ANTICHOLINERGICS

Dr.Amudhan Arvind

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system

they inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells

Anticholinergicdrugs

Antinicotinic drugs

Ganglionic

blockers

Neuromuscular

blockers

Antimuscarinicdrugs

ANTIMUSCARINIC DRUGS

Antimuscarinicdrugs

Naturally occurring

antimuscarinic

Semisynthetic

Derivatives

Synthetic antimuscarinics

AntimuscarinicAgents

Natural Alkaloids

Atropine

Hyoscine(scopolamine)

Extract of Belladona

SemisyntheticHomatropineEncatropine

MethylatropineMethscopoline

Synthetic Tropicamide

GlycopyrrolatePirenzeline

STRUCTURE

Atropine is a product resulted from esterification

of tropic and tropine base

In scopolamine, there is an oxygen bridging

(epoxide)

In homatropine, hydroxymethyl of atropine is

replaced by an OH-radical (tertiary)

PHARMACOKINETIC

Tertiary group:

lipid soluble

distribution is wide

absorption from gut and across conjunctiva is good

absorption across skin in suitable vehicle is good.

Significant concentration is reached within 0.5-1h (eg.

scopolamine)

Quaternary group:

not very lipid soluble

distribution is confined to peripheral tissues (no central

toxicity)

absorption from the site of application is poor

Metabolism:

1/2 is metabolized by hepatic esterase (atropinase)

1/3 is excreted unchanged in the urine

80% excreted in the urine with an half-life of 2h

the effects on the eye persist 40-72h

PHARMACODYNAMIC

Interaction with muscarinic receptors: reversible,

competitive

Receptor selectivity:

Atropine: -selective for muscarinic receptors

non-selective for muscarinic receptor subtypes

But, pirenzepine a selective antagonist for m1-

receptors(stomach parietal cells)

Quaternary group:

not very selective for muscarinic receptors

can also antagonize Nicotinic-receptors in autonomic

ganglia

Tissue selectivity:

Tissues more sensitive to:

Atropine: salivary, sweat and bronchial glands

Pirenzepine (telenzepine, more effective): acid

secretion from parietal cells (stomach)

Scopolamine: more effective on vestibular

disturbances (eg. Motion sickness)

SOURCE

Atropine

- From Atropa belladonnea

Datura stromonium

Occurs as l-form, not stable

racemizes to dl-form rapidly

commercial products contain dl-form

l-form is 100-times as potent as d- or dl-forms

-Scopolamine From Hyosciamus niger

Occurs as l-form

its l- form is stable

Muscarinic antagonists prevent the effects of ACh

by blocking its binding to muscarinic receptors on

effector cells at parasympathetic neuroeffector

junctions, in peripheral ganglia, and in the CNS.

In general, muscarinic antagonists cause little

blockade of nicotinic receptors.

The quaternary ammonium antagonists generally

exhibit a greater degree of nicotinic blocking activity

and therefore are more likely to interfere with

ganglionic or neuromuscular transmission.

Most clinically available muscarinic antagonists are

nonselective and their actions differ little from those

of atropine, the prototype of the group.

No subtypeselective antagonist, including

pirenzepine, is completely selective

STRUCTURE-ACTIVITY RELATIONSHIPS

An intact ester of tropine and tropic acid is

essential for antimuscarinic action,

The presence of a free OH group in the acyl portion

of the ester also is important for activity.

When given parenterally, quaternary ammonium

derivatives more potent than their parent

compounds in both muscarinic and ganglionic

(nicotinic) blocking activities.

The quaternary derivatives, when given orally, are

poorly and unreliably absorbed.

MECHANISM OF ACTION.

Atropine and related compounds compete with

ACh and other muscarinic agonists for a

common binding site on the muscarinic

receptor.

Since antagonism by atropine is competitive, it can

be overcome if the concentration of ACh at

muscarinic receptors of the effector organ is

increased sufficiently.

Muscarinic receptor antagonists inhibit responses

to postganglionic cholinergic nerve stimulation less

effectively than they inhibit responses to injected

choline esters.

