Anticholinergics

1. ANTICHOLINERGICS
Dr.Amudhan Arvind

2. An anticholinergic agent is a
substance that blocks the neurotransmitter
acetylcholine in the central and the
peripheral nervous system
they inhibit parasympathetic nerve
impulses by selectively blocking the binding
of the neurotransmitter acetylcholine to its
receptor in nerve cells

3. Anticholinergic
drugs
Antinicotinic drugs
Ganglionic
blockers
Neuromuscular
blockers
Antimuscarinic
drugs

4. ANTIMUSCARINIC DRUGS
Antimuscarinic
drugs
Naturally
occurring
antimuscarinic
Semisynthetic
Derivatives
Synthetic
antimuscarinics

5. Antimuscarinic
Agents
Natural Alkaloids
Atropine
Hyoscine
(scopolamine)
Extract of
Belladona
Semisynthetic
Homatropine
Encatropine
Methylatropine
Methscopoline
Synthetic
Tropicamide
Glycopyrrolate
Pirenzeline

8. STRUCTURE
 Atropine is a product resulted from esterification
of tropic and tropine base
 In scopolamine, there is an oxygen bridging
(epoxide)
 In homatropine, hydroxymethyl of atropine is
replaced by an OH-radical (tertiary)

9. PHARMACOKINETIC
 Tertiary group:
 lipid soluble
 distribution is wide
 absorption from gut and across conjunctiva is good
 absorption across skin in suitable vehicle is good.
 Significant concentration is reached within 0.5-1h (eg.
scopolamine)
 Quaternary group:
 not very lipid soluble
 distribution is confined to peripheral tissues (no central
toxicity)
 absorption from the site of application is poor

10.  Metabolism:
 1/2 is metabolized by hepatic esterase (atropinase)
 1/3 is excreted unchanged in the urine
 80% excreted in the urine with an half-life of 2h
 the effects on the eye persist 40-72h

11. PHARMACODYNAMIC
 Interaction with muscarinic receptors: reversible,
competitive
 Receptor selectivity:
 Atropine: -selective for muscarinic receptors
 non-selective for muscarinic receptor subtypes
 But, pirenzepine a selective antagonist for m1-
receptors(stomach parietal cells)
 Quaternary group:
 not very selective for muscarinic receptors
 can also antagonize Nicotinic-receptors in autonomic
ganglia

12.  Tissue selectivity:
 Tissues more sensitive to:
 Atropine: salivary, sweat and bronchial glands
 Pirenzepine (telenzepine, more effective): acid
secretion from parietal cells (stomach)
 Scopolamine: more effective on vestibular
disturbances (eg. Motion sickness)

13. SOURCE
 Atropine
 - From Atropa belladonnea
Datura stromonium
 Occurs as l-form, not stable
 racemizes to dl-form rapidly
 commercial products contain dl-form
 l-form is 100-times as potent as d- or dl-forms
 -Scopolamine
 From Hyosciamus niger
 Occurs as l-form
 its l- form is stable

16.  Muscarinic antagonists prevent the effects of ACh
by blocking its binding to muscarinic receptors on
effector cells at parasympathetic neuroeffector
junctions, in peripheral ganglia, and in the CNS.
 In general, muscarinic antagonists cause little
blockade of nicotinic receptors.
 The quaternary ammonium antagonists generally
exhibit a greater degree of nicotinic blocking activity
and therefore are more likely to interfere with
ganglionic or neuromuscular transmission.

17.  Most clinically available muscarinic antagonists are
nonselective and their actions differ little from those
of atropine, the prototype of the group.
 No subtypeselective antagonist, including
pirenzepine, is completely selective

18. STRUCTURE-ACTIVITY RELATIONSHIPS
 An intact ester of tropine and tropic acid is
essential for antimuscarinic action,
 The presence of a free OH group in the acyl portion
of the ester also is important for activity.
 When given parenterally, quaternary ammonium
derivatives more potent than their parent
compounds in both muscarinic and ganglionic
(nicotinic) blocking activities.
 The quaternary derivatives, when given orally, are
poorly and unreliably absorbed.

19. MECHANISM OF ACTION.
 Atropine and related compounds compete with
ACh and other muscarinic agonists for a
common binding site on the muscarinic
receptor.
 Since antagonism by atropine is competitive, it can
be overcome if the concentration of ACh at
muscarinic receptors of the effector organ is
increased sufficiently.
 Muscarinic receptor antagonists inhibit responses
to postganglionic cholinergic nerve stimulation less
effectively than they inhibit responses to injected
choline esters.

20. EFFECTS OF ATROPINE IN RELATION
TO DOSE

21. PHARMACOLOGICAL EFFECTS OF
MUSCARINIC ANTAGONISTS
CNS
 In clinical dose:
 - With atropine:
 - a long lasting sedation with slow onset
 - stimulation of vagal nuclei in the brain stem
 With scopolamine:
 - sedative effect is more powerful (drowsiness, amnesia)

22.  In toxic dose: (both atropine and scopolamine)
 Excitement
 Agitation
 Hallucination
 Coma
 Disorientation
 Delerium

23.  EYE
 Mydriasis
 Paralysis of ciliary muscle (cycloplegia):
 Loss of accommodation
 Adjustment of eye for far vision
 Photophobia
 Blurred vision
 Lasts for 7-10 days
 Acute glaucoma attack in patient with narrow irido-
corneal angle due to impairment of drainage
 Reduction of lacrimal secretion leading dry sandy
eye

24. CARDIOVASCULAR SYSTEM
 Low dose central vagal stimulation
 initial bradycardia
 followed by tachycardia resulting from peripheral
anticholinergic efffec and thus unopposed sympathetic
activity
 Moderate dose tachycardia due to unopposed
sympathetic activity
 Atroventricular conduction:
 accelereted due to unopposed sympathetic activity
 PR shortening in ECG
 in toxic doses, conduction block

25.  At toxic doses:
 suppression of thermoregulatory sweating
cutaneous vasodilatation at Release of hiatamine
by blush areas (face, neck, ear)
 The net CV effects:
 Tachycardia
 Slight elevation in blood pressure due to vasomotor
centre stimulation

26. RESPIRATORY SYSTEM
 Some bronchodilatation
 Inhibition of bronchial secretion
 Premedication in anaesthesiology: Used before
inhalant anesthetics to reduce
 -Bronchial secretions
 -laryngospasm
 -risk of airway obstructions
 -postoperative pneumonia

27. GASTROINTESTINAL TRACT
 Inhibition of saliva secretion → Dry mouth
 Gastric secretion:
 Blocked to lesser extent by atropine.
 But, is blocked by pirenzepine and telenzepine
 Volume of secretion and amount of acid, pepsin and
mucine are all reduced
 Large doses of atropine are necessary to reduce gastric
secretions

28.  Motility of gut is more powerfully depressed by
atropine than gastrointestinal secretions
 Smooth musles of gut wall are paralysed
 Propulsive movements are diminished
 Sphincter muscles are not able to relax,constipation
 Gastric emptying time prolonged
 Intestinal transit time is lengthened
 Some antimuscarinics have direct spasmolytic effect
as well

29. GENITO-URINARY TRACT
 Smooth muscles of ureter and bladder wall are
relaxed
 This is useful in the treatment of spastic pain due to
mild urinary inflammations
 Sphincter muscles of bladder become unable to
relax.
 urinary retention
 may be hazardous in elder with prostate
hypertrophy
 Helpful in increasing bladder capacity
 Controls detrusor hypereflexia in neurogenic
bladder

30.  EFFECTS ON SWEAT GLAND
 Thermoregulatory sweating is depressed by
atropine
 In adults, large doses of atropine can increase body
temperature
 In infants and children, even ordinary doses may
cause atropine fever

31.  Other actions:
 Markedly decreases salivary,lacrimal and
tracheobronchial secretion
 Decrease secretion of acid,pepsin and mucus of
stomach
 Mild local anaesthetic action on cornea

32. ATROPINE SUBSTITUTES
 Most of semisynthgetic belladona alkaloid
derivatives and synthetic compounds are atropine
sucbstitutes
 Differs only slightly from atropine

33. USES
 Respiratory system:
 Ipratropium and tiotropium .
 Used in Asthma and COPD
 These agents often are used with inhaled long-acting
β2 adrenergic receptor agonists,
 Ipratropium is administered four times daily via a
metered-dose inhaler ornebulizer;
 tiotropium is administered once daily via a dry powder
inhaler.
 Ipratropium also is FDA-approved for use in nasal
inhalers for the treatment of the rhinorrhea associated
with the common cold or with allergic or
nonallergicperennial rhinitis..

