parkinsonism dan anticholinergic

7/21/2019 Parkinsonism Dan Anticholinergic

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Parkinsonism

• Parkinsonism is characterized by acombination of rigidity, bradykinesia,tremor, and postural instability thatcan occur for a variety of reasons butis usually idiopathic (Parkinson'sdisease or paralysis agitans).

• Cognitive decline occurs in manypatients as the disease advances



Top: Dopaminergic neurons (red) originating in the substantia nigranormally inhibit the !"!ergic output from the striatum, #hereas

cholinergic neurons (orange) e$ert an e$citatory e%ect. Bottom: &nparkinsonism, there is a selective loss of dopaminergic neurons



• Cardinal Features"radykinesiaPostural instability

esting tremor (may have postural andaction components)igidity



• Motor SymptomsDecreased de$terityDysarthriaDysphagia

estinating gaitle$ed posturereezing at initiation of movementypomimia

ypophonia*icrographia+lo# turning



• Autonomic Symptoms"ladder and anal sphincter disturbancesConstipation

Diaphoresisrthostatic blood pressure changesParo$ysmal -ushing+e$ual disturbances



• Mental Status Changes"radyphreniaConfusional state

DementiaPsychosis (paranoia, hallucinosis)+leep disturbance



• Otheratiguabilityily skin

Pedal edema+eborrheaeight loss



Common types of gait abnormalities



eneral algorithm for treating early idiopathic

Parkinson's disease.



!lgorithm for treating advanced idiopathicParkinson's disease. C, controlled release/ C*0,

catechol11methyltransferase



!nticholinergic *edications

• !nticholinergic drugs can be e%ectivefor tremor and dystonic features insome patients but rarely sho#substantial bene2t for bradykinesia orother disabilities.

• 0hey can be used as monotherapy orin con3unction #ith otherantiparkinsonian drugs.



Amantadine• !mantadine is often e%ective for mild symptoms,

especially tremor. &t may also decrease dyskinesia atrelatively high doses (455 mg6day).

• &ts precise mechanism of action is unkno#n but mayinvolve dopaminergic or nondopaminergic mechanismssuch as inhibition of 71methyl1d1aspartate receptors.

• !dverse e%ects include sedation, vivid dreams, dry

mouth, depression, hallucinations, an$iety, dizziness,psychosis, and confusion. 8ivedo reticularis (a di%usemottling of the skin) is a common but reversible sidee%ect



Levodopa and Carbidopa/Levodopa• 8evodopa, the most e%ective drug

available, is the immediate precursor ofdopamine. &t crosses the blood1brain

barrier, #hereas dopamine does not.• 0he decision to start 81dopa as soon as the

diagnosis is made or only #hen symptomscompromise social, occupational, orpsychological #ell1being hasgenerated controversy



Cholinergic nerves are sho#n in blue/ noradrenergic in red/ and dopaminergic in green.7ote that some sympathetic postganglionic 2bers release acetylcholine or dopaminerather than norepinephrine. 0he adrenal medulla, a modi2ed sympathetic ganglion,

receives sympathetic preganglionic 2bers and releases epinephrine and norepinephrineinto the blood. !Ch, acetylcholine/ D, dopamine/ 9pi, epinephrine/ *, muscarinic



Cholinoceptor1!ctivating :Cholinesterase1&nhibiting Drugs

• !cetylcholine1receptor stimulants and cholinesteraseinhibitors together make up a large group of drugsthat mimic acetylcholine (cholinomimetic agents)

• Cholinoceptor stimulants are classi2ed

pharmacologically by their spectrum of action,depending on the type of receptor;muscarinic ornicotinic;that is activated.

• Cholinomimetics are also classi2ed by their

mechanism of action because some bind directly to(and activate) cholinoceptors #hereas others actindirectly by inhibiting the hydrolysis of endogenousacetylcholine



!nticholinergic

• Cholinergic blocking drugs also arecalled anticholinergics orparasympathomimetic blocking

drugs.

