Pharmacology Lecture 6: Atropine

Atropine

Pharmacokinetics

• Well absorbed orally, mucously, and parenterally
• Distributed throughout the body (intra and extracellularly) and passes the blood-brain barrier
• Partially metabolized in the liver (70%)
• Excreted in urine partially unchanged (30%)
• Acidification of urine increases its urinary excretion (70%)

Pharmacodynamics

Local Actions

• Eye:
  • 1% eye drops: onset 60 minutes, duration 7-10 days
  • Paralysis of ciliary muscles (cycloplegia) and ciliary muscle paralysis (passive mydriasis)
  • Narrow angle of filtration and loss of light reflex
  • Decreased lacrimation
• Skin and mucous membranes:
  • Local anodyne (analgesic) action

Systemic Parasympatholytic Actions

• Blocks all types of muscarinic receptors (M1-M5)
• Eye:
  • Single oral or parenteral dose: no mydriasis
  • Doubled dose: mydriasis for 6-8 hours
• CVS:
  • Heart:
    • Tachycardia due to vagal tone predominance
    • No effect on maximal heart rate due to exercise
    • Initial bradycardia may occur due to initial stimulation of CIC in CNS or initial block of presynaptic M1-receptors
  • Blood vessels:
    • Small therapeutic dose: minimal effect
    • Large dose especially in children: atropine flush of face and chest
  • Blood pressure:
    • Small therapeutic dose: minimal effect
    • Reverses hypotension of ACh and Carbachol (M+N)
    • Abolishes hypotension of Bethanichol (M only)
• Respiratory tract:
  • Bronchodilation
  • Dry bronchial secretions and decreased mucociliary clearance
• GIT:
  • Decreased salivary secretion (xerostomia)
  • Decreased gastric HCl (Pirenzepine and Telenzepine are more selective M1-blockers)
  • Relaxation of wall (antispasmodic)
  • Constipation due to spasm of sphincters
• Urinary bladder:
  • Relaxation of ureter and detrusor muscle
  • Retention of urine
  • Spasm of sphincters and trigone
• Skin:
  • Decreased sweat (anhidrosis)
  • Dry, red, and hot skin

CNS Actions

• Mainly CNS stimulant:
  • Restlessness
  • Excitation
  • Hallucination
  • Mania (central anticholinergic syndrome, toxic psychosis)
• Medulla:
  • Analeptic
  • CIC (explains initial bradycardia)
  • Anti-emetic
• Basal ganglia:
  • Anti-parkinsonian (Benztropine is more selective)

Therapeutic Uses of Atropine

• Antidote for parasympathomimetic poisoning (e.g., Organophosphorus)
• Mydriatic in iridocyclitis, uveitis, and corneal ulcer
• Vagotonia and vasovagal attacks (carotid sinus syndrome)
• Heart block due to β-blockers, digitalis, and myocardial infarction
• Bronchial asthma (Ipratropium and Tiotropium)
• Peptic ulcer (Pirenzepine and Telenzepine)
• Colic (e.g., intestinal, biliary, and renal)
• Diarrhea
• Nocturnal enuresis and urinary incontinence (Emepronium and Oxybutynin)
• Hyperhidrosis
• Preanesthetic medication (Hyoscine)
• Vomiting and motion sickness (Hyoscine)
• Parkinsonism (Benztropine)

Adverse Effects and Toxicity of Atropine

• Manifestations:
  • Toxic psychosis
  • Parasympatholytic manifestations:
    • Mydriasis
    • Photophobia
    • Blurring of vision
    • Glaucoma
    • Dry, red, and hot skin
    • Dry mouth
    • Tachycardia
    • Distension
    • Constipation
    • Retention of urine
  • Allergy

Management of Atropine Poisoning

• Physostigmine (I.M. or I.V.) to correct peripheral and central manifestations
• If psychosis: Diazepam
• If hyperthermia: Ice bags and cold baths
• If oral poisoning: Stomach wash
• If respiratory failure: Artificial respiration

Contraindications of Atropine

• Fever
• Glaucoma
• Bronchial asthma
• Tachycardia
• Constipation and paralytic ileus
• Enlarged prostate (Benign Prostatic Hyperplasia)
• After neostigmine in curare poisoning
• Allergy to Atropine