Acetylcholine is a neurotransmitter that functions in the autonomic nervous system, neuromuscular junctions, and cognitive processes. It binds to muscarinic and nicotinic receptors to stimulate parasympathetic responses. There are two main types of cholinergic drugs: direct-acting cholinergic agonists that mimic acetylcholine, and indirect-acting drugs that inhibit acetylcholinesterase to increase endogenous acetylcholine levels. Anticholinergic drugs act as competitive antagonists at muscarinic receptors to block acetylcholine's effects. They are used to treat various conditions by reducing parasympathetic activity.

1. Syed Tajamul
BHCNMT

2. INTRODUCTION
• Acetylecholine (Ach) is a neurotransmitter discovered by Otto Loewi in early 20th century from a frogs Heart.
• Transmits signals between nerve cells(neurons) and neuron and Muscles(neuromuscular junctions) and the
functions are:
• 1. Autonomic NS: stimulation of Parasympathetic nervous system
• 1. Neuromuscular Junctions: released at end plates of motor neurons at NMJs— contraction—essential for
movements and motor control
• 2. Cognitive functions— arousal of cognitive functions, decreased Ach is linked to Alzheimer’s Disease
• 3. Heart Function— binds receptors at SA node— decreases heart rate
• 4. Respiratory System—Bronchoconstriction
• 5. GI System— stimulates salivation, increases GI motility, relax Sphicters
• 6. Urinary System— contraction of Bladder detrusor muscle and relax of internal Urethral sphincter—
promotes emptying of bladder.
• Eye Functions—constricts of pupil (Miosis) – helps adjust the shape of lense
• All these functions of parasympathetic response is know as “Rest and Digest’ or ‘ Feed and Breed’ opposite
to ‘Fight and Flight’ of sympathetic NS.

4. 1. CHOLINERGIC DRUGS (cholinomimitic drugs)

5. 1. Direct Acting Cholinergic agonists/
Stimulants/Cholinomimitics
Pharmacokinetics
• Agents:
• 1. Esters of Choline
• Acetylecholine chloride( Miochole E) 1% opthalmic sol.
• Methacholine powder for inhalation 100mg
• Bethanechol 5-10mg PO, 5mg/ml SC
• Carbachol 0.75-3% opth. Sol.
• 2. Alkaloids
• Pilocarpine Opth. 0.5,-10%, 4% gel, 5mg PO
• Arecholine 1-2mg/hr. Slow infusion
• Muscarine 1-2mg IV
• Nicotine patches 40mg/day
• Absorption is poor and distribution is also poor for Esters of Choline and rapid for
Alkaloids
• Rapid hydrolysis— Ach to choline and acetate except Methacholine
• Elimination: Kidneys through urine
Mechanism of action
• Binds and activates Muscarinic and Nicotinic receptors—activation of
parasympathatic system.
• 1. Muscarinic agonist—all MR are G-protien coupled type—-increase cGMP
concentration—increase K flux in cardiac cells and decrease K flux in ganglion and
smooth muscles, Also increase cAMP levels induced by Catecholamines—reduce
physiological response
• 2. Nicotine —Na, K Ion channels( alpha & Beta receptors)—conformational changes
by electrical and ionic changes in the cell— Depolarization of nerve cell and
neuromuscular end plates.
• Clinical Uses:
• 1. CVs— negative Chronotropy( decrease in heart rate),

7. Adverse Effects
• CV: bradycardia, Heartblock,
Hypotension, Cardiac Arrest
• GI: N/V, Cramps, Diarrhoea,
Increased salivation
• GU: Urinary Urgency,
Micturation,
• Flushing, sweating, swallowing
difficulties.
Contra-indication
• Bradycardia, hypotension,
• Peptic Ulcer, intestinal
obstruction,
• Bladder obstruction,
• Epilepsy, Parkinsonism,
• Hepatic and renal dysfunction

8. 2. Indirect Acting Cholinergic agonists ( Anti
Cholinestrase drugs)
• Acetylcholine is inactivated by hydrolysis by naturally occurring enzyme
Cholinesterase into Choline and acetate. These drugs prevent degradation of
Acetylcholine at cholinergic sites.
• Some like agents are widely used in pesticide like organophosphate and
carbamates
• Agents:
• A. Edophoniums—Edrophonium 10mg/ml IM,IV, Ambenonium 10mg PO,
Donepezil 5-10mg PO
• B. Carbamates—Neostigmine 15mg PO, 0.2-2.5mg/ml IV, IM; physostigmine
1mg/ml IM, IV, 0.25-0.75 Opth. Sol.; Tacrine 10, -40mg PO, Ravistagimine1.5-
6mg/ml sol PO
• C. Organophosphates- Di-isopropyl Flurophosphate(DEP), tetra Ethylene
pyrophosphate(TEPP)— highly toxic not used in therapeutic purposes for human
beings