EFFECTS OF ATROPINE IN RELATION

TO DOSE

PHARMACOLOGICAL EFFECTS OF

MUSCARINIC ANTAGONISTS

CNS

In clinical dose:

- With atropine:

- a long lasting sedation with slow onset

- stimulation of vagal nuclei in the brain stem

With scopolamine:

- sedative effect is more powerful (drowsiness, amnesia)

In toxic dose: (both atropine and scopolamine)

Excitement

Agitation

Hallucination

Coma

Disorientation

Delerium

EYE

Mydriasis

Paralysis of ciliary muscle (cycloplegia):

Loss of accommodation

Adjustment of eye for far vision

Photophobia

Blurred vision

Lasts for 7-10 days

Acute glaucoma attack in patient with narrow irido-

corneal angle due to impairment of drainage

Reduction of lacrimal secretion leading dry sandy

eye

CARDIOVASCULAR SYSTEM

Low dose central vagal stimulation

initial bradycardia

followed by tachycardia resulting from peripheral

anticholinergic efffec and thus unopposed sympathetic

activity

Moderate dose tachycardia due to unopposed

sympathetic activity

Atroventricular conduction:

accelereted due to unopposed sympathetic activity

PR shortening in ECG

in toxic doses, conduction block

At toxic doses:

suppression of thermoregulatory sweating

cutaneous vasodilatation at Release of hiatamine

by blush areas (face, neck, ear)

The net CV effects:

Tachycardia

Slight elevation in blood pressure due to vasomotor

centre stimulation

RESPIRATORY SYSTEM

Some bronchodilatation

Inhibition of bronchial secretion

Premedication in anaesthesiology: Used before

inhalant anesthetics to reduce

-Bronchial secretions

-laryngospasm

-risk of airway obstructions

-postoperative pneumonia

GASTROINTESTINAL TRACT

Inhibition of saliva secretion → Dry mouth

Gastric secretion:

Blocked to lesser extent by atropine.

But, is blocked by pirenzepine and telenzepine

Volume of secretion and amount of acid, pepsin and

mucine are all reduced

Large doses of atropine are necessary to reduce gastric

secretions

Motility of gut is more powerfully depressed by

atropine than gastrointestinal secretions

Smooth musles of gut wall are paralysed

Propulsive movements are diminished

Sphincter muscles are not able to relax,constipation

Gastric emptying time prolonged

Intestinal transit time is lengthened

Some antimuscarinics have direct spasmolytic effect

as well

GENITO-URINARY TRACT

Smooth muscles of ureter and bladder wall are

relaxed

This is useful in the treatment of spastic pain due to

mild urinary inflammations

Sphincter muscles of bladder become unable to

relax.

urinary retention

may be hazardous in elder with prostate

hypertrophy

Helpful in increasing bladder capacity

Controls detrusor hypereflexia in neurogenic

bladder

EFFECTS ON SWEAT GLAND

Thermoregulatory sweating is depressed by

atropine

In adults, large doses of atropine can increase body

temperature

In infants and children, even ordinary doses may

cause atropine fever

Other actions:

Markedly decreases salivary,lacrimal and

tracheobronchial secretion

Decrease secretion of acid,pepsin and mucus of

stomach

Mild local anaesthetic action on cornea

ATROPINE SUBSTITUTES

Most of semisynthgetic belladona alkaloid

derivatives and synthetic compounds are atropine

sucbstitutes

Differs only slightly from atropine

USES

Respiratory system:

Ipratropium and tiotropium .

Used in Asthma and COPD

These agents often are used with inhaled long-acting β2 adrenergic receptor agonists,

Ipratropium is administered four times daily via a metered-dose inhaler ornebulizer;

tiotropium is administered once daily via a dry powder inhaler.

Ipratropium also is FDA-approved for use in nasal inhalers for the treatment of the rhinorrhea associated with the common cold or with allergic or nonallergicperennial rhinitis..

GENITOURINARY TRACT.

Overactive urinary bladder can be successfully treated with muscarinic receptor antagonists.

