ANS Pharmacology

A group of volunteers are involved in a phase 1 clinical trial of a new autonomic drug. When administered by intravenous bolus, the blood pressure increases. When given orally for 1 week, the blood pressure decreases. Which of the following standard agents does the new drug most resemble after 1 week? (A) Antimuscarinic (B) Alpha-2 selective sympathomimetic (C) Alpha-1 selective sympathomimetic (D) Alpha sympatholytic (E) Beta sympatholytic

(B) Alpha-2 selective sympathomimetic clonidine alpha 2 receptors on vessles causes increase in BP but build up in brain eventually causes BP decrease

Mr Green has just been diagnosed with dysautonomia (chronic idiopathic autonomic insufficiency). You are considering different therapies for his disease. Pyridostigmine and neostigmine may cause which one of the following in this patient? (A) Bronchodilation (B) Cycloplegia (C) Diarrhea (D) Irreversible inhibition of acetylcholinesterase (E) Reduced gastric acid secretion

(C) Diarrhea extreme resting and digesting

A 3-year-old child is admitted to the emergency department after taking a drug from her parents' medicine cabinet and swallowing multiple tablets. The signs suggest that the drug is a cholinomimetic with little or no vascular effect, and little or no CNS effect. Which of the following is the most likely cause of these effects? (A) Acetylcholine (B) Bethanechol (C) Neostigmine (D) Pilocarpine (E) Atenolol

(C) Neostigmine muscarinic receptors on vascular endothelial cells are not innervated and respond only to direct acting drugs A-D are cholinomimetics but would cause vascular effects

A 72-year-old woman receives succinylcholine as an adjuvant muscle relaxant during knee surgery. This drug initially acts by (A) blocking ACh at nicotinic receptors of neuromuscular endplate (B)blocking ACh at nicotinic receptors in the adrenal medulla (C) increasing Na+ and K+ permeability of the postsynaptic neuromuscular membrane (D) blocking the transmission of the action potential along the nerve axon (E) blocking the release of ACh from neuromuscular presynaptic vesicles

(C) increasing Na+ and K+ permeability of the postsynaptic neuromuscular membrane causes twitching initially because it activates the receptor (depolarizes)

A 56-year-old man has hypertension and an enlarged prostate, which biopsy shows to be benign prostatic hyperplasia. He complains of urinary retention. Which of the following drugs would be the most appropriate initial therapy? (A) Beta-2 agonist (B) Beta blocker (C) Antimuscarinic (D) Alpha blocker (E) Alpha-1 agonist

(D) Alpha blocker

Which one of the following drugs has a very high affinity for the phosphorus atom in parathion and is often used to treat life- threatening insecticide toxicity? (A) Atropine (B) Bethanechol (C) Physostigmine (D) Neostigmine (E) Pralidoxime

(E) Pralidoxime can remove the phosphate to reverse "irreversible" binding of toxins

Antinicotinic (ganglionic blocker)

- nicotinic competitive antagonist (somatic muscular system) - non-depolarizing (binds to receptor but does nothing except block Ach from binding) - paralysis without initial twitching - muscle relaxation anesthesia during surgery

malathion, parathion, nerve gas (sarin, tabun)

- organophosphates poisoning (not a drug) - parasympathomimetic - indirect muscarinic and nicotinic agonist - IRREVERSIBLY inhibits acetylcholinesterase from decreasing acetylcholine concentration - SLUDGE BBB (extreme rest digest)

Atropine

- parasympatholytic (anticholinergic) - muscarinic antagonist (blocks ACh receptor = "fight-flight") - increase HR, relax bronchial, dilated pupils - anticholinesterases poisoning antidote - tx COPD, bladder spasms, preop med, GI motion sickness

Scopolamine

- parasympatholytic (anticholinergic) - muscarinic antagonist (blocks ACh receptor = "fight-flight") - increase HR, relax bronchial, dilated pupils - tx COPD, bladder spasms, preop med, GI motion sickness

Bethanechol

- parasympathomimetic - direct muscarinic agonist (mimics acetylcholine "rest digest") - decrease HR, increase peristalsis, increase secretions, lower intraocular pressure, bladder contraction - tx glaucoma, urinary retention

Succinylcholine

- parasympathomimetic - direct nicotinic agonist (mimics acetylcholine "rest digest") - depolarizing blockade (initial twitch then paralysis) - neuromuscular blockade during surgery - short half-life (some people have SNPs that increase half-life)

Physostigmine

- parasympathomimetic - indirect muscarinic and nicotinic agonist - inhibits acetylcholinesterase from decreasing acetylcholine concentration (increased "rest digest") - increased secretions, bronchoconstriction, lower HR, lower BP - reversal of central nervous system anticholinergic syndrome (acetylcholine antagonists block receptors - flooding system with acetylcholine overcomes blockade)

Neostigmine

- parasympathomimetic - indirect muscarinic and nicotinic agonist - inhibits acetylcholinesterase from decreasing acetylcholine concentration (increased "rest digest") - increased secretions, bronchoconstriction, lower HR, lower BP - reversal of nondepolarizing muscle relaxants after surgery (acetylcholine antagonists block receptors - flooding system with acetylcholine overcomes blockade)

Prazosin, Doxazosin

- sympatholytic - alpha-1 adrenergic antagonists (blockers) - promotes vasodilation, reduces blood pressure - tx hypertension, urinary retention due to enlarged prostate (old men)

Epinephrine

- sympathomimetic "fight flight" - direct androgenic agonist - nonselective (activates both alpha and beta) - tx anaphylactic shock, bronchospasm, hypotension/shock

Clonidine

- sympathomimetic (acts like sympatholytic) - direct alpha 2 selective agonist - acts on presynaptic a2 in medulla, inhibits norepinephrine, reduces sympathetic acvitivty, reduces blood pressure - initial increases blood pressure acting on periphery, accumulation in brain leads to decreased blood pressure - tx hypertension, ADHD, intraocular pressure

A patient presents at the emergency department with threatened anaphylaxis. Respiratory obstruction appears likely if she is not treated immediately. Her past medical history includes hypertension, for which she is receiving an adrenoceptor blocker. The emergency physician plans to use epinephrine to treat her anaphylactic reaction. Which of the following effects of epinephrine would be blocked by prazosin but not by metoprolol? (A) Cardiac stimulation (B) Increased cAMP in fat cells (C) Mydriasis (D) Relaxation of bronchial smooth muscle

?

antidote for too much cholinergic stimulation

Atropine (muscarinic antagonist competes with acetylcholine to reduce side effects) pralidoxime (cleaves irreversibly bound phosphate inhibiting acetylesterase to decrease the concentration of acetylcholine)

antidote for anticholinergic syndrome

Physostigmine (- inhibits acetylcholinesterase which increases acetylcholine concentration enabling "rest digest")

Pralidoxime (2-PAM)

cleaves the phosphate group of organophosphates and nerve gas to remove their otherwise irreversible inhibition of acetylcholinesterase

beta 2 adrenergic receptors

located in lungs

beta 1 adrenergic receptors

located primarily in the heart

Reversal of Antinicotinic (ganglionic blocker)

neostigmine (acetylesterase inhibitor to flood system with acetylcholine which competes for receptors) atropine (antagonist blocks muscarinic receptors from acetylcholine flood to prevent SLUDGE BBB symptoms)