Parasympathomimetic (Anticholinergic) Drugs

Drug Mechanism of Action Pharmacological Effects Clinical and Other Pharmacokinetics Toxicities & Interactions Contraindications
Applications
Direct-acting, muscarinic agonists
Activates muscarinic (M) It is selective to cardiovascular Diagnosis of asthma Poorly absorbed and poorly distributed into the Dyspnea, headache, dyspnea, light Uncontrolled hypertension,
receptors muscarinic receptors and decrease central nervous system, hydrolyzed in the headedness, pruritus & throat Myocardial infarction or
Methacholine • increases IP3 and DAG cardiac contrality gastrointestinal tract (Less active by oral route). irritation stroke, Aortic aneurysm,
Less active on nicotinic receptors asthma
Nonselective muscarinic and As acetylcholine Used topically almost Poorly absorbed and poorly distributed into the Retinal detachment, Clouding of Acute iritis,
nicotinic agonist exclusively for central nervous system, hydrolyzed in the corneal stroma
glaucoma. Cannot be gastrointestinal tract (Less active by oral route),
Carbachol used systemically due used topically, does not enter central nervous
to unpredictable system (CNS). Resistant to acetylcholinesterase
nicotinic actions as compared to acetylcholine
Activates muscarinic (M) Activates M1 through M3 receptors Postoperative and Poorly absorbed and poorly distributed into the Excessive parasympathomimetic Asthma, Bradycardia,
receptors in all peripheral tissues •causes neurogenic central nervous system, hydrolyzed in the effects, especially bronchospasm in Hypotension, epilepsy, peptic
• increases IP3 and DAG increased secretion, smooth muscle ileus and urinary gastrointestinal tract (Less active by oral route). asthmatics • cyclospasm, diarrhea, ulcer, hyperthyroidism,
Bethanechol contraction (except vascular smooth retention, Resistant to Acetylcholinesterase as compared urinary urgency, vasodilation, reflex parkinsonism
muscle relaxes), and changes in heart to acetylcholine. Less active on nicotinic tachycardia, sweating & Seizure
rate receptors. Duration: < 30minutes
Activates muscarinic (M1) Activates M1 receptors •causes used to treat the Well absorbed orally, peak plasma Excessive Narrow angle glaucoma, acute
receptors increased symptoms of dry mouth concentration achieved in 1.5-2.0hrs. parasympathomimetic effects, iritis & asthma
Cevimeline • increases IP3 and DAG Salivary and lacrimal secretion in patients with especially urinary urgency,
Sjogren's syndrome sweating, shievering, nausea,
dizziness & rhinitis
DIRECT-ACTING MUSCARINIC ALKALOIDS OR SYNTHETICS
Like bethanechol, Activates M1 through M3 receptors in all peripheral tissues Glaucoma; Sjogren’s Oral lozenge and topical Excessive Narrow angle glaucoma, acute
Pilocarpine partial agonist •causes increased secretion, smooth muscle contraction (except syndrome Parasympathomimetic iritis & asthma
vascular smooth muscle relaxes), and changes in heart rate effects,
DIRECT-ACTING NICOTINIC AGONISTS
Agonist at both NN and NM Activates autonomic postganglionic Medical use in Highly lipid soluble and well Increased gastrointestinal (GI) activity, nausea, Additive
receptors. First stimulate neurons (both sympathetic and smoking cessation • absorbed orally, Oral gum, vomiting, diarrhea acutely • increased blood with CNS stimulants
Nicotine the receptors then block parasympathetic) and skeletal muscle nonmedical use in patch for smoking cessation pressure • high doses cause seizures • long-term
the stimulation of neuromuscular end plates •enters CNS and smoking and in GI and cardiovascular risk factor
receptors. activates NN receptors insecticides
A partial agonist at NN Varenicline is a partial nicotinic Smoking cessation High lipid solubility, oral Hypertension, sweating, sensory disturbance, Dosage adjustment is required
receptors acetylcholine receptor agonist, designed to activity • Duration: ~12 h diarrhea, polyuria, menstrual disturbance, Reports for theophylline, warfarin and
Varenicline partially activate this system while Half-life ~ 24 hours of agitation, violent behavior, depressed mood, Insulin. Should be used carefully
displacing nicotine at its sites of action in • 93% of recovered drug in suicidal ideation and behavior, worsening of pre- in patients with the history of
the brain urine unchanged existing psychiatric illness, seizures seizures.
