anti parkinson's drugs parkinsonism a neurological syndrome usually resulting from deficiency...
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Anti Parkinson's DrugsAnti Parkinson's Drugs
ParkinsonismParkinsonism A neurological syndrome usually resulting A neurological syndrome usually resulting
from deficiency of the neurotransmitter from deficiency of the neurotransmitter dopamine as the consequence of degenerative, dopamine as the consequence of degenerative, vascular, or inflammatory changes in the basal vascular, or inflammatory changes in the basal ganglia. ganglia.
Characterized by rhythmical muscular tremors, Characterized by rhythmical muscular tremors, rigidity of movement, bradykinesia, droopy rigidity of movement, bradykinesia, droopy posture. posture.
Coronal slices of human brain showing the basal Coronal slices of human brain showing the basal
ganglia.ganglia.ROSTRAL: striatum, globus pallidus (GPe and GPi)ROSTRAL: striatum, globus pallidus (GPe and GPi)CAUDAL: subthalamic nucleus (STN), substantia CAUDAL: subthalamic nucleus (STN), substantia nigra (SN)nigra (SN)
Signs Signs
Remember RAFTRemember RAFT
R R = rigidity of skeletal muscles= rigidity of skeletal musclesA A = akinesia (loss of voluntary movement)= akinesia (loss of voluntary movement)F F = flat facies= flat faciesT T = tremor at rest (not always)= tremor at rest (not always)
CLASSIC FEATURESCLASSIC FEATURES
SHUFFLING GAIT SHUFFLING GAIT STOOPING POSTURE STOOPING POSTURE DECREASED ARM SWING DECREASED ARM SWING TURNING EN BLOCTURNING EN BLOC DYSPHONIA DYSPHONIA MOOD DISTURBANCES MOOD DISTURBANCES SLEEP DISTURBANCESSLEEP DISTURBANCES MEMORY LOSSMEMORY LOSS
Secondary Parkinsonism Secondary Parkinsonism
Sometimes parkinsonism like symptoms Sometimes parkinsonism like symptoms follow after viral encephalitis or multiple follow after viral encephalitis or multiple vascular lesions.vascular lesions.
Phenothiazines and Haloperidol – action block Phenothiazines and Haloperidol – action block dopamine receptors – may produce Parkinson's dopamine receptors – may produce Parkinson's symptoms.symptoms.
Strictly not used in the pt.’s with Strictly not used in the pt.’s with parkinsonism. parkinsonism.
Dopamine Dopamine
Dopamine: Dopamine:
does not cross: blood-brain barrier does not cross: blood-brain barrier
ineffective if administered peripherallyineffective if administered peripherally
Drugs usedDrugs used
LevodopaLevodopa CarbidopaCarbidopa BromocriptineBromocriptine AmantadineAmantadine Anticholinergic agentsAnticholinergic agents Deprenyl ( Selegiline)Deprenyl ( Selegiline)
Levodopa Levodopa
L-DOPA: L-DOPA: metabolic precursor of dopamine metabolic precursor of dopamine enters the brain enters the brain decarboxylation to dopamine decarboxylation to dopamine
L-DOPA L-DOPA
Rapid absorption from small intestine, Rapid absorption from small intestine, influenced by: influenced by:
gastric emptying rate gastric emptying rate local pH local pH Food– avoid heavy mealsFood– avoid heavy meals Excretion : urineExcretion : urine Amount reaching brain : very lessAmount reaching brain : very less Rest : peripheral decarboxylation to dopamine.Rest : peripheral decarboxylation to dopamine.
To achieve therapeutic brain levels, To achieve therapeutic brain levels, either: either:
Large quantities to be givenLarge quantities to be given
With a dopa decarboxylase inhibitor, such as With a dopa decarboxylase inhibitor, such as Carbidopa Carbidopa
Carbidopa does not penetrate BBBCarbidopa does not penetrate BBB
Clinical Use :Levodopa Clinical Use :Levodopa
Does not stop disease progression Does not stop disease progression
May reduce Parkinson's disease mortality rate May reduce Parkinson's disease mortality rate
Most effective in diminishing bradykinesia Most effective in diminishing bradykinesia
Adverse Effects :Levodopa Adverse Effects :Levodopa
GIT ; vomiting, tolerance develops.GIT ; vomiting, tolerance develops. CVS : Tachycardia, Ventricular extra systolesCVS : Tachycardia, Ventricular extra systoles MC : Postural/orthostatic hypotensionMC : Postural/orthostatic hypotension HTN : if large doses takenHTN : if large doses taken Arrhythmias Arrhythmias Dyskinesias Dyskinesias MC: Choreoathetosis MC: Choreoathetosis
Behavioral Effect : depression, agitation, Behavioral Effect : depression, agitation, insomnia , anxiety, confusion, delusions insomnia , anxiety, confusion, delusions
Precipitation/worsening: Gout Precipitation/worsening: Gout
Mydriasis– adrenergic action Mydriasis– adrenergic action
Contraindications Contraindications
Psychotic patients Psychotic patients Angle-closure glaucoma Angle-closure glaucoma History of melanoma/suspicious undiagnosed History of melanoma/suspicious undiagnosed
skin lesions. skin lesions. Vit. B-6.- increases peripheral breakdownVit. B-6.- increases peripheral breakdown Careful management : CVS disease, PUDCareful management : CVS disease, PUD Not with MAO – I > HTN crisis.Not with MAO – I > HTN crisis.