34. GENITOURINARY TRACT.
 Overactive urinary bladder can be successfully treated with
muscarinic receptor antagonists.
 These agents can lower intravesicular pressure, increase
capacity, and reduce the frequency of contractions by
antagonizing parasympathetic control of the bladder; they also
may alter bladder sensation during filling
 Muscarinic antagonists can be used to treat enuresis in
children
 In overactive bladder
 oxybutynin
 tolterodine
 trospium chloride
 Darifenacin ,
 Solifenacin , and
 Fesoterodine
 Flavoxate

35.  The most important adverse reactions are
consequences of muscarinic receptor blockade and
include xerostomia, blurred vision, and GI side effects
such as constipation and dyspepsia.
 CNS-related antimuscarinic effects, including
drowsiness, dizziness, and confusion, can occur and are
particularly problematic in elderly patients.
 CNS effects appear to be less likely with trospium, a
quaternary amine, and with darifenacin and solifenacin;
 The latter agents are relatively selective for M3
receptors and therefore have minimal effects on M1
receptors in the CNS, which appear to play an important
role in memory and cognition

36. GI TRACT
 As antisecretory.
 In Peptic ulcer.
 Pirenzepine
 Telenzepine.
 In reducing spasticity or motility of the GI tract (e.g.,
atropine,hyoscyamine and scopolamine) alone or in
combination with sedatives or antianxiety
agents(e.g., chlordiazepoxide

37.  Reduce tone and motility
 M3-selective antagonists might achieve more selectivity
 Glycopyrrolate also is used to reduce GI tone and
motility.
 Diarrhea associated with irritation of the lower
bowel, may respond to atropine-like drugs, an effect
that likely involves actions on ion transport as well
as motility.
 Dicyclomine is a weak muscarinic receptor
antagonist that also has nonspecific direct
spasmolytic effects on smooth muscle of the GI
tract.
 It is occasionally used in the treatment of diarrhea-
predominant irritable bowel syndrome.

38. EYE.
 Produce mydriasis and cycloplegia.
 For breaking or preventing the development of
adhesions between the iris and the lens.
 Complete cycloplegia may be necessary in the
treatment of iridocyclitis and choroiditis and for
accurate measurement of refractive errors.
 Homatropine hydrobromide
 Cyclopentolate hydrochloride
 Tropicamide

39. CARDIOVASCULAR SYSTEM.
 Atropine may be considered in the initial treatment of patients
with acute myocardial infarction in whom excessive vagal tone
causes sinus bradycardia or AV nodal block.
 Doses that are too low can cause a paradoxical bradycardia ,
while excessive doses will cause tachycardia that may extend the
infarct by increasing the demand for oxygen.
 It has little effect on most ventricular rhythms.
 Eliminate premature ventricular contractions associated with a
very slow atrial rate.
 Reduce the degree of AV block when increased vagal tone is
a major factor in the conduction defect, such as the second-
degree AV block that can be produced by digitalis.
 Selective M2 receptor antagonists would be of potential utility
in blocking ACh-mediated bradycardia or AV block.

40. CENTRAL NERVOUS SYSTEM.
 In prevention of motion sickness.
 Scopolamine is the most effective agent
 A transdermal preparation of scopolamine is used
prophylactically for the prevention of motion sickness.
 In the treatment of Parkinson disease.
 Benztropine
 Trihexyphenidyl
 Biperiden
 Selective M1 and M4 muscarinic antagonists may be
efficacious for the treatment of Parkinson disease
 While selective M3 antagonists may be useful in the
treatment of obesity and associated metabolic
abnormalities.

41.  Uses in Anesthesia.
 Atropine commonly is given to block responses to
vagal reflexes induced by surgical manipulation of
visceral organs.
 Atropine or glycopyrrolate is used with neostigmine
to block its parasympathomimetic effects
 Serious cardiac arrhythmias have occasionally
occurred, perhaps because of the initial bradycardia
produced by atropine combined with the
cholinomimetic effects of neostigmine.

42. ANTICHOLINESTERASE POISONING
 Atropine is not an actual antidote for organophosphate
poisoning.
 By blocking the action of acetylcholine at Muscarinic
receptors, atropine also serves as a treatment for
poisoning by organophosphate insecticides
 Atropine is often used in conjunction with oximes
 Atropine is given as a treatment for SLUDGE
syndrome (salivation, lacrimation, urination, diaphoresi
s, gastrointestinal motility, emesis) symptoms caused
by organophosphate poisoning.

