
Uptake 1 inhibitors
What are some side effects of the peripheral actions of uptake 1 inhibitors?
Tachycardia
Cardiac dysthymias
Which type of muscarinic receptor is found in the GI tract?
M1
Which type of muscarinic receptor is found in the SA node?
M2
What type of drug can be used to stimulate bladder emptying?
Muscarinic cholinoceptor agonist
What type of drug can be used to increase GI activity?
Muscarinic cholinoceptor agonist
Which receptor leads to relaxation of the bladder smooth muscle?
β2
