A PowerPoint presentation on Anti Muscarinic drugs it has a broad information on different drugs like Anti-Muscarinic drugs Anti-Nicotinic drugs and some information on Ganglionic blocking drugs with their general information including different brands, different generics, their pictures, dosage, side effort and treatment measures etc. May this information may be helpful to you. Regards. SYED MASOOD AHMED QUADRI

1. ANTI-MUSCARINIC DRUGS
By
SYED MASOODAHMED QUADRI

3. Characteristics of important
subtypes of Muscarinic receptor
 By pharmacological as well as molecular cloning techniques,
muscarinic receptors have been divided into 5 subtypes M1, M2, M3,
M4 and M5.
 The major subtype that are present on effector cells as well as on
prejunctional nerve endings, and are expressed both in peripheral
organs as well as in the CNS.
 The M4 and M5 receptors are present mainly on nerve endings in
certain areas of the brain and regulate the release of other
neurotransmitters.
 Most organs have more than onesubtype, but usually one subtype
predominatesin a given tissue.

4. Three main types of
Muscarinic receptor
 M1 :-
 The M1 is primarily a
neuronal receptor
located on ganglion
cells and central
neurones, especially
in cortex,
hippocampus and
corpus striatum. It
plays a major role in
mediating gastric
secretion, relaxation
of lower esophageal
sphincter (LES) on
vagal stimulation and
in learning, memory,
motor functions, etc.
 M2 :-
 Cardiac muscarinic
receptors are
predominantly M2
and mediate vagal
bradycardia.Autorece
ptors on cholinergic
nerve endings are also
of M2 subtype.
Smooth muscles
express some M2
receptors well which,
like M3,media
contraction.
 M3 :-
 Visceral smooth
muscle contraction
and glandular
secretions are elicited
through M3 receptors,
which also mediate
vasodilatation .
Together the M2 and
M3 receptors mediate
most of the well-
recognized muscarinic
actions including
contraction of LES.

5. Some Anti-muscarinic Drugs
 Tertiary amines - atropine, scopolamine, homatropine,
tolterodine, trihexyphenidyl.
 Quaternary ammonium compounds - glycopyrrolate,
Ipratropium.

6. Effect of Muscarin on different tissues

7. Some short notes on Anti-
Muscarinic action

8. Muscarinic drugs mechanism
of action
competitively block muscarinic receptors. Atropine
and scopolamine block all M receptors. Other
antimuscarinic drugs are selective.Tertiary
antimuscarinics don't block Nn. Quarernary block
muscarinic but also Nn.

9. Anti-muscarinics on CNS
 Antimuscarinic onCNS high dose :-
 Amnesia, malaise, restlessness, irritability, disorientation, halluciations, delirium.
Coma.
 Antimuscarinics on CNS intermediate dose :-
 Mild vagal stimulation. Fatigue, sedation, drowsiness, depression of vestibular,
reduction in parkinsonian tremor and rigidity.

10. Antimuscarinics on Heart
 Antimuscarinics on heart intermediate dose :-
 Tachycardia. Many types of reflex vagal cardiac slowing can be abolished. Atria -
increase in automaticity and contractility. AV node - increase in conduction and
automaticity, decrease in refractoriness. Ventricles - minimal direct effect.
 Antimuscarinics on heart low dose :-
 Decrease in heart rates (due to blockade of M2 presynaptic autoreceptors and to
central vagal stimulation.

11. Antimuscarinics on
Cardiovascular (CV) vessels
 Antimuscarinics on CV vessels after high dose :-
 Dilation of cutaneous blood vessels (unknown mechanism) in children can cause
atropine flush.
 Antimuscarinics on Cardiovascular vessels therapeutic dose :-
 Negligible effects (but vasodilation and hypotension caused by choline esters are
antagonized).

12. Antimuscarinics on
GASTROINTESTINAL TRACK
 Antimuscarinics on GIT :-
 Decreased gastric secretion, decreased tone, contractions, peristaltic activity.
Relaxation of LES, gallbladder, bile ducts.

