This document discusses anticholinergic and mucolytic drugs. It provides detailed information on the mechanism of action, effects, uses, and properties of various anticholinergic medications including atropine, scopolamine, and glycopyrrolate. It also discusses the mechanisms and examples of mucolytic drugs such as N-acetylcysteine, sodium bicarbonate, bromhexine, and dornase alfa, which are used to thin mucus in respiratory conditions. The document provides dosage guidelines and comparisons of anticholinergic and mucolytic drug properties.

1. ANTICHOLINERGICS and
MUCOLYTICS
Dr ZIKRULLAH
Department of Anaesthesiology & critical Care
JAWAHARLAL NEHRU MEDICAL
COLLEGE,ALIGARH

2. INTRODUCTION
• Blocks the action of ACETYLCHOLINE on
MUSCARINIC RECEPTORS
• Also called as CHOLINERGIC BLOCKING
AGENTS or PARASYMPATHOLYTICS

3. MECHANISM OF ACTION AND
EFFECTS
• Act by occupying receptor sites at
PARASYMPATHETIC NERVE ENDINGS,
thereby leaving fewer receptor sites free to
respond to ACETYLCHOLINE
• Distribution of cholinergic receptor is broad so
effects of ANTICHOLINERGICS will be
diffuse.

4. CHOLINERGIC SYSTEM
• NEUROTRANSMITTER
• RECEPTORS
• EFFECTS OF CHOLINERGIC SYSTEM

5. NEUOTRANSMITTER
CHOLINE + ACETYLCoA
ACETYLCHOLINE
CHOLINE
ACETYLASE
CHOLINE + ACETATE
ACETYL
CHOLINESTERASE

6. M1 M2 M3 M4 M5
LOCATION -CNS
-Gastric
Glands
-Heart
-Autorecept
ors
-SM(visceral)
-Exocrine
glands
-Vascular
endothelial
cells
-CNS
-Heart
-CNS
EFFECTS Acid
secretion
-Bradycardia
-Av block
Contractility
of ventricles
-SM
Contraction
-Secretion
-Vasodialati
on
? ?
ANTAGONI
STS
Pirenzipin
e
Methoctramin
e
HHSF No No

7. • NICOTINIC RECEPTORS
NM – Neuromuscular junctions
NN - Ganglion cells
- Adrenal medullary cells
- Spinal cord &
- Brain

8. EFFECTS OF CHOLINERGIC
SYSTEM
• CVS -Bradycardia
-Decreased velocity of conduction in
AV node & Purkinje fibres
-Decreased contractility of atria and
ventricles
• BLOOD VESSELS -Vasodilatation

9. • GIT - Increased tone and peristalsis
- Sphincters relax
- Evacuation of bowel
- Increased acid secretion
• RESPIRATORY SYSTEM
-Constriction of bronchial muscles
-Precipitation of asthmatic attack

10. • RENAL SYSTEM
-Increased peristalsis of ureter
-Detrussor contracts Voiding
-Trigone relax of
-Sphincter relax Bladder
• GLANDS -Increased secretions from all
parasympathetically innervated
glands

11. ANTICHOLINERGIC DRUGS
• CLASSIFICATION
NATURAL ALKALOIDS
Atropine
Hyoscine(Scopolamine)
SEMISYNTHETIC DERIVATIVES
Homatropine
Ipratropium bromide
Tiotropium bromide

12. SYNTHETIC COMPOUNDS
Cyclopentolate Mydriasis
Tropicamide
Glycopyrrolate Quarternary
Propantheline ammonium
Oxyphenonium compounds
Dicyclomine Tertiary
Pirenzepine Amines
Telenzepine
Biperiden Central
Benzhexol anticholinergics
Benztropine

13. ACTIONS/EFFECTS
• CNS -Excitation / Depression
-Anti motionsickness property
• CVS -Tachycardia
(transient initial bradycardia)
-Increased A-V conduction
-Increased contractility of atria &
ventricle

14. • GIT -Decreased tone & contraction
Constipation
• RESPIRATORY SYSTEM
-Bronchodilatation
(especially in COPD & Asthma)
• RENAL SYSTEM -Relax Ureter & Bladder
-Urinary retention
(especially in elderly)

15. • EYE -Mydriasis &
-Cycloplegia
• GLANDS - Decreased secretions of all
exocrine glands
• BODY TEMPERATURE
-Inhibits sweating
Increased
-(+) temperature regulating temp.
centre in Hypothalamus

16. SENSITIVITY OF DIFFERENT
TISSUES
Salivary glands / Sweat glands /
Tracheobronchial glands
Eye & Heart
Smooth muscles of Gut & Bladder
Gastric secretions

17. PHARMACOKINETICS
• Good absorpsion from g.i.t.
• I/V or I/M route used intraoperatively
• Atropine
Onset of action– 1 min
Duration– 30-60 min
18% eliminated unchanged in urine
~50% is metabolised in liver
• Glycopyrrolate
Onset of action– 2-3 min
Duration– 2-3 Hrs
80% is excreted unchanged in urine

18. • Scopolamine
Broken down almost entirely in body
Only 1% appearing unchanged in
urine
• Atropine Easily cross BBB
Scopolamine
Glycopyrolate – minimally cross BBB

19. CLINICAL USES
PRE MEDICATION
• To produce sedation
• Antisialogogue effect
• Dose:
Atropine – 0.01-0.02mg/kg (0.4-0.6mg) i.m.
Scopolamine – 0.3-0.5mg i.m.
Glyco-p – Usually ½ of Atropine
i.e 0.005-0.01mg/kg i.m.

