anticholinergic drugs
TRANSCRIPT
ANTICHOLINERGIC DRUGS
Presented by:Dr. Vishalkr. Kandhway
ANTICHOLINERGIC DRUGS
Anti cholinergic drugsAre those which antagonise the effect of neurotransmitter Acetylcholine (ACh) on autonomic effectors & in the CNS exerted through “Muscarinic receptors”. Though nicotinic antagonists also block certain actions of Ach, they are referred to as “Ganglion blockers” & “Neuromuscular blockers”
• Muscarinic receptor site-• Heart• Salivary glands• Smooth muscles of GIT• Genitourinary tract • Urinary bladder
• Nicotinic acetyl choline receptor site-– Nerve endings of neuromuscular junction.
• Acetylcholine is also the neurotransmitter at postganglionic nicotinic receptors located at the NMJ (Neuromuscular junction) & autonomic ganglia.
• Effects of anticholinergic drugs at nicotinic cholinergic receptors is little / nil as compared at muscarinic receptors.
• Anticholinergic drugs are considered – selectively antimuscarinic.
Naturally Occurring (Tertiary Amine)
Atropine Scopolamine(Alkaloids of belladonna plants
Synthetic compound(Glycopyrrolate)
(Quaternery Ammoniums Derivatives)
• More potent than parent compounds
• Lack CNS activity because of poor penetration in brain
Classification• Natural alkaloid – Atropine,
Scopolamine(hyoscine)
• Semi-synthetic derivative – Homatropine, Atropine mithonitrate, Ipratropium bromide.
• Synthetic compound – a) Mydriatics : Cyclopentolate, tropicamide
b)Anti-seceretory -
Quarternary : Glycopyrolate, Propantheline, Isopropamide.
Tertiary amines : Pirenzepine, Dicyclomine c)Vasicoselective : Oxybutynin, flavoxate.
d)Anti-parkinsonian : Benzhexol, biperiden.
Mechanism of action• Anticholinergic are the class of drugs that
block the neurotransmitter acetylcholine in CNS and PNS.
• Anticholinergic drugs combine reversibly with muscarinic cholinergic receptors thus preventing access of neurotransmitter acetylcholine in these sites.
Muscarinic Receptor Subtypes
M1 M2 M3 M4 M5
Location • CNS• Stomach
• Heart• CNS• Airway
Smooth Muscle
• CNS• Salivary
glands• Airway
smooth muscle
• Vascular endothelial cells
• CNS• Heart
• CNS
Clinical Effects • HydrogenIon Secretion
• Bradycardia • Salivation • Bronchodilati
on • Vasodilation
? ?
Clinically selective drugs available
Yes No No No No
Atropine
• Atropine sulphate is a tertiary amine & the naturally occuring levorotatory form is active.
• Administered IV/IM in a range of 0.01-0.02 mg/kg upto adult dose of 0.4-0.6 mg.
• Larger IV doses upto 2 mg may be required to completely block the cardiac vagal nerves in treating severe bradycardia.
Pharmacological Actions• CNS : -Atropine has CNS stimulant action. However
these effects are not appriciable at low doses. -Atropine stimulates many medullary centres –
vagal, respiratory, vasomotor. - It depresses vestibular exitation and has anti-
motion sickness property. - It supresses tremor & rigidity of parkinsonism. - High doses cause cortical exitation, restlessness,
disorientation, hallucination & delirium followed by respiratory depression & coma.
• CVS : - Most prominent effect is to cause tachycardia
due to blockade of M2 receptors at SA node.
• Eye : - Topical instillation of atropine causes
mydriasis, abolition of light reflex and cycloplegia resulting in photophobia & blurring of near vision.
• Smooth muscles : - All visceral smooth muscles that receive
parasympathetic motor innervation are relaxed by atropine due to M3 blockade.
- Tone & amplitude of contractions of stomach & intestine are reduced, the passage of chyme is slowed – constipation may occur & spasm may be relieved.
- Atropine causes bronchodilatation & reduces airway resistance especially in COPD & Asthma patients.
- Atropine has relaxant action on ureter & urinary bladder.
• Glands : - Atropine markedly decreases sweat, salivary,
tracheobronchial & lacrimal secretions by M3 blockade.
- Skin & eyes become dry, talking & swallowing may be difficult.
• Body temperature : - Rise in body temperature occur at high doses due to
both inhibition of sweating as well as stimulation of temperature regulating centre in the hypothalamus.
- Children are highly succeptible to Atropine fever.• Local anaesthetic : Atropine has mild anesthetic
action on the cornea.