13. Antimuscarinics on Genitourinary
System
 Antimuscarinics on Genitourinary system :-
 Relaxation of pelves, calyces, ureters. Decreases peristalsis, relaxation of detrusor
muscle (increased capacity).

14. Antimuscarinics on respiratory
system
 Antimuscarinics on respiratory system :-
 Bronchial relaxation, decreased secretions, decreased mucociliary clearance
(except ipratropium).

15. Antimuscarinics on eyes
 Antimuscarinics on eyes :-
 Relaxation of sphincter of iris (mydriasis), relaxation of ciliary muscle (cycloplegia,
accommodation is lost) hinders outflow of aqueous humor thru schlemm's canal.
When atropine is given locally, these effects last for 3 days. Decreased lacrimal
gland secretion.

16. Antimuscarinics on skin
 Antimuscarinics on skin :-
 Decreased sweat. Raises body temperature. Infants and children are prone to
atropine fever.

17. Antimuscarinic toxicity
 Antimuscarinic toxicity :-
 Skin rashes, urticarial, fever. Therapeutic index >100 adults, but a dose of 5mg
can be lethal to children. Serious atropine poisoning appears in 30 minutes, lasts
for 2-7 days. Death due to respiratory failure may follow coma and collapse.
 Poisoning by antimuscarinics :-
 mydriasis, blurring of vision, dryness conjunctiva, difficulty speaking, dyspnea,
respiratory depression, dry hot red skin, dryness of mouth, difficulty swallonging,
no bowel sounds, difficulty in micturition, tachycardia, arrhythmias, fatigue,
ataxia, restlessness, delirium, hallucinations, coma.

18. Diagnosis of antimuscarinic
poisoning
 Diagnosis of antimuscarinic poisoning :-
 IM injection of physostigmine. If signs of muscarinic activation do not occur,
poisoning with antimuscarinic drug is almost always certain.

19. Treatment for poisoning
 Antimuscarinic treatment :-
 maintenance of vital signs, alleviation of convulsion with diazepam, temp control
with ice bag and alcohol sponges.

20. Contraindications of
Anti-Muscarinics
 Contraindications of antimuscarinics :-
 glaucoma, prostatic hypertrophy, urinary tract obstruction, GI tract obstruction, a
dynamic ileus, gastric ulcer, infectious diarrhea, UC, chron's disease,
tachyarrhythmia’s, coronary artery disease, hyperthyroidism, children, elderly.

21. Therapeutic uses of antimuscarinics
 Therapeutic uses of antimuscarinics :-
 Funduscopic exam (mydriasis), measurements of refractive errors, iritis,
chroiditis. IBS diahrea, renal colic, enuresis, urinary incontinence (to
reduce frequency), preoperative lung surgery to reduce secretions,
bronchial asthma and copd (ipratropium), cardio resuscitation (when
vagal hyperactivity is the cause of cardiac arrest), sinus or nodal
bradycardia, AV block due to increased vagal tone. CNS - prevention of
motion sickness (scopolamine), parkinsons (triexyphenidyl).To
counteract parasympathomimetic effects of neostigmine in myasthenic
patients. Poisoning by AchE inhibitors or mushrooms containing
muscarine.

22. Brief details on drug indication

23.  Atropine-
 Visceral hypermotility and spasms, excessive salivation, cardio disorders,
cholinesterase inhibitor overdose, ophthalmology, preanesthetic medication.
 Scopolamine-
 Motion sickness, ophthalmology, preanesthetic medication.
 Homatropine-
 Ophthalmology.

24.  Ipratropium-
 bronchospastic disorders.
 Ganglionic stimulating drugs-
 nicotine, tetramethylammonium (carbachol, cholinesterase inhibitors,
succinylcholine less used).
 Ganglionic blocking drugs-
 hexamethonium, mecamylamine (glycopyrrolate, ipratropium, tubocurarine less
used).

