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Pharmacology Quiz

Autonomic Pharmacology

Autonomic pharmacology is the study of drugs that act on the autonomic nervous system, the involuntary system that controls the heart, blood vessels, glands, gut, bladder, eye and airways. Almost every drug here works by imitating or blocking one of two neurotransmitters, acetylcholine and noradrenaline, at one of a small number of receptor types. Once the receptors and where they sit are learned, the four great drug classes and their effects follow logically. These notes cover the layout of the autonomic system, its transmitters and receptors, and the four classes: cholinergic agonists, cholinergic antagonists, adrenergic agonists and adrenergic antagonists, with the drugs and clinical uses most often tested. A 20-question practice set follows.

The Autonomic System and Its Transmitters

The autonomic nervous system has two divisions that mostly oppose each other. The sympathetic division drives the fight-or-flight response; the parasympathetic division drives rest-and-digest. Each reaches its target organ through a two-neuron chain with a synapse in a ganglion.

The whole of autonomic pharmacology turns on which transmitter is released at which synapse and onto which receptor. Learn this map first, because every drug is then simply an agonist or an antagonist at one point on it.

  • Acetylcholine is the transmitter at all autonomic ganglia (both divisions), at all parasympathetic target organs, and at the sympathetic supply to sweat glands. Fibres releasing it are called cholinergic.
  • Noradrenaline is the transmitter at most sympathetic target organs. Fibres releasing it are called adrenergic.
  • The adrenal medulla is a modified sympathetic ganglion that releases adrenaline into the blood as a hormone.
  • Cholinergic receptors are of two kinds: nicotinic receptors (at ganglia and the neuromuscular junction) and muscarinic receptors (at parasympathetic target organs).
  • Adrenergic receptors are of two families: alpha (alpha 1 and alpha 2) and beta (beta 1, beta 2 and beta 3).
  • Key receptor locations: beta 1 mainly in the heart; beta 2 in bronchial and vascular smooth muscle; alpha 1 in blood vessels and the bladder neck; muscarinic M2 in the heart and M3 in glands, gut, bladder and eye.

Cholinergic Drugs (Parasympathomimetics and Blockers)

Cholinergic agonists reproduce the effects of parasympathetic stimulation; cholinergic antagonists, chiefly the antimuscarinics, block them. The predictable rest-and-digest picture makes their effects easy to remember.

  • Direct cholinergic agonists act on muscarinic receptors: pilocarpine is used in glaucoma and dry mouth; bethanechol stimulates the bladder and gut.
  • Indirect agonists (anticholinesterases) block the enzyme that breaks down acetylcholine, so more accumulates. Neostigmine and pyridostigmine treat myasthenia gravis and reverse muscle relaxants; donepezil and rivastigmine are used in Alzheimer's disease; physostigmine crosses into the brain.
  • Organophosphate insecticides and nerve agents are irreversible anticholinesterases; poisoning causes the SLUDGE picture of salivation, lacrimation, urination, defecation, gastrointestinal upset and emesis, plus small pupils and bronchospasm. It is treated with atropine plus pralidoxime.
  • Muscarinic antagonists (antimuscarinics) block parasympathetic effects: atropine raises the heart rate, dries secretions and dilates the pupil; hyoscine (scopolamine) prevents motion sickness; ipratropium and tiotropium open the airways in asthma and chronic obstructive pulmonary disease; oxybutynin and tolterodine calm an overactive bladder.
  • The classic atropine toxidrome is remembered as dry as a bone, red as a beet, hot as a hare, blind as a bat and mad as a hatter: dry mouth, flushed skin, fever, blurred vision and confusion.
  • Nicotinic effects are separate: ganglion blockers and neuromuscular blockers such as suxamethonium and the curare-like agents act at nicotinic receptors.

Adrenergic Agonists (Sympathomimetics)

Adrenergic agonists imitate the sympathetic system. Their effects depend entirely on which receptor they hit, so the drug is best learned by its receptor selectivity.

  • Adrenaline (epinephrine) acts on alpha and beta receptors; it is the drug of anaphylaxis and cardiac arrest and is added to local anaesthetics to constrict vessels.
  • Noradrenaline acts mainly on alpha 1 (and beta 1); it is a vasopressor used to raise blood pressure in shock.
  • Alpha 1 agonists such as phenylephrine and oxymetazoline constrict vessels; they are used as nasal decongestants and to raise blood pressure.
  • Alpha 2 agonists such as clonidine act centrally to lower sympathetic outflow and so lower blood pressure.
  • Beta 1 agonists such as dobutamine increase the force of the heartbeat and are used in acute heart failure.
  • Beta 2 agonists such as salbutamol (albuterol) and salmeterol relax bronchial muscle and are the mainstay of asthma treatment; they also relax the uterus.
  • Indirect sympathomimetics such as amphetamine and ephedrine release stored noradrenaline; dopamine acts on dopaminergic and adrenergic receptors in a dose-dependent way.