These agents can lower intravesicular pressure, increase capacity, and reduce the frequency of contractions by antagonizing parasympathetic control of the bladder; they also may alter bladder sensation during filling

Muscarinic antagonists can be used to treat enuresis in children

In overactive bladder

oxybutynin

tolterodine

trospium chloride

Darifenacin ,

Solifenacin , and

Fesoterodine

Flavoxate

The most important adverse reactions are consequences of muscarinic receptor blockade and include xerostomia, blurred vision, and GI side effects such as constipation and dyspepsia.

CNS-related antimuscarinic effects, including drowsiness, dizziness, and confusion, can occur and are particularly problematic in elderly patients.

CNS effects appear to be less likely with trospium, a quaternary amine, and with darifenacin and solifenacin;

The latter agents are relatively selective for M3 receptors and therefore have minimal effects on M1 receptors in the CNS, which appear to play an important role in memory and cognition

GI TRACT

As antisecretory.

In Peptic ulcer.

Pirenzepine

Telenzepine.

In reducing spasticity or motility of the GI tract (e.g.,

atropine,hyoscyamine and scopolamine) alone or in

combination with sedatives or antianxiety

agents(e.g., chlordiazepoxide

Reduce tone and motility

M3-selective antagonists might achieve more selectivity

Glycopyrrolate also is used to reduce GI tone and

motility.

Diarrhea associated with irritation of the lower

bowel, may respond to atropine-like drugs, an effect

that likely involves actions on ion transport as well

as motility.

Dicyclomine is a weak muscarinic receptor

antagonist that also has nonspecific direct

spasmolytic effects on smooth muscle of the GI

tract.

It is occasionally used in the treatment of diarrhea-

predominant irritable bowel syndrome.

EYE.

Produce mydriasis and cycloplegia.

For breaking or preventing the development of

adhesions between the iris and the lens.

Complete cycloplegia may be necessary in the

treatment of iridocyclitis and choroiditis and for

accurate measurement of refractive errors.

Homatropine hydrobromide

Cyclopentolate hydrochloride

Tropicamide

CARDIOVASCULAR SYSTEM.

Atropine may be considered in the initial treatment of patients with acute myocardial infarction in whom excessive vagal tone causes sinus bradycardia or AV nodal block.

Doses that are too low can cause a paradoxical bradycardia , while excessive doses will cause tachycardia that may extend the infarct by increasing the demand for oxygen.

It has little effect on most ventricular rhythms.

Eliminate premature ventricular contractions associated with a very slow atrial rate.

Reduce the degree of AV block when increased vagal tone is a major factor in the conduction defect, such as the second-degree AV block that can be produced by digitalis.

Selective M2 receptor antagonists would be of potential utility in blocking ACh-mediated bradycardia or AV block.

CENTRAL NERVOUS SYSTEM.

In prevention of motion sickness.

Scopolamine is the most effective agent

A transdermal preparation of scopolamine is used

prophylactically for the prevention of motion sickness.

In the treatment of Parkinson disease.

Benztropine

Trihexyphenidyl

Biperiden

Selective M1 and M4 muscarinic antagonists may be

efficacious for the treatment of Parkinson disease

While selective M3 antagonists may be useful in the

treatment of obesity and associated metabolic

abnormalities.

Uses in Anesthesia.

Atropine commonly is given to block responses to

vagal reflexes induced by surgical manipulation of

visceral organs.

Atropine or glycopyrrolate is used with neostigmine

to block its parasympathomimetic effects

Serious cardiac arrhythmias have occasionally

occurred, perhaps because of the initial bradycardia

produced by atropine combined with the

cholinomimetic effects of neostigmine.

ANTICHOLINESTERASE POISONING

Atropine is not an actual antidote for organophosphate

poisoning.

By blocking the action of acetylcholine at Muscarinic

receptors, atropine also serves as a treatment for

poisoning by organophosphate insecticides

Atropine is often used in conjunction with oximes

Atropine is given as a treatment for SLUDGE

syndrome (salivation, lacrimation, urination, diaphoresi

s, gastrointestinal motility, emesis) symptoms caused

by organophosphate poisoning.

