Autonomic Nervous System Neuropharmacology Flashcards
What kind of drug is Doxazosin?
Alpha-1 receptor antagonist
Antimuscarinic drugs are also called ___________.
parasympatholytics
What does the protein CHT do?
Choline transporter – it pumps choline into the presynaptic terminal to be made into acetylcholine
What is the rate-limiting step in acetylcholine synthesis?
Presynaptic uptake of choline by CHT
CHT is inhibited by ____________.
hemicholinium
VAT (vesicle-associated transporter) is inhibited by ___________.
vesamicol
What is bethanecol’s bioavailability?
Not good; because it is a similar compound to acetylcholine, it has a permanent charge
Nicotine does what to the sympathetic and parasympathetic pathways?
It stimulates them, leading to a mixture of effects: for instance, GI motility can be increased (due to PNS stimulation), while at the same time arousal can result as an effect of stimulating the SNS.
There are three main categories of choline esterase inhibitors: reversible, short-acting; reversible, long-acting; and irreversible, long-acting. List some from each category.
RSA: edrophonium
RLA: neostigmine, phyostigmine
ILA: isofluorophate (a nerve gas)
What is the main pharmacokinetic difference between neostigmine and phyostigmine?
Phyostigmine is more lipid-soluble and thus has better distribution throughout the body.
Atropine has a high specificity for ____________ receptors.
muscarinic
Describe the pharmacokinetic distinction between tertiary and quaternary antimuscarinics.
Tertiary compounds can penetrate into the CNS, while quaternary compounds cannot
Blocking the ganglionic receptors (nicotinic acetylcholine) leads to differing effects based on which branch of the autonomic nervous system has greater control over the tone of the organ in question. Describe two main differences.
The SNS controls vascular tone, so inhibiting the SNS ganglia leads to vasodilation. The PNS controls the tone of most other organs, so inhibiting PNS ganglia leads to SNS-like stimulation in the gut, for example.
Ganglion blockers are _____________ available.
no longer clinically
What is DOPA?
Dihydroxyphenylalanine –precursor of both dopamine and norepinephrine
What drug inhibits the rate-limiting step in catecholamine synthesis?
Metyrosine, which inhibits the enzyme tyrosine hydroxylase
What is the chemical backbone of most adrenergic drugs?
Phenylethylamine
“Monoamines” includes both ____________.
catecholamines and 5-hydroxytryptamines (serotonin)
What protein removes norepinephrine from the synaptic cleft?
Norepinephrine transporter (NET)
What protein moves monoamine precursors into vesicles?
VMAT (vesicle monoamine transporter)
Where are MAOs located and why is this important?
Monoamine oxidases are located on mitochondria and degrade monoamines; this is significant because monoamines must be pumped into vesicles to be shielded from MAOs.
What does bretylium do?
It inhibits the exocytosis of vesicles containing catecholamines.
What drugs block NET?
Cocaine and tricyclic antidepressants
How do amphetamines and pseudoephedrine work?
They reverse NET proteins (thus sending NE back out) as they are taken up by neurons
Are catecholamines effective orally?
No – there are hepatic enzymes that break them down, namely COMT (catechol-O-methyl transferase)
How does reserpine work? What classification does it fall into?
It inhibits the storage of catecholamines, thus ensuring that more catecholamines get metabolized or degraded; it is a sympatholytic.
All of the -zocin drugs block __________.
alpha-1 adrenergic receptors
What drugs are beta-1 selective antagonists?
Metoprolol and atenolol
The most specific neurotransmitter-modifying drugs target ______________.
a specific postsynaptic receptor
What type of amino acid facilitates the hydrolysis of acetylcholine?
Serine
Describe the pharmacokinetics of atropine and scopalamine and why it is clinically important.
Both distribute easily into the CNS, so they both have undesirable side effects when used at higher doses.
Isoproterenol activates what receptors?
Beta-1 and beta-2 (“I SO PROTEct the ßaßies”)
Which beta-blockers also block the alpha-1 receptor (and are thus vasodilatory)?
Carvedilol (-dilate) and labetalol (it goes “LABove and beyond”
What does stimulation of alpha-2 receptors on the brain stem cause?
Decreased SNS activity (hence clonidine is a depressant)
