L5-7 PHRM200001 Adrenergic & Cholinergic Pharmacology Flashcards
Para/Sys, which has short pre-gang and is catabolic
Symp
Sweat glands have ___ receptors
Mus ACh
Adrenals have ___receptors
Nic ACh
Loewis experiment
Stimulation of the vagus nerve reduced the beating of the donor heart and then that of the recipient heart - demonstrated that chemical transmitters are involved as another tissue was affected
Where are muscarinic cholinergic receptors found?
Post-ganglionic para
Where are nicotinic cholinergic receptors found?
Skeletal muscle responses and ganglion transmission
2 examples of Catecholamines
NA and A
Why is DOPA decarboxylase inhibited by Carbidopa in treating Parkinson’s?
If there isn’t enough L-DOPA present, side effects occur and hence the conversion of L-DOPA to dopamine needs to be inhibited.
Name 4 different pathways NA can be metabolised.
1) Uptake 1 - reuptake via neuron (high affinity) and NA is repackaged into synaptic vesicles
2) Monoamine oxidase can metabolise NA after its re-uptake into the neuron (high affinity)
3) Uptake 2 - Extraneuronal uptake (low affinity)
4) COMT (Catechol-O-methyltransferase) found post-junctionally after NA is taken up by the cell
What drug can inhibit NA re-uptake?
Coccaine
Indirectly acting sympathomimetics and 3 examples.
Drugs mimicking NS that act as substrates taken up by synaptic vesicle (displace NA) and metabolized by MAO. Quite a fast process, with no AP required.
1) Amphetamine
2) Ephedrine (pseudoephedrine)
3) Tyramine (dietary product substrate for MAO)
Adrenaline synthesis
Tyr is converted by Tyrosine hydroxylase -> L-DOPA converted by DOPA decarboxylase -> Dopamine converted by Dopamine B-hydroxylase -> NA converted by PNMT (Phenylehtanolamine-N-methyl transferase -> Adrenaline
How does the alpha-2 mechanism work in adrenoreceptors?
-ve feedback loop when signaled by G-protein
ACh Synthesis
Choline goes into cell via choline carrier -> Choline-acetyltransferase converts it into ACh with a AcetylCoA and has a by product CoA and ACh enters the vesicle
Effect of Botulinum toxin
It acts as a protease, breaking down SNARE proteins needed for vesicle fusion. Hence, ACh vesicle can’t fuse and release ACh into synapse hence a decrease in ACh. Only way effects are overcome is the resynthesis of SNARE proteins as the BoTox effects are quite long-lasting as it is extremely potent.
Physostigma is the plant that Physostigmine is derived from and it an ____ selective for ______
Anticholinesterase, parasympathetic junctions, treats glaucoma
Neostigmine
Anticholinesterase selective for NMJ, reverses effect of (non-depol) neuromuscular blockers, treats mysasthenia gravis
Muscarinic receptor effects SLUD
Salivation
Lacrimation (Crying)
Urination
Defecation
-sweating, slowing of heart, bronchoconstriction, vasodilation (non-neural effect)
Effects of Atropine, Hyoscine, Ipratropium etc (Muscarinic receptor antagonists)
Anti-SLUD
- Ocular: dilation of pupil
- Tachycardia (small)
d-Tubocurarine
Competitive reversible nicotinic antagonist. Selective for nicotinic receptors on NMJ.
hexamethonium
Ganglion-blocking drug acting on both para and symp NS. Cues large drop in BP. Selective for ganglia.
