Class anticholinergic drugs

THIS CLASS IS IN BRIEF FOR UNDER GRADUATE UNDERSTANDING AND EXAMINATION PURPOSE

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. Central Nervous System (CNS)-Brain and spinal
cord
Peripheral Nervous System (PNS)-Located outside
the brain & spinalcordAutonomicNervous
System (ANS) &the somatic
The PNS receives stimuli from the CNS & initiates
responses to the stimuli after it’s interpreted by the
brain

6. Acetylcholine–preganglionic
PostganglionicAch
Exception-postganglionicsympatheticfibresto
apocrineglands
Cholinergicfibres
All somaticmotarneurons
Allpreganglionicfibres
Postganglionicparasympatheticfibres

7. 75% of all parasympathetic nerve fibers are in the
vagusnerves
These nerves supply the thoracic and abdominal
organs, which innervate the heart, lungs, esophagus,
stomach, small intestine, proximal half of the colon,
liver , gallbladder, pancreas and upper portions of the
ureters

10. Natural alkaloids:Atropine,Hyoscine(Scopolamine),
2.Semisynthetic derivatives
Mydriatics:Homatropine,
Antiasthmatics:Iprotropium,Tiotropiumbromide
GIspasmolytics:Hyoscinebutyl bromide
3.Syntheticcompounds
Mydriatic-Tropicamide,cyclopentolate
GIspasmolytics:
Quaternary-Oxyphenonium,clidinium,pipenzolate,
isopropamide,glycopyrolate,
Tertiary-Dicyclomine
Antiulcerdrugs:Pirenzepine(M1-blockers),telenzapine
vasicoselective:Flavoxate,Oxybutynin,Tolteridine
Antiparkinsonian(central M-cholinolytics):Benztropine,
Biperiden,Trihexyphenidyl(benzhexol)

11. Abelladonna alkaloid has a
highaffinity for muscarinic
receptors, it is a competitive
inhibitorof muscarinicreceptors
preventing ACH from
bindingto that site.
Atropine

12. Antimuscarinicagents:
These agents block muscarinic receptors and
inhibit muscarinic functions, they are useful in
different clinical situations, they have no actions on
skeletal neuromuscular junctions or autonomic
ganglia because they do not block nicotinic
receptors.

13. Low dose-M1receptor on cholinergic N
auto-inhibitarycholinergic action
bradycardia
Moderate dose-M2receptor on post
junctionalSAN, AVNblkescape the heart
from inhibitiontachycardia+Unopposed
adrenergic actionchronotropic,dronotropic
Toxic dose-M3receptor-endothelium
blockadeNO release is blockedsmooth
muscledonotrelaxprevention of
cholinergic mediated dilation
Blood pressure-tachycardia andvasomotarcentrestimulation tends to increase blood
pressure, while histamine release and direct vasodilation tends to decrease BP

14. 50
100
150
200
A B C D
1min
ATROPINE BLOCKS
M-EFFECTS OF ACH
Blood pressure
[mm Hg]
ACh
2mcgi.v.
ACh
50mcg
ACh
50mcg
ACh
5mg
M-
effect
M-
effect
N-
effect
Atropine
2mgi.v.
ACh

15. CNS. Atropine has an overall stimulant action. Itsstimulant
effects are not appreciable at low doseswhich produce
peripheral effects because of restrictedentry intothe brain.
Hyoscineproduces centraldepressant effectseven at low
doses.
Medullarcenters-vagal, respiratory, and vasоmotor.
By blocking the relative cholinergicover activityin
basal ganglia, it suppresses tremor and rigidity
in parkinsonism.
High doses cause cortical excitation,restlessness,
disorientation, hallucinations, and delirium
followed by respiratory depression and coma.

16. Autonomic control of pupil (A)and site of
actionofmydriatics(B) andmiotics(C)
Topicalinstillation of atropine (0.1%)
causesmydriasis, abolition of light reflex,
andcycloplegia, lasting7–10days.
Thisresults in photophobiaand blurring
of near vision.
Theintraocular tension rises, speciallyin
narrow angleglaucoma

17. Allvisceral smooth muscles withparasympathetic
innervationare relaxed (M
3-blokade).
Tone and amplitude of GIT are reduced.
Spasm may bereduced, constipation may occur.
Peristalsis is onlyincompletely suppressed because it is
primarily regulatedby local reflexes and other
neurotransmitters (serotonin, encephalin, etc.).

18. Atropine causesbronchodilationand reducedairway
resistance, especially in asthma patients.
Inflammatory mediators(histamine, PGs, and kinins)
increase vagalactivityin addition to their direct action
onbronchial muscleand glands. Atropine attenuates
theiraction byantagonizing the reflex vagal component.
Ithasa relaxantaction on the ureter and urinary
bladder. Urinaryretention can occur in older men with
prostatichyperplasia.

19. Glands. Atropine decreases sweat, salivary,tracheo-
bronchial, and lacrimal secretion (M3-blockade).Skin
andeyes become dry, talking, and swallowingmaybe
very difficult.
Atropine decreasesthesecretion of acid and pep-
sin andincreasesmucus in the stomach.
Body temperature-Rise in body temperature occurs at
higher doses, and is due to both inhibition of sweating
as wellas stimulation of the temperature regulating
centrein thehypothalamus. Children are highly
susceptible.