20. SEDATION
Scopolamine – Agent of choice
- 100X more potent than
atropine
- decreases activity of RAS
-Amnesia
-Enhance sedative effect of other
drugs ex- Opioids & BZD.
Atropine – Produces sedation & amnesia
Glyco-p – Lacks sedative axn

21. ANTISIALOGOGUE
Scopolamine
- 3X more potent than atropine
- Agent of choice when
ANTISECRETORY
EFFECT + SEDATION is required.
Glycopyrolate
- 2X more potent than atropine
- Agent of choice when
ANTISECRETORY
EFFECT without SEDATION is
required.

22. BRADYCARDIA
- Atropine (15-70mcg/kg) i.v. increases H/R
- Effect less pronounced & onset slower with
Scopolamine & Glyco-p.

23. COMBINATION WITH
ANTICHOLINESTERASES
- During pharmacological Antagonism of
NDMRs by Anticholinesterases.
-To prevent Parasympathomimetic effects
of Anticholinesterases
- Atropine: Rapid onset & longer duration
-Glyco-p: Slower onset & short duration

24. COPD & BRONCHIAL ASTHMA
- Cause bronchodilatation
- Decrease Airway resistance & increase
dead space.
AEROSOL: Bronchodilatation is more
prominent.
CV side effects are less.

25. MYDRIASIS & CYCLOPLEGIA
-Mydriatic effect: Scopolamine > Atropine>
Glyco-p
-Scopolamine used cautiouly in patients
with GLAUCOMA
-Usual doses of Atropine & Glyco-p in
Premedication & for reflex Bradycardia
don’t produce any adverse effect in
Glaucomatic patients

26. BILIARY & URETERAL COLIC
Antispasmodic axn
PARKINSONISM
- Central anticholinergics
- Drug induced Extrapyramidal
Syndrome
MOTION SICKNESS

27. HICCUPS
- Atropine 0.5mg i.v. used for terminating
hiccups following placement of LMA.

28. ATROPINE HYOSCINE GLYCOPYRROL
ATE
SEDATION + +++ 0
ANTISECRETOR
Y
++ +++ +++
HEART RATE +++ + ++
SMOOTH
MUSCLE
RELAXATION
++ + ++
MYDRIASIS + +++ 0
ANTIMOTION
SICKNESS
PROPERTIES
+ +++ 0
GASTRIC ACID
SECRETION
+ + +

29. Ipratropium-(nonselective on all
muscarinic receptor)
• Asthma and bronchospastic disorders
• Quaternary ammonium compound.
• Poorly absorbed when inhaled and few
extrapulmonary affects
• Supplied as metered dose inhaler that dispenses
18 microgram per puff
TIOTROPIUM- SELECTIVE M1 AND M3
RECEPTOR

30. Contraindications
• BPH
• Myasthenia gravis
• Hyperthyroidism
• Glaucoma
• Tachydysrhythmias
• Not in situations whereby delaying of gastric
emptying is a concern

31. Recent advances:
• Nano-atropine-
– Under clinical trial
– Dry powder inhaler
– Organophosphorus poisoning
ADVANTAGES
- ease of administration
- rapid bioavailability
- less side affects

32. MUCOLYTICS -moa
• Alter consistency of gel layer of mucus
Act by –
1. Weakening intermolecular forces that bind
adjacent glycoprotein chains
– Disruption of intermolecular Disulfide Bonds (NAC,
Mesna)
2. Alteration of pH to weaken carbohydrate side
chains of glycoproteins (Sodium bicarbonate)
3. Destruction of protein (Proteolysis) contained in the
glycoprotein core
– Breaking down of DNA in mucus (Dornase alpha)

34. MUCOLYTICS
• Agents capable of dissolving, digesting or
liquefying mucus –reducing their viscosity.
• Classified under ‘mucokinetic drugs’ - a class
of drugs which aid in the clearance of mucus
from the airways, lungs, bronchi, and trachea.
• Useful in patients in the intensive care unit
(ICU) with compromised lung function who
often have excessive pulmonary secretions and
have difficulty clearing mucus.

35. MUCOLYTIC drugs
• N-acetylcysteine (NAC)
• Sodium bicarbonate.
• Ambroxol
• Bromhexine
• Dornase alpha (Pulmozyme)
• Others – carbocisteine, erdosteine, letosteine,
sobrerol, stepronin, tiopronin.

36. N-acetylcysteine (NAC)
• Sulfhydryl - containing tripeptide.
• Better known as the antidote for acetaminophen
overdose.
• Used to help clear mucus in COPD, cystic fibrosis,
pneumonia, and in tracheostomy care
• Primarily a mucolytic agent that acts by disrupting
the disulfide bridges between mucoprotein strands in
mucus.
• NAC can be taken orally, inhalation or direct
instillation.