43.  Other Therapeutic Uses of Muscarinic
Antagonists.
 Methscopolamine –In temporary relief of symptoms
of allergic rhinitis, sinusitis, and the common cold.
 Homatropine potent as a ganglionic blocking
agent,primarily used with hydrocodone as an
antitussive combination

44.  MUSHROOM INTOXICATION
 I) Intoxications with rapid onset (eg. within 2
hours)
 II) Intoxications with slow onset (eg. within 2 to 6
hours)

45.  Rapid acting mushroom intoxications
 1. -Mushrooms: Inocybe, Clitocybe
 -posses high amount of muscarine
 -cause severe parasympathomimetic effects
 -onset of intoxication symptoms: within 15-30mins
 -antidote: Atropine
 2. -Mushrooms: Psilocibe, Copelandin, Pancoulus,
Gymnopilus species
 -posses psychoactive alkaloids such as psilocybin and
psilocin
 -cause delirium, euphoria, hallucination
 -induce no sleep
 - symptoms last 2-4 hours
 -Treatment: Diazepam, phenothiazines

46.  3. -Mushrooms: A. muscaria, A. pantherina, A.
cothurnate, A. gemmata
 -posses GABA antagonists such as ibotenic acid and
mushimol
 -cause delirium, euphoria, hallucination
 -but do induce sleep and coma
 -symptoms resemble those of atropine, but not responsive
physostigmine
 -symptoms last 2-9 hours
 - no antidote available
 4. -Mushroom: Coprinus atramentarius
 -contain coprin which inhibits aldehyde dehydrogenase
 -cause disulfiram-like effects (aldehyde reaction!)
 -toxic effects appear, when alcohol is drunken 2-3h after
ingestion of mushrooms

47.  Slow acting mushroom intoxications
 Amanita phalloides group
 -Mushrooms: A. phalloides, A. verna, A. virosa
 -Toxins: Phalloidin and α-Amanitin
 α-Amanitin Inhibition of Depression of mRNA RNA-
polymerase-II protein synthesis
 - hepatotoxicity Tissue necrosis
 - nephrotoxicity
 - CNS toxicity

48.  Intoxications have 3 phases
 1sth phase:
 - resembles muscarine intoxication
 - symptoms appear 8-12h after mushroom ingestion
 2nd phase:
 - symptoms in the first phase lessen and disappear within 24-
48h
 - patient becomes asymptomatic in appearance
 - but, biochemical hepatic changes continue developing
 eg. - increase in transaminase activity
 - elevation of biliuribin levels
 - prolongation of prothrombin time
 - lasts 2-6 days
 -the patient may be discharged from the hospital considering
healed

49.  3rd phase:
 - begins abruptly with signs and symptoms of
hepatotoxicity and nephrotoxicity: -
 jaundice
 - encephalopathy
 - coagulopathy
 - hypoglycemia
 - acute renal insufficiency
 1/3th of patients die within a week or so

50. ATROPINE POISONING
 In overdoses, atropine is poisonous.
 Atropine is incapacitating at doses of 10 to 20 mg per
person.
 Its LD50 is estimated to be 453 mg per person
 The antidote to atropine is physostigmine or
pilocarpine
 These associations reflect the specific changes of
warm, dry skin from decreased sweating, blurry vision,
decreased sweating/lacrimation, vasodilation
 This set of symptoms is known as anticholinergic
toxidrome
"hot as a hare, blind as a bat, dry as a bone, red
as a beet, and mad as a hatter".

51.  ADVERSE EFFECTS OF ANTIMUSCARINICS
 -Mydriasis and cycloplegia, when used against gut
disorders
 -Blockade of all parasympathetic functions:
 -dry mouth, sandy eye
 -mydriasis
 -tachycardia, hot and flushed skin
 -agitation, delirium, hallucination
 -elevation of body temperature (children)

52.  -Treatment of adverse effects:
 -due to overdose of atropine and its tertiary
congeners
 Physostigmine:
 - 1-4mg, iv. in adults
 - 0.5-1mg iv. in children
 - Severe hyperthermia: - cooling blanket
 - Seizures: -iv. diazepam

