Topic Map (pages 236-243)

1. Micturition control - bladder anatomy, sympathetic vs parasympathetic control of voiding, and drugs acting on M3/β3/α1 receptors (bethanechol, oxybutynin, mirabegron, tamsulosin)
2. Adrenergic receptor tissue distribution (α1, α2, β1, β2, β3) and their effects around the body
3. G-protein-linked second messengers - Gq/Gi/Gs system for every receptor class (adrenergic, cholinergic, dopamine, histamine, vasopressin) and the signaling cascade diagram (DAG, PKC, cAMP, PKA)
4. Presynaptic neurotransmitter terminals - Noradrenergic, Cholinergic, Dopaminergic, Serotonergic synapse diagrams (synthesis, storage, release, reuptake, degradation) + how amphetamines/cocaine hijack these
5. Cholinomimetic agents - direct agonists (bethanechol, carbachol, methacholine, pilocarpine) and indirect agonists/anticholinesterases (donepezil, neostigmine, pyridostigmine, physostigmine)
6. Anticholinesterase poisoning - organophosphate toxicity (DUMBBELSS), antidotes (atropine, pralidoxime)
7. Muscarinic antagonists - atropine and family (drugs, organ system effects, adverse effects mnemonics like "Hot as a hare")
8. Sympathomimetics (direct) - epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol, phenylephrine, midodrine, mirabegron - receptor selectivity and hemodynamics
9. Indirect sympathomimetics - amphetamine, cocaine, ephedrine and their mechanisms
10. Physiologic effects of sympathomimetics graphs - blood pressure/heart rate curves for NE, Epi, Isoproterenol, and the α-blockade experiments (epinephrine reversal, phenylephrine)
11. Sympatholytics - α2-agonists (clonidine), α-blockers (phenoxybenzamine, phentolamine, prazosin family), β-blocker-adjacent (mirtazapine)

Topic Map (pages 236-243)

1. Micturition control - bladder anatomy, sympathetic vs parasympathetic control of voiding, and drugs acting on M3/β3/α1 receptors (bethanechol, oxybutynin, mirabegron, tamsulosin)
2. Adrenergic receptor tissue distribution (α1, α2, β1, β2, β3) and their effects around the body
3. G-protein-linked second messengers - Gq/Gi/Gs system for every receptor class (adrenergic, cholinergic, dopamine, histamine, vasopressin) and the signaling cascade diagram (DAG, PKC, cAMP, PKA)
4. Presynaptic neurotransmitter terminals - Noradrenergic, Cholinergic, Dopaminergic, Serotonergic synapse diagrams (synthesis, storage, release, reuptake, degradation) + how amphetamines/cocaine hijack these
5. Cholinomimetic agents - direct agonists (bethanechol, carbachol, methacholine, pilocarpine) and indirect agonists/anticholinesterases (donepezil, neostigmine, pyridostigmine, physostigmine)
6. Anticholinesterase poisoning - organophosphate toxicity (DUMBBELSS), antidotes (atropine, pralidoxime)
7. Muscarinic antagonists - atropine and family (drugs, organ system effects, adverse effects mnemonics like "Hot as a hare")
8. Sympathomimetics (direct) - epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol, phenylephrine, midodrine, mirabegron - receptor selectivity and hemodynamics
9. Indirect sympathomimetics - amphetamine, cocaine, ephedrine and their mechanisms
10. Physiologic effects of sympathomimetics graphs - blood pressure/heart rate curves for NE, Epi, Isoproterenol, and the α-blockade experiments (epinephrine reversal, phenylephrine)
11. Sympatholytics - α2-agonists (clonidine), α-blockers (phenoxybenzamine, phentolamine, prazosin family), β-blocker-adjacent (mirtazapine)

LECTURE: Micturition (Urination) Control — p.236

Step 0: What is "micturition"?

Step 1: The big picture sentence

"Micturition center in pons regulates involuntary bladder function via coordination of sympathetic and parasympathetic nervous systems."