• 9$amples of cholinergic blockingdrugs include atropine, scopolamine,

and propantheline



ACTO!S

• Cholinergic blocking drugs inhibit theactivity of acetylcholine inparasympathetic nerve 2bers

• hen the activity of acetylcholine isinhibited, nerve impulses travelingalong parasympathetic nerve 2bers

cannot pass from the nerve 2ber tothe e%ector organ or structure.



Sites of actions of cholinergic antagonists



!ntimuscarinic !gents

!tropine

• a tertiary amine belladonna alkaloid, has ahigh a<nity for muscarinic receptors,

#here it binds competitively, preventingacetylcholine from binding to those sites .

• !tropine acts both centrally and

peripherally.



Competition o" atropine and scopolamine #ithacetylcholine "or the muscarinic receptor



Dose1dependent e%ects of atropine



Pharmacokinetics=

!tropine is readily absorbed, partiallymetabolized by the liver, andeliminated primarily in the urine.

&t has a half1life of about 4 hours.



0herapeutic uses

– phthalmic= &n the eye, topical atropinee$erts both mydriatic and cycloplegic

e%ects+horter1acting antimuscarinics(cyclopentolante and tropicamide) havelargely replaced atropine due toprolonged mydriasis observed #ithatropine (>1?4 days versus @1A4 hours#ith other agents).



– !ntispasmodic= !tropine is used as anantispasmodic agent to rela$ the & tract andbladder.

– !ntidote for cholinergic agonists= !tropine is used

for the treatment of overdoses of cholinesteraseinhibitor insecticides and some types of mushroompoisoning (certain mushrooms contain cholinergicsubstances that block cholinesterases).

–

!ntisecretory= 0he drug is sometimes used as anantisecretory agent to block secretions in theupper and lo#er respiratory tracts prior to surgery.



!dverse e%ects=

• Depending on the dose, atropine maycause dry mouth, blurred vision,tachycardia, and constipation.

•

9%ects on the C7+ include restlessness,confusion, hallucinations, and delirium,#hich may progress to depression, collapseof the circulatory and respiratory systems,and death.

• 8o# doses of cholinesterase inhibitors suchas physostigmine may be used toovercome atropine to$icity.



• &n older individuals, the use of atropine toinduce mydriasis and cycloplegia is consideredto be too risky, because it may e$acerbate anattack of glaucoma in someone #ith a latent

condition.

• &n other older individuals, atropine may induceurinary retention that is troublesome.

•

Children are sensitive to e%ects of atropine,the rapid increases in body temperature that itmay elicit. 0his may be dangerous in children.



+copolamine

!ctions=

• +copolamine is one of the moste%ective antimotion sickness drugs .

• +copolamine also has the unusual e%ectof blocking short1term memory.

• &n contrast to atropine, scopolamineproduces sedation, but at higher dosesit can produce e$citement instead.+copolamine may produce euphoria andis sub3ect to abuse



Pharmacokinetics and adverse e%ects=

• 0hese aspects are similar to those ofatropine



0ropicamide and cyclopentolate

• 0hese agents are used as ophthalmicsolutions for similar conditions asatropine (mydriasis and cyclopegia).

• Duration of action is shorter thanthat of atropine/ tropicamideproduces mydriasis for @ hours and

cyclopentolate for A4 hours.

$%ects o" the Cholinergic



$%ects o" the CholinergicBloc&ing

'rugs



A'($)S$ )$ACTO!S

• Central nervous system—headache, fushing,nervousness, dro#siness, #eakness, insomnia,nasal congestion, fever

B Eyes—blurred vision, mydriasis, photophobia,cycloplegia, increased ocular tension

B Gastrointestinal tract—nausea, vomiting, dicultyin s#allo#ing, heartburn

B Urinary tract—urinary hesitancy and retention,dysuria

B Cardiovascular system—palpitations, bradycardia(after lo# doses of atropine), tachycardia (afterhigher doses of atropine)

B Other—urticaria, anaphylactic shock, other skinmanifestations

!d % l b d i h



!dverse e%ects commonly observed #ithcholinergic antagonists



CO!T)A!'CATO!S

parkinsonism dan anticholinergic

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