Anticholinergic drugs work by competitively blocking the neurotransmitter acetylcholine at muscarinic receptors. They are classified based on their origin and effects. Anticholinergics have effects throughout the body, including the central nervous system, cardiovascular, respiratory, gastrointestinal, and genitourinary systems. Their effects are used clinically for pre-operative medication, sedation, reducing secretions, and treating bradycardia. Overdose can cause symptoms like increased heart rate and temperature, dilated pupils, dry mouth and skin, flushed skin, and delirium. Anti-emetics work by several mechanisms at receptor sites involved in vomiting. Common classes include anticholinergics, antihistamines, but

1. Anti-cholinergic and anti emetics.
Pharmacology and anesthetic implications.

2. Anticholinergic Drugs
These drugs competitively antagonize the effects of the neurotransmitter
acetylcholine at cholinergic post ganglionic sites designated as muscarinic
receptors.

3. Classification:
 Natural alkaloids Atropine, Hyoscine(Scopolamine).
 Semisynthetic derivatives Homatropine,Atropine methonitrate, Hyoscine
butylbromide, Ipratropium bromide, Tiotropium bromide.
 Synthetic compounds
(a) Mydriatics: Cyclopentolate, Tropicamide
(b) Antisecretory-antispasmodics :
(i) Quaternary compounds: Propantheline,Oxyphenonium, Clidiniurn,
Pipenzolate,methylbromide, Isopropamide,Glycopyrrolate.
(ii) Tertiary amines: Dicyclomine, Valethama,Pirenzepine.
(c) Vasicoselective: Oxybutynin, Flavoxate,Tolterodine.
(d) Antiparkinsonian: Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden

4. Structure

5. Muscarinic Receptors

6. Effects on various organ systems:
 CVS:
Causes tachycardia.
Low doses can cause paradoxical bradycardia. <0.4mg
Large doses can cause atropine flush
 Respiratory:
Inhibits secretions from the respiratory tract. Decreases airway
resistance and increases anatomical dead space.
 CNS:
Cerebral stimulation may present as excitation,restlessness, or
hallucinations. Cerebral depression,including sedation and amnesia,
are prominent after scopolamine

8. Contd..
 Gastrointestinal:
Salivary secretions are markedly reduced by anticholinergic
drugs.
Gastric secretions are also decreased, but larger doses are
necessary. Decreased intestinal motility and peristalsis prolong
gastric emptying time.
Lower esophageal sphincter pressure is reduced.
 Genitourinary:
 Ophthalmic:
 Thermoregulation:

9. Comparative Effects:

10. Pharmacokinetics:
 IM/IV administration.
 Atropine onset of action 1min. Duration 30-60min.
 Glycopyrrolate has a slower onset of action 2-3min but a
longer duration of action.
 Atropine and Scopolamine are highly lipid soluble and
cross the blood brain barrier.(tertiary amines)
 They also cross the placenta but fetal heart rate is not
significantly altered.

11. Clinical Uses:
 1.Pre-op medication: Atropine 0.01-0.02mg/kg IV
 2.Sedation: Scopolamine 0.3-0.5mg IM
 3.Anti-sialagouge effect: Scopolamine0.3-
0.5mg IM>Glycopyrrolate 0.005-0.01mg/kg>Atropine
0.01-0.02mg/kg IV
 4.Treatment of bradycardia: Vagolytic dose Atropine
3mg.
 5.Combination with anticholinesterase drugs

12. Other uses:
 Bronchodialtation: Ipratropium bromide
 Biliary and smooth muscle relaxation:
 Mydriasis and cycloplegia:
 Antagonism of gastric hydrogen ion secretion
 Prevention of motion induced nausea
 Parkinsons disease

13. Central Anticholinergic
Syndrome
 Atropine more than scopolamine
 Symptoms: Restlessness and hallucinations to
somnolence and unconsciousness.
 MOA: Blockade of muscarinic receptors and competitive
inhibition of effects of acetylcholine in the CNS.
 Treatment: PHYSOSTIGMINE 15-60mcg/kg IV. Repeat
every 1-2hrs.

14. Overdose:
 Hot as a hare: (increased body temperature- ATROPINE
FEVER)
 Blind as a bat :Mydriasis
 Dry as bone-:Dry mouth, dry eyes, decreased sweat
 Red as beet: Flushed face
 Mad as a hatter: Delirium

15. Anti-emetics

16. Mechanism of vomiting
 Nausea: Defined as a feeling of unease or discomfort in the stomach with an urge
to vomit.
 Vomiting: forceful expulsion of gastric contents through nose or mouth.