• "Micturition center in pons" — The pons is a part of your brainstem (the stalk at the base of the brain that connects the brain to the spinal cord). There is a specific cluster of nerve cells there whose job is to act like a "traffic controller" for your bladder. It decides, without you consciously thinking about it, whether your bladder should be storing urine or emptying it.
• "regulates involuntary bladder function" — "Involuntary" means not under your conscious control. You don't consciously tell your bladder wall to squeeze — this happens automatically, coordinated by that pons center, as opposed to your external sphincter muscle, which you can consciously control (that's why you can "hold it in").
• "via coordination of sympathetic and parasympathetic nervous systems" — This is the key concept of the entire chapter, so let's build it from scratch.

Step 2: The Autonomic Nervous System (background you need first)

1. Sympathetic nervous system = "fight or flight." Active when you're stressed, exercising, or in danger. It generally: speeds up the heart, dilates pupils, diverts blood to muscles, and — importantly for the bladder — helps you HOLD urine in (storage mode).
2. Parasympathetic nervous system = "rest and digest." Active when you're calm, after eating, at rest. It slows the heart, aids digestion, and — for the bladder — helps you RELEASE urine (voiding mode).

Step 3: The two textbook lines with arrows

⊕ sympathetic → ↑ urinary retention ⊕ parasympathetic → ↑ urine voiding

• Sympathetic activation → increased urinary retention. When the sympathetic system fires, it makes the bladder muscle relax (so it can stretch and fill up) AND makes the exit valve (sphincter) squeeze shut. Result: urine is retained/held in.
• Parasympathetic activation → increased urine voiding. When the parasympathetic system fires, it makes the bladder wall muscle squeeze AND makes the exit valve relax open. Result: urine comes out.

Step 4: The diagram — bladder anatomy and its nerve supply

1. Pelvic nerve (parasympathetic input) — This carries the "let it go" signal. It releases acetylcholine (ACh), a chemical messenger, which acts on receptors called M3 (muscarinic type 3) receptors located on the detrusor muscle (the smooth muscle that makes up the wall of the bladder — think of it as a balloon-like muscular sac). When M3 receptors are stimulated, the detrusor contracts, squeezing urine out. This is labeled point ① in the diagram (M3-receptor).
2. Hypogastric nerve (sympathetic input) — This carries the "hold it" signal. It releases norepinephrine, which acts on two different receptor types simultaneously to do two opposite-but-complementary jobs:
   • β3-receptors (point ②) on the detrusor muscle body — stimulation here relaxes the bladder wall muscle, letting the bladder expand and store more urine without a sudden urge to pee.
   • α1-receptors (point ③) on the internal urethral sphincter (the involuntary "gate" muscle at the bladder's exit) — stimulation here contracts/tightens this gate, sealing urine inside.
   So sympathetic activation does two things at once: relaxes the tank (detrusor) so it can hold more, and clamps the exit valve (internal sphincter) shut. Both actions favor storage.
3. Pudendal nerve (somatic input) — Note this is called "somatic," not autonomic. Somatic nerves control skeletal (voluntary) muscle — the kind you consciously move, like your biceps. This nerve controls the external urethral sphincter, a ring of skeletal muscle you can voluntarily squeeze to hold urine in even when your bladder is screaming to empty (this is the "I really need to pee but I'm holding it" muscle). It acts through nicotinic receptors (marked with the ℞-like N symbol in the diagram) — a different receptor type than the muscarinic ones used by the true autonomic nerves.

Step 5: The drug table — one line at a time

"Some autonomic drugs act on smooth muscle receptors to treat bladder dysfunction. Baby one more time."

• Mechanism: ⊕ M3 receptor → contraction of detrusor smooth muscle → ↑ bladder emptying.
• Plain English: This drug mimics acetylcholine and switches ON the M3 receptor artificially. That makes the bladder wall squeeze even if the body isn't sending a strong natural "pee now" signal.
• Application: Urinary retention — used when a patient's bladder is over-full and won't empty (e.g., after surgery or with certain nerve damage), essentially force-starting the emptying reflex.

• Mechanism: ⊖ (blocks) M3 receptor → relaxation of detrusor smooth muscle → ↓ detrusor overactivity.
• Plain English: This is the opposite drug — it blocks acetylcholine from working on M3, so the bladder wall muscle calms down and stops contracting randomly/excessively.
• Application: Urgency incontinence — this is the condition where the bladder muscle spasms/contracts involuntarily, causing sudden, hard-to-control urges to urinate (overactive bladder). Blocking M3 calms those spasms.