Other Therapeutic Uses of Muscarinic

Antagonists.

Methscopolamine –In temporary relief of symptoms

of allergic rhinitis, sinusitis, and the common cold.

Homatropine potent as a ganglionic blocking

agent,primarily used with hydrocodone as an

antitussive combination

MUSHROOM INTOXICATION

I) Intoxications with rapid onset (eg. within 2

hours)

II) Intoxications with slow onset (eg. within 2 to 6

hours)

Rapid acting mushroom intoxications

1. -Mushrooms: Inocybe, Clitocybe

-posses high amount of muscarine

-cause severe parasympathomimetic effects

-onset of intoxication symptoms: within 15-30mins

-antidote: Atropine

2. -Mushrooms: Psilocibe, Copelandin, Pancoulus, Gymnopilus species

-posses psychoactive alkaloids such as psilocybin and psilocin

-cause delirium, euphoria, hallucination

-induce no sleep

- symptoms last 2-4 hours

-Treatment: Diazepam, phenothiazines

3. -Mushrooms: A. muscaria, A. pantherina, A. cothurnate, A. gemmata

-posses GABA antagonists such as ibotenic acid and mushimol

-cause delirium, euphoria, hallucination

-but do induce sleep and coma

-symptoms resemble those of atropine, but not responsive physostigmine

-symptoms last 2-9 hours

- no antidote available

4. -Mushroom: Coprinus atramentarius

-contain coprin which inhibits aldehyde dehydrogenase

-cause disulfiram-like effects (aldehyde reaction!)

-toxic effects appear, when alcohol is drunken 2-3h after ingestion of mushrooms

Slow acting mushroom intoxications

Amanita phalloides group

-Mushrooms: A. phalloides, A. verna, A. virosa

-Toxins: Phalloidin and α-Amanitin

α-Amanitin Inhibition of Depression of mRNA RNA-

polymerase-II protein synthesis

- hepatotoxicity Tissue necrosis

- nephrotoxicity

- CNS toxicity

Intoxications have 3 phases

1sth phase: - resembles muscarine intoxication

- symptoms appear 8-12h after mushroom ingestion

2nd phase: - symptoms in the first phase lessen and disappear within 24-

48h

- patient becomes asymptomatic in appearance

- but, biochemical hepatic changes continue developing

eg. - increase in transaminase activity

- elevation of biliuribin levels

- prolongation of prothrombin time

- lasts 2-6 days

-the patient may be discharged from the hospital considering healed

3rd phase:

- begins abruptly with signs and symptoms of

hepatotoxicity and nephrotoxicity: -

jaundice

- encephalopathy

- coagulopathy

- hypoglycemia

- acute renal insufficiency

1/3th of patients die within a week or so

ATROPINE POISONING

In overdoses, atropine is poisonous.

Atropine is incapacitating at doses of 10 to 20 mg per person.

Its LD50 is estimated to be 453 mg per person

The antidote to atropine is physostigmine or pilocarpine

These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased sweating/lacrimation, vasodilation

This set of symptoms is known as anticholinergictoxidrome

"hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter".

ADVERSE EFFECTS OF ANTIMUSCARINICS

-Mydriasis and cycloplegia, when used against gut

disorders

-Blockade of all parasympathetic functions:

-dry mouth, sandy eye

-mydriasis

-tachycardia, hot and flushed skin

-agitation, delirium, hallucination

-elevation of body temperature (children)

-Treatment of adverse effects:

-due to overdose of atropine and its tertiary

congeners

Physostigmine:

- 1-4mg, iv. in adults

- 0.5-1mg iv. in children

- Severe hyperthermia: - cooling blanket

- Seizures: -iv. diazepam

CONTRAINDICATIONS OF ANTIMUSCARINICS

- Glaucoma (angle closure)

- Prostatic hypertrophy (elderly)

- Peptic ulcer (slowing of gastric emptying)

Exception: Pirenzepine, Telenzepine

Central antimuscarinics used against

Parkinson’s disease

Trihexyphenidyl 6-20mg

Procyclidine 7.5-30mg

Orphenanrine 150-400mg

Ethopropazine 150-300mg

Chlorphenoxamine 150-460mg

Biperiden 2-12mg

Benzotropine mesylate

Ganglion-blocking agents competitively block the action of

acetylcholine and similar agonists at nicotinic (Nn)

receptors of both parasympathetic and sympathetic

autonomic ganglia.