9. Pharmacokinetics
• Absorption: from skin, lungs and
conjunctiva very poor, limited in oral
Preps. — needs large doses except
Physostigmine
• Metabolism: microsmal enzymes CYP
450 & UDPof Liver
• T1/2: 20 to 120 mins
• Well distributed except CNS
• OPs are readily absorbed through all
routes –distributed to CNS—making
them Dangerous-
Mechanism of Action
• These agents inhibit majorly
acetylecholinestrase and also
butyrylcholinestrase at some levels,
increases the levels of endogenous
acetylcholine.
• Edrophoniums & Carbamates Reversibly
binds to Hydrogen bonds of enzyme on
active sites of acetylcholine— preventing
access to Acetylcholine—also known as
reversible Cholinesterase inhibitors
• OPs undergo initial binding and
hydrolyzes by the enzyme – stable
Phosphorous enzyme—hydrolyzes in
water at very slow rate(100s of Hours)—
known as aging which is dangerous.

10. Adverse effects
• CNS; Miosis, Blurred Vision, headache dizziness, drowsiness, CNS
depression
• CV: Bradycardia, Heartblock, Hypotension, cardiac Arrest
• GI: N/V salivation, Involuntry defecation, diarrhoea
• GU: Increased Urinary Urgency,

11. Clinical Uses Of Cholinergic agents
• Opthalamic: Glucoma—Pilocarpine- Constricts pupil Sjogrens Syndrome—stimulate tears and
saliva(xerostomia).
• Alzheimer’s disease— Donepezil, Revistgmine—improve cognitive functions
• Myasthenia gravis— pyridostigmine— improve muscle strength
• Urinary retention—edrophonium—relax internal Sphincter
• Cardiac arrhythmias — acetylcholine , carbachol –pacemakers of heart – negative chronotropic
• Post-operative Ileus—Bethanechol— stimulates intestinal smoooth muscles
• Neuromuscular Blockade Reversal— Neostigmine— restoring Muscle functions post surgery.
• Antidotes for OP Poisoning:
• Atropine 2mgIV/ 15mins.
• Pralidoxime(PAM) IV BD/ TID
• Diacetylmonoxime(DAM)

12. • Drugs which bind with cholinergic receptors and block the action of
acetylcholine— also known as Muscarinic antagonist or
Parasympatholytics or Cholinolytics.

13. Classification
• I- Natural
• Atropine
• Scopolamine
• II-Semisynthetic or Atropine Derivatives
• Homatropine, Atropine Sulhate, Hyoscine Butyl bromide, Atropine Methonitrate,
Ipratropium Bromide, Tiotropiumbromide
• III. Synthetic
• A. Mydriatics—Cyclopentolate, Tropiccanamide
• B. quaternary Amine— Proenthaline, Claidinum, Mepenzolate bromide,
Glycopyrolate, Isopropamide
• C. Tertiary Amines— Dicylomine, Pirenzepine, Valethamate
• D. Vasicoselective— Oxybutynin, Flavoxate, Tolterodine
• E. Antiparkinsonian— Procylidine

14. I-Natural Occurring Anticholinergics
Pharmacokinetics
• Atropine( Source- Atropa Beladona & Datura
Stramonium)0.4-0.6 tab; 0.5-1mg/ml IV,IM,
SC, 2% opth Sol.
• Scopolamine(Hyocine)0.25mg tabs; 0.3-
1mg/ml IV, IM, 10mg Suppository
• Readily absorbed,
• Metabolism: Liver
• Bioavalilblity: 10-27%
• Dstribution: to all Tissues inc. placental
barrier; prolonged effect in eyes
• Elimination: 5-50% unchanged
through urine
Pharmacodynamics
• Atropine- competitive
antagonist(surmountable)—block the
action of acetylcholine at muscarinic
receptors—inhibit the action of
adenylyl cylclase— prevent
contraction of smooth muscles,
exocrine glands & increases heart
rate

15. Clinical Uses
• CVs: blockade of M2receptors in heart— increases heart rate
• GIs: relives hyper-motility, reduces salivary( antisialagogue) & gastric secretions, produce
antispasmodic effects on biliary tract, motion sickness, pain, menstrual cramps
• Resp. System: relax smooth muscles of bronchi, reduces secretions
• GUs: relax muscles of bladder wall and slows voiding , prevents bladder spasm, Noctural
enuresis in children
• Eye: produces medriases (dialation of Pupil) and cycloplegia, increase in focal length
photophobia
• CNs: antagonise the respiratory centre depression causes by high doses of
Anticholinestrase
• Thermoregulation: Atropine causes increase in 1-2F of body temp. Can go up to 104F.
• Used as per aesthetic medication
• Atiparkinsonism and OP poisoning

16. II- Semi Synthetic or Atropine derivatives
Pharmacokinetics
• Homatropine 5mg PO; 2-5% eye drops
• Atropine sulphate 2mg IV, IM
• Hyocine Butyle bromide 20-40mg PO, IM, IV,
SC
• Ipratropium Bromide: Aerosol 20-40mg/ puff,
0.4-ml Neb.
• Oral absorption: slow and readily for
ipratropium bromide with 10% of
bioavailability and <1% for Hyocine Butyle
Bromide.
• T1/2: 7mins to 1.2 hrs
• Elimination: about 72% -kidneys through
urine
Pharmacodynamics
• Similar to those of natural anticholinergics
• Ipratropium bromide blocks MR resulting in
decrease in the formation of cGMP on
intracellular calcium results in decrease in
contractility of smooth muscles.

