Autonomic Nervous System & Receptor Pharmacology Flashcards

Comprehensive vocabulary flashcards covering autonomic nervous system pharmacology, cholinergic and adrenergic transmission, and quantitative drug-receptor interaction concepts.

Acetylcholine (ACh)

Prototype cholinergic agonist given IV with poor lipid solubility, permanent positive charge, short duration of action due to BuChE, and non-selective actions at multiple cholinergic sites.

Bethanechol

Synthetic choline ester selective for bladder and GI $M_3$ receptors that is relatively resistant to hydrolysis by AChE/BuChE, used clinically to treat postoperative and postpartum urinary retention.

Pilocarpine

Non-selective muscarinic alkaloid agonist used orally as a sialagogue for xerostomia or Sjögren's syndrome, and topically as a second-line treatment for glaucoma.

Atropine

Prototype belladonna alkaloid that acts as a competitive antagonist for all muscarinic receptor subtypes, readily crosses the blood-brain barrier, and produces dose-dependent tissue responses including tachycardia, mydriasis, and reduced secretions.

Anticholinergic Side Effects Mnemonic

Classic clinical mnemonic describing antimuscarinic toxicity: "Hot as a hare, dry as a bone, blind as a bat, red as a beet, mad as a hatter."

Ipratropium bromide

Inhaled quaternary ammonium antimuscarinic bronchodilator used for asthma and COPD that remains permanently ionized, preventing significant systemic absorption.

OnabotulinumtoxinA

Neurotoxic protease derived from Clostridium botulinum that cleaves SNAP-25 to block presynaptic acetylcholine exocytosis, causing flaccid muscle paralysis lasting 3 to 4 months.

Muscarinic $M_3$ Receptor

$G_q$-protein-coupled receptor expressed in smooth muscle, glands, and vascular endothelium that signals via PLC, $IP_3$, and DAG to increase intracellular $Ca^{2+}$, mediating contraction, secretion, and NO-induced vasodilation.

Muscarinic $M_2$ Receptor

$G_i$-protein-coupled receptor located predominantly in cardiac tissue (SA and AV nodes) that decreases cAMP levels and increases $K^+$ efflux, causing negative chronotropic, inotropic, and dromotropic effects.

Mecamylamine

Non-competitive antagonist of neuronal ganglionic nicotinic ($N_N$) receptors that blocks autonomic postganglionic nerve transmission and reveals the dominant division of the autonomic nervous system controlling targeted tissues.

Tyramine

Dietary sympathomimetic amine found in aged cheeses and fermented foods that displaces vesicular norepinephrine, triggering non-vesicular release via reverse transport through NET and potentially causing a hypertensive crisis in patients taking MAOIs.

Methyldopa

Centrally acting $\alpha_2$ adrenergic agonist prodrug converted to methyl-norepinephrine that reduces sympathetic outflow from the brainstem, used as a safe treatment for gestational hypertension.

Cocaine

Presynaptic uptake inhibitor that blocks the norepinephrine transporter (NET), enhancing synaptic concentrations of norepinephrine and potentiating adrenergic responses.

Baroreceptor Reflex

Compensatory autonomic reflex initiated by stretch-activated receptors in the carotid sinus and aortic arch that alters sympathetic and parasympathetic outflow to maintain mean arterial pressure near its set point.

Equilibrium Dissociation Constant ($K_D$)

Quantitative measure of drug-receptor binding affinity defined as the concentration of drug required to occupy $50\%$ of total receptor population at equilibrium, where lower $K_D$ indicates higher affinity.

Fractional Receptor Occupancy (FRO)

Proportion of total receptors bound by drug at equilibrium, defined mathematically by the equation $FRO = \frac{[RD]}{[R_T]} = \frac{[D]}{K_D + [D]}$.

$$EC_{50}$$

Effective concentration of an agonist that produces $50\%$ of its maximal possible response ($E_{max}$), serving as the standard measure of drug potency.

Competitive Antagonist

Reversible receptor ligand that competes with agonists for the same orthosteric binding site, shifting the agonist concentration-response curve to the right by a factor of $1 + \frac{[B]}{K_B}$ without reducing $E_{max}$.

Non-Competitive Antagonist

Receptor antagonist (irreversible or allosteric) whose inhibitory effect cannot be overcome by increasing agonist concentration, ultimately decreasing maximal achievable effect ($E_{max}$) once spare receptors are depleted.

Partial Agonist

Receptor ligand with low intrinsic efficacy ($0 < e < 1.0$) that cannot elicit a maximal response even at $100\%$ receptor occupancy, acting as a functional antagonist in the presence of a full agonist.

Inverse Agonist

Ligand that selectively binds to and stabilizes the inactive conformation ($R_i$) of a receptor, suppressing basal or constitutive receptor activity below baseline.

Spare Receptors

Phenomenon where a maximal cellular response ($E_{max}$) is elicited at a drug concentration occupying less than $100\%$ of available receptors, typically due to downstream signal amplification ($EC_{50} < K_D$).

Receptor Down-Regulation

Adaptive decrease in total receptor density caused by chronic or repeated agonist exposure through receptor phosphorylation, endocytosis, and lysosomal degradation, contributing to pharmacodynamic tolerance.

Catecholamine Synthesis Pathway

Enzymatic cascade converting Tyrosine $\rightarrow$ DOPA $\rightarrow$ Dopamine $\rightarrow$ Norepinephrine $\rightarrow$ Epinephrine, mediated sequentially by Tyrosine hydroxylase, L-Aromatic amino acid decarboxylase, Dopamine $\beta$-hydroxylase, and PNMT.

Acetylcholinesterase (AChE)

Enzyme located at cholinergic synapses that rapidly terminates neurotransmission by hydrolyzing acetylcholine into choline and acetate.