Autonomic Nervous System (ANS) Drug Classification (K.D.

Tripathi)

Drugs acting on the ANS are broadly classified into parasympathomimetics (cholinergics),
parasympatholytics (anticholinergics), sympathomimetics (adrenergics), and
sympatholytics (antiadrenergics). Each category is subdivided by receptor selectivity and
mechanism (e.g. direct vs. indirect, selective agonist vs. antagonist). Below we summarize these
major classes, their mechanisms, common side effects, typical therapeutic doses, and routes of
administration, following Tripathi’s schema. Tables highlight representative drugs and key
features; the text explains each class in detail for study and revision.

Cholinergic Drugs (Parasympathomimetics)

Mechanism: Cholinergic drugs enhance acetylcholine (ACh) signaling. Direct-acting agonists

bind ACh receptors (muscarinic or nicotinic) mimicking ACh, whereas indirect-acting agents
inhibit acetylcholinesterase (AChE), raising synaptic ACh levels. Direct muscarinic agonists
(e.g. bethanechol, pilocarpine) selectively stimulate M-receptors. Nicotinic agonists (e.g.
nicotine) act at ganglionic/muscle nicotinic receptors. Reversible AChE inhibitors (e.g.
neostigmine, physostigmine, donepezil) prolong ACh action; organophosphate (irreversible)
inhibitors (e.g. malathion, parathion) cause long-lasting ACh accumulation.

Effects: Muscarinic activation produces “SLUDGE” effects: salivation, lacrimation, urination,

diarrhea, GI cramps, emesis; plus miosis, bronchospasm, bradycardia and hypotension from
vagal tone. Nicotinic stimulation excites autonomic ganglia (raising sympathetic tone, blood
pressure) and at neuromuscular junction causes muscle contraction. Excessive cholinergic
activity leads to overdose symptoms (wheezing, bradycardia, sweating, nausea).

Clinical Uses: Bethanechol (postoperative urinary retention), pilocarpine (glaucoma, Sjögren’s),

nicotine (smoking cessation), physostigmine (anticholinergic overdose), neostigmine
(myasthenia gravis, NMJ blockade reversal), donepezil (Alzheimer’s), insecticide antidotes, and
nerve agent treatments.

 Dose Example: Bethanechol 10–50 mg PO every 3–4 hours (urinary retention);

Neostigmine 0.03–0.07 mg/kg IV (reversal of NM blockade).
 Administration: Oral, IV/IM injection, subcutaneous, inhalation (e.g. nebulized agents),
and eye drops (pilocarpine).

Side Effects: Common adverse effects are due to parasympathetic overstimulation: abdominal
cramps, diarrhea, salivation, sweating, flushing, bronchospasm, hypotension with reflex
tachycardia, miosis and lacrimation. Neostigmine in particular causes bradycardia,
hypersalivation and bronchoconstriction.

Table: Cholinergic Drug Classes

 Class / Represent Mechanism of Major Side Typical Route
Target ative Action Effects Dose
Drugs (Adult)
Direct Bethanech Stimulate Diarrhea, Bethanecho Oral
muscarinic ol, muscarinic abdominal l: 10– (tablets)
agonists Pilocarpi receptors cramps, 50 mg PO
ne, (M1–M3) in salivation, 3–4×/day
Methachol organs bronchospasm
ine ,
hypotension,
bronchoconst
riction
Direct Nicotine Stimulate ↑BP, Nicotine Transderm
nicotinic (patch, nicotinic tachycardia patch: 7– al,
agonists gum); receptors at (from 21 mg/day inhalatio
Succinylc ganglia ganglionic ; n
holine (↑symp/paras symp), Succinylch (smoke),
(depolari ymp tone) and muscle oline: IV
zing NMJ NMJ fasciculatio 0.6 mg/kg
blocker) (fasciculatio ns then IV
ns) paralysis (intubatio
(succinylcho n)
line);
nausea,
dizziness
Indirect Neostigmi Inhibit Bradycardia, Neostigmin Oral,
AChE ne, acetylcholine bronchospasm e: 0.03– IV/IM,
inhibitors Physostig sterase → , bronchial 0.07 mg/k eye drops
(reversible mine, ↑ACh levels secretions, g IV (physosti
) Donepezil (muscarinic + salivation, (reversal) gmine)
, nicotinic) nausea ;
Pyridosti Pyridostig
gmine mine:
60 mg PO
qid (MG)
Indirect Malathion Irreversibly Profound No Topical
AChE , phosphorylate SLUDGE, therapeuti (eye),
inhibitors Parathion AChE → seizures, c “dose” Inhalatio
(organophos (insectic prolonged ACh paralysis, (toxins); n/GI
phates) ides), action respiratory Pralidoxim (pesticid
Echothiop failure; e (2-PAM) es)
 hate cholinergic used as
(glaucoma crisis antidote
), Sarin
(nerve
gas)