17. III- Synthetic Antichloinergics
A. Mydriatrics
• Agents which induce dilation of pupil in the eye to allow
examination of eye and deep structures & also reduces spasm of
ciliary muscles of the eye.
• Agents:
• Cyclopentolate 0.5-1% sol
• Tropicamide 0.5-5% sol.
• Mechanism of action: Muscarinic anatgonism
• Adverse effects: Cycloplegia, Blurred Vision, Photophobia,
Xerostomia

18. III- Synthetic Antichloinergics
B. Quaternary Amines
• Propenthaline 15-30mg PO
• Oxyphenonium 5-10mg PO
• Clinidium2.5-10mg PO
• Isopropamide 5mg tab
• Glycopyrolate0.1-0.3mg/ml IM, 1-2mg Po
• Mechanism of action:
• Competitive antagonist - anti muscarinic effect at
receptors of smooth muscles and postganglionic nerves
• Indications:
• IBS, gastric. And Deudonal Ucers, infantile colic,
diarrhoea, chronic cholelithiasis, GI spasms, hyper
secretions of COPD, abdominal Muscle cramps r/t
mestruation and renal colic, preoperatively to reduce
hyper secretions,
C. Tertiary Amines
• Dicyclomine 20mg PO , 5-10mg PO for children
• Pirezepine 50mg PO
• Valethamate 10-20mg IM, IV, 10mg PO
• Mechanism of action: competitive antagonism of
acetylcholine at muscarinic receptors
• Indications:
• Antispasmodic, controls of hypersecretions of
phayrangial, bronchial wall and gastric secretion in
stomach ulcers, cervical dialaton in firs stage of labor,
• Adverse effects of Quats & Teriary amines
• dry mouth, blurry vision, constipation , drowsiness,
sedation, memory problems and trouble urinating and
Hallucination

19. III- Synthetic Antichloinergics
D. Vasicoselective Drugs
• Medications used to treat urinary bladder
difficulties- frequent urination, inability to
control urine by decreasing the muscle
spasms of UB.
• Agents:
• Floavoxate( urispas) 100-200mg PO Tablets
• Oxybutynin(oxypas) 2.5mg-5mg po Tabs
• Tolterodine 1-4mg Po tabs
Mechanism of action
• Oxybuynin— selective M1, M2 receptor block
in smooth muscles of bladder— detrusor
Muscle activity is markedly decreased
• Tolterodine—metabolised in liver to active
form 5-hydroxy methylene derivative—
selective M2, M3 receptor block—inhibition
of smooth muscles of bladder
• Oxybutynin- Unclear mechanism of action
• Uses
• Urinary incontinence, multiple urinary
syndromes, suprapubic Pain, Noctural enuresis,
bladder hypertonicity spasms

20. Nursing Implications In use of Antichlinergic
drugs
• Assessment:
• Conduct a thorough patient assessment, including medical history,
allergies, and current medications to identify any potential
contraindications or interactions.
• Assess for conditions that might increase the risk of adverse effects,
such as glaucoma, urinary retention, or gastrointestinal disorders
• Monitoring:
• Monitor vital signs, especially heart rate, to detect any signs of
tachycardia or arrhythmias associated with anticholinergic use.
• Observe for adverse effects like urinary retention, as anticholinergics
can affect bladder function.
• Keep an eye out for central nervous system effects such as confusion
or dizziness, especially in elderly patients.
• Hydration and Oral Care:
• Encourage patients to maintain adequate hydration due to the
potential for dry mouth as a side effect.
• Provide proper oral care to prevent oral health issues related to
reduced salivary flow.
• Fall Prevention:
• Be cautious with elderly patients, as anticholinergics can contribute
to dizziness and increased fall risk.
• Ensure patients are aware of potential balance and coordination
issues.
• Medication Administration:
• Administer anticholinergic medications as prescribed, adhering to the
correct dosage and timing.
• Be aware of specific administration requirements for different
formulations (e.g., oral, transdermal, inhalation).
• Patient Communication:
• Establish open communication with patients to address any concerns
or questions they might have about their medication.
• Documentation:
• Document the administration of the medication, any observed side
effects, and the patient's response to the treatment plan.
• Patient Education:
• Instruct patients on measures to manage side effects, such as using
artificial saliva, avoiding activities requiring clear vision, and
maintaining proper hydration.
• Educate patients about the purpose of the medication, its potential
side effects, and the importance of adhering to the prescribed dosage
schedule.
• Inform patients about common side effects such as dry mouth,
blurred vision, constipation, and potential CNS effects.

21. Adverse Effects