25.  Tolterodine-
 Neurogenic bladder, urinary urge incontinence.
 Trihexyphenidyl-
 Parkinsons.
 Glycopyrrolate-
 visceral hypermotility and spasms, cardiovascular disorders, preanesthetic
medication.

26. In Brief

27.  Acetylcholine is the main contractile neurotransmitter of the
detrusor muscle – it stimulates the muscarinic receptors. Anti-
muscarinic medications are, therefore, used to treat overactive
bladder, to :-
• reduce intravesical pressure,
• reduce uninhibited contractions.

28. Available Medication’s
 The available medications are:
• listed:
oral oxybutynin IR (Ditropan), propantheline (Pro-
Banthine), imipramine (Tofranil) and, as a second-line,
the oxybutynin transdermal patch (Oxytrol).
• private script:
tolteridine IR (Detrusitol), solifenacin (Vesicare),
darifenacin (Enablex), and the oxybutynin transdermal
patch (Oxytrol).

29. Medication in detail

30.  Oxybutynin IR ( Ditropan XL,
Urotrol )
1. This is an anticholinergic,
antispasmodic and local
anaesthetic.
2. It is more selective for the salivary
gland than the bladder, so dry
mouth and constipation are
common.
3. However, most side effects are
caused by an active metabolite
from first pass mechanism in the
gut.
4. It has well-documented
effectiveness at doses of 2.5–5mg
up to 4 times a day

31.  Oxybutynin patch (oxytrol )
1. This has no more systemic side effects than placebo, with minimal
discontinuation due to dry mouth.
2. It releases oxybutynin 3.9 mg/day and the patch is changed twice a
week.
3. There may be redness at the application site.

32.  Solifenacin
 Brand Name(s):
India : Soliten (5 mg) | Bispec (10
mg) | Solicept (5mg) | Bispec (5 mg) | Soliten
(10 mg) |Vesiact (5mg)
 Foreign Names : VESIcare
1. Solifenacin is more selective for
M3 receptors in the bladder than
in the salivary glands, so there are
low rates of dry mouth and a low
discontinuation rate.
2. Again, there is well-documented
effectiveness with doses of 5–10
mg once a day.

33.  Darifenacin ( Enablex )
1. Darifenacin is a relatively selective M3 receptor antagonist with low
discontinuation rates and good effectiveness.
2. It is given as a once daily oral dose of 7.5–15 mg.

34.  Tolterodine IR ( Detrol LA )
1. Tolterodine in a nonselective muscarinic receptor antagonist with
more affinity for the bladder than the salivary gland.
2. It is effective at 1–2 mg twice a day.

35.  Propantheline (Spastheline )
Foreign Names
• Propanthelini Bromidum (Latin)
• Propanthelin bromid (German)
• Propanthéline bromure de (French)
• Propantelina, bromuro de (Spanish)
1. Propantheline is a nonselective muscarinic receptor antagonist with
poor GIT absorption, a short half-life, a poor side-effect profile, and
varying effectiveness.

36.  Imipramine (Tofranil )
1. Imipramine has systemic
antimuscarinic actions and
blocks reuptake of serotonin
and noradrenaline.
2. It therefore has cardiovascular
side effects and can cause
drowsiness in therapeutic
antidepressant dosages.
3. Use low dosage to benefit
nocturnal enuresis and
nocturia

37. Side Effects
The side effects of antimuscarinic drugs include:
 dry mouth with difficulty swallowing and thirst
 dilation of the pupils with difficulty accommodating and sensitivity to
light - i.e. blurred vision
 increased intraocular pressure
 hot and flushed skin
 dry skin
 bradycardia followed by tachycardia, palpitations and arrhythmias
 difficulty with micturition - urinary retention
 Constipation
 More rarely:
 fever
 confusion, mania, hallucinations
 rashes

38. Summary

39.  For many years, antimuscarinic drugs have been the first-line
pharmacological treatment for urgency, frequency, and urge
incontinence, all symptoms of the disorder termed overactive
bladder.
 Antimuscarinic treatment is not always effective and is associated
with side-effects that limit its clinical use.
 They may not be the perfect treatment for all patients with this
disorder, but their value for individual patients should not be
underestimated.
 Further clinical trials with improvement in quality of life as the
primary endpoint are needed and may give a fair reflection of the
clinical value of antimuscarinic drugs.