Anticholinergic Drugs (Parasympatholytics)

Mechanism: Anticholinergics block acetylcholine at muscarinic and/or nicotinic receptors.

Muscarinic antagonists (e.g. atropine, scopolamine, ipratropium) block M‐receptors in the heart,
glands, bronchi and GI tract, thereby suppressing parasympathetic activity. Nicotinic blockers
include ganglionic blockers (e.g. hexamethonium) and neuromuscular blockers (e.g.
tubocurarine), but neuromuscular agents are generally classified under the somatic
neuromuscular junction. Here we focus on muscarinic blockers.

Effects: By inhibiting M receptors, these drugs increase heart rate and conduction (block vagal
tone), decrease secretions (dry mouth, dry eyes), relax bronchial and GI smooth muscle
(bronchodilation, decreased motility), dilate pupils (mydriasis), and can cause urinary retention.
In high doses they impair sweating (leading to hyperthermia) and can precipitate acute glaucoma
(via iris dilation).

Clinical Uses: Atropine is used for bradycardia (0.5–1 mg IV), organophosphate poisoning, and
pre-anesthesia (reduce secretions). Scopolamine (motion sickness), ipratropium/tiotropium
(inhaled for COPD/asthma), oxybutynin (overactive bladder), tropicamide (pupil dilation), and
dicyclomine (GI spasm) are key examples.

 Dose Example: Atropine 0.5–1 mg IV/IM (bradycardia or cholinergic overdose);

Ipratropium inhaler 2 puffs (42 µg/puff) 4×/day.
 Administration: Oral, IV/IM injection (atropine), inhalation (ipratropium/tiotropium),
transdermal patch (scopolamine), topical eye drops (tropicamide).

Side Effects: Typical anticholinergic (“antimuscarinic”) effects include “hot as a hare, blind as
a bat, dry as a bone, red as a beet, mad as a hatter”: tachycardia, mydriasis and blurred
vision, dry mouth, decreased sweating (fever risk), flushed skin, urinary retention, constipation,
and central effects (confusion, delirium especially in elderly). Tachycardia and hyperthermia can
be pronounced in overdose. Atropine may precipitate acute angle-closure glaucoma (↑intraocular
pressure).
Table: Anticholinergic Drug Classes

