F5 Autonomic pharmacology Flashcards
describe how an action potential block occurs
- blockage of voltage-gated sodium ion channels (main channel that triggers depolarisation)
- prevents excitation of both pre and postsynaptic cells
what 2 drugs can block action potentials?
- lidocaine (local anaesthetic)
- lamotrigine (anti epileptic)
describe lamotrigine effects
- acts in the CNS
- voltage-gated sodium ion channel blocker
describe how lidocaine can block sodium ion channel pore
- blocks the pore of the channel after it has opened by docking into it
- prevents the passage of ions so no triggering of an action potential
what does the inhibition of synthetic enzymes lead to?
depletion of transmitter
what is methyl-DOPA and what happens when it is supplied?
- a false substrate for DOPA decarboxylase
- gets converted by DOPA decarboxylase and produces methyl-dopamine (can’t be converted into noradrenaline)
what does the production of methyl-dopamine by DOPA decarboxylase lead to?
- saturation of cell by making false products that aren’t useful or making noradrenaline
- depletion of vesicles
what can not be converted into noradrenaline?
methyl-dopamine
what is the precursor for noradrenaline?
dopamine
how can L-DOPA be used?
- therapy in Parkinson’s disease
- gets converted into dopamine in the CNS and alleviates some symptoms
what can prevent vesicle loading?
- inhibition of vesicle transporter
- reserpine blocks NA uptake (and other monoamines)
what does reserpine do?
blocks neurotransmitter loading
what happens if neurotransmitter fails to load?
- vesicles fail to load / package
- stores are depleted by ongoing activity
- there won’t be anymore neurotransmitter released because they’re not packaged into vesicles
what does calcium trigger in synapses?
- vesicle fusion and transmitter release
what does conotoxin do?
- blocks calcium channels
- used in experiments for further studies on how to block calcium channels, not used therapeutically
what does botulinum toxin (botox) do?
- degrades vesicle release machinery
- very potent, a small amount can shut down synaptic transmission
what does antagonism of ionotropic receptors cause?
prevents depolarisation of the postsynaptic cell
what are the several mechanisms of antagonism of ionotropic receptors?
- occupy NT binding site
- prevent channel opening
- block the open pore
explain the mechanism of the antagonists of ionotropic receptors: occupy NT binding site
competitive antagonist and blocks ion channel
explain the mechanism of the antagonists of ionotropic receptors: prevent channel opening
make a molecule that binds to an allosteric site which will cause a conformational change in the binding site
explain the mechanism of the antagonists of ionotropic receptors: block the open pore
- similar to Lidocaine
- binds to the pore of the open channel which prevents any influx
what does antagonism of metabotropic receptors cause?
- prevents target cells from responding to released NT
what do antagonists that bind to metabotropic receptors do?
occupy binding site or allosteric site or inhibit G protein activation
what does inhibition of transporters / degradation enzymes lead to?
prolonged activation of postsynaptic cell
what does amitriptyline do?
- inhibits NA uptake
- antidepressant that inhibits noradrenaline reuptake
- leads to more NA at the synapse to bring about more signalling
how are drugs used on the ANS? 2 methods
- aimed at correcting defects in the ANS itself
- (more commonly) exploit the ANS to correct other problems
give examples of defects in the ANS that drugs can be used to target
- primary or secondary autonomic dysfunction
- diabetic neuropathy (neurons in the CNS are dying off so drugs are used to correct this issue)
give some examples of issues that can be corrected by drugs targeting the ANS that are not ANS specific
- hypertension
- asthma
- incontinence
give 3 examples of antagonist drugs (1 mAChR blocker, 1 beta AR blocker and 1 alpha AR blocker)
- Tropicamide (mAChR blocker)
- Atenolol (beta AR blcoker)
- Tamsulosin (alpha AR blocker)
give 3 examples of agonist drugs (1 beta AR agonist, 1 mAChR agonist and 1 nAChR agonist)
- Salbutamol (beta AR agonist)
- Pilocarpine (mAChR agonist)
- Nicotine (nAChR agonist)
what are the indications for beta blockers?
- hypertension
- angina
- arrhythmias
what are the contraindications for beta blockers?
- asthma
- COPD
- bradycardia (slow heart rate)
- severe peripheral arterial disease
what is bradycardia a contraindication for beta blockers?
- beta blockers reduce heart rate
- don’t want to reduce a heart rate that is already slow
side effects of beta blockers
- bronchospasm
- GI disturbances
- hypotension
- bradycardia
- visual disturbances
- headache
- dizziness
general effects of beta blockers
- counteracts sympathetic input
- reduce cardiac output
- risk of pulmonary side effects
what are antimuscarinics?
- antagonists for muscarinic acetylcholine receptors
- eg. Hyoscine, Atropine, Oxybutynin
what are the indications for antimuscarinics?
- bradycardia
- GI disorders
- urinary incontinence
- ophthalmology
- premedicants to dry bronchial and salivary secretions (especially during surgery
contra-indications for antimuscarinics
- glaucoma
- myasthenia graves (muscle weakness)
- urinary retention
side effects of antimuscarinics
- dry mouth
- blurred vision
- constipation
- tachycardia
- palpitation
- arrhythmias
general effects of antimuscarinics
- enhances sympathetic activities, counteracts parasympathetic input
- inhibits glandular secretion
- blocks smooth muscle contraction
what can cause over dilation of pupils?
- too much activation of sympathetic nervous system
- too much suppression of the parasympathetic system
what are on and off target side effects?
- on target: hitting the right target in the wrong place
- off target: hitting the wrong target
what are pharmacodynamics?
what target does the drug bind to?
what are pharmacokinetics?
where does the drug go in the body?