40. Some short notes on Anti-Nicotinic
Action

41.  Nicotinic receptors are selectively activated by
nicotine and blocked by tubocurarine or
hexamethonium.
 They are rosette-like pentameric structures
which enclose a ligand gated cation channel;
their activation causes opening of the channel
and rapid flow of cations resulting in
depolarization and an action potential.
 On the basis of location and selective agonists
and antagonists two subtypes NM and NN
(previously labelled N 1 and N 2) are recognized.

42. Two types of Nicotinic
receptors
 NM:
 These are present at skeletal
muscle end plate are
selectively stimulated by
phenyl trimethyl ammonium
(PTMA) and blocked by
tubocurarine.They mediate
skeletal muscle contraction.
 NN:
 These are present on
ganglionic cells (sympathetic
as well as parasympathetic),
adrenal medullary cells
(embryologically derived from
the same site as ganglionic
cells) and in spinal cord and
certain areas of brain.They are
selectively stimulated by
dimethyl phenyl piperazinium
(DMPP), blocked by
hexamethonium, and
constitute the primary
pathway of transmission in
ganglia.

43. NEUROMUSCULAR BLOCKERS

44. About NEUROMUSCULAR BLOCKERS
 Neuromuscular junction blocking agents
(NMBA’s) act on cholinergic receptors on the
skeletal muscle endplate to produce muscle
paralysis.
 They are used during anaesthesia to facilitate
endotracheal intubation and provide surgically
required muscle relaxation.

45. NEUROMUSCULAR BLOCKING DRUGS
 Depolarizing
 Succinylcholine (short acting)
 Non-depolarizing
 Short acting
 Mivacurium
 Intermediate acting

 Cisatracurium
 Vecuronium
 Rocuornium
 Long acting
 Doxacurium
 Pancuronium
 Pipecuronium

46. Medication in detail

47.  Atracurium (Tracrium ® )
 May be given undiluted by IV bolus.
 Dosing (Adults):
 initially 0.4 to 0.5 mg/kg IV bolus, followed by 0.08 to 0.1
mg/kg every 20 to 45 minutes after initial dose.
 Continuous infusion: initially 0.4 to 0.5 mg IV bolus,
followed by 9 to 10 mcg/kg/min. Maintenance infusion
rates of 5 to 9 mcg/kg/min are usually adequate. (Range:
2 to 15 mcg/kg/min).
 Toxic metabolite (laudanosine) may accumulate in
renal failure.
[Supplied: 50 mg/5 ml ; 100 mg/10ml vial]

48.  Cisatracurium (Nimbex ® )
 Dosing (Adults):
 Intermittent: initial dose: 0.15 to 0.2 mg/kg IV bolus
followed by 0.03 mg/kg IV every 40 to 60 minutes.
 Continuous infusion: 0.15 to 0.2 mg/kg IV bolus followed
by 1 to 3 mcg/kg/min.The average infusion rate for long
term use in the ICU is at 3 mcg/kg/min (range: 0.5 to 10.2
mcg/kg/min). In some cases, re-administration of the
bolus dose may be req'd while titrating. Dosage
reductions are not required in renal or hepatic failure.
 Drug of choice in the following cases:
 (1) hemodynamically significant increases in HR (eg
>20%) while paralyzed with pancuronium or MAP>110.
 (2) Concurrent corticosteroid administration (>72hrs)
 (3) Significant renal dysfunction (CRCL < 30 ml/min)
 (4)History of asthma or bronchospasm.