Adrenergic Antagonists (Blockers)

Adrenergic antagonists block the sympathetic system. The alpha blockers and beta blockers are among the most widely used drugs in medicine, so their selectivity and uses are heavily tested.

  • Alpha 1 blockers such as prazosin, doxazosin and tamsulosin relax vascular and prostatic smooth muscle; they treat hypertension and the urinary symptoms of an enlarged prostate. A first-dose fall in blood pressure on standing is characteristic.
  • Non-selective alpha blockers such as phenoxybenzamine and phentolamine are used before surgery for phaeochromocytoma, a catecholamine-secreting tumour.
  • Beta blockers end in -olol. Non-selective ones (propranolol) block beta 1 and beta 2; cardioselective ones (atenolol, metoprolol, bisoprolol) block mainly beta 1.
  • Beta blockers slow the heart and lower its workload, so they are used in hypertension, angina, after myocardial infarction, in heart failure (started low and slowly) and in arrhythmias; propranolol also treats tremor, anxiety and migraine prophylaxis.
  • Non-selective beta blockers are used with caution in asthma because blocking beta 2 can cause bronchospasm; cardioselective agents are safer but not risk-free.
  • Carvedilol and labetalol block both alpha and beta receptors and are used in heart failure and hypertension.
  • Abruptly stopping a beta blocker can cause rebound tachycardia and worsening angina, so the dose is tapered.

Key Terms

Muscarinic receptor
A type of acetylcholine receptor found at parasympathetic target organs (heart, glands, gut, bladder, eye). Agonists such as pilocarpine stimulate it; antimuscarinics such as atropine block it.
Anticholinesterase
A drug that inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine, so the transmitter accumulates. Neostigmine treats myasthenia gravis; organophosphates are toxic irreversible examples.
Beta 2 agonist
A sympathomimetic selective for beta 2 receptors on bronchial smooth muscle, such as salbutamol, causing bronchodilation. It is the mainstay of asthma relief.
Cardioselective beta blocker
A beta antagonist that blocks mainly beta 1 receptors in the heart, such as atenolol or metoprolol, so it slows the heart with less risk of the bronchospasm caused by blocking beta 2.

Practice Quiz — 20 Questions

correct out of 20

  1. The neurotransmitter at all autonomic ganglia is:

    • A.Noradrenaline
    • B.Acetylcholine
    • C.Dopamine
    • D.Adrenaline
    B. Acetylcholine — Acetylcholine acting on nicotinic receptors transmits at the ganglia of both autonomic divisions.

  2. Noradrenaline is the transmitter at most target organs of which division?

    • A.Parasympathetic
    • B.Sympathetic
    • C.Somatic
    • D.Enteric only
    B. Sympathetic — Most sympathetic postganglionic fibres release noradrenaline; the sweat glands are the cholinergic exception.

  3. Beta 1 adrenergic receptors are located mainly in the:

    • A.Bronchi
    • B.Heart
    • C.Blood vessels of skeletal muscle
    • D.Gut glands
    B. Heart — Beta 1 receptors predominate in the heart; beta 2 predominate in bronchial and vascular smooth muscle.

  4. Salbutamol relieves asthma by acting as an agonist at which receptor?

    • A.Alpha 1
    • B.Beta 1
    • C.Beta 2
    • D.Muscarinic
    C. Beta 2 — Beta 2 agonists such as salbutamol relax bronchial smooth muscle and open the airways.

  5. Pilocarpine, used in glaucoma, is a:

    • A.Muscarinic agonist
    • B.Muscarinic antagonist
    • C.Beta blocker
    • D.Alpha agonist
    A. Muscarinic agonist — Pilocarpine is a direct muscarinic agonist; it constricts the pupil and improves aqueous drainage.

  6. Neostigmine is used in myasthenia gravis because it:

    • A.Blocks muscarinic receptors
    • B.Inhibits acetylcholinesterase so acetylcholine accumulates
    • C.Releases noradrenaline
    • D.Blocks nicotinic receptors
    B. Inhibits acetylcholinesterase so acetylcholine accumulates — As an anticholinesterase it raises acetylcholine at the neuromuscular junction, improving muscle strength.