• Mechanism: ⊕ β3 receptor → relaxation of detrusor smooth muscle → ↑ bladder capacity.
• Plain English: "Sympathomimetic" means "mimics the sympathetic nervous system." This drug artificially switches on β3 (the same receptor the sympathetic nerve normally uses to relax the bladder), so the bladder wall relaxes and can hold more urine before you feel the urge.
• Application: Also urgency incontinence — a different drug strategy achieving a similar calming goal via a different receptor.

• Mechanism: ⊖ (blocks) α1-receptor → relaxation of smooth muscle (bladder neck, prostate) → ↓ urinary obstruction.
• Plain English: Normally α1 receptors clamp the internal sphincter/bladder-neck shut. Blocking them relaxes that muscle, opening up the exit channel.
• Application: BPH = Benign Prostatic Hyperplasia — this is a very common condition in older men where the prostate gland (which wraps around the urethra, the tube urine flows through) enlarges non-cancerously and squeezes the urethra, making it hard to pee. Relaxing the α1-controlled muscle around the bladder neck/prostate widens that channel and eases urine flow.

Step 6: Tissue distribution of adrenergic receptors (bottom table)

• α1 — found on blood vessel smooth muscle and organ (visceral) smooth muscle. Effect: vasoconstriction (blood vessels narrow, raising blood pressure) and smooth muscle contraction elsewhere (like the bladder sphincter we just discussed).
• α2 — found on the pancreas, nerve endings ("presynaptic terminals"), and salivary glands. Effect: it's mostly an "off switch" — inhibits insulin release, inhibits further neurotransmitter release (a self-limiting feedback loop), and inhibits saliva production (this is why stress/fear can cause dry mouth).
• β1 — found on the heart and kidney. Effect: increases heart rate and contractility (force of each heartbeat), and increases renin secretion (renin is a kidney hormone that raises blood pressure).
• β2 — found on the airways (bronchioles), heart, liver, blood vessels, and pancreas. Effect: bronchodilation (widens airways — this is why inhalers for asthma use β2-stimulating drugs), plus increases heart rate/contractility, triggers the liver to release stored sugar (glycogenolysis), relaxes blood vessels (vasodilation), and boosts insulin release.
• β3 — found on fat tissue (adipose) and, as we saw, the bladder. Effect: increases lipolysis (fat breakdown) and relaxes the bladder wall.

1. Adrenergic/cholinergic receptor second messengers (the Gq/Gi/Gs signaling table, p. 237)
2. The synapse diagrams — noradrenergic, cholinergic, dopaminergic, serotonergic terminals (p. 238)
3. Cholinomimetics + organophosphate poisoning (DUMBBELSS) (p. 239)
4. Atropine / muscarinic antagonists family (p. 240)
5. Sympathomimetics + hemodynamic graphs + sympatholytics (p. 241-243)

LECTURE (Continued): Everything Else in This Autonomic Pharmacology Chapter

SECTION 2: G-Protein-Linked Second Messengers (p. 237)

Step 0: What is a "second messenger" and why does this table exist?

• Gq → activates an enzyme called phospholipase C → produces IP3 and DAG → releases calcium inside the cell → generally causes muscle contraction or gland secretion.
• Gi ("i" = inhibitory) → decreases cAMP (a different internal signal molecule) → generally inhibits/slows things down.
• Gs ("s" = stimulatory) → increases cAMP → generally activates/speeds things up.