Carbidopa Carbidopa
Peripheral decarboxylase inhibitor which Peripheral decarboxylase inhibitor which doesn't cross the BBBdoesn't cross the BBB
To decrease peripheral decarboxylation of To decrease peripheral decarboxylation of
L-dopa.L-dopa. Carbidopa leads to decreased side-effects and Carbidopa leads to decreased side-effects and
decreased dosage of L-dopa required.decreased dosage of L-dopa required.
Dopamine Agonists Dopamine Agonists
Directly activate dopamine receptors Directly activate dopamine receptors Not requiring enzymatic activation Not requiring enzymatic activation
Bromocriptine Bromocriptine
Clinical Use :Bromocriptine Clinical Use :Bromocriptine
Compared with Levodopa: Compared with Levodopa: Less incidence of response fluctuation and Less incidence of response fluctuation and
Dyskinesias Dyskinesias
Adverse Effects Adverse Effects GIT : nausea, vomiting GIT : nausea, vomiting Peptic ulceration with bleeding Peptic ulceration with bleeding CVS : postural hypotensionCVS : postural hypotension Behavioural : confusion, hallucinations, delusionsBehavioural : confusion, hallucinations, delusions
Contraindications Contraindications
History/presence of psychosis History/presence of psychosis Recent myocardial infarction Recent myocardial infarction
Relative contraindications :Relative contraindications : Peripheral vascular disease or peptic ulcerPeripheral vascular disease or peptic ulcer
Monoamine Oxidase InhibitorsMonoamine Oxidase Inhibitors MAO-A : serotonin/ norepinephrine MAO-A : serotonin/ norepinephrine MAO-B : metabolizes dopamine MAO-B : metabolizes dopamine
Selegiline : Selective MAO - B inhibitorSelegiline : Selective MAO - B inhibitor Adjunctive treatment to L-DOPA Adjunctive treatment to L-DOPA
C I : C I : Meperidine Meperidine Tricyclic antidepressants Tricyclic antidepressants SSRISSRI
Amantadine Amantadine
Antiviral drug Antiviral drug Mechanism of action: unclear Mechanism of action: unclear
Clinical Use Clinical Use Short-term benefits; less potent Levodopa Short-term benefits; less potent Levodopa Improves rigidity, tremor, bradykinesia Improves rigidity, tremor, bradykinesia
Adverse Effect Adverse Effect Hallucinations, confusion, irritability, Hallucinations, confusion, irritability,
depression depression Over dosage: acute psychosis Over dosage: acute psychosis Livedo reticularis: -- reddish blue skin Livedo reticularis: -- reddish blue skin
mottling, affecting extremities mottling, affecting extremities CHF, orthostatic hypotension , peripheral CHF, orthostatic hypotension , peripheral
edema edema GIT: nausea, vomitingGIT: nausea, vomiting With caution : CHF, convulsions.With caution : CHF, convulsions.
AnticholinergicsAnticholinergics
Clinical Use Clinical Use Improvement: rigidity/tremor Improvement: rigidity/tremor Minor effect: bradykinesia Minor effect: bradykinesia
Benztropine Benztropine Biperiden Biperiden Orphenadrine Orphenadrine Procyclidine Procyclidine Trihexyphenidyl Trihexyphenidyl
CI :CI : Prostatic hyperplasia Prostatic hyperplasia Obstructive gastrointestinal disease Obstructive gastrointestinal disease
Catechol o methyl tranferace inhibitorsCatechol o methyl tranferace inhibitors When peripheral dopamine decarboxylase When peripheral dopamine decarboxylase
activity is inhibited, a significant amount of activity is inhibited, a significant amount of methyl dopa is formed which competes with methyl dopa is formed which competes with levodopa for active transport into the CNS.levodopa for active transport into the CNS.
Inhibition of COMT by Tolcapone Inhibition of COMT by Tolcapone /entacapone leads to increased central uptake /entacapone leads to increased central uptake of levodopa. of levodopa.
Physiologic postural tremor Physiologic postural tremor (normal)(normal)
Drug-Induced– Drug-Induced– Bronchodilators Bronchodilators Tricyclic antidepressants Tricyclic antidepressants Lithium Lithium
Rx : Propranolol. Rx : Propranolol.
Chorea Chorea
Dopaminergic nigrostriatal pathway over Dopaminergic nigrostriatal pathway over activity activity
Anti-Dopaminergic agents:Anti-Dopaminergic agents: Reserpine Reserpine Phenothiazines and Butryophenones Phenothiazines and Butryophenones
(haloperidol) (haloperidol)
DRUGS USED IN ALZHEIMER DRUGS USED IN ALZHEIMER DISEASEDISEASE
Alzheimer dementia 3 distinguishing featuresAlzheimer dementia 3 distinguishing features Accumulation of senile plaquesAccumulation of senile plaques Neurifibrillary tanglesNeurifibrillary tangles Loss of cortical neurons –cholinergicLoss of cortical neurons –cholinergic Drugs used—inhibition of acetyl choline esteraceDrugs used—inhibition of acetyl choline esterace Donepezil, galantamine, rivastigmine & tacrineDonepezil, galantamine, rivastigmine & tacrine Galantamine competitive inhibitorGalantamