Pharmacology of ANS 2 Flashcards
How is Acetylcholine synthesised and released?
- When neuron stimulates, granules containing ACh fuse with membrane and ACh diffuses into synaptic cleft
- ACh interacts with muscarinic or nicotinic receptors producing response in post-synaptic cell
- Choline taken into neuron and acetylated
- Synthesised in pre-synaptic nerve terminal
- Acetyl coenzyme A
What toxin triggers the release of acetylcholine?
- Black widow spider bite
How is acetylcholine broken down?
- Rapidly broken down by membrane-bound enzyme acetylcholinesterase (AChE)
- Choline reabsorbed at pre-synaptic terminal
What actions would drugs do that mimic ACh at muscarinic receptors?
- Constriction of pupil and reduction in ocular pressure
- Increased salivation
- Reduced heart rate
- Increased GI motility
- Contraction of bladder
- Sweating
What drugs mimic ACh at muscarinic receptors?
- Pilocarpine- may be used as eye drops to treat glaucoma
- Bethanechol- simulates muscle contraction and occasionally used in urinary retention or to stimulate return of normal GI function after anaesthesia
What happens when drugs block ACh muscirinic receptors?
- Pupil dilation (mydriasis)
- Reduced secretions
- Increased heart rate
- GI motility decreased
- Urinary tract smooth muscle relaxed
What drugs block ACh muscarinic receptors?
- Atropine- reduces secretions
- Ipatropium- bronchodilator
- Hyoscine- motion sickness or to facilitate endoscopy
- Tropicamide- as eye drops to induce mydriasis
What occurs at the neuromuscular junction?
- Somatic system utilises ACh but there are nicotinic 2 receptors on post-synaptic membrane
- ACh broken down by acetylcholinesterase
How do drugs affect transmission at the neuromuscular junction
- Those that act directly on muscarinic receptors do not affect NMJ
- Drugs that affect synthesis, packaging, release or metabolism of ACh will affect both sympathetic and somatic
What drug prevents ACh release?
- Botulinum toxin is poison isolated from clostridium botulinum
- Inhibits ACh release and used to treat dystonia caused by stroke/cerebral palsy
- Injected directly into affected muscle (so won’t cause general paralysis or affect ANS)
Give an example and use of a short acting anticholinesterase
- Edrophonium
- Diagnosis of myasthenia gravis
Give an example and use of a medium duration anticholinesterase
- Neostigmine
- Treatment of myasthenia gravis
Give an example and use of irreversible anticholinesterases
- Organophosphates and poison gases like dyflos and Sarin
- Pesticides
What types of drugs are used to in the early stages of Alzheimer’s disease?
- Drugs that inhibit AChE in the CNS
- Donepezil
Describe the synthesis and release of noradrenaline
- When pre-synaptic neuron is stimulates, NA is released into synaptic cleft
- NA interacts with adrenergic receptors on target tissue
- Tyrosine taken up by pre-synaptic neuron and converted to NA and packaged into vesicles
What receptors are acetylcholine nicotinic?
- Post-ganglionic parasympathetic
- Post-ganglionic sympathetic for sweat glands
Which synapses have noradrenaline as the neurotransmitter?
- Pre-ganglionic parasympathetic (cranial)
- Pre-ganglionic sympathetic (thoracic and lumbar)
How is noradrenaline removed?
- Free NA in cytosol of pre-synaptic cell is metabolised by monamine oxidase (MAO)
- In ANS, most of NA in synapse is returned to pre-synaptic cell by specific transport mechanisms
- Free NA in the synapse is also taken up by neighbouring cells and metabolised by catechol-O-methyl transferase (COMT)
What drugs modify noradrenaline synthesis or reuptake?
- Reserpine- blocks packaging of NA into the granules
- Amphetamine- displaces NA from granules
- Cocaine and some antidepressants- blocks reuptake of NA from synapse
Which drugs block NA metabolism?
- MAO inhibitors- first drug family used as antidepressants. Side effects- atropine-like effects- dry mouth, blurred vision
- COMT inhibitors- may be used in Parkinson’s to prevent dopamine breakdown
What drug actions would mimic NA actions on SNS- sympathomimetics?
- Relaxation of smooth muscle
- Tachycardia- increased heart rate and force
- Decreased blood flow to skin and GI tract
- Increased blood flow to muscles
Which drugs mimic the actions of NA on the SNS?
- Salbutamol- bronchodilator used in asthma and prevents premature labour
- Adrenaline- added to local anaesthetics to reduce diffusion, also used in cardiac arrest
- Dobutamine- stimulates the heart
What would happen if a drug blocked NA actions on sympathetic nervous system (sympatholytics)?
- Bradycardia- slowing of heart rate
- Hypotension- reduced cardiac output
- Increased blood flow to skin and GI tract
Which drugs block the actions of NA on the sympathetic nervous system?
- Propanolol- angina, hypertension and anxiety
- Prazosin- resistant hypertension and benign prostate hypertrophy