Adrenergic receptors row-by-row

• α1 (Gq) → ↑ vascular smooth muscle contraction (blood vessels narrow → blood pressure rises), ↑ pupillary dilator muscle contraction (this widens/dilates the pupil — called mydriasis, from Greek, just meaning "pupil dilation"), ↑ bladder sphincter muscle contraction (holds urine in, as we covered).
• α2 (Gi) → ↓ sympathetic ("adrenergic") outflow, ↓ insulin release, ↓ lipolysis (fat breakdown), ↑ platelet aggregation (clumping — helps clotting), ↓ aqueous humor production (aqueous humor is the clear fluid inside the front of your eye; less production lowers eye pressure — relevant in glaucoma treatment).
• β1 (Gs) → ↑ heart rate, ↑ contractility ("one heart" — the mnemonic trick here is β1 has "1" heart, i.e., it's the heart receptor), ↑ renin release (renin is a hormone from the kidney that raises blood pressure via a hormone cascade).
• β2 (Gs) → vasodilation, bronchodilation ("two lungs" — mnemonic: β2 acts on 2 lungs, widening airways — this is exactly why asthma inhalers are β2 agonists), ↑ aqueous humor production, ↑ lipolysis, ↑ insulin release, ↑ glycogenolysis (breakdown of stored sugar, glycogen, into usable glucose), ↓ cellular K+ uptake (this matters clinically — β2 agonists like albuterol can shift potassium into cells, which is actually used therapeutically to treat dangerously high blood potassium).
• β3 (Gs) → ↑ lipolysis, ↑ thermogenesis in skeletal muscle (generating body heat by burning fuel), ↑ bladder relaxation (as covered).

Cholinergic (acetylcholine) receptors

• M1 (Gq) → found in the brain, mediates higher cognitive functions.
• M2 (Gi) → found in the heart, ↓ heart rate, ↓ AV node conduction velocity (AV node = the electrical relay station in the heart that passes signals from upper chambers to lower chambers), ↓ atrial contractility.
• M3 (Gq) → ↑ exocrine gland secretions (sweat, tears, saliva, mucus — glands that secrete outward through a duct), ↑ gut peristalsis (the wave-like muscle contractions that push food through your intestines) and gastric acid secretion, bladder contraction (covered), ↑ pupillary sphincter muscle contraction (this constricts the pupil — called miosis, the opposite of mydriasis), ciliary muscle contraction (this changes the shape of the eye's lens for near vision, called accommodation — the eye's "autofocus" mechanism).

Dopamine receptors

• D1 (Gs) → relaxes renal (kidney) vascular smooth muscle — widens kidney blood vessels.
• D2 (Gi) → modulates neurotransmitter release, especially in the brain's striatum, where it activates the "direct pathway" and inhibits the "indirect pathway" — these are movement-control circuits in the brain (this is why Parkinson's disease, which involves dopamine loss, causes movement problems, and why antipsychotic drugs that block D2 can cause movement side effects).

Histamine receptors

• H1 (Gq) → bronchoconstriction (airway narrowing — opposite of β2!), increased airway mucus, increased vascular permeability (blood vessel walls become "leakier," letting fluid escape into tissue — this causes swelling), and pruritus (medical word for itching).
• H2 (Gs) → increased gastric (stomach) acid secretion — this is why "H2 blocker" drugs like famotidine reduce stomach acid for heartburn/ulcers.

Vasopressin receptors

• V1 (Gq) → vascular smooth muscle contraction (vasoconstriction, raises blood pressure).
• V2 (Gs) → increases water (H2O) permeability and reabsorption in the kidney's collecting tubules by upregulating aquaporin-2 (aquaporins are literal water-channel proteins that let water pass through cell membranes — think of them as tiny water pipes inserted into the cell wall on demand). Also triggers release of vWF (von Willebrand Factor), a clotting protein.

The diagram at the bottom (Gq/Gs pathway picture)

SECTION 3: Presynaptic Neurotransmitter Terminals (p. 238)

Step 0: Setting the scene — what is a synapse?

Top text block — Noradrenergic synapse narrative

"Release of norepinephrine from a sympathetic nerve ending is modulated by NE itself, acting on presynaptic α2-autoreceptors → negative feedback."

• Norepinephrine (NE) is the main sympathetic neurotransmitter (chemical messenger).
• "Modulated by NE itself... α2-autoreceptors → negative feedback": this describes a self-braking system. When the nerve releases NE into the gap, some of that NE loops back and binds receptors on the same nerve terminal that released it (these are called autoreceptors because they respond to their own neuron's product). Binding α2 autoreceptors tells the nerve "okay, enough NE released, slow down" — a classic negative feedback loop, the same concept as a thermostat shutting off the heater once the room is warm enough.

