Glossary of ANS pharmacology 2

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what organ is anatomically considered a sympathetic ganglion?
the adrenal medulla
Describe the sympathetic post ganglionic fibers.
They are usually long, and multiple fibers will arise from a single sympathetic ganglion
What are 4 very common sympathetic responses?
increased heart rate, blood flow shift to muscles, increase blood glucose, and pupil dilation
Most sympathetic post ganglionic neurons release NE. What is the exceptipon.?
sympathetic post ganglionics acting on sweat glands release Ach.
What enzyme synthesizes Ach from acetyl coA and choline?
Choline acetyl transferase
where are muscarinic Ach receptors found?
terminus of postganglionic parasympathetics and terminus of sympathetic postganglionics that innervate sweat glands
where are nicotinic Ach receptors found?
in the sympathetic and parasympathetic ganglia as well as at the NMJ.
What is the synthesis pathway (including enzymes) for the catecholamines?
tyrosine hydroxylase makes DOPA from tyrosine. Aromatic acid L decarboxylase then makes dopamine. Dopamine B hydroxylase then makes NE. Phenylethanolamine N-methyltransferase then makes Epi.
What are the major ways to inactivate NE? Ach?
reuptake, acetylcholinesterase
list major effects of alpha 1 receptors...
vascular smooth muscle contraction, intestinal smooth muscle relaxes...
list major effects of alpha 2 receptors...
decreased insulin secretion, platelets aggregate, vascular smooth muscle contracts
list major effects of beta 1 receptors..
force of contraction and contraction rate in heart increase, lipolysis, increased renin secretion in kidneys
list major effects of beta 2 receptors...
smooth muscle relaxation of vessels, bronchi, GI, GU; stimulates glycogenolysis and neogenesis
How do muscarinic agonists affect blood vessels? why is this odd?
they cause vasodilation, but vessels are not innervated by cholinergic nerves...
clinical uses for choline esters...
relief of post op GI atony, urinary retention; wide angle glaucoma relief
what parts of the cholinesterase enzyme binds the choline and acetyl parts of Ach respectively?
anionic site, esteratic site
what are therapeutic uses of cholinesterase inhibitors?
both glaucomas, post op GI atony and urine retention, myasthenia gravis, reverses effects of NMJ blockers, competes with atropine
what are signs of toxicity with cholinesterase inhibitors?
diarrhea, urination, miosis, bronchospasm, bradycardia, excitation of skeletal muscle, lacrimation, sweating, salivation
(primary cause of death is respiratory paralysis)
what is the antidote for cholinesterase poisoning?
what are the two main muscarinic receptor antagonists?
atropine and scopolamine
what are the side effects of atropine?
hot as a hare, dry as a bone, red as a beat, blind as a bat, mad as a hatter.
What is both diagnostic and therapeutic for atropine poisoning?
Ach-E inhibitor
what is the major antimuscarinic used for diagnostic purposes in opthamology and why?
cyclopentolate is used becauses it causes mydriasis for examination and cycloplegia for measurement
what is our model competitve antagonist of the NMJ?
what are our two model depolarizing agents of the NMJ?
succinylcholine and decamethonium
what type of neuromuscular blocker will cause muscle fasiculations before paralysis?
depolarizing agents
Why do patients on succinyl choline need to be on an IV drip?
succinyl choline is metabolized by a cholinesterase rather quickly.
can neuromuscular blockers cross the blood brain barriers?
no they cannot
what effects does ganglionic blockade induced by tubocurarine have?
BP falls, then tachycardia ensues as a reflex
what neuromuscular blocker induces more release of histamine?
Patiens in CHF on diuretics or digitalis, or pt's with extensive soft tissue trauma should only use NM blockers that are competitve antagonists; why?
Potassium electrolyte imbalance is off, thus prolonged apnea; therefore, depolarizing agents cannot be used.
how do cholinesterase inhibitors interact with NM blockers?
they compete with NM competitive antagonists, but enhance the depolarizing agents
how do inhalation anesthetics affect NM blockers?
They enhance competitive NM blockers
If a patient is on aminoglycosides or tetracycline, how should dose of NM blocker be adjusted?
it should be decreased bc they enhance the effect
malignant hyperthermia can be induced by what two drugs?
halothane and succinylcholine
what internal signaling pathways do each of the adrenergic receptors stimulate??
alpha 1: Gq
alpha 2: Gi
Beta 1 and 2: Gs
what effects could alpha 2 receptors have on presynaptic cells?
they may activate G protein gated K+ channels to stimulate hyperpolarization and thus inhibition of NT release.
What two enzymes metabolize catecholamines?
MAO and catechol-o-methyl transferase (COMT)
What is the major catecholamine metabolite in the CNS? in the peripheries?
lower doses of epinephrine affect BP and pulse how?
increase systolic and decrease diastolic and pulse increase. (I think the overall BP will decrease a bit) This is all due to Beta receptor response.
What do high doses of Epi do to heart rate and BP?
They stimulate alpha receptors to predominate bc there are more of them than the beta receptors. This causes increase in the BP.
which receptor does NE not stimulate?
beta 2
how does NE effect heart rate and BP?
It increases both systolic and diastolic due to lack of beta 2 stimulation. heart rate DECREASES due to reflex bradycardia from the increased blood pressure
dopamine affects what receptors? therapeutic uses?
dopamine receptors (decreases arterial resistance and increases blood flow in renal, coronary, and splanchnic vessels), alpha 1 and 2, beta 1. It is used for shock
what receptors does dobutamine activate? therapeutic uses?
it is a beta agonist that is used for cardiogenic shock
what receptors does albuterol stimulate? therapeutic uses?
Beta 2 agonist that is used in asthma
isoproterenol activates what receptors? what are its effects on BP and heart rate.
It is a Beta 1 and 2 agonist. It increases heart rate and the vasodilation from the beta2 receptors causes a decrease in blood pressure.
what receptors does phenylephrine stimulate? therapeutic uses?
alpha 1 stimulation, good for hypotensive emergencies. pupil dilator...
metaraminol acts on what receptors?
mainly stimulates alpha 1 but can be an indirect agonist that stimulates catecholamine release that stimulates beta receptors.
clonidine acts on what receptors?
it is an alpha agonist that mainly acts on alpha 2's in the brain, thus it is good for hypertension with renal disease since there is no decrease in blood flow to the kidneys
how does alpha methyldopa work?
it is an alpha agonist that works centrally like clonidine, but it acts indirectly by chemically modifying the catecholamines.
what two drugs are indirect general agonists that are able to be taken orally, and can cross the blood brain barrier to produce CNS stimulation?
ephedrine and amphetamine
what drug is used to treat chronic hypotension because it has a longer resistance to metabolism?
what are the nonselective antagonists?
propranolol, nadolol, timolol, pindolol, labetol, carvedilol
what are the beta 1 selective antagonists?
metoprolol, atenolol, esmolol, acebutalol
what receptors does phentolamine antagonize and what is the effect?
it is a competitive alpha antagonist. It reduces peripheral resistance and thus BP
what receptors does prazosin antagonize and what is the effect?
it is a competitive alpha antagonist. It reduces peripheral resistance and thus BP
what are three indirect acting adrenal receptor antagonists and their mechanisms?
alpha methyl para tyrosine: interferes with synthesis of catecholamines
reserpine: blocks transport of NE into storage granules.
guanadrel: prevents NT release (according to lecture it is a direct acting antagonist...)

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