Autonomic pharmacology

Sympathetic / adrenergic

Main neurotransmitter

Receptors

• Norepinephrine at many postganglionic terminals;

• epinephrine from adrenal medulla

• Alpha and beta adrenergic receptors.

Sympathetic / adrenergic

Typical effect

Key drugs

• Fight-or-flight:

  • heart rate and vascular tone changes;

  • bronchodilation via beta-2.

• Epinephrine, phenylephrine, albuterol, propranolol, prazosin.

Parasympathetic / cholinergic

Parasympathetic / cholinergic

Main neurotransmitter

Receptors

• Acetylcholine.

• Nicotinic and muscarinic receptors.

Parasympathetic / cholinergic

Typical effect

Key drugs

• Rest-and-digest: secretions, GI motility and bladder contraction.

• Atropine, pilocarpine, neostigmine, ipratropium.

Adrenergic receptors:

Alpha-1 (Gq)

Vascular smooth-muscle contraction -> vasoconstriction.

Alpha-1 (Gq)

Agonists:

Antagonists:

• phenylephrine, oxymetazoline.

• prazosin, terazosin, tamsulosin

Adrenergic receptors:

Alpha-2 (Gi)

Presynaptic inhibition of NE release;

decreases cAMP.

Adrenergic receptors:

Alpha-2 (Gi) antagonist

Clonidine, methyldopa, guanfacine; yohimbine

Adrenergic receptors:

Beta-1 (Gs)

Heart: increased rate, contractility and conduction.

Beta-1 (Gs)

Agonist

Antagonist/ beta blockers

Dobutamine

metoprolol/propranolol

Adrenergic receptors:

Beta-2 (Gs)

Bronchodilation and smooth-muscle relaxation.

Adrenergic receptors:

Beta-2 (Gs)

SABA:

LABA:

albuterol/salbutamol, terbutaline.

salmeterol, formoterol.

Adrenergic receptors:

D1

Renal/mesenteric vasodilation in classic pharmacology teaching.

Fenoldopam

is a selective D1 agonist example.

Cholinergic drugs

Direct muscarinic agonists

Promote muscarinic effects;

bethanechol may stimulate bladder emptying

Bethanechol, pilocarpine (class examples).

Cholinergic drugs

Acetylcholinesterase inhibitors

Increase ACh at synapses;

myasthenia gravis association.

Neostigmine, pyridostigmine; edrophonium in diagnostic history.

Cholinergic drugs

Antimuscarinics

Reduce secretions;

atropine treats symptomatic bradycardia;

ipratropium bronchodilates

Atropine, scopolamine, ipratropium.

Cholinergic drugs

Neuromuscular blockers

• Nondepolarizing agents rocuronium;

• depolarizing succinylcholine.

Act at Nm nicotinic receptors;

used for paralysis during procedures.

Epinephrine

• is the key emergency drug for anaphylaxis because

• alpha-1 vasoconstriction supports blood pressure and

• beta-2 stimulation helps bronchodilation.

Common adrenergic adverse-effect patterns

Common adrenergic adverse-effect patterns

• Beta-2 agonists such as albuterol

can cause tremor, palpitations and tachycardia

Common adrenergic adverse-effect patterns

• Alpha-1 agonists

can raise blood pressure;

topical nasal decongestants can cause rebound congestion with prolonged use.

Common adrenergic adverse-effect patterns

• Beta-blockers

nonselective agents

can cause bradycardia;

may worsen bronchospasm in susceptible patients.