"Amphetamines use the NE transporter (NET) to enter the presynaptic terminal, where they displace the vesicular monoamine transporter (VMAT) to enter threshold within the presynaptic terminal vesicles."

• NET (norepinephrine transporter) is a protein "door" on the nerve terminal's surface whose normal job is to recycle NE back inside the nerve after it's been released (called reuptake) so it can be reused.
• Amphetamines hijack this door — they use NET to sneak into the nerve terminal (like using someone's ID card to get through a locked door).
• VMAT (vesicular monoamine transporter) is a different protein that normally packages NE into small storage sacs called vesicles inside the nerve terminal, keeping it safely stored until needed.
• Amphetamines displace NE from VMAT and vesicles, freeing up stored NE.

"This displaces NE from the vesicles. Once NE reaches a concentration threshold, and NE is expelled into the synaptic cleft, contributing to the characteristics and effects of ↑NE observed in patients taking amphetamines."

• Plain English: Amphetamines don't work the "normal" way (triggering the nerve to fire an electrical signal that releases neurotransmitter through controlled vesicle release). Instead, they sneak in through NET, kick stored NE out of its storage vesicles, and once enough NE builds up loose inside the cell, it gets forced back out into the synapse through the NET door running in reverse. This floods the synapse with far more NE than normal — explaining amphetamines' powerful stimulant effects (increased alertness, heart rate, blood pressure).

The Cholinergic diagram (bottom left)

• Cholinergic inhibitor box: Botulinum toxin — this toxin (used medically as "Botox") physically blocks the release of ACh vesicles, causing paralysis (this is why Botox smooths wrinkles — it paralyzes tiny facial muscles — and why botulism, the disease, causes life-threatening paralysis).
• Cholinergic stimulant box: AChE inhibitors (e.g., donepezil) — these drugs block the AChE enzyme from breaking down ACh, so ACh lingers longer in the synapse and its effect is prolonged/boosted (donepezil is used in Alzheimer's disease to boost the brain's dwindling ACh signaling).

The Dopaminergic diagram (bottom right)

• Dopaminergic stimulant box: amphetamine, methylphenidate, cocaine — same trick as before: these drugs exploit DAT (the reuptake transporter) to either block reuptake (cocaine, methylphenidate — leaving more dopamine sitting in the synapse acting on receptors longer) or reverse it to dump extra dopamine out (amphetamine). This flood of dopamine is central to why these drugs are addictive/euphoric — dopamine is the brain's core "reward" chemical.

The Serotonergic diagram (top right)

• Serotonergic stimulant box: amphetamine, cocaine, SSRIs — SSRIs (Selective Serotonin Reuptake Inhibitors, common antidepressants like fluoxetine/sertraline) block SERT, so serotonin lingers longer in the synapse, boosting mood-regulating signaling. Amphetamine and cocaine can also affect this transporter similarly to how they affect NET and DAT.

SECTION 4: Cholinomimetic Agents & Anticholinesterase Poisoning (p. 239)

Direct agonists (drugs that directly turn ON ACh receptors)

• Bethanechol — "Activates bladder smooth muscle; acts on muscarinic receptors; resistant to AChE breakdown (mnemonic: "Bethany, call me to activate your bladder")." Application: urinary retention (as we saw on the bladder page). Being "resistant to AChE" means the body's normal breakdown enzyme can't destroy it quickly, so it lasts longer than natural ACh.
• Carbachol — described as a "carbon copy of acetylcholine" (a pun on "carba-" sounding like "carbon"), also resistant to AChE. Application: constricts the pupil, used during eye surgery to induce miosis (pupil constriction) intraoperatively (during the operation).
• Methacholine — stimulates muscarinic receptors in the airway when inhaled. Application: the methacholine challenge test, used to diagnose asthma — if inhaling this drug triggers airway narrowing/bronchospasm, it confirms the airways are hyper-reactive (a hallmark of asthma).
• Pilocarpine — contracts the eye's ciliary muscle (open-angle glaucoma) and pupillary sphincter (closed-angle glaucoma), and is resistant to AChE, and can cross the blood-brain barrier (the protective filter around the brain that blocks most drugs/chemicals from entering). Mnemonic: "you cry, drool, and sweat on your pilocarpine" (i.e., it stimulates all the exocrine glands — tears, saliva, sweat). Application: treats both types of glaucoma (a disease of high pressure inside the eye that can damage vision) and xerostomia (dry mouth) in Sjögren syndrome (an autoimmune disease that attacks moisture-producing glands).