53.  CONTRAINDICATIONS OF ANTIMUSCARINICS
 - Glaucoma (angle closure)
 - Prostatic hypertrophy (elderly)
 - Peptic ulcer (slowing of gastric emptying)
 Exception: Pirenzepine, Telenzepine

54.  Central antimuscarinics used against
Parkinson’s disease
 Trihexyphenidyl 6-20mg
 Procyclidine 7.5-30mg
 Orphenanrine 150-400mg
 Ethopropazine 150-300mg
 Chlorphenoxamine 150-460mg
 Biperiden 2-12mg
 Benzotropine mesylate

55.  Ganglion-blocking agents competitively block the action of
acetylcholine and similar agonists at nicotinic (Nn)
receptors of both parasympathetic and sympathetic
autonomic ganglia.

56.  Ganglionic blockers
 Hexamethonium : acts mainly by channel blocker
 Decamethonium
 Quaternary -Tetraethyl ammonium:
 short acting
 -Pentolinium
 -Chlorizondamine
 -Trimetaphan:
 very short acting
 -Mecamylamine
 Secondary -Pempidine

57.  Mechanism of ganglionic block:
 1) Depolarizing block, eg. by sustained
depolarization: Ach, nicotine, carbamoylcholine
 2) Nondepolarizing competitive antagonism of Ni
receptors
 3) Channel block: Hexamethonium

58.  Results of ganglion blockade
 CNS:
 - Quaternary group is devoid of such effects
 - Secondary group readily enters CNS: sedation, tremor,
choreiform movements,mental disturbances
 EYE:
 - Moderate mydriasis (since p.sympathetic influence on
iris is dominant)
 - Cycloplegia with loss of accommodation

59.  CVS:
 - Sympathetic CV reflexes are depressed
 - Sympathetic influence on arteriols and veins are
diminished, PVR and venous return are reduced,
vasodilatation, hypotension (orthostatic), tachycardia
 GUT:
 - Secretions and motility are inhibited
 - Some degree of constipation
 Urinary system:
 - Urination is blocked
 - Urine retention in a man with prostate hypertrophy
 Thermoregulatory sweating is blocked.

60. THERAPEUTIC USES:
 1) Hypertension:
 - rapid tolerance development and orthostatic
hypotension
 -now more effective agents are available
 2) Acute hypertensive crisis in a patient with
dissecting aortic aneurism.
 Trimetaphan: 0.5-3mg/min by iv infusion
 Disadvantage: tolerance development within 48h
 3) Production of controlled hypotension to minimize
haemorrhage at the operative field.
 Trimetaphan: 1-4mg/min by iv infusion
 4) Autonomic hyperreflexia (or reflex sympathetic
dystrophy)

61.  Side effects:
 The most serious one is orthostatic
hypotension

62. NEUROMUSCULAR BLOCKERS
 Block synaptic transmission at the neuromuscular
junction
 Affect synaptic transmission only at skeletal muscle
 Does not affect nerve transmission, action potential
generation
 Act at nicotinic acetylcholine receptor NM

63. Classification:
Neuromuscular blocking agents:-
1) Depolarizing muscle relaxants.
2) Non-depolarizing muscle relaxants

64. Depolarizing Muscle relaxants:
 Succinylcholine (short acting)
Non-depolarizing Muscle relaxants:
Short acting:
 Mivacurium
Intermediate –acting:
 Atracurium,
 Cisatracurium,
 Vecuronium,
 Rocuronium
Long acting :
 Doxacurium
 Pancuronium
 Pipecuronium

65. MECHANISM OF ACTION
SUXAMETHONIUM:
• Block transmission by causing prolonged depolarization
of endplate at neuromuscular junction.
• Manifestation by initial series of muscle twitches
(fasciculation) followed by flaccid paralysis.
• It immediately metabolize in plasma by Pseudo-
cholinesterase which is synthesized by liver so to prevent
its metabolism in plasma it should be given at faster rate.

66. SYSTEMIC EFFECTS
 Cardiovascular: Produces muscarinic effects as
acetylcholine , therefore causes bradycardia ( but when
given high doses causes tachycardia because of
stimulation of nicotinic receptors at sympathetic
ganglions.)
 Hyperkalemia: Occurs due to excessive muscle
fasciculations. Ventricular fibrillation can occur due to
hyperkalemia.
 CNS: Increases intracranial tension ( due to contraction
of neck vessels)
 Eye: Increases intraocular pressure.

67.  GIT: Increases intra-gastric pressure , salivation, peristalsis.
 Muscle pains ( myalgia): This is a very common problem in
post operative period. These are due to excessive muscle
contractions.
 Malignant hyperthermia
 Severe Anaphylaxis
 Masseter Spasm : Sch can cause masseter spasm
especially in children & patients susceptible for malignant
hyperthermia.
Doesnot require reversal rather cholinesterase inhibitors
(neostigmine) can prolong the depolarizing block (because
these agents also inhibits the pseudocholinesterase)

69. NON-DEPOLARIZING MUSCLE
RELAXANTS:
Mechanism of action:
• It blocks nicotinic receptors competitively resulting
in inhibition of sodium channels and excitatory post-
synaptic potential.
• It binds at the same site at which acetylcholine
binds.
• All NDMR are quarternary ammonium compounds
& highly water soluble i.e. hydrophilic. So, they do
not cross blood brain barrier & placenta except
Gallamine.

70. BROAD CLASSIFICATION
 These are broadly divided into steroidal compounds
and benzylisoquinoline (BZIQ) compunds.
 STEROIDAL COMPOUNS: (vagolytic properties)
It includes PANCURONIUM,VECURONIUM ,
PIPECURONIUM,ROCURONIUM,
RAPACURONIUM,DOXACURIUM
 BZIQ(Benzylisoquinoline): (hystamine realease)
It includes d-Tubocurare, Metocurine, Doxacurium,
Atracurium, Mivacurium, Cisatracurium
 OTHERS includes Gallamine, Alcuronium

71. DIFFERENCES BETWEEN DEPOLARIZING & NON-
DEPOLARIZING BLOCK
Depolarizing Nondepolarizing
Also called Phase I block -
Block preceded by muscle
fasciculations
No fasciculations
Depolarizing blocking drugs are called
Leptocurare
Called pachycurare
Does not require reversal rather
cholinesterase inhibitors (Neostigmine)
can prolong the depolarizing block (
because these agents also inhibit the
pseudocholinesterase).
Reversed by cholinesterase
inhibitors like Neostigmine.

72. NDMR ARE USED IN ANAESTHESIA FOR:
 Maintenance of anaesthesia.
 For intubation where succinylcholine is contraindicated (
Rocuronium is of choice)
 For precurarization to prevent postoperative myalgias by
succinylcholine.

73. STEROIDAL COMPOUNDS
Pancuronium
 Very commonly used as it is inexpensive.
 It releases noradrenaline & can cause tachycardia & hypertension.
Because of this there are increased chances of arrhythmia with
halothane
Pipercuronium
 It is a pancuronium derivative with no vagolytic activity, so cardiovascular
stable, slightly more potent
Vercuronium
 It is very commonly used now a days. It is cardiovascular stable. Shorter
duration of action.
 It is the muscle relaxant of choice in cardiac patient.
Rocuronium
 8 times more potent than vecuronium and it also has earlier onset of
action
 Because of onset comparable to succinylcholine it is suitable for rapid
sequence intubation as an alternative to succinylcholine.

74. BENZYLISOQUINOLINE COMPOUNDS
 D- Tubocurare
 It is named so because it was carried in bamboo tubes &
used as arrow poison for hunting by Amazon people.
 It has highest propensity to release histamine
 It causes maximum ganglion blockade. Because of
ganglion blocking & histamine releasing property it can
produce severe hypotension.
 Due to histamine release it can produce severe
bronchospasm.

75. REVERSAL OF BLOCK
 Drugs used for reversal of block are cholinesterase inhibitors
(anticholinesterases).
 Reversal should be given only after some evidence of
spontaneous recovery appear.
Mechanism of Action
 It inactivate the enzyme acetylcholinesterase which is
responsible for break down of actetylcholine, thus increasing
the amount of acetylcholine available for competition with non
depolarizing agent thereby re-establishing neuromuscular
transmission.
 Anticholinesterases used for reversal are:
 Neostigmine
 Pyridostigmine
 Edrophonium
 Physostigmine

76. FACTORS PROLONGING THE NEUROMUSCULAR
BLOCAKDE
 Neonates
 Old age
 Obesity
 Hepatic disease (both depolarizer & NMDR)
 Renal disease ( only NDMR)
 Inhalational agents : Prolong the block by both
depolarizers & NDMR. Inhalational agents decrease the
requirement of relaxant .The maximum relaxation is by
ether followed by desflurane
 Antibiotics: Both depolarizers & NMDR
 Aminoglycosides.
 Tetracyclines.