Class Representa Mechanism of Major Side Typical Route

tive Drugs Action Effects Dose
(Adult)
Muscarinic Atropine, Block M1–M3 Tachycardi Atropine: IV/IM,
antagonists Scopolamin receptors a, dry 0.5–1 mg oral,
(belladonna e, (heart, mouth, IV/IM q3–5 patch,
alkaloids) Homatropin glands, constipati min (max eye drops
e smooth on, 3 mg);
muscle); urinary Scopolamine
dose- retention, patch
dependent blurred 1.5 mg/72
systemic vision h
parasympathol (mydriasis
ysis ,
cycloplegi
a), heat
intoleranc
e,
agitation
Antimuscari Ipratropiu Block M3 in Dry mouth, Ipratropium Inhalatio
nic m, bronchi → cough, : 2 n
bronchodila Tiotropium bronchodilati urinary inhalations (nebulize
tors (long- on, retention (42 µg r or MDI)
acting) ↓secretions (rare) each) QID;
Tiotropium:
18 µg
inhaled
once daily
Antimuscari Oxybutynin Block smooth As above Oxybutynin: Oral; eye
nic anti- , muscle (especiall 5 mg PO drops
spasmodics Tolterodin muscarinic y dry 2–3×/day;
e receptors (↓ mouth, Dicyclomine
(bladder); bladder/GI constipati : 20 mg PO
Dicyclomin spasms); on, QID;
e (GI); tropicamide blurred Tropicamide
vision) : 1 drop
 Tropicamid causes pupil (0.5–1%)
e (eye) dilation eye 15–
30 min
pre-exam
Ganglionic Hexamethon Block Orthostati Not used Oral, IV
blockers ium, nicotinic c therapeutic (historic
Mecamylami receptors at hypotensio ally al)
ne autonomic n, (research
ganglia (both constipati use)
symp & on, dry
parasymp) → mouth,
↓BP, sexual
orthostasis, dysfunctio
dry mouth, n
etc. (no
longer used
clinically)

Adrenergic Drugs (Sympathomimetics)

Mechanism: These drugs stimulate adrenergic (α and β) receptors or enhance norepinephrine

(NE)/epinephrine effects. Direct agonists bind receptors: α₁ (e.g. phenylephrine causes
vasoconstriction), α₂ (e.g. clonidine decreases sympathetic outflow), β₁ (e.g. dobutamine
↑cardiac output), β₂ (e.g. albuterol bronchodilates), or mixed (e.g. epinephrine activates α₁, α₂, β₁,
β₂). Indirect agents increase endogenous catecholamines: amphetamines and ephedrine release
NE (and some act on α/β themselves), cocaine blocks NE reuptake, and MAO inhibitors prevent
NE degradation.

Effects: Sympathetic stimulation causes “fight-or-flight” responses: ↑heart rate and contractility
(β₁), vasoconstriction or dilation (α₁ on vessels → ↑BP; β₂ on skeletal muscle vessels →
vasodilation), bronchodilation (β₂), mydriasis (α₁), glycogenolysis (β₂), and decreased GI/bladder
motility (α and β). Thus, these drugs raise blood pressure and cardiac output (epinephrine, NE,
phenylephrine), relieve bronchospasm (albuterol, epinephrine), or cause CNS stimulation
(amphetamines).

Clinical Uses: Epinephrine (emergency anaphylaxis, cardiac arrest), norepinephrine (septic

shock), phenylephrine (nasal decongestant, hypotension), clonidine (hypertension, ADHD),
dopamine (shock, bradycardia), dobutamine (heart failure), β₂-agonists albuterol/salmeterol
(asthma/COPD), isoproterenol (heart block), pseudoephedrine (oral decongestant),
amphetamines (ADHD, narcolepsy), cocaine (local anesthesia/vasoconstriction), etc.
  Dose Examples: Epinephrine 0.3–0.5 mg IM (1:1000) for anaphylaxis; Phenylephrine
nasal spray 0.125% solution 2–4 sprays; Albuterol inhaler 2 puffs (90 μg/puff) Q4–6h;
Clonidine 0.1 mg PO BID (starting).
 Administration: IV infusion (dopamine, dobutamine), IM/SC injection (epinephrine), oral
tablets (clonidine, pseudoephedrine, midodrine), inhalation (β₂-agonists), topical
(phenylephrine eye drops, ophthalmic apraclonidine), intranasal (epinephrine,
phenylephrine sprays).

Side Effects: Overstimulation can cause hypertension, tachycardia, palpitations, anxiety,

tremor, headache, insomnia, hyperglycemia (β₂ effect) and arrhythmias. α₁-agonists often
cause reflex bradycardia and hypertension; β₂-agonists cause tremor and tachycardia;
dopamine/dobutamine cause arrhythmias. Amphetamines cause insomnia, appetite suppression,
and potential abuse. Clonidine may cause sedation, dry mouth, and rebound hypertension if
stopped abruptly.

