Autonomic Nervous System Pharmacology: Cholinergic and Adrenergic Agents

Comprehensive review flashcards covering autonomic nervous system pharmacology, including direct/indirect cholinergic agonists, muscarinic antagonists, cholinesterase reactivators, adrenergic agonists, and alpha/beta receptor blockers.

What is the receptor target and primary ocular mechanism of pilocarpine?

It is a direct muscarinic agonist (primarily $M_3$) that stimulates circular sphincter contraction causing miosis, and ciliary muscle contraction causing accommodation for near vision and opening of the trabecular meshwork to lower intraocular pressure.

Why is pilocarpine contraindicated in patients with uncontrolled asthma or COPD?

Because it stimulates $M_3$ muscarinic receptors, causing $M_3$-mediated bronchoconstriction.

Through which receptor and mechanism does atropine increase heart rate?

It increases heart rate by competitively blocking vagal $M_2$ muscarinic receptor input to the SA and AV nodes of the heart.

Why is atropine strictly contraindicated in patients with angle-closure glaucoma?

It causes passive mydriasis (pupil dilation), which bunches iris tissue, blocking the trabecular meshwork and precipitating acute intraocular pressure spikes.

What is the mechanism of action of varenicline in smoking cessation therapy?

It acts as a partial agonist at neuronal nicotinic acetylcholine receptors ($\alpha_4\beta_2\ N_N$ subtype), producing moderate baseline dopamine release to relieve withdrawal cravings while competitively blocking nicotine binding.

What is the molecular mechanism of action of Botulinum Toxin (Botox)?

It cleaves vesicular proteins within presynaptic cholinergic terminals to inhibit acetylcholine (ACh) release, preventing neuromuscular and autonomic transmission.

What is the clinical indication and mechanism of bethanechol?

It is a direct muscarinic agonist ($M_1-M_5$) resistant to acetylcholinesterase breakdown, used to treat urinary retention (postpartum, postoperative, or chronic hypotonic bladder) by promoting detrusor contraction and sphincter relaxation.

How does cevimeline compare to pilocarpine in the management of xerostomia?

Cevimeline is an oral direct $M_3$ agonist that produces more localized salivation with less diaphoresis (sweating) compared to pilocarpine.

Why is physostigmine suitable for treating central anticholinergic toxicity, whereas neostigmine is not?

Physostigmine is a tertiary amine that crosses the blood-brain barrier (BBB), whereas neostigmine is a polar quaternary ammonium compound that cannot cross the BBB.

Why is pyridostigmine preferred over neostigmine for long-term oral maintenance in Myasthenia Gravis?

Pyridostigmine has superior oral bioavailability, a longer duration of action, and is better tolerated than neostigmine.

What is the mechanism of action and clinical indication for donepezil?

It is a centrally acting reversible acetylcholinesterase (AChE) inhibitor that increases cortical acetylcholine levels to treat Alzheimer's disease and cognitive impairment.

Why must Pralidoxime (2-PAM) be administered as soon as possible after organophosphate exposure?

It nucleophilically cleaves the organophosphate group from acetylcholinesterase (AChE) to reactivate the enzyme, but it must be given before the chemical complex undergoes 'aging' (irreversible chemical bond consolidation).

Which manifestation of organophosphate poisoning is NOT reversed by atropine?

Nicotinic skeletal muscle paralysis at the neuromuscular junction (which specifically requires Pralidoxime / 2-PAM for enzyme reactivation).

Why is tropicamide preferred over atropine for routine diagnostic funduscopic eye examinations?

Tropicamide has a short duration of action ($\approx 4-8\text{ hours}$), whereas atropine's mydriatic and cycloplegic effects can persist for up to $2\text{ weeks}$.

What is the primary mechanism and indication of dicyclomine?

It is an oral muscarinic antagonist selective for $M_3$ receptors on gastrointestinal smooth muscle, prescribed as an antispasmodic for Irritable Bowel Syndrome (IBS) to decrease intestinal hypermotility and cramping.

What advantage does darifenacin's $M_3$ receptor selectivity offer in treating overactive bladder?

Its high selectivity for detrusor smooth muscle $M_3$ receptors minimizes common anticholinergic adverse effects such as dry mouth and central nervous system disturbances.

What dual pharmacological mechanism is exhibited by oxybutynin?

It combines antimuscarinic action ($M_3$ preference) with a direct smooth muscle relaxant (spasmolytic) effect.

What is the primary advantage of delivering ipratropium via inhalation for COPD?