Ganglionic blockers

Hexamethonium : acts mainly by channel blocker

Decamethonium

Quaternary -Tetraethyl ammonium:

short acting

-Pentolinium

-Chlorizondamine

-Trimetaphan:

very short acting

-Mecamylamine

Secondary -Pempidine

Mechanism of ganglionic block:

1) Depolarizing block, eg. by sustained

depolarization: Ach, nicotine, carbamoylcholine

2) Nondepolarizing competitive antagonism of Ni

receptors

3) Channel block: Hexamethonium

Results of ganglion blockade

CNS:

- Quaternary group is devoid of such effects

- Secondary group readily enters CNS: sedation, tremor,

choreiform movements,mental disturbances

EYE:

- Moderate mydriasis (since p.sympathetic influence on

iris is dominant)

- Cycloplegia with loss of accommodation

CVS:

- Sympathetic CV reflexes are depressed

- Sympathetic influence on arteriols and veins are

diminished, PVR and venous return are reduced,

vasodilatation, hypotension (orthostatic), tachycardia

GUT:

- Secretions and motility are inhibited

- Some degree of constipation

Urinary system:

- Urination is blocked

- Urine retention in a man with prostate hypertrophy

Thermoregulatory sweating is blocked.

THERAPEUTIC USES:

1) Hypertension:

- rapid tolerance development and orthostatic hypotension

-now more effective agents are available

2) Acute hypertensive crisis in a patient with dissecting aortic aneurism.

Trimetaphan: 0.5-3mg/min by iv infusion

Disadvantage: tolerance development within 48h

3) Production of controlled hypotension to minimize haemorrhage at the operative field.

Trimetaphan: 1-4mg/min by iv infusion

4) Autonomic hyperreflexia (or reflex sympathetic dystrophy)

Side effects:

The most serious one is orthostatic

hypotension

NEUROMUSCULAR BLOCKERS

Block synaptic transmission at the neuromuscular

junction

Affect synaptic transmission only at skeletal muscle

Does not affect nerve transmission, action potential

generation

Act at nicotinic acetylcholine receptor NM

Classification:

Neuromuscular blocking agents:-1) Depolarizing muscle relaxants.

2) Non-depolarizing muscle relaxants

Depolarizing Muscle relaxants: Succinylcholine (short acting)

Non-depolarizing Muscle relaxants:

Short acting: Mivacurium

Intermediate –acting: Atracurium,

Cisatracurium,

Vecuronium,

Rocuronium

Long acting : Doxacurium

Pancuronium

Pipecuronium

MECHANISM OF ACTION

SUXAMETHONIUM:

• Block transmission by causing prolonged depolarization

of endplate at neuromuscular junction.

• Manifestation by initial series of muscle twitches

(fasciculation) followed by flaccid paralysis.

• It immediately metabolize in plasma by Pseudo-

cholinesterase which is synthesized by liver so to prevent its metabolism in plasma it should be given at faster rate.

SYSTEMIC EFFECTS

Cardiovascular: Produces muscarinic effects as

acetylcholine , therefore causes bradycardia ( but when

given high doses causes tachycardia because of

stimulation of nicotinic receptors at sympathetic

ganglions.)

Hyperkalemia: Occurs due to excessive muscle

fasciculations. Ventricular fibrillation can occur due to

hyperkalemia.

CNS: Increases intracranial tension ( due to contraction

of neck vessels)

Eye: Increases intraocular pressure.

GIT: Increases intra-gastric pressure , salivation, peristalsis.

Muscle pains ( myalgia): This is a very common problem in

post operative period. These are due to excessive muscle

contractions.