Indirect agonists (anticholinesterases — block the enzyme that destroys ACh, so natural ACh builds up)

• Donepezil, rivastigmine, galantamine — "1st line for Alzheimer disease (mnemonic: Dona Riva forgot the gala — playing on 'forgetting,' referencing Alzheimer's memory loss)." These boost brain ACh levels to partially offset the memory-related decline in Alzheimer's disease.
• Neostigmine — increases ACh; "Neo = no blood-brain barrier penetration due to positive charge" (its chemical structure carries a permanent positive charge, and charged molecules generally can't cross the fatty, tightly-sealed blood-brain barrier). Applications: postoperative and neurogenic ileus (ileus = a temporary paralysis/slowdown of bowel movement, common after surgery) and urinary retention, plus myasthenia gravis (an autoimmune disease where the immune system attacks ACh receptors at the muscle, causing weakness — boosting ACh helps overcome this), and reversal of neuromuscular junction blockade (undoing the effects of paralytic drugs used during anesthesia, postoperatively).
• Pyridostigmine — "↑ ACh, ↑ muscle strength, long-acting, does NOT penetrate CNS. Mnemonic: Pyridostigmine gets rid of myasthenia gravis." Used to control chronic muscle weakness symptoms.
• Physostigmine — "↑ ACh, freely crosses the blood-brain barrier (uncharged) → CNS. Mnemonic: physostigmine 'phyxes' atropine overdose." This is the antidote for anticholinergic toxicity — when someone has taken too much of a drug that blocks ACh (like atropine or certain antihistamines), physostigmine, because it can enter the brain, reverses the CNS symptoms of that overdose.

Anticholinesterase (organophosphate) poisoning

"Often due to organophosphates (eg, fenthion, parathion, malathion) that irreversibly inhibit AChE. Organophosphates commonly used as insecticides; poisoning usually seen in farmers."

• Organophosphates are a class of pesticide chemicals. Because they permanently ("irreversibly") disable the AChE enzyme, ACh builds up everywhere in the body uncontrollably, overstimulating every ACh receptor at once — a medical emergency.

• Diarrhea
• Urination
• Miosis (pupil constriction)
• Bradycardia (slow heart rate)
• Bronchospasm (airway constriction/wheezing)
• Emesis (vomiting)
• Lacrimation (excessive tearing)
• Salivation
• Sweating
• Nicotinic effects: neuromuscular blockade (muscle paralysis, "similar to succinylcholine," a paralytic drug used in anesthesia).
• CNS effects: respiratory depression, lethargy, seizures, coma.

SECTION 5: Muscarinic Antagonists — the Atropine Family (p. 240)

Drug list by main clinical use

• Atropine, homatropine, tropicamide — act on the eye.
• Benztropine, trihexyphenidyl, glycopyrrolate — act on the CNS (central nervous system).
• Hyoscyamine, dicyclomine — act on the GI (gastrointestinal) tract.
• Ipratropium, tiotropium — act on the respiratory system.
• Solifenacin, oxybutynin, tolterodine, fesoterodine — act on the genitourinary system (bladder — this is the oxybutynin we already met on the bladder page).
• Scopolamine — acts on CNS.

Atropine (the prototype/classic example) — organ system by organ system

• Eye: ↑ pupil dilation (mydriasis), and cycloplegia (paralysis of the ciliary muscle, so the eye can't focus/accommodate — this is why eye doctors sometimes use atropine-like drops before an eye exam, to relax focusing muscles for accurate measurement).
• Airway: bronchodilation, ↓ secretions.
• Heart: ↑ heart rate (because it blocks the vagus nerve's normal slowing effect on the heart — remove the brake, and the heart speeds up).
• Stomach: ↓ acid secretion.
• Gut: ↓ motility (movement/peristalsis slows).
• Bladder: ↓ urgency in cystitis (bladder inflammation) — reduces the urgent, spasmodic contractions.