37. MOA of nac
• Disruption of Disulfide Bonds
– Acetylcysteine breaks the bonds by substituting a
sulfhydril radical –HS

38. NAC (contd.)
• Available in a liquid preparation (10 or 20%
solution) that can be given as an aerosol spray, or
injected directly into the airways.
• Aerosolized NAC should be avoided when possible
because it is irritating to the airways and can
provoke coughing and bronchospasm - particularly
in asthmatics.
• Direct instillation of NAC into the tracheal tube is
preferred, especially when there is an obstruction.
• Daily use of NAC is not advised because the drug
solution is hypertonic and can provoke
bronchorrhea

39. Dosage of acetylcysteine
• Dosage
– 3-5 mL of a 20% solution TID or QID
• Maximum dose 10 mL.
– 6-10 mL of a 10% solution TID or QID
• Maximum dose 20 mL.
• 1-2 mL of a 10% or 20% solution for
direct instillation.
• Oral dosage:
Available as 200 mg , 600 mg tablets
and given in twice daily dosage.

40. L-CYSTEINE ETHYL ESTER
HYDROCHLORIDE:
• Given orally
• It is biotransformed in liver to N-acetyl
cysteine .
• Used in COPD patients.
• Has no GIT side effects as compared to
N-Acetyl cysteine.

41. Adverse effects of acetylcysteine
• Bronchospasm – concurrent bronchodilater may
be needed.
• Nausea /Rhinorrhoea.
• Causes decreased ciliary activity-Suction should
be ready for patient who cannot cough or who is
intubated
• Reacts with metal and rubber.
• Acetylcysteine has been assigned to pregnancy
category B . Recommended in pregnancy when
benefits outweigh risks.

42. disadvantages
• Should not be mixed with antibiotics in the same nebulizer -
Inactivates some antibiotics if they are aerosolized with NAC
• Nausea & Vomiting
– Disagreeable odor (smells like rotten eggs) due to the
hydrogen sulfide.
• Has a shelf life of 96 hours after opening.

43. sodium bicarbonate
• Weak base.
• MOA- Causes Alteration of pH
– 2% NaHCO3 solution is used to increase the pH of
mucus by weakening carbohydrate side chains
– Can be injected directly into the trachea or
aerosolized.
• Available as 1.4%, 5%, and 7.5% solutions.
• Dosage: 2-5 mL of a 2.5% solution .
– Mixed with equal volume of sterile water and
aerosolised.

44. BROMHEXINE
• A derivative of an alkaloid – vasicine obtained from
Adhatoda vasica .
• It induces thin copious bronchial secretion
• It depolymerises mucopolysaccharides directly as
well as by liberating lysosomal enzymes .

45. Bromhexine undergoes extensive first-pass
metabolism in the liver. Excreted 80% by the
kidney.
• Side effects : Rhinorrhoea & Lacrymation, gastric irritation,
hypersensitivity .
• Disrupts gastric mucosal barrier -Used cautiously in patients
with peptic Ulceration.
Oral Preparation :
Tablets- 8mg
Syrup 4mg / 5ml

46. Ambroxol
• A metabolite of bromhexine
• MOA- similar to bromhexine
When administered orally onset of action occurs
at about 30 minutes.
The breakdown of mucopolysaccharide side
chains makes the sputum thinner and less
viscous and therefore more easily removed by
coughing.

47. • It also stimulates synthesis and release
of surfactant by type II pneumocytes.
Disadvantages :
Known to increase liver transaminase activity in
some patients.
Crosses the placenta-Contraindicated in first
trimester of pregnancy
Preparations : oral tablets available as 10,
30,50,100, 120 mg tablets . Dose is 30- 120 mg
daily in two divided doses.
Syrup : 30mg / 5ml.

48. DORNASE ALPHA (PULMOZYME)
• Highly purified solution of recombinant human
deoxyribonuclease I (rhDNase), an enzyme
which selectively cleaves DNA
• Produced in Chinese hamster ovary cells
• Hydrolyzes the DNA present in mucus of cystic
fibrosis patients and reduces viscosity in the
lungs, promoting improved clearance of
secretions

49. Function of dorNase - alfa

50. Concentration and Dosage
• Supplied in single dose vials .
• Concentration is 1 mg/mL (0.1% solution) and
each vial contains 2.5 mg /2.5 mL.
• Administered as one unit dose vial (2.5 mL) /day
through nebuliser.
• Should not be mixed or diluted with other drugs.

51. • Daily administration of Pulmozyme
(dornase alfa) Inhalation Solution in conjunction
with standard therapies is indicated in the
management of cystic fibrosis patients to improve
pulmonary function.
• Shown to reduce the risk of respiratory tract
infections requiring parenteral antibiotics in these
patients

52. Common Side Effects of dornase
alfa.
• Voice Alteration
• Pharyngitis/Laryngitis
• Rash
• Chest pain
• Conjunctivitis

53. THANKS