49.  Doxacurium (Nuromax OD ® )
 Dosing (Adults): (usual)
 Anesthesia adjunct: initial, 0.05 mg/kg and 0.08
mg/kg IV to provide neuromuscular block for an
average 100 min and 160 min, respectively.
Maintenance, 0.005 mg/kg and 0.01 mg/kg IV to
provide neuromuscular blockage for an average of
30 min and 45 min, respectively.
 Endotracheal intubation: 0.05 mg/kg IV.
 Endotracheal intubation: (with succinylcholine)
initial, 0.025 mg/kg IV.
[ Supplied: 1 mg/ml Solution]

50.  Mivacurium (Mivacron ® )
 Short-acting arizing neuromuscular blocking
agent.
 Dosing (Adults)
 Endotracheal intubation: 0.15 mg/kg IV bolus. For
extended neuromuscular block, IV average infusion
rates of 6 to 7 mcg/kg/min are used. Recovery from
muscular paralysis occurs within 15 to 30 minutes.

51.  Pancuronium (Pavulon ® )
 Non-depolarizing skeletal muscle blocker--
competes with acetylcholine at the
neuromuscular junction.
 Dosing (Adults)
 Intermittent dosing: 0.1 to 0.2 mg/kg (usually 0.1)
every 1 to 3 hours (range: 0.04 to 0.2 mg/kg).
 Continuous infusion: Loading dose: 0.04 to 0.10
mg/kg , followed by 1 to 1.7 mcg/kg/min or 0.06 to
0.1 mg/kg/hr

52.  Rocuronium (Zemuron ® )
 Dosing (Adults) (usual):
 Intubation(rapid sequence intubation): initial, 0.6-
1.2 mg/kg IV. tracheal intubation: initial, 0.6 mg/kg
IV. Maintenance, 0.1-0.2 mg/kg IV repeated as
needed.
 Maintenance (continuous IV infusion): 0.01-0.012
mg/kg/minute.
 Skeletal muscle relaxation: initial, 0.6 mg/kg IV.
Maintenance: 0.1-0.2 mg/kg IV repeated as needed.
Alternatively: maintenance (continuous IV infusion):
0.01-0.012 mg/kg/minute

53.  Succinylcholine
 Depolarizing skeletal muscle blocker. Indications:
procedures of short duration such as endotracheal
intubation.
 Dosing (Adults):
 Intermittent: 0.6 mg/kg (0.3 to 1.1) over 10-30
seconds, up to 150mg total dose. Maintenance: 0.04
to 0.07 mg/kg every 5-10 minutes as needed.
 Continuous infusion: 2.5 mg/min (0.5 to 10
mg/min).
Dilute to 1-2 mg/ml.

54.  Vecuronium (Norcuron ® )
 Dosing (Adults)
 Intermittent dosing: initially 0.08 to 0.1 mg/kg IBW
IV bolus. (Higher initial doses-up to 0.3 mg/kg-may
be used for rapid onset. Maintenance: 0.01 to 0.015
mg/kg every 25 to 45 minutes as needed.
 Continuous infusion: initial IV bolus (0.08 to 0.3
mg/kg), followed by (after 20-40min), 1 mcg/kg/min
infusion (usual range: 0.8 to 1.2 mcg/kg/min).
Dosage reductions are not req'd in renal failure.

55. Ganglionic blocking Drugs

56. Pharmacology of Ganglionic
Blocker’s
 A ganglionic blocker (or ganglioplegic) is a type of
medication that inhibits postganglionic transmission,
primarily by acting as a nicotinic antagonist .
 Because ganglionic blockers block the parasympathetic
nervous system and sympathetic nervous system, the
effect of these drugs depends upon the dominant tone in
the organ system.

57.  Ganglionic blockers on CVS :-
 Moderate HR increase, decreasedCO (b/c of
peripheral venous pooling decreases preload),
marked decrease in venous tone and peripheral
resistance (hypotension in upright position), skin
blood flow is decreased, spanchnic and renal
blood flow are decreased.