Nicotinic receptor agonist, neuromuscular blockade, muscle paralysis, Muscle relaxation, as Highly polar, used IV, Initial muscle spasms and postoperative pain Benzodiazepine, NSAIDS,
moderately selective for an adjunct to general metabolized by • Prolonged action in persons with abnormal acetazolamide and acebutalol
Succinylcholine neuromuscular end plate anesthesia, to Pseudocholinesterase butyrylcholinesterases, rare ventricular
(NM receptors) facilitate tracheal • Duration: 5–10 min dysrhythmias, cardiac arrest and death in pediatric
intubation patients
SHORT-ACTING CHOLINESTERASE INHIBITOR (ALCOHOL)
 Binds briefly to active site of Amplifies all actions of ACh Diagnosis and acute Administered via a Parenteral route Parasympathomimetic excess: especially Additive with
Acetylcholinesterase (AChE) •increases parasympathetic treatment of myasthenia quaternary amine nausea, vomiting, diarrhea, urinary parasympathomimetics
Edrophonium and prevents access of activity and somatic gravis Reversal of NM block does not enter CNS (Highly polar) • urgency
acetylcholine (ACh) neuromuscular transmission by non- epolarizing drugs Duration: 5–10 min

Indirect-acting, carbamates
Binds briefly to active site of Prevents postoperative Reversal of NM block, Moderately polar but Increased parasympathetic effects, Mechanical urinary or intestinal obstruction,
Acetylcholinesterase (AChE) and abnominal distention and treatment of orally active especially nausea, vomiting, diarrhea, Concomitant use of Cholinesterase inhibitors,
Neostigmine prevents access of acetylcholine urinary retention. myasthenia gravis • Duration: 2–4 h bronchospasm, cardiac arrhythmias, Halogenated hydrocarbon anesthetics, Aminoglycoside
(ACh), small direct Nicotinic salivation, lacrimation, diaphoresis, miosia, antibiotics, Calcium channel blockers
action urinary urgency
Binds briefly to active site of Like neostigmine Treatment of Moderately polar but Increased parasympathetic effects, Mechanical urinary or intestinal obstruction,
Acetylcholinesterase and prevents myasthenia orally active especially nausea, vomiting, diarrhea, Concomitant use of Cholinesterase inhibitors,
Pyridostigmine access of acetylcholine • Duration: 4–8 h bronchospasm, cardiac arrhythmias, Halogenated hydrocarbon anesthetics, Aminoglycoside
salivation, lacrimation, diaphoresis, miosia, antibiotics, Calcium channel blockers
urinary urgency
Binds briefly to active site of Increases intestinal and Reversal of severe Lipid soluble , cross Increased parasympathetic effects, Mechanical urinary or intestinal obstruction,
acetylcholinesterase(AChE) and cardiac motility. atropine poisoning BBB, • can be used especially nausea, vomiting, diarrhea, cardiovascular disease, asthma, gangrene and diabetes,
Physostigmine prevents access of acetylcholine Reverses CNS effects of (IV) • occasionally topically in the eye • bronchospasm, cardiac arrhythmias, Concomitant use of Cholinesterase inhibitors,
(ACh) atropine used in acute Duration: 2–4 h salivation, lacrimation, diaphoresis, miosia, Halogenated hydrocarbon anesthetics, Aminoglycoside
glaucoma (topical) urinary urgency & seizures antibiotics, Calcium channel blockers
Binds briefly to active site of Glaucoma, Myasthenia Increased parasympathetic effects, Concomitant use of choline esters, Concomitant use of
acetylcholinesterase(AChE) and gravis, Urinary and especially nausea, vomiting, diarrhea, Cholinesterase inhibitors, Halogenated hydrocarbon
Ambenonium prevents access of acetylcholine gastrointestinal bronchospasm, cardiac arrhythmias, anesthetics, Aminoglycoside antibiotics, Calcium
(ACh) retention salivation, lacrimation, diaphoresis, miosia, channel blockers
urinary urgency & seizures
LONG-ACTING CHOLINESTERASE INHIBITORS (ORGANOPHOSPHATES)
Forms covalent bond with Amplifies all actions of Obsolete • was used Topical use only Brow ache, uveitis, blurred Obsolete
AChE, but hydrolyzed and ACh in glaucoma vision
Echothiophate released • increases parasympathetic
activity and somatic
neuromuscular transmission
Like Echothiophate Like Echothiophate Insecticide relatively safe for mammals and birds
Malathion because metabolized by other enzymes to
inactive products
Like Echothiophate Like Echothiophate Nsecticide, dangerous for all animals
Parathion dangerous for all
animals
Like Echothiophate Nerve gas, used
exclusively in
Sarin, others
warfare and
terrorism