Malignant hyperthermia

Severe Anaphylaxis

Masseter Spasm : Sch can cause masseter spasm

especially in children & patients susceptible for malignant

hyperthermia.

Doesnot require reversal rather cholinesterase inhibitors

(neostigmine) can prolong the depolarizing block (because these agents also inhibits the pseudocholinesterase)

NON-DEPOLARIZING MUSCLE

RELAXANTS:Mechanism of action:

• It blocks nicotinic receptors competitively resulting

in inhibition of sodium channels and excitatory post-

synaptic potential.

• It binds at the same site at which acetylcholine

binds.

• All NDMR are quarternary ammonium compounds

& highly water soluble i.e. hydrophilic. So, they do

not cross blood brain barrier & placenta except

Gallamine.

BROAD CLASSIFICATION

These are broadly divided into steroidal compounds

and benzylisoquinoline (BZIQ) compunds.

STEROIDAL COMPOUNS: (vagolytic properties)

It includes PANCURONIUM,VECURONIUM ,

PIPECURONIUM,ROCURONIUM,

RAPACURONIUM,DOXACURIUM

BZIQ(Benzylisoquinoline): (hystamine realease)

It includes d-Tubocurare, Metocurine, Doxacurium,

Atracurium, Mivacurium, Cisatracurium

OTHERS includes Gallamine, Alcuronium

DIFFERENCES BETWEEN DEPOLARIZING & NON-

DEPOLARIZING BLOCK

Depolarizing Nondepolarizing

Also called Phase I block -

Block preceded by muscle

fasciculations

No fasciculations

Depolarizing blocking drugs are called

Leptocurare

Called pachycurare

Does not require reversal rather

cholinesterase inhibitors (Neostigmine)

can prolong the depolarizing block (

because these agents also inhibit the

pseudocholinesterase).

Reversed by cholinesterase

inhibitors like Neostigmine.

NDMR ARE USED IN ANAESTHESIA FOR:

Maintenance of anaesthesia.

For intubation where succinylcholine is contraindicated (

Rocuronium is of choice)

For precurarization to prevent postoperative myalgias by

succinylcholine.

STEROIDAL COMPOUNDSPancuronium

Very commonly used as it is inexpensive.

It releases noradrenaline & can cause tachycardia & hypertension. Because of this there are increased chances of arrhythmia with halothane

Pipercuronium

It is a pancuronium derivative with no vagolytic activity, so cardiovascular stable, slightly more potent

Vercuronium

It is very commonly used now a days. It is cardiovascular stable. Shorter duration of action.

It is the muscle relaxant of choice in cardiac patient.

Rocuronium

8 times more potent than vecuronium and it also has earlier onset of action

Because of onset comparable to succinylcholine it is suitable for rapid sequence intubation as an alternative to succinylcholine.

BENZYLISOQUINOLINE COMPOUNDS

D- Tubocurare

It is named so because it was carried in bamboo tubes &

used as arrow poison for hunting by Amazon people.

It has highest propensity to release histamine

It causes maximum ganglion blockade. Because of

ganglion blocking & histamine releasing property it can

produce severe hypotension.

Due to histamine release it can produce severe

bronchospasm.

REVERSAL OF BLOCK

Drugs used for reversal of block are cholinesterase inhibitors (anticholinesterases).

Reversal should be given only after some evidence of spontaneous recovery appear.

Mechanism of Action

It inactivate the enzyme acetylcholinesterase which is responsible for break down of actetylcholine, thus increasing the amount of acetylcholine available for competition with non depolarizing agent thereby re-establishing neuromuscular transmission.

Anticholinesterases used for reversal are:

Neostigmine

Pyridostigmine

Edrophonium

Physostigmine

FACTORS PROLONGING THE NEUROMUSCULAR

BLOCAKDE

Neonates

Old age

Obesity

Hepatic disease (both depolarizer & NMDR)

Renal disease ( only NDMR)

Inhalational agents : Prolong the block by both

depolarizers & NDMR. Inhalational agents decrease the

requirement of relaxant .The maximum relaxation is by

ether followed by desflurane

Antibiotics: Both depolarizers & NMDR

Aminoglycosides.