58. Ganglionic blocker on heart
 Ganglionic blocker on heart effect :-
 Tachycardia (M2).
 Ganglionic blocker on arterioles:-
 vasodilation, orthostatic hypotension .
 Ganglionic blocker on veins :-
 vasodilation, venous pooling, decreased cardiac
output.

59. Ganglionic blocker on eye
 Ganglionic blocker on iris :-
 Mydriasis.
 Ganglionic blocker on ciliary muscle :-
 Cycloplegia.

60. Ganglionic blocker on GI
tract
 Ganglionic blocker on GI tract:-
 Decreased motility and tone, constipation.

61. Ganglionic blocker on
urinary bladder
 Ganglionic blocker on urinary bladder:-
 urine retention.

62. Ganglionic blocker on
exocrine glands
 Ganglionic blocker on exocrine glands:-
 reduced secretion.

63. Ganglionic blocker on sweat
glands
 Ganglionic blocker on sweat glands:-
 reduced secretion (anhydriosis).

64. Therapeutic Uses
- Ganglionic blockers are used less frequently now than
they were in the past, because more selective agents are
now available. However, they are still used in some
emergency situations, such as aortic dissection
or autonomic dysreflexia.

65. Drug’s Available
The first ganglion-blocker to be used clinically
wasTetraethylammonium, although it was
soon superseded by better drugs.
Other examples include :-
Hexamethonium, Pentolinium, Mecamylamine,
Trimetaphan, and Pempidine.

66.  Hexamethonium (Methium)
 It was formerly used to treat disorders, such
as chronic hypertension, of the peripheral
nervous system, which is innervated only by
the sympathetic nervous system.The non-
specificity of this treatment led to
discontinuing its use.

67.  Pentolinium (Ansolysen)
 Is a ganglionic blocking agent which acts as
a nicotinic acetylcholine receptor antagonist. It can
be used as an antihypertensive drug during surgery
or to control hypertensive crises. It works by binding
to the acetylcholinereceptor of adrenergic nerves
and thereby inhibiting the release of noradrenaline
and adrenaline. Blocking this receptor leads
to smooth muscle relaxation and vasodilatation.
Pentolinium can be given orally,
injected intramuscularly or
administered intravenously.

68.  Mecamylamine
 A nicotinic antagonist that is well absorbed from
the gastrointestinal tract and crosses the blood-
brain barrier. Mecamylamine has been used as a
ganglionic blocker in treating hypertension, but,
like most ganglionic blockers, is more often used
now as a research tool.

69. Brands of Mecamylamine
 Inversine
 2.5 mg
 Vecamyl
 2.5 mg

70.  Trimetaphan camsilate or trimethaphan
camsylate (USA), trade name Arfonad, is a drug
that counteracts cholinergic transmission at
the ganglion type of nicotinic receptors of
the autonomic ganglia and therefore blocks both
the sympathetic nervous system and
the parasympathetic nervous system. It acts as a
non-depolarizing competitive antagonist at the
nicotinic acetylcholine receptor, is short-acting,
and is given intravenously.

71.  Pempidine
 Is a ganglion-blocking drug, first reported in
1958 by two research groups working
independently, and introduced as an oral
treatment for hypertension.

72.  Pharmacokinetics of ganglionic blocker’s:-
 Hexamethonoium is quaternary ammonium,
mecamyalamine is secondary amine (active by
oral and enters CNS).

73. Side Effects
 Cardiovascular: Orthostatic(postural) hypotension,
Tachycardia,
 GIT: Dry-mouth, GIT atony,urine retention, digestive
problems,
 Sexual Dysfunction: Failure of erection and ejaculation.
 Blocks baroreceptor reflex.
 Blocks parasympathetic mediated pupil contraction and
accommodation.

75. PREPARED BY
SYED MASOOD AHMED QUADRI
MESCO COLLEGE OF
PHARMACY