Inhalation delivers the drug directly to bronchial tissue ($M_3$ receptors) to produce bronchodilation while preventing systemic absorption and minimizing systemic anticholinergic side effects.

How do low-dose and high-dose physiological responses to epinephrine differ?

At low doses, $\beta_2$ vasodilation and $\beta_1$ increases in heart rate and contractility predominate; at high doses, $\alpha_1$-mediated vasoconstriction dominates, raising blood pressure alongside $\beta_2$ bronchodilation.

Why does norepinephrine administration lead to reflex bradycardia despite activating cardiac $\beta_1$ receptors?

Intense $\alpha_1$-mediated vasoconstriction sharply increases systemic vascular resistance and blood pressure, triggering baroreceptor reflex activation that overrides direct $\beta_1$ chronotropic stimulation.

What are the dose-dependent receptor affinities and cardiovascular effects of dopamine?

Low dose activates renal/visceral $D_1$ receptors (vasodilation); medium dose activates cardiac $\beta_1$ receptors (increased contractility); high dose activates peripheral $\alpha_1$ receptors (widespread vasoconstriction).

What adverse effect occurs with prolonged topical use (>3–5 days) of phenylephrine or oxymetazoline nasal spray?

Severe rebound nasal congestion (Rhinitis medicamentosa).

What critical danger is associated with the abrupt discontinuation of clonidine?

It can trigger a severe, life-threatening rebound hypertensive crisis.

Why is methyldopa preferred in pregnancy, and what unique adverse hematologic test is associated with it?

It has documented long-term fetal safety for chronic hypertension; approximately $20\%$ of patients develop a positive direct Coombs test, carrying a $1-5\%$ risk of hemolytic anemia.

What is the primary indication and half-life of dobutamine?

It is a selective $\beta_1$ agonist used for cardiogenic shock and cardiac echo stress testing, administered exclusively via IV because its half-life is approximately $2\text{ minutes}$ ($t_{1/2} \approx 2\,\text{min}$).

What is the mechanism of mirabegron and its primary cardiovascular adverse effect at high doses?

It is a selective $\beta_3$ agonist that relaxes bladder detrusor muscle in overactive bladder; high doses can cause hypertension and sinus tachycardia via off-target $\beta_1$ cardiac receptor activation.

What is the receptor target and therapeutic indication for fenoldopam?

It is a selective dopamine $D_1$ agonist that produces rapid vasodilation in renal, mesenteric, and coronary beds, indicated for severe hypertension and hypertensive emergencies.

How do amphetamines and cocaine differ in their indirect sympathomimetic mechanisms?

Amphetamines displace stored norepinephrine (NE) into the cytosol and reverse the direction of the norepinephrine transporter (NET); cocaine competitively blocks NE reuptake via NET.

What hallmark adverse effect is associated with initiating therapy with selective $\alpha_1$-blockers like prazosin or terazosin?

First-dose syncope and orthostatic hypotension.

Why does tamsulosin have a lower incidence of orthostatic hypotension than non-subtype selective $\alpha_1$-blockers?

It exhibits high competitive selectivity for the $\alpha_{1A}$ receptor subtype located in the prostate and bladder neck, improving urine outflow with minimal vascular $\alpha_1$ blockade.

How do phentolamine and phenoxybenzamine differ in receptor binding dynamics?

Phentolamine is a competitive, reversible non-selective $\alpha_1/\alpha_2$ antagonist; phenoxybenzamine is a non-competitive, irreversible covalent non-selective $\alpha_1/\alpha_2$ antagonist.

How do the organ clearance pathways of metoprolol and atenolol differ?

Metoprolol is cleared primarily by the liver (hepatic impairment consideration), whereas atenolol is eliminated mostly by the kidneys (requiring dosage adjustment in renal impairment).

What unique pharmacological property distinguishes nebivolol from other selective $\beta_1$-blockers?

It combines competitive $\beta_1$ receptor antagonism with endothelial nitric oxide (NO) release stimulation, producing direct vasodilation.

What four adverse effects are summarized by the '4Bs' mnemonic for propranolol?

Bradycardia ($\beta_1$), Heart block ($\beta_1$), Bronchospasm ($\beta_2$), and Blood sugar masking ($\beta_2$).

What receptor profile makes labetalol effective in hypertensive crises and preeclampsia?

It is a dual reversible competitive antagonist of $\beta_1$, $\beta_2$, and $\alpha_1$ receptors, reducing cardiac workload ($\beta_1$) while causing peripheral vasodilation ($\alpha_1$) without reflex tachycardia.