20. Localanaestheticaction. Atropine has a mild
anaestheticaction on the cornea.
Thesensitivity of different organs and tissues
to atropine varies and can be graded as
Saliva, sweat, bronchial secretion > eye >
bronchial muscles > heart > intestinal and
bladder smooth muscles > gastric glands
and gastric smoothmuscles
“

21. Atropine andhyoscineare rapidly absorbed from
GIT. Applied to the eyes they penetrate the cornea.
Passage across BBB is somewhat restricted.
50% ofatropine is metabolized in the liver and
excreted unchangedin urine.
Ithas t
1/23–4h.
Hyoscineis morecompletely metabolized and has
betterBBB penetration.
Somerabbits have a specific atropine
esterase which degrades atropine very rapidly.

22. Scopalamine(hyoscine): Abelladdonaalkaloid
produce peripheral effects similar to atropine, it has
greater actions on CNS and longer duration of
action.
Mosteffectivein motionsickness, it is effective also
in blocking short term memory, it produce sedation
but at higher doses cause excitement.
DepressesCNS and causes amnesia, drowsiness,
euphoria, relaxation and sleep.
Givenparenterally, orally andtransdermally.

23. Itisinhalationalderivative of atropine useful in
treating asthma and COPD in patients unable to take
adrenergic agonist. Usefulin rhinorrhea. Also
excellent bronchodilator.
OpthalmicAgents-likehomatropine,cyclopentolate,
andtropicamideused mainly in ophthalmology.

24. Benztropine-used in drug induced Parkinson’s
disease. Useful for dystonic reactions caused by
antipsychotics.
Trihexyphenidyl-also used for treating Extra
Pyramidal Symptoms caused by some antipsychotics.

25. Flavoxate-relieves dysuria, urgency, frequency and pain
withgenito-urinary infections
Oxybutynin-has direct antispasmodic effects on
smooth muscle and anticholinergic effects. Decreases
frequency of voiding.
Tolterodine-is competitive, Antimuscarinic
anticholinergic that inhibits contraction. More
selective for this area than elsewhere in the body.

26. Trimethaphan-They act on nicotinic receptors of the
autonomic ganglia.
-They have no selectivity toward the parasympathetic
or sympathetic ganglia .
-The effect of these drugs is complex and
unpredictable so rarely used therapeutically,
-Used mainly in experimental pharmacology.
-Increase peristalsis and secretions.
-On largedose ofnicotine
-A)Bloodpressure falls because of ganglionicblockade
-B)Activityboth in GIT and UB musculature decrease.

27. Short acting competitive nicotinic ganglionic blocker
that must be given byi.vinfusion
It is used for the emergency lowering of the blood
pressure in hypertension caused by pulmonary
edema or dissecting aortic aneurysm, when other
agents cannot be used.
Neuromuscular blockingdrugs-
-Drugs that block cholinergic transmission between
motor nerve ending and the nicotinic receptors on
the neuromuscular end plate of the skeletal muscle.
-They are structural analogs of ACH.

28. Mydriaticandcycloplegicagent in the eye to permit
measurement of refractive errors.Mydriasisand
cycloplegiafor surgery
RS-Inbronchospasm whether related to asthma or
COPDbronchodilatingeffects
CVS-Atropineis used to increase heart rate in
symptomaticbradycardiasand higher blocks
GIT-Antispasmodic agent: Relax GIT and bladder.
Helpfulin treating irritable colon or colitis

29. Useful in gastritis,pylorospasmand ulcerative colitis as
they slow motility
Antispasmoticeffects seen in overactive bladder and in
urinary incontinence
Antidote for cholinergic agonists: To treat
organophsphoruspoisoning (present in insecticides),
and mushroom poisoning.
Antisecretoryagent: To block the secretion of upper
and lower respiratory tracts prior to surgery.
Helps toprevent vagal stimulation and potential
bradycardia

31. CNS-Parkinson’s Disease-
Useful in those with minimal side effects
Those who cannot take Levodopa
Helpful in decreasing salivation, spasticity and tremors

32. Absorption ofotherdrugs is slowed because atropine
delays gastric emptying.So doseoflevodopa,in
parkinsonism may haveto beincreased. But the extent of
digoxin andtetracyclinesabsorption may be increased.
Antacidsinterfere with the absorption ofanticholinergics.
Antihistaminics, tricyclic antidepressants,phenothiazines,
pethidinehave anticholinergicpropertyadditive side
effects
MAOinhibitors interfere with the metabolism ofcentral
antiparkinsoniandrugs (biperidenand others)delirium
may occur.

33. BPH
Myasthenia gravis
Hyperthyroidism
Glaucoma
Tachydysrhythmias

34. Drymouth, difficulty in swallowing and talking;
Difficultyinmicturition
Dilatedpupils, photophobia, blurringof nearvision;
palpitation; excitement, psychotic behavior,
Ataxia, delirium, hallucinations; hypotension, weakand
rapidpulse, cardiovascular collapse withrespiratory
depression;
Convulsionand coma (in very high doses).
It is very risky in individuals with glaucoma and BPH

35. Diagnosis:1mg neostigmines.c.fails to induce
typical M-effects.
Treatment:Gastric lavage with tannic acid (KMnO4is
ineffective in oxidation of atropine). The patient must
be kept in a dark quiet room.Galantamineorphyso-
stigmine(1-3mgs.c./i.v.), diazepam against
convulsion.

36. THANK YOU
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