Pharmacology 7 - Cholinomimetic antagonists Flashcards
Give another name for nicotinic receptor antagonists
Ganglion blocking drugs
List some nicotinic receptor antagonists
- Hexamethonium
- Trimetaphan
- Venom’s and toxins (eg. alpha-bungarotoxin - issue is the somatic effect)
List the effects of nicotinic receptor antagonists
- Hypotension
- Pupil dilation
- Decreased GI function (constipation)
- Bladder dysfunction
- Bronchodilation
- Decreased secretions (dry mouth, can’t sweat)
- Increased heart rate
What is the clinical use of hexamethonium?
Anti-hypertensive (the first)
What is the clinical use of trimetaphan?
Hypotension during surgery - it is short acting
List the muscarinic receptor antagonists
- Atropine
- Hyoscine
What is the effect of atropine?
- Normal dose has little CNS effect (sedation)
- Toxic dose causes restlessness and agitation
- Less M1 selective
What is the effect of hyoscine?
- Normal dose causes sedation and amnesia
- Toxic dose causes CNS depression or paradoxical CNS excitation (associated with pain - rare)
- Penetrates deeper into the brain
What muscarinic receptor antagonist is used in examination of the retina?
Tropicamide - causes pupil dilation by paralysing the muscle that causes pupil constriction
List the clinical uses of muscarinic receptor antagonists
- Anaesthetic premedication
- Motion sickness (prevent PS nerve going to the vomiting centre) - hyoscine patch
- Parkinsons disease - Cholinergic/Dopaminergic balance in basal ganglia
- Used in Asthma (causes vasodilation of the airways)
- IBS (M3 receptor antagonists decrease gut activity)
List the unwanted effects of muscarinic receptor antagonists (eg. atropine)
- Hot as a hare - due to decreased sweating and thermoregulation
- Dry as a bone - decreased secretions
- Blind as a bat - cylcopegia (paralysis of ciliary muscle)
- CNS disturbance (mad as a hatter)
How is atropine poisoning treated?
- Using an anticholinesterase (physostigmine)
- Bethanechol (a stable acetylcholine)
- Ecothiopate (irreversible cholinomimetic - not given in practice but in theory)
What is hexamethonium and trimetaphan’s mode of action?
- Trimetaphan blocks the receptor
- Hexamethonium is better at blocking the ion channel
- Incomplete block of channel pore
- Use-dependent
Define use-dependent block
- The more open an ion channel is, the more likely the drug is to bind to the channel (the antagonist is therefore more effective)
- With receptors, the antagonist can always bind
Is affinity needed for a drug to block an ion channel?
No - physical barrier, doesn’t bind to anything
How do nicotinic receptor antagonists cause hypotension?
- Increased heart rate (acts against the hypotension)
- Blood vessels will dilate (as sympathetic control is lost), TPR decreases
- Stops renin secretion (reduced aldosterone production and water retention therefore reduced blood volume)
List the effects of muscarinic antagonists
- Pupil dilation
- Bronchodilation
- Bladder dysfunction
- Decreased sweating
- Tachycardia
- Gut dysfunction
- Lack of secretions
- Sedation
How are muscarinic receptor antagonists useful in parkinsons?
- Parkinsons is loss of dopaminergic neurones from the substancia nigra, and therefore a decrease in dopamine
- Muscarinic receptors (M4) inhibit dopamine receptor (D1) production.
- Muscarinic receptor antagonists remove the negative feedback on D1 receptors, so the response to dopamine becomes more effective
Why is ipratropium bromide used rather than atropine in asthma treatment?
- Ipatropium bromide is hydrophilic so does not diffuse into the blood
- This causes a local effect and reduces side effects
How are muscarinic receptor antagonists useful as anaesthetics?
- Bronchodilation (access to anaesthetics)
- Tachycardia (protects the heart rate from anaesthetics, which cause bradycardia)
- Lack of secretions (preventing saliva going back down the airways when sedated)
How does botulinum toxin work?
- Prevents acetylcholine exocytosis
- Binds to SNARE protein irreversibly (most potent toxin on the planet)
- Used in botox (paralyses skeletal muscle/ sweat glands)
