Pharmacology I · Exam 1 · Lecture 3
Cholinergic Drug Chart
Every cholinergic and anticholinergic drug in the lecture — 18 agents across 5 groups, plus the 5 pairs that actually get confused.
Every cholinergic drug in Lecture 3, read as what it does at the receptor → what it is used for → what to watch for. Slide cited on every drug.
The companion to the receptor chart. That page is organized by
receptor; this one is organized by drug. Read them together:
the receptor chart is here, and the muscarinic
and nicotinic cards on it are what every drug below is acting on.
The pairs section is the one to read first. Almost every hard
question in this half of the lecture is two drugs that look interchangeable and are separated
by a single axis — and one of them, physostigmine against neostigmine, is an answer
Dr. Wood gave at the exam review in exactly those terms.
The five groups start here
Direct-acting agonists
Bind the receptor themselves
Indirect-acting — cholinesterase inhibitors
Raise the acetylcholine that is already there
Antimuscarinics
Block muscarinic only
Ganglionic blockers
Block the entire autonomic output
Neuromuscular blockers
Nicotinic, at the muscle end plate
Two of these block nicotinic receptors and three do not. The antimuscarinics leave the neuromuscular junction and the autonomic ganglia alone entirely — which is why atropine does not paralyze anyone. The ganglionic blockers and the neuromuscular blockers are the nicotinic pair, and they differ only in which nicotinic receptor they reach.
The pairs that get confused learn these first
Each of these is two drugs that look interchangeable and are separated by exactly one axis. Get the axis and the pair comes free.
Bethanechol vs carbachol
Bethanechol — muscarinic ONLY.
against
Carbachol — muscarinic AND nicotinic.
Separated byWhether it also hits nicotinic receptors. Carbachol's nicotinic action is why it releases epinephrine from the adrenal medulla; bethanechol has no such effect.
Slides 30, 32
Physostigmine vs neostigmine
Physostigmine — enters the central nervous system.
against
Neostigmine — does not.
Separated byThe blood-brain barrier. That is why physostigmine is the antidote when anticholinergic toxicity is central, and neostigmine is the one used peripherally in surgery. Dr. Wood built a whole review answer on this axis.
Slides 36, 38
Edrophonium vs pyridostigmine
Edrophonium — short-acting.
against
Pyridostigmine — long-acting.
Separated byDiagnose against maintain. Edrophonium diagnoses myasthenia gravis; pyridostigmine manages it chronically. Neostigmine sits between them, treating symptoms.
Slides 35, 39
Non-depolarizing vs depolarizing blockade
Non-depolarizing — competitive antagonist, reversible.
against
Succinylcholine — agonist, not reversible this way.
Separated byWhether a cholinesterase inhibitor helps. Raising acetylcholine outcompetes a competitive blocker and restores function; against succinylcholine, more acetylcholine does nothing, because the problem is that the receptor is already over-stimulated.
Slides 64, 67
Atropine at low against high dose
Low dose — bradycardia.
against
High dose — tachycardia.
Separated byThe dose itself. It is the one place in this lecture where the same drug does opposite things to the same organ, which is exactly the kind of detail a question is built on.
Slides 52
Direct-acting agonists Bind the receptor themselves
Also called parasympathomimetics. Two families: the choline esters (acetylcholine, carbachol, bethanechol) and the natural alkaloids (pilocarpine).
Bethanechol
At the receptorMuscarinic only — it lacks nicotinic activity. Not hydrolyzed by acetylcholinesterase, so it lasts.
Used forBladder and gastrointestinal atony.
Watch forSweating, salivation, flushing.
Slide 30
Carbachol
At the receptorMuscarinic AND nicotinic. Its nicotinic action releases epinephrine from the adrenal medulla.
Used forOphthalmic use; profound cardiovascular and gastrointestinal effects.
Watch forMay first stimulate, then depress those systems.
Slide 32
Pilocarpine
At the receptorMuscarinic. A natural alkaloid rather than a choline ester.
Used forMiosis, ciliary muscle contraction and lowering of intraocular pressure.
Watch forThe eye drug of the group.
Slide 33
Indirect-acting — cholinesterase inhibitors Raise the acetylcholine that is already there
They inhibit acetylcholinesterase, so acetylcholine accumulates and acts at both muscarinic and nicotinic sites. Whether a given one reaches the brain is what separates them clinically.
Edrophonium
At the receptorReversible. The short-acting prototype.
Used forDIAGNOSING myasthenia gravis — short action is the point.
Watch forAlso reverses a competitive neuromuscular blockade.
Slide 35
Physostigmine
At the receptorReversible, and it reaches the central nervous system.
Used forAntidote for anticholinergic overdose — atropine, phenothiazines, tricyclic antidepressants. Also raises intestinal and bladder motility, causes miosis and lowers intraocular pressure.
Watch forConvulsions at high doses, bradycardia, reduced cardiac output, and paralysis of skeletal muscle from accumulated acetylcholine.
Slide 36
Neostigmine
At the receptorReversible. Poorly absorbed from the gut and does NOT enter the central nervous system.
Used forAntidote for competitive neuromuscular blockers; symptomatic treatment of myasthenia gravis; stimulating bladder and bowel.