Table: Adrenergic (Sympathomimetic) Drug Classes

Class / Representat Mechanism of Major Typical Route

Receptor ive Drugs Action Side Dose
Effects (Adult)
Nonselectiv Epinephrine Epinephrine: Tachycard Epinephrine IM
e α/β , α₁=α₁=β ia, : 0.3– injection
agonist Norepinephr ₁=β₁ hypertens 0.5 mg IM ; IV
ine agonist; NE: ion, (1:1000) infusion
α₁,α₁,β tremor for
₁ agonist (epi), anaphylaxis
(no β₁) bradycard ; IV
ia infusion
(reflex, for cardiac
phenyleph arrest; NE:
rine- 2–
like) 12 mcg/min
IV infusion
Selective Phenylephri Stimulate Hypertens Phenylephri Oral;
α₁ ne, α₁ ion, ne: 10– Intranasa
agonists Midodrine, receptors → reflex 20 mg PO l; Eye
Oxymetazoli vasoconstrict bradycard (hypotensio drops
ne (nasal) ion (↑BP, ia, n); 0.125% (2.5–
nasal headache, nasal spray 10%)
decongestant) tachyphyl 2–3 sprays
axis QID
(nasal
 spray
rebound)
Selective Clonidine, Stimulate Dry Clonidine: Oral;
α₁ Methyldopa, presynaptic mouth, 0.1 mg PO Transderm
agonists Apraclonidi α₁ sedation, BID, al patch;
ne receptors bradycard ↑gradually Eye drops
(central) → ia, (max
↓sympathetic rebound 0.6 mg/day
outflow hypertens );
(↓BP); ion if Apraclonidi
Apraclonidine withdrawn ne eye
: ↓aqueous drop: 1%
humor solution 1
drop TID
β₁ Dobutamine Stimulate Tachycard Dobutamine: IV
agonists β₁ in heart ia, 2– infusion
(cardiosele → arrhythmi 20 µg/kg/m
ctive) ↑contractili as, ↑BP in IV
ty, ↑HR; (via infusion
mild β₁ cardiac (acute
(vasodilation output) HF/cardioge
) nic shock)
β₁ Albuterol Stimulate Tremor, Albuterol Inhalatio
agonists (salbutamol β₁ in tachycard inhaler: 2 n, oral
(selective) ), bronchial ia puffs Q4–
Salmeterol, smooth muscle (reflex), 6h PRN;
Terbutaline → nervousne Terbutaline
bronchodilati ss, : 2.5 mg
on; also hypokalem PO TID
vasodilation ia
in muscles
Mixed Ephedrine, Release NE Hypertens Pseudoephed Oral
(α+β, Pseudoephed and/or ion, rine:
indirect) rine, directly weak tachycard 60 mg PO
Amphetamine α/β agonism ia, Q4–6h
insomnia, (decongesta
anxiety, nt);
urinary Amphetamine
retention : 5–10 mg
PO BID
(ADHD)
 Indirect Cocaine, Inhibit NE Cocaine: (Not Local/top
sympathomim MAO reuptake coronary typically ical
etics inhibitors (cocaine), vasospasm dosed (cocaine)
(phenelzine inhibit NE , therapeutic ; Oral
), Tyramine breakdown arrhythmi ally); (MAOI)
(dietary) (MAOI), or a; MAOIs: Cocaine:
displace NE hypertens local
(tyramine) ive anesthetic
crisis 10–20%
with cream/solut
tyramine; ion
Tyramine:
HA, HTN
crises

Antiadrenergic Drugs (Sympatholytics)

Mechanism: These agents block adrenergic receptors or inhibit sympathetic tone. α-Blockers
(phenoxybenzamine, prazosin) competitively (or irreversibly) block α-receptors. α₁-blockers (e.g.
prazosin) cause vasodilation and are used for hypertension and BPH; α₂-blockers (yohimbine)
can increase NE release (rarely used clinically). β-Blockers (propranolol, atenolol, metoprolol,
etc.) antagonize β-receptors. Nonselective β-blockers (propranolol) block β₁ and β₂, while
cardioselective blockers (atenolol, metoprolol) primarily block β₁. Some have partial agonist
(pindolol) or intrinsic sympathomimetic activity.