  7. Organophosphate poisoning is treated with atropine plus:

    • A.Neostigmine
    • B.Pralidoxime
    • C.Propranolol
    • D.Adrenaline
    B. Pralidoxime — Atropine blocks the muscarinic effects and pralidoxime reactivates the inhibited enzyme.

  8. The SLUDGE syndrome of cholinergic excess includes all EXCEPT:

    • A.Salivation
    • B.Lacrimation
    • C.Dry mouth
    • D.Urination
    C. Dry mouth — Cholinergic excess causes wet effects; a dry mouth is a feature of antimuscarinic (atropine) toxicity instead.

  9. Atropine increases the heart rate because it blocks:

    • A.Beta 1 receptors in the heart
    • B.Muscarinic M2 receptors in the heart
    • C.Alpha 1 receptors
    • D.Nicotinic receptors
    B. Muscarinic M2 receptors in the heart — By blocking cardiac M2 muscarinic receptors atropine removes vagal slowing, so the rate rises.

  10. Which drug is an antimuscarinic used as an inhaler in chronic obstructive pulmonary disease?

    • A.Salbutamol
    • B.Ipratropium
    • C.Prazosin
    • D.Bethanechol
    B. Ipratropium — Ipratropium and tiotropium are inhaled antimuscarinics that produce bronchodilation.

  11. The atropine toxidrome is classically described as dry as a bone and:

    • A.Cold as ice
    • B.Mad as a hatter
    • C.Slow as a snail
    • D.Weak as water
    B. Mad as a hatter — Antimuscarinic toxicity gives dry, flushed, hot skin, blurred vision and confusion, mad as a hatter.

  12. The first-line drug for anaphylaxis is:

    • A.Noradrenaline
    • B.Adrenaline
    • C.Dobutamine
    • D.Atropine
    B. Adrenaline — Adrenaline, acting on alpha and beta receptors, is the drug of choice in anaphylaxis and cardiac arrest.

  13. Clonidine lowers blood pressure by acting as an agonist at:

    • A.Central alpha 2 receptors
    • B.Peripheral alpha 1 receptors
    • C.Beta 1 receptors
    • D.Muscarinic receptors
    A. Central alpha 2 receptors — Clonidine stimulates central alpha 2 receptors, reducing sympathetic outflow and lowering blood pressure.

  14. Phenylephrine is used as a nasal decongestant because as an alpha 1 agonist it:

    • A.Dilates blood vessels
    • B.Constricts blood vessels
    • C.Slows the heart
    • D.Opens the airways
    B. Constricts blood vessels — Alpha 1 stimulation constricts the nasal vessels, reducing congestion.

  15. Tamsulosin relieves the urinary symptoms of prostate enlargement by blocking:

    • A.Beta 2 receptors
    • B.Alpha 1 receptors
    • C.Muscarinic receptors
    • D.Nicotinic receptors
    B. Alpha 1 receptors — Alpha 1 blockade relaxes smooth muscle in the bladder neck and prostate, easing urine flow.

  16. Beta blockers characteristically have generic names ending in:

    • A.-pril
    • B.-olol
    • C.-sartan
    • D.-pine
    B. -olol — Beta blockers end in -olol, such as propranolol, atenolol and metoprolol.

  17. Non-selective beta blockers are used cautiously in asthma because blocking beta 2 can cause:

    • A.Bronchodilation
    • B.Bronchospasm
    • C.Tachycardia
    • D.Hypertension
    B. Bronchospasm — Beta 2 blockade can constrict the airways, so cardioselective agents are preferred in airway disease.

  18. Dobutamine is used in acute heart failure because as a beta 1 agonist it:

    • A.Slows the heart
    • B.Increases the force of contraction
    • C.Dilates the bronchi
    • D.Constricts blood vessels
    B. Increases the force of contraction — Beta 1 stimulation increases myocardial contractility, supporting the failing heart.

  19. Before surgery for a phaeochromocytoma, alpha blockade is established first with:

    • A.Atenolol
    • B.Phenoxybenzamine
    • C.Salbutamol
    • D.Neostigmine
    B. Phenoxybenzamine — Phenoxybenzamine gives alpha blockade before any beta blocker, to prevent an unopposed hypertensive crisis.

  20. Labetalol and carvedilol are useful because they block:

    • A.Only beta 1 receptors
    • B.Both alpha and beta receptors
    • C.Only muscarinic receptors
    • D.Only alpha 2 receptors
    B. Both alpha and beta receptors — These combined blockers act at both alpha and beta receptors, useful in hypertension and heart failure.

References