What is the difference in potency between agonists and antagonists?
They both possess affinity, but only agonists possess efficacy
Which of the following drugs has efficacy for the muscarinic acetylcholine receptor? Acetylcholine Atropine Acetyl-cholinesterase Adrenaline Acetate
Where are nicotinic receptors located?
On the first ganglion of every ANS
What are the nicotinic receptor antagonists also called and where do they act on?
On the nicotinic receptor or block the ion channel (usually have 2 mechanisms, where it can block the receptor or the ion channel), so also called ganglion blocking drugs
What are some examples of nicotinic receptor antagonists?
Hexamethonium, Trimetaphan (main clinically used)
How do nicotinic receptor antagonists work?
They are use-dependent block -> most effective when channel is open as is a channel blocker not competitive antagonist so isn't surmountable; also incomplete, slows the ion movement but doesn't stop them
Which of the following effects would be observed at REST after treatment with a ganglion blocking drug? Increased heart rate Pupil constriction Bronchodilation Detrusor contraction Increased gut motility
Increased heart rate and bronchodilation -> NB: when using nicotinic receptor antagonists the more dominant arm of ANS is blocked causing opposite arm symptoms
Why do nicotinic receptor antagonists cause hypotension?
Due to the CVS effects as it reduces renin secretion and causes dilation of blood vessels
What smooth muscle effects do nicotinic receptor antagonists cause?
Pupil dilation, decreased GI tone, bladder dysfunction, bronchodilation
What exocrine effects do nicotinic receptor antagonists cause?
What is the clinical use of hexamethonium?
Anti-hypertensive (1st) but had loads of side effects
What is the clinical use of trimetaphan?
Causing hypotension during surgery (short-acting)
Where are muscarinic receptors present?
On effector organs of mainly PSNS (and some SNS)
What are some examples of muscarinic receptor antagonists?
Atropine and Hyoscine -> both plant based
Which physiological responses would be influenced by the muscarinic receptor antagonists?
What are the CNS effects of atropine?
Normal dose -> little effect; toxic dose -> mild restlessness and agitation (less M1 selective)
What are the CNS effects of hyoscine?
Normal dose -> Sedation, amnesia; toxic dose -> CNS depression or paradoxical CNS excitation (associated with pain)
What is the clinical use of Tropicamide?
Examination of the retina
What are the clinical uses of muscarinic receptor antagonists?
Opthalmic, anaethetic premedication, neurological
What are the anaesthetic premedication in muscarinic receptor antagonists?
Blocks constriction, blocks copious watery secretion and blocks decrease in rate and contractility -> can cause sedation
What are the neurological uses of muscarinic receptor antagonists?
For motion sickness as it controls eye movements to maintain vision whilst in motion and stopping the relay to the vomiting centre, causing sensory mismatch as your eyes are telling you one thing and the balance centre is saying something else, which is all fed back to the vomiting centre, so you feel nauseous (hyoscine patch)
How are muscarinic receptor antagonists used in Parkinson's disease?
Cholinergic/dopaminergic balance in basal ganglia for fine control of movement -> DA neurones originitating from substantia nigra moving DA into striatum, which are massively reduced in PD -> M4 receptors have a negative effect on DA receptor, which is further trying to dampen down the DA response, which by reducing M4 effect, increases DA release as it inhibits cholinergic in basal ganglia
What are the respiratory uses of muscarinic receptor antagonists?
Asthma/obstructive airway disease -> blocks constriction - Ipratropium Bromide used as it is easier to trap in lungs as it is more difficult to cross membranes, so can only affect muscarinic receptors in the lungs
What are the GI uses of muscarinic receptor antagonists?
IBS which are M3 selective antagonists so lose the other muscarinic side effects -> blocks increased motility and tone and secretion
What are the unwanted effects of muscarinic receptor antagonists?
Hot as hell (decreased sweating, thermoregulation), Dry as a bone (decreased secretions), blind as a bat (cyclopegia), mad as a hatter (CNS disturbance)
Which of the following drugs would you administer to treat an atropine overdose? Bethanechol Ecothiopate Hyoscine Physostigmine Pralidoxime
Bethanechol (muscarinic receptor agonist) Ecothiopate (irreversible anticholinesterase) Hyoscine (atropine-like) ^^^Physostigmine (reversible anticholinesterase)^^^ Pralidoxime (reverses anti-cholinesterase poisoning)
What are some other parasympatholytics?
Botulinum toxin - used in botox (localised and injected directly into skeletal muscle), acts interfering with SNARE complex - blocking the vesicles of ACh from joining to the presynaptic membrane
What are the actions of directly acting sympathomimetics on each of the receptors?
Mimic NA/A by binding to and stimulating adrenoceptors -> prinicpally used for action on CVS, eyes and lungs
What is the mechanism of action of trimetaphan?
Nicotinic receptor blockade (mainly, but does both)
What is the mechanism of action of hexamethonium?
Ion channel blocker (mainly, but does both)