Applications

• Watch for exacerbation of COPD, asthma, and peptic ulcers in susceptible patients — because atropine dries secretions and can thicken mucus (bad for COPD/asthma) and its other effects can aggravate ulcers in certain contexts; this is a caution line, not a primary use.

Adverse Effects — classic mnemonic "anticholinergic toxidrome"

↑ body temperature (due to ↓sweating), ↓ flushed skin, disorientation, dry mouth, constipation, urinary retention (in older adults due to mydriasis) — wait, let me be precise using the mnemonic phrases given:

• "Hot as a hare" = ↑ body temperature, due to decreased sweating (you can't cool down by sweating, so you overheat).
• "Dry as a bone" = dry mouth, decreased secretions.
• "Red as a beet" = flushed skin (blood vessels dilate to try to dump heat since sweating is blocked).
• "Blind as a bat" = blurred vision/cycloplegia (can't focus).
• "Mad as a hatter" = confusion/disorientation (CNS effects; historically linked to mercury poisoning causing dementia-like symptoms in hat-makers, hence the phrase, but here it just means confusion).
• "Full as a flask" = urinary retention.
• "Jimson weed (Datura) → gardener's pupil (mydriasis)" — Jimson weed is a plant containing natural atropine-like chemicals; gardeners handling it can accidentally dilate one pupil by touching their eye after touching the plant.

SECTION 6: Sympathomimetics (p. 241) + Physiologic Effect Graphs (p. 242) + Sympatholytics (p. 243)

Direct sympathomimetics (directly activate adrenergic receptors) — listed by receptor selectivity

• Albuterol, salmeterol, terbutaline — β2 > β1 selective. Application: acute asthma/COPD (albuterol, short-acting "rescue inhaler"), long-term asthma control (salmeterol, long-acting), and tocolysis (terbutaline can relax the uterus to delay premature labor, since uterine muscle also has β2 receptors). Hemodynamic effect: "little effect" — minimal heart rate/blood pressure change because they're selective for the lung's β2, sparing the heart's β1 relatively.
• Dobutamine — β1 > β2, α. Application: cardiac stress testing, acute decompensated heart failure (an "inotrope," meaning it increases the force of heart contraction). Effect: ↑ heart rate, ↑ cardiac output (CO = the total blood volume the heart pumps per minute).
• Dopamine — D1=D2 > β > α (at increasing doses it recruits more receptor types — low dose favors dopamine receptors [dilates kidney vessels], higher doses recruit β [heart stimulation], even higher doses recruit α [vasoconstriction]). Application: unstable bradycardia, shock, decompensated heart failure (inotrope).
• Epinephrine — β > α (at low/normal doses, β effects dominate; at very high doses α effects can dominate). Applications: anaphylaxis (severe allergic reaction — the EpiPen drug), asthma, shock, open-angle glaucoma (topical epinephrine can lower eye pressure via vasoconstriction, decreasing fluid production). Note: at high doses, α vasoconstriction can predominate over β vasodilation, so effects vary by dose.
• Fenoldopam — D1 selective. Application: postoperative hypertension, hypertensive crisis; "vasodilator (coronary, splanchnic [gut-related organs], renal, and peripheral), promotes natriuresis" (natriuresis = excreting more sodium in urine, which helps lower blood pressure).
• Isoproterenol — β1 = β2. Used for electrophysiologic evaluation of unstable bradycardia, tachyarrhythmias — "can worsen ischemia" (since it strongly increases heart rate/workload, it can worsen the mismatch between oxygen supply and demand in a heart with clogged arteries).
• Midodrine — α1. Application: autonomic insufficiency, postural (orthostatic) hypotension — vasoconstricts to raise blood pressure when standing up.
• Mirabegron — β3. (Already covered — bladder relaxation.) Mnemonic given: "think intra-β3-gron."
• Norepinephrine — α1 > α2 > β1. Application: septic shock (a life-threatening drop in blood pressure from severe infection) — the drug's strong α-mediated vasoconstriction raises blood pressure.
• Phenylephrine — α1 > α2. Application: nasal congestion (as decongestant, mydriatic (dilates pupils) rhinitis, ocular procedures.
• Cocaine — indirect sympathomimetic, reuptake inhibitor and local anesthetic. Causes vasoconstriction and local anesthesia. "Caution when giving β-blockers if cocaine intoxication is suspected → unopposed α1 activation → ↑↑↑ BP, coronary vasospasm" — this is a crucial safety point: if you block β receptors in a cocaine-intoxicated patient, you remove the (relatively helpful) vasodilating counterbalance, leaving the α1-driven vasoconstriction "unopposed," dangerously spiking blood pressure and potentially causing a heart attack via coronary artery spasm.
• Amphetamine — indirect general agonist, releases stored catecholamines (norepinephrine/dopamine). Application: narcolepsy, obesity, ADHD.
• Ephedrine — indirect general agonist, releases stored catecholamines. Application: nasal decongestion (pseudoephedrine), urinary incontinence, hypotension.

