32 - Drugs Affecting Nervous System Flashcards
Exception to the rule that sympathetic nervous system releases noradrenaline to target
Sweat glands, where sympathetic nervous system releases ACh onto muscarinic AChR
Botulinumtoxin function
Stops membrane fusion between ACh vesicles and synaptic membrane by degrading SNARE proteins on vesicle.
Effect of botulism
Flaccid paralysis
What is targeted by botulinumtoxin?
Has selectivity for uptake into cholinergic neurons. Mechanism not known.
Conditions that are treatable with botulinumtoxin
1)
2)
1) Blepharospasm - Overactive blink response, makes someone functionally blind. Botox relaxes muscles involved in blinking.
2) Excessive underarm sweating - Botox inhibits ACh function of muscarinic receptors in sweat glands
Selectivities of anticholinesterase drugs
Selective between NMJ and postganglionic parasympathetic juncitons
Examples of anticholinesterase drugs
1)
2)
3)
1) Edrophonium
2) Neostigmine/pyridostigmine
3) Donepezil
Edrophonium
Anticholinesterase drug
Short duration
Used to diagnose myasthenia gravis
Neostigmine/pyridostigmine
Medium-duration anticholinesterase drug
Used to treat symptoms of myasthenia gravis
Used to reverse effect of non-depolarising neuromuscular blockers
Donepazil
Anticholinesterase
Enters CNS, used to treat symptom of Alzheimer’s (reduction in ACh signalling in CNS)
Myasthenia gravis
Autoimmune disease, where antibodies are made against nicotinic receptors on skeletal muscle motor endplates.
Leads to blockage, C’ disruption of post-synaptic membrane –> Loss, internalisation of nicotinic receptors
What can be used to treat myasthenia gravis symptoms?
Anticholinesterse drugs.
Reduces degradation of ACh on motor endplate.
This isn’t a cure, as the number of functional nicotinic receptors decreases with time, so eventually anticholinesterase drugs won’t have an effect.
Can also use immunosuppressants to slow release of anti-nicotinic Ig
Test for myasthenia gravis
Tensilon test
Tensilon test
Diagnostic test for myasthenia gravis Administer edrophonium (trade name Tensilon), see if motor weakness lessens
Type of ACh receptors in autonomic ganglia
Nicotinic N (Nn) ACh receptors
Use of autonomic nicotinic ACh agonists
Smoking cessation
Use nicotine patches, varenicline
Clinical uses of somatic nicotinic ACh antagonists
Pre-surgical muscle relaxation (EG: non-depolarising: tubocurarine, vecuronium)
Example of a ganglionic nicotinic ACh antagonist
Hexamethonium
Autonomic muscarinic agonism effects 1) 2) 3) 4) 5)
1) SLUD - salivation, lacrimation, urination, defecation
2) Sweating
3) Bronchoconstriction
4) Bradycardia
5) Vasodilatation (non-neural effect)
Example of a therapeutic autonomic muscarinic agonist
Pilocarpine, for treating glaucoma
Autonomic muscarinic antagonism effects 1) 2) 3) 4)
1) Decreased salivation, lacrimation, urination, defecation
2) Reduced sweating
3) Tachycardia
4) Bronchodilation
Examples of anti-muscarinic drugs
1)
2)
3)
1) Atropine
2) Hyoscene
3) Ipratropium
Atropine 1) 2) 3) 4) 5) 6)
1) Anti-muscarinic
2) Reduces secretions (for surgery)
3) Bronchodilation
4) Bradycardia
5) Pupil dilation (for examining eye)
6) Treating AChE-inhibitor poisoning (EG: with organophosphates)
Hyoscene
Anti-muscarinic
For motion sickness
Ipratropium
Anti-muscarinic
For treating COPD
Drugs that block NA reupatake
Cocaine
Tricyclics
How is NA metabolised?
After being reuptaken, is degraded by monoamine oxidase
Indirectly-acting sympathomimetics
Enters synaptic vesicle containing NA.
Displaces NA in vesicle, leading to release of NA into synaptic cleft
Name for drugs that displace NA from vesicle
Indirectly-acting sympathomimetics
Examples of indirectly-acting sympathomimetics
1)
2)
3)
1) Amphetamines
2) Ephedrines
3) Tyramine
Tyramine
1)
2)
3)
1) An indirectly-acting sympathomimetic
2) Found in old cheeses, vegemite, salami
3) Can cause unwanted cardiovascular effects (EG: hypertension) in patients taking MAOI
Example of an alpha, beta, and alpha and beta specific adrenoceptor agonist
1) Alpha - Phenylephrine
2) Beta - Isoprenaline
3) Alpha/beta - Adrenaline
Why is salbutamol and not isoprenaline used to treat asthma?
Isoprenaline is more potent vaodilator (beta2), but also is a stronger beta1 agonist (cardiovascular effects). Salbutamol is a much more potent agonist of beta2 receptors than beta1.
Beta1 and beta2 adrenoceptor antagonist
Propranolol
Beta1 adrenoceptor agonism effect
Increased heart rate, force of contractility
Beta1 adrenoceptor agonist
Dobutamine (useful in heart failure)
Beta1 adrenoceptor antagonist
Atenolol (useful in hypertension)
Alpha 1 and 2 adrenoceptor antagonist
Phentolamine (vasodilation)
Alpha1 adrenoceptor agonist
Phenylephrine (nasal decongestant)
Alpha1 adrenoceptor antagonist
Prazosin (treat hypertension)
Alpha2 adrenoceptors
Pre-junctional receptors.
Inhibit neurotransmitter release.