Tetracyclines.

Local Anaesthetics : Except procaine local anaesthetics

prolong the action by stabilizing post synaptic membrane.

Hypothermia : Decreases metabolism of muscle relaxants.

Hypocalcemia: Calcium is required for producing action

potential. Action of NDMR is enhanced.

Hypokalemia : NMDR block is enhanced.

Acid base imbalances especially acidosis.

Calcium channel blockers

Dantrolene

Neuromuscular disease

Hypermagnesemia.

DRUGS WHICH ANTAGONISE

NEUROMUSCULAR BLOCKADE

They reverse the block by NDMR only

Phenytoin

Carbamazepine

Calcium

Cholinesterase inhibitors

Azathioprine

Steroids.

SUGAMMADEX

An agent for reversal of neuromuscular blockade by

the agent rocuronium in general anaesthesia.

It is the first selective relaxant binding

agent (SRBA) .

Sugammadex is a modified γ-cyclodextrin

The rocuronium molecule bound within

sugammadex's lipophilic core, is rendered

unavailable to bind to the acetylcholine receptor at

the neuromuscular junction.

No need to rely on anticholinesterase

DRUGS WITH ANTICHOLNERGIC ACTION

ANTIHISTAMINES (H-1 BLOCKERS) Chlorpheniramine

Cyproheptadine

Diphenhydramine

Hydroxyzine

CARDIOVASCULAR MEDICATIONS Furosemide

Digoxin

Nifedipine

Disopyramide

ANTIDEPRESSANTS Amoxapine

Amitriptyline

Clomipramine

Desipramine

Doxepin

Imipramine

Nortriptyline

Protriptyline

Paroxetine

GASTROINTESTINAL MEDICATIONS

Antidiarrheal Medications Diphenoxylate

Atropine

Antispasmodic Medications Belladonna

Clidinium

Chlordiazepoxide

Dicyclomine

Hyoscyamine

Propantheline

Antiulcer Medications Cimetidine

Ranitidine

ANTIPSYCHOTIC MEDICATIONS Chlorpromazine

Clozapine

Olanzapine

Thioridazine

MUSCLE RELAXANTS

Cyclobenzaprine

Dantrolene

Orphenadrine

URINARY INCONTINENCE

Oxybutynin

Probantheline

Solifenacin

Tolterodine

Trospium

ANTIVERTIGO MEDICATIONS

Meclizine

Scopolamine

PHENOTHIAZINE ANTIEMETICS

Prochlorperazine

Promethazine

NEWER ANTICHOLINERGICS

Umeclinidium bromide:

An anticholinergic drug approved for use in

combination with vilanterol (as umeclidinium

bromide/vilanterol) for the treatment of COPD

Aclinidium

An anticholinergic for the long-term management of

chronic obstructive pulmonary disease (COPD). It

has a much higher propensity to bind to muscarinic

receptors than nicotinic receptors.

FDA approved on July 24, 2012.

DARIFENACIN

Darifenacin is a medication used to treat urinary

incontinence.

Darifenacin works by blocking the M3 muscarinic

acetylcholine receptor, which is primarily

responsible for bladder muscle contractions.

It thereby decreases the urgency to urinate. It

should not be used in people with urinary retention.

98% bound to plasma proteins

Hepatic metabolism. Primarily mediated by the

cytochrome P450 enzymes CYP2D6 and CYP3A4.

SOLIFENACIN

Solifenacin is a competitive cholinergic

receptor antagonist.

The binding of acetylcholine to these receptors,

particularly the M3 receptor subtype, plays a critical role

in the contraction of smooth muscle.

By preventing the binding of acetylcholine to these

receptors, solifenacin reduces smooth muscle tone in

the bladder, allowing the bladder to retain larger

volumes of urine and reducing the number of micturition,

urgency and incontinence episodes.

Because of a long elimination half life, a once-a-day

dose can offer 24 hour control of the urinary

bladder smooth muscle tone.