17. PCRF Parvicellular: Reticular Formation
NTS: Nucleus tractus Solitarius
SP: Substance P

19. Classification:

20. Anticholinergics
 Hyocine: short duration of action produces sedation and
anticholinergic side effects.
 Blocks conduction of cholinergic impulses from vestibular
apparatus to vomiting center.
 Transdermal patch containing 1.5mg effective for 72hrs.
 Dicyclomine: prophylaxis of motion sickness and morning
sickness.

21. H1 Anti-Histaminics
 Anti emetic effect is due to sedative and anticholinergic
properties.
 Effective for morning sickness and post-op vomiting.
 Dimenhydrinate, diphenhydramine, cyclizine and
meclizine.
 Cyclizine and Meclizine have less sedative effect.
Cyclizine has shortest duration of action 8hrs.Meclizine
has longest duration of action 24hrs.
 S/E: sedation and dryness of mouth.

22. Butyrophenones
 Droperidol: 0.625-1.25mg at the end of procedure.
Blocks dopamine D2 receptors in CTZ.
S/E: QT prolongation at high doses. (5-15mg)
BLACK BOX WARING
Use carefully in patients with Parkinsons and EPS. Can cause
dysphoria and akathesia in patients.
 Prochlorperazine: multiple receptors- histaminergic,
dopaminergic, muscarinic.
 S/E: Anti cholinergic effects and extra-pyramidal symptoms

23. Metoclopramide
 MOA: peripherally as a cholinomimetic and centrally as dopamine
receptor antagonist.
 Increases the LES tone, speeds gastric emptying and lowers gastric fluid
volume. Anti-emetic effect by blocking dopamine receptors in CTZ.
 Pharmacokinetics: rapidly absorbed after oral administration. Peak
plasma conc in 40-120mins. Elimination t1/2 2-4hrs. Readily crosses blood
brain barrier.
 Excreted in urine, dose reduction in patients with renal
dysfunction.

25.  Drug interaction:
Anticholinergics block the GI effects of metoclopramide.
Decreases the absorbtion of orally adminsitered cimetidine.
Phenothiazines used along with it can increase chances of EPS
 S/E: Rapid IV injection can cause abdominal cramping.
Hypertensive crisis in patient with phaeochromocytoma
Sedation nervousness and akathesia. Extrapyramidal
symptoms.
DOSE- 0.25mg/kg oral, IM, IV. 10-20mg.

26. 5-HT3 Receptor Antagonists
The 5-HT3 receptor mediates
vomiting and is located
peripherally(abdominal vagal
afferents) and centrally CTZ of
the area postrema and the
NTS.
PHARMACOKINETICS:
Readily absorbed after oral
administration. Readily crosses
blood brain barrier.
Ondansetron metabolized by
Cyt P-450.
Liver failure impairs clearence
several fold.

28. Uses and side effects
 Generally administered at the end of surgery.
 Dose: 12.5mg dolasetron 1mg granisetron 4mg
ondansetron
 S/E: headache, diarrhea, cardiac dysrhythmia,
conduction disturbance
Prolongation of QTc interval (dolasetron)

29. Elimination t1/2 Dose
Ondanserton 3-4hrs 4mg
Tropisetron 7hrs 2mg, 5mg
Granisetron 9hrs 1mg
Palonosetron 40hrs 0.075mg

30. Dexamethasone
 Exerts anti-emetic effects through central inhibition of NTS
but not on area postrema.
 Dose- 4mg
 Given at the time of induction due to slow onset of
action.
 No significant long lasting side effects.

31. Neurokinin-1 receptor antagnist
 Substance P is a regulatory peptide that acts at NK-1
receptors found in vagal afferents in the gastrointestinal
tract.
 NK-1 antagonists inhibit substance P at central and
peripheral receptors.
 Aprepitant DOSE- 40mg (currently approved by the FDA)
 Superior for the prevention of vomiting but not for
prevention of nausea.

34. References
 Millers 7th edition
 Clinical Anesthesiology- Morgan 5th edition
 Stoeltings handbook of pharmacology and physiology in
anesthetic practice. 4th edition
 Clinical Anesthesia Barash 7th edition
 Essentials of Medical Pharmacology by KD Tripathi

35. THE END
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