Watch forSalivation, flushing, low blood pressure, nausea, abdominal pain, diarrhea, bronchospasm.
Slide 38
Pyridostigmine
At the receptorReversible, peripheral.
Used forCHRONIC management of myasthenia gravis — where edrophonium diagnoses it.
Watch forSame peripheral cholinergic effects as neostigmine.
Slide 39
Donepezil, rivastigmine, galantamine
At the receptorReversible, central.
Used forSlowing the progression of Alzheimer disease, which is associated with a deficiency of central cholinergic neurons.
Watch forGastrointestinal distress.
Slide 40
Organophosphates — the irreversible inhibitors
At the receptorIrreversible. Agricultural insecticides, and used in suicide and homicide.
Used forNo therapeutic use. Toxicity shows as nicotinic or muscarinic signs, or both.
Watch forPralidoxime reactivates the enzyme — but it does not enter the central nervous system, and cannot overcome reversible inhibitors such as physostigmine.
Slide 42
Antimuscarinics Block muscarinic only
They block the muscarinic receptors of parasympathetic nerves, and the few sympathetic cholinergic fibers to salivary and sweat glands. They do NOT block nicotinic receptors — little or no action at the neuromuscular junction or the autonomic ganglia.
Atropine
At the receptorCompetitive at muscarinic receptors, centrally and peripherally. Greatest effect on bronchial tissue and on sweat and saliva.
Used forBlocking secretions before surgery or in end-of-life care; dilating the pupil; antispasmodic in the gut; antidote for cholinesterase inhibitor insecticides and some mushroom poisoning.
Watch forBradycardia at LOWER doses, tachycardia at HIGHER doses — the dose paradox. Also dry mouth, blurred vision, “sandy eyes”, urinary retention, constipation, and restlessness through to delirium.
Slide 51
Scopolamine
At the receptorPeripheral effects like atropine, but greater central action at therapeutic doses.
Used forPreventing motion sickness; anesthetic adjunct; short-term memory blocking; reducing secretions.
Watch forAs atropine. Wash hands after handling the patch — touching the eye afterwards blurs vision.
Slide 54
Ipratropium, tiotropium
At the receptorMuscarinic blockade in the airway.
Used forObstructive airway disease.
Watch forInhaled, so systemic anticholinergic effects are limited.
Slide 55
Glycopyrrolate
At the receptorPeripheral muscarinic blockade.
Used forDrying secretions — the drooling agent.
Watch forThe peripheral counterpart to scopolamine's central action.
Slide 55
Oxybutynin and the other bladder agents
At the receptorMuscarinic blockade at the bladder — darifenacin, fesoterodine, solifenacin, tolterodine, trospium.
Used forLowering pressure inside the bladder and increasing its capacity — urinary incontinence.
Watch forSame mechanism as glycopyrrolate in a different organ; the split between them is licensing rather than pharmacology.
Slide 56
Ganglionic blockers Block the entire autonomic output
They act at the nicotinic receptors of both sympathetic and parasympathetic ganglia, so they shut off the whole autonomic outflow. Rarely used clinically.
Nicotine
At the receptorNicotinic at the ganglia. The one agent in the group that is not a competitive antagonist.
Used forNo therapeutic use here — recreational.
Watch forStimulates at low concentration and BLOCKS at high concentration.
Slide 59
The blockers as a class
At the receptorNicotinic receptors of sympathetic and parasympathetic ganglia alike. All except nicotine are non-depolarizing competitive antagonists.
Used forRarely used clinically.
Watch forThe predominant sympathetic effect is vasodilation; the predominant parasympathetic effects are bladder and bowel atony, cycloplegia, dry mouth and tachycardia.
Slide 58
Neuromuscular blockers Nicotinic, at the muscle end plate
Structural analogs of acetylcholine acting at the nicotinic receptors of the skeletal muscle end plate — as antagonists (non-depolarizing) or as agonists (depolarizing).
Non-depolarizing — rocuronium, vecuronium, pancuronium, cisatracurium
At the receptorCompetitive antagonists at the end-plate nicotinic receptor: they sit on it and keep acetylcholine off.
Used forSkeletal muscle relaxation during surgery.
Watch forThey CAN be reversed — raise acetylcholine with neostigmine, pyridostigmine or edrophonium and it outcompetes the blocker. Paralysis arrives in order: face and eye first, then fingers, limbs, neck, trunk, intercostals.
Slide 64
Succinylcholine — the only depolarizing agent
At the receptorAn agonist: it binds the receptor and depolarizes, then is not cleared by acetylcholinesterase, so the stimulation persists. Phase I opens the sodium channel and depolarizes; Phase II is resistance to further depolarization, and that is where the flaccid paralysis appears.
Used forRapid sequence intubation and intubation at induction — rapid onset, short duration.
Watch forBroken down by plasma pseudocholinesterase; a genetic deficiency causes prolonged paralysis and apnea. With halothane it can trigger malignant hyperthermia — rigidity, metabolic acidosis, tachycardia, hyperpyrexia — treated by cooling and dantrolene. Respiratory muscles are paralyzed last.
Slide 70