Cholinergic

Antagonists
 CHOLINERGIC ANTAGONISTS
 For agents that bind to cholinoceptors (muscarinic or nicotinic)
and prevent the effects of acetylcholine (ACh) and other
cholinergic agonists.

 They are commonly known as anticholinergic agents (a

misnomer, as they antagonize only muscarinic receptors),
antimuscarinic agents (more accurate terminology), or
parasympatholytics.
 A second group of drugs, the ganglionic blockers (CHAPTER 5), shows a preference for the nicotinic
receptors of the sympathetic and parasympathetic ganglia. Clinically, they are the least
important of the cholinergic antagonists.

 A third family of compounds, the neuromuscular-blocking agents (CHPTER 5) (mostly nicotinic

antagonists), interfere with transmission of efferent impulses to skeletal muscles. These agents
are used as skeletal muscle relaxant adjuvants in anesthesia during surgery, intubation, and
various orthopedic procedures.
 Neurotransmission at cholinergic neurons
Neurotransmission in cholinergic neurons involves sequential six steps:

Synthesis and release of acetylcholine from the cholinergic neuron. AcCoA = acetyl coenzyme A
 ANTIMUSCARINIC AGENTS
Commonly known as anticholinergic drugs, these
agents block muscarinic receptors, causing
inhibition of muscarinic functions.

In addition, these drugs block the few exceptional

sympathetic neurons that are cholinergic, such as
those innervating the salivary and sweat glands.

Because they do not block nicotinic receptors, the

antimuscarinic drugs have little or no action at skeletal
neuromuscular junctions (NMJs) or autonomic ganglia.
ANTIMUSCARINIC AGENTS

ATROPINE SCOPOLAMINE

IPRATROPIUM & Tropicamide and

TIOTROPIUM cyclopentolate

Benztropine and
trihexyphenidyl
 1 - ATROPINE
 Tertiary amine belladonna alkaloid
 High affinity for muscarinic receptors
 Acts centrally & peripherally
 Actions last about 4 hours (except in eyedays)
 Greatest inhibitory effects are on bronchial
tissue & sweat, saliva secretion.
 1 - ATROPINE
ACTIONS
(A)EYE  myadriasis, unresponsiveness to light,
cycloplegia.

(B)GASTROINTESTINAL  antispasmodic
(reduce activity of GIT), although gastric motility
reduce, HCL production not affected (so x
effective for peptic ulcer tx)
 1 - ATROPINE
ACTIONS
(C) CARDIOVASCULAR  low dose : slight
decrease in HR (blockade of M1 receptor, allowing ↑ Ach released),
higher doses : progressive ↑ in HR (blocking the M2
receptors on SA node)

(D) SECRETIONS  dryness of mouth, sweat &

lacrimal glands similarly affected.
 1 - ATROPINE
Therapeutic uses
(A) Opthalmic : mydriatic & cycloplegic effects
permits the measurements of refractive errors.

(B) Antispasmodic : relax GIT

(C) Cardio : tx bradycardia of varying etiologies
(D) Antisecretory : block secretions in upper &
lower respy tracts prior to surgery
(E) Antidote for cholinergic agonist : tx
organophosphate poisoning, overdose
anticholinesterases (physostigmine), mushroom
poisoning.
 1 - ATROPINE
ADVERSE EFFECTS
Dry mouth, blurred vision,
tachycardia, urinary retention &
constipation

CNS – restlessness, confusion,

hallucination, delirium  may
progress into  depression,
circulatory & respy system collapse,
death.

(low dose of cholinesterase inhibitor may overcome

atropine toxicity)
 2 - SCOPOLAMINE

 Tertiary amine plant alkaloid

 Peripheral effects similar to
atropine
 Has greater action on CNS
and longer duration of action
cf atropine
 2 - SCOPOLAMINE
ACTIONS
Effective anti-motion sickness drugs, unusual effect of
blocking short term memory. Produces sedation, but in
↑ doses, produce excitement (produces euphoria susceptible
to abuse)

THERAPEUTIC USES
Prevention of motion sickness & postoperative nausea
and vomiting.
 3 – IPRATROPIUM & TIOTROPIUM
 Quaternary derivatives of atropine
 Approved for bronchodilators (maintenance tx of
bronchospasm associated with COPD)

 Ipra : used in acute management of

bronchospasm in athma
 Tio : OD dosing (cf Ipra QID)