• Sensitivity of different organs & tissues to atropine varies & can be graded as –
• Saliva, sweat, bronchial secretion > eye, bronchial muscle, heart > smooth muscle of intestine, bladder > gastric glands & smooth muscles.
Uses• As anti-secretory : - Pre-anesthetic medication : reduces excessive
salivation & respiratory secretions. - Peptic ulcer : decreses gastric secretions & provide
symptomatic relief in peptic ulcer now been superseded by H2 blockers.
• As anti-spasmodic : - If there is no mechanical obstruction intestinal & renal
colic, abdominal cramps symptomatic relief is affordable.
- Gastritis, gastric hypermortility. - To relive urinary frequency & urgency.
• Can be given in patients of Bronchial Asthma • As mydiatric & cycloplegic.• As cardiac vagolytic• For central actions in Parkinsonism as an
adjuvant to levodopa.• To antagonise muscarinic effects of anti-
Cholinesterase i.e OP Poisoning with dose 2mg IV with repeated doses and early mushroom poisoning.
Side effects
• Belladona poisoning due to drug overdose.• Dry mouth, difficutly in swallowing and talking.• Dry ,flushed and hot skin.• Fever difficulty in micturition , decreased bowel
sounds.• Dilated pupil, photophobia, blurring of near vision.• Excitement, ataxia, delirium, hallucination.• Convulsion and coma may occur in severe poisoning.
• Treatment : Physostigmine 15- 60 micro gram / kg IV every
1- 2 hourly. • Contraindications : - Narrow angle glaucoma - BPH - Hyperthyroidism - CAD
Glycopyrolate• Glycopyrolate is a synthetic product that differs from atropine in
being a quaternary amine.• The pre-medication dose is 0.005 – 0.01 mg/kg upto 0.2-0.3 mg
in adults.• Clinical consideration :• Because of its quaternary structure, glycopyrolate can’t cross
BBB & is almost devoid of CNS & Opthalmic activity.• Potent inhibition of salivary gland & respiratory tract secretions
is the primary rationale for using glycopyrolate as pre-medication.
• Heart rate increases after IV administration.• It has longer duration of action than atropine sulphate i.e 2-4
hrs.
Scopolamine• Scopolamine is a naturally occuring tertiary amine.• It’s dose is 0.3-0.5 micro gram I/M.• Clinical Consideration :• Lipid soluble.• Easy penetrate BBB.• More potent antisialagogue than Atropine & causes greater
CNS effects • Clinical doses results in restlessness, drowsiness, amnesia,
dizziness & delirium.• It has the added virtue of preventing motion sickness.• The lipid solubility allows trans-dermal absorption & has
been used to prevent post-operative nausea & vomiting• Best avoided in patients with closed angle glaucoma.
DifferencesAtropine Glycopyrrolate
1. Lipid solubility - Lipid soluble - Poorly soluble (Quaternary ammonium compound)
2. Blood brain barrier crossing
- Good - Minimum ability of crossing BBB
3. Metabolization - 50% from liver -
4. Excretion - 18% unchanged - 80% unchanged
5. Treatment - bradycardia at low dose - 0.2 – 0.4 mg IV -Dose for intra operative bradycardia 1.2 mg -Max dose for bradycardia 3 mgHiccups (Occurring after
laryngeal mask placement) - 0.5 mg IV
Intra operative bradycardia
6. Heart rate Increases Increases
Differences
Atropine Glycopyrrolate
7. Effect on smooth muscles
Decreases tone of smooth muscles of biliary tract & ureter
8. Antisialagauge effect
- Less then scopolamine More
9. T½ - 2.3 hrs Prolonged in uremic patients 1.25 hrs
Comparative effects of anticholinergic drugs Sedation Antisialagogue Increase Heart
RateRelax smooth
MusclesAtropine + + +++ ++
Scopolamine +++ +++ + +
Glycopyrrolate 0 ++ ++ ++
Mydriasis cycloplegia
Prevent Motion induced Nausea
Decrease Gastric
Hydrogen Ion secretion
Alter Fetal Heart Rates
Atropine + + + 0
Scopolamine +++ +++ + ?
Glycopyrrolate 0 0 + 0
Central Anticholinergic Syndrome • Anticholinergic drugs like scopolamine, atropine can enter
central nervous system (CNS) and produce some unusual symptoms which are characterized in a syndrome which is known as central anticholinergic syndrome. Symptoms are -– Restlessness– Hallucination to somnolence – Unconsciousness
Glycopyrrolate does not easily cross BBB & not likely cause CACS.
• References :- Stoelting’s Pharmacology & Physiology. Morgan & Mikhail’s Clinical Anesthesiology. KD Tripathi Essentials of Medical Pharmacology.
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