Physiologic effects graphs (p. 242) — reading blood pressure/heart rate curves

"NE ↑ systolic and diastolic pressures as a result of α1-mediated vasoconstriction → ↑ mean arterial pressure → reflex bradycardia. However, isoproterenol (rarely used) has little α effect but has ↑ heart rate through β1 and β2-mediated vasodilation, resulting in ↓ mean arterial pressure, offsetting reflex bradycardia reflex activity."

Sympatholytics (p. 243) — drugs that reduce sympathetic activity

• Clonidine, guanfacine — Applications: hypertensive urgency (limited situations), ADHD, Tourette syndrome (symptom control), hypertension in opioid withdrawal (helps blunt the surge of sympathetic symptoms during opioid detox). Adverse effects: CNS depression, bradycardia, hypotension, rebound hypertension with abrupt cessation (stopping suddenly can cause a dangerous BP spike, so these drugs must be tapered off slowly, not stopped cold).
• α-methyldopa — Application: hypertension in pregnancy (a preferred, safer option for pregnant patients). Adverse effect: Direct Coombs positive hemolysis (a lab test turns positive, indicating the drug triggers antibody-mediated destruction of red blood cells), lupus-like syndrome, hyperprolactinemia (elevated prolactin hormone, which can cause unexpected milk production/menstrual irregularities).
• Tizanidine — Application: relief of muscle spasticity (tightness). Adverse effects: hypotension, weakness, xerostomia (dry mouth, same term as before).

• Nonselective — phenoxybenzamine — irreversible blocker. Application: pheochromocytoma (a rare adrenal gland tumor that secretes massive amounts of catecholamines/adrenaline-like hormones) — given preoperatively to prevent a catecholamine (hypertensive) crisis during tumor surgery, since manipulating the tumor can dump huge amounts of hormone into the bloodstream suddenly.
• Phentolamine — reversible, competitive inhibitor. Given to patients on MAO inhibitors (a class of antidepressant) who eat tyramine-containing foods (aged cheese, cured meats — these can trigger dangerous hypertensive spikes in patients on MAOIs) and for severe cocaine-induced hypertension (2nd line). Also used to treat norepinephrine extravasation (when an IV infusion of a vasoconstricting drug accidentally leaks into surrounding tissue instead of the vein, phentolamine is injected locally to reverse the tissue-damaging vasoconstriction).
• α1-selective (drugs ending in "-osin"): prazosin, terazosin, doxazosin, tamsulosin — Application: urinary symptoms of BPH (as covered before — tamsulosin especially), hypertension (except tamsulosin, which is more bladder-selective and used less for BP), and PTSD (prazosin specifically is used off-label to reduce nightmares in PTSD). Adverse effects: 1st-dose orthostatic hypotension (a sharp BP drop specifically after the very first dose, as the body isn't yet adjusted) and dizziness/headache.
• α2-selective: mirtazapine — this is technically an antidepressant, included here because of its α2 receptor activity. Application: depression. Adverse effects: sedation, increased serum cholesterol, increased appetite (mirtazapine is actually sometimes used deliberately in underweight or nauseated patients because of this appetite-boosting side effect).

Summary of the whole chapter's "big idea"