Effects: α₁-blockade causes vasodilation → orthostatic hypotension, nasal congestion, reflex

tachycardia; it relaxes smooth muscle in bladder neck (useful in BPH). β-blockade reduces heart
rate, contractility, and conduction velocity (treats hypertension, angina, arrhythmias).
Nonselective β-blockers can cause bronchoconstriction (β₂ block) and mask hypoglycemia
symptoms. Centrally-acting agents (not covered here) reduce sympathetic outflow.

Clinical Uses: Pheochromocytoma preoperative (phenoxybenzamine, 10–20 mg PO BID),

hypertension (prazosin 1–5 mg daily), benign prostatic hyperplasia (prazosin, tamsulosin),
angina/migraine (propranolol 40 mg BID), heart failure (metoprolol), arrhythmias,
hyperthyroidism, glaucoma (timolol eye drops), anxiety (propranolol for stage fright).

 Dose Examples: Prazosin: start 1 mg PO TID, titrate up (max ~20 mg/day). Propranolol:
40 mg PO BID start (maintenance 120–240 mg/day). Atenolol: 25–50 mg PO daily (max
100 mg). Phenoxybenzamine: 10 mg PO Q8–12h (titrate).
 Administration: Oral (most alpha/beta blockers), IV (esmolol, propranolol for
arrhythmias), eye drops (β-blockers for glaucoma).

Side Effects: α₁-blockers cause first-dose syncope, dizziness, reflex tachycardia, nasal
congestion, and inhibition of ejaculation. β-blockers can cause bradycardia, fatigue, cold
extremities, depression, and bronchospasm (nonselective agents). Both classes can exacerbate
asthma (β-blockers) or peptic ulcer (α₂-blockers). Abrupt withdrawal of β-blockers may cause
rebound hypertension or angina.

Table: Antiadrenergic Drug Classes

Class / Representati Mechanism of Major Side Typical Dose Route

Selectivit ve Drugs Action Effects (Adult)
y
Nonselecti Phenoxybenza Irreversibly Orthostatic Phenoxybenza Oral
ve α- mine blocks α₁ hypotension mine: 10 mg
blockers (irreversibl and α₁ , reflex PO 2×/day,
e) receptors → tachycardia titrate to
↓vasoconstri , nasal BP response
ction (↑↑ congestion,
HR) edema
Selective Prazosin, Competitively Dizziness, Prazosin: Oral
α₁- Terazosin, block α₁ → orthostatic 1 mg PO 2–
blockers Doxazosin ↓BP (↓TPR), hypotension 3×/day (max
relax urinary (first-dose ~20 mg/day)
sphincter syncope),
(BPH) headache
β- Propranolol, Block β₁ Bradycardia Propranolol: Oral,
blockers Timolol, and β₁: , fatigue, 40 mg PO IV;
(nonselect Nadolol ↓HR, bronchospas BID (↑ to Eye
ive) ↓contractili m (β₁ 120– drops
ty; block), 240 mg/day)
propranolol mask ; Timolol
is prototype hypoglycemi eye drop
a, sexual 0.25–0.5% 1
dysfunction drop BID
(glaucoma)
β₁- Atenolol, Block β₁ Bradycardia Atenolol: Oral;
selective Metoprolol, (heart) > , fatigue, 50 mg PO IV
blockers Acebutolol β₁ → depression, daily (25– (esmol
↓cardiac AV block 100 mg); ol)
output with (less Metoprolol:
less bronchospas 50 mg BID
 bronchial m than (up to
effect nonselectiv 200 mg/day)
e)
Partial Pindolol, Weak β- Similar to Pindolol: Oral
agonist Acebutolol agonist with β-blockers 5–30 mg PO
β- β-blocking but less 2–3×/day
blockers effects (ISA) bradycardia
→ less ;
resting contraindic
bradycardia ated in
asthma

All doses above are approximate starting or maintenance doses; individual titration is required.
Side effects and routes reflect general class effects.

References: Information is based on standard pharmacology texts and references (e.g. K.D.
Tripathi) and verified by clinical drug monographs.