Cholinoceptor blocking drugs

1
Cholinoceptor blocking drugs
2

• Cholinoceptor blocking drugs (cholinoceptor
  antagonists) are divided into
• Muscarinic receptor blockers block muscarinic
  receptors
• Nicotinic receptor blockers block nicotinic
  receptors and include
• a) Ganglion blocking drugs
• b) Neuromuscular junction
  blockers

3
Muscarinic receptor blockers(antimuscarinic or
parasympatholytic because they block the effects
of parasympathetic autonomic discharge)

• I- Natural
• 1- Atropine
• 2- Scopolamine (hyoscine)
• II- Synthetic Substitutes
• a) Tertiary amines
• Propantheline
• Pirenzepine
• Dicyclomine
• Tropicamide
• Benztropine
• Oxybutynin
• b) Quaternary amines
• 1. Ipratropium
• 2. Trospium

4
Properties of muscarinic receptor blockers
Natural Tertiary amines Quaternary amines
Absorption Well absorbed from skin and conjunctiva Well absorbed from skin and conjunctiva Poor
Distribution to the CNS Distributed to the CNS. More with scopolamine Distributed to the CNS. More with scopolamine Poor
Metabolism Atropine is rapidly metabolized. Effect on parasympathetic function declines rapidly in all organs except the eye (72h)
Mechanism of action Competitive antagonist for endogenous acetylcholine at muscarinic receptors (effect is reversed by increasing acetylcholine concentration) Competitive antagonist for endogenous acetylcholine at muscarinic receptors (effect is reversed by increasing acetylcholine concentration) Competitive antagonist for endogenous acetylcholine at muscarinic receptors (effect is reversed by increasing acetylcholine concentration)
5
Action of acetylcholine at cholinergic receptors
Organ Receptor Action
Eye Circular muscle of the iris M3 Contracts
Eye Ciliary muscle M3 Contracts
Heart Sino-atrial node M2 Slows
Heart Myocardium M2 Negative inotropic action (more in atria) and negative chronotropic action
Blood vessels Endothelium M3 Vasodilatation
Bronchioles Bronchioles M3 Contraction
GIT Smooth muscle walls M3 Contraction
GIT Sphincters M3 Relax
GIT Glands M3 Secretion
Urinary bladder Wall M3 Contracts
Urinary bladder Sphincter M3 Relax
Pregnant uterus Pregnant uterus M3 Contracts
Glands Glands M3 Secretion
6
Effect of muscarinic receptor blockers on CNS
Atropine Scopolamine
CNS Usual doses cause minimal vagal stimulation. Toxic doses cause excitement Ordinary doses cause CNS depression producing drowsiness and amnesia (preanesthetic medications). Toxic doses cause excitement
7
Organ system effects of atropine
M1 Nerves (including M1 inhibitory receptors on vagal post ganglionic neurons which decrease acetylcholine release) Initial bradycardia with small doses
M2 Heart (SA node and AV node) ( smooth muscles) 1- Tachycardia (following bradycardia in small doses) 2- increase AV conduction
M3 Constrictor pupillae Ciliary body Endothelium Glands Smooth muscles of bronchioles, GIT and urinary bladder 1- Mydraisia and cycloplegia 2- Vasodilatation of skin blood vessels with toxic doses 3- Decreased motility of GIT, ureter and urinary bladder (not uterus) 4- Decreased secretion of glands (dry eye, dry mouth, decreased bronchial secretion). Gastric secretion is affected at high doses that produce side effects
8
Adverse effects of atropine

• 1- Mydraisia and cycloplegia
• 2- Tachycardia (but usually no effect on blood
  pressure)
• 2- Vasodilatation of skin blood vessels with
  toxic doses (leading to flushing)
• 3- Decreased motility of GIT and urinary bladder
  (causing retention of urine)
• 4- Decreased secretion of glands (dry eye, dry
  mouth, decreased bronchial secretion).

9
Adverse effects of atropine

• Depend on therapeutic use
• Treatment is usually directed at one organ. Other
  organ effects are considered as side effects.
• Therefore mydriasis and cycloplegia are side
  effects of the use of atropine to treat increased
  intestinal motility but are therapeutic uses in
  opthalmology

10
Contraindications of atropine

• 1- Patients with angle closure glaucoma
• 2- Patients with shallow anterior chamber
• 3- Senile hyperplasia of the prostate
• 4- Patients with gastric ulcer (increase symptoms
  due to slowing gastric emptying)

11
Therapeutic uses of atropine

• 1- Preanesthetic mediction
• Given half an hour before general anesthesia to
• Decrease salivary and bronchial secretion
• Protect the heart from excessive vagal tone which
  may occur during anesthesia
• Counteract the depressant effect of morphine on
  the respiratory center
• 2- Antispasmodic
• 3- Treatment of severe bradycardia
• 4- Antidote to parasympathomimetics
• 5- Hyperhidrosis
• 6- Treatment of poisoning with cholinoceptor
  stimulants (as cholinesterase inhibitors)

12
Scopolamine (hyoscine)

• Similar to atropine but has more CNS depressant
  actions
• Effect on other organs, adverse effects ,
  contraindications and uses are similar to
  atropine. It is preferred than atropine in
  preanesthetic medication because of its CNS
  depressant action (causing sedation and amnesia)
• In addition, it is used to treat vertigo and
  motion sickness

13
Synthetic atropine substitutes

• Divided into 4 groups according to clinical uses
• 1- Mydriatic atropine substitutes
• 2- Bronchodilator atropine substitutes

14
Mydriatic atropine substitutes
Drug Duration of effect (days)
Atropine 7-10
Scopolamine 3-7
Homatropine 1-3
Cyclopentolate 1
Tropicamide 0.25
15
Uses for atropine substitutes1- Mydriasis

• Indications for mydriasis are either
• Short period mydriasis as in opthalmological
  examination Short acting mydriatics as alpha
  adrenoreceptor stimulants are preferred
• Long period mydriasis as in prevention of
  adhesion in uveitis and iritis
• Mydriasis and cycloplegia as in opthalmological
  examination for the errors of refraction
• Atropine substitutes are used topically as eye
  drops or ointment in 2 and 3. The shorter acting
  drugs are preferred
• Adverse effects prolonged mydriasis and
  cycloplegia leading to blurred vision and
  precipitation of glaucoma in patients with narrow
  anterior chamber

16
2- BronchodilatationIpratropium and tiotropium

• Indications
• 1- Bronchial asthma
• 2- Chronic obstructive pulmonary disease (COPD)
• Administration
• by inhalation as aerosol (to provide maximal
  concentration at the site of action)
• Effect
• bronchodilatation and reduction of bronchial
  secretion
• Adverse effects
• minimal (not absorbed)
• Tiotropium is long acting and is given once daily

17
3- Urinary disorders

• 1-Urolithiasis to relieve smooth muscle spasm
• 2- Symptomatic treatment of urgency associated
  with inflammation of the bladder (in combination
  with the specific antimicrobial)
• 3- Bladder spasm after urologic surgery
• 4- Reduction of involuntary voiding in patients
  with neurologic diseases

18

• Drugs used for urinary disorders
• 1- Selective M3 blocker
• a) Oxybutynin
• b) Darifenacin
• c) Solifenacin
• d) Tolterodine
• 2- Unselective M3 blocker
• Trospium

19
4- Treatment of parkinsonism