77.  Local Anaesthetics : Except procaine local anaesthetics
prolong the action by stabilizing post synaptic membrane.
 Hypothermia : Decreases metabolism of muscle relaxants.
 Hypocalcemia: Calcium is required for producing action
potential. Action of NDMR is enhanced.
 Hypokalemia : NMDR block is enhanced.
 Acid base imbalances especially acidosis.
 Calcium channel blockers
 Dantrolene
 Neuromuscular disease
 Hypermagnesemia.

78. DRUGS WHICH ANTAGONISE
NEUROMUSCULAR BLOCKADE
 They reverse the block by NDMR only
 Phenytoin
 Carbamazepine
 Calcium
 Cholinesterase inhibitors
 Azathioprine
 Steroids.

79. SUGAMMADEX
 An agent for reversal of neuromuscular blockade by
the agent rocuronium in general anaesthesia.
 It is the first selective relaxant binding
agent (SRBA) .
 Sugammadex is a modified γ-cyclodextrin
 The rocuronium molecule bound within
sugammadex's lipophilic core, is rendered
unavailable to bind to the acetylcholine receptor at
the neuromuscular junction.
 No need to rely on anticholinesterase

80. DRUGS WITH ANTICHOLNERGIC ACTION
 ANTIHISTAMINES (H-1
BLOCKERS)
 Chlorpheniramine
 Cyproheptadine
 Diphenhydramine
 Hydroxyzine
 CARDIOVASCULAR
MEDICATIONS
 Furosemide
 Digoxin
 Nifedipine
 Disopyramide
 ANTIDEPRESSANTS
 Amoxapine
 Amitriptyline
 Clomipramine
 Desipramine
 Doxepin
 Imipramine
 Nortriptyline
 Protriptyline
 Paroxetine

81.  GASTROINTESTINAL
MEDICATIONS
 Antidiarrheal Medications
 Diphenoxylate
 Atropine
 Antispasmodic
Medications
 Belladonna
 Clidinium
 Chlordiazepoxide
 Dicyclomine
 Hyoscyamine
 Propantheline
 Antiulcer Medications
 Cimetidine
 Ranitidine
 ANTIPSYCHOTIC
MEDICATIONS
 Chlorpromazine
 Clozapine
 Olanzapine
 Thioridazine

82.  MUSCLE RELAXANTS
 Cyclobenzaprine
 Dantrolene
 Orphenadrine
URINARY
INCONTINENCE
 Oxybutynin
 Probantheline
 Solifenacin
 Tolterodine
 Trospium
 ANTIVERTIGO
MEDICATIONS
 Meclizine
 Scopolamine
PHENOTHIAZINE
ANTIEMETICS
 Prochlorperazine
 Promethazine

83. NEWER ANTICHOLINERGICS
 Umeclinidium bromide:
 An anticholinergic drug approved for use in
combination with vilanterol (as umeclidinium
bromide/vilanterol) for the treatment of COPD
 Aclinidium
 An anticholinergic for the long-term management of
chronic obstructive pulmonary disease (COPD). It
has a much higher propensity to bind to muscarinic
receptors than nicotinic receptors.
 FDA approved on July 24, 2012.

84. DARIFENACIN
 Darifenacin is a medication used to treat urinary
incontinence.
 Darifenacin works by blocking the M3 muscarinic
acetylcholine receptor, which is primarily
responsible for bladder muscle contractions.
 It thereby decreases the urgency to urinate. It
should not be used in people with urinary retention.
 98% bound to plasma proteins
 Hepatic metabolism. Primarily mediated by the
cytochrome P450 enzymes CYP2D6 and CYP3A4.

85. SOLIFENACIN
 Solifenacin is a competitive cholinergic
receptor antagonist.
 The binding of acetylcholine to these receptors,
particularly the M3 receptor subtype, plays a critical role
in the contraction of smooth muscle.
 By preventing the binding of acetylcholine to these
receptors, solifenacin reduces smooth muscle tone in
the bladder, allowing the bladder to retain larger
volumes of urine and reducing the number of micturition,
urgency and incontinence episodes.
 Because of a long elimination half life, a once-a-day
dose can offer 24 hour control of the urinary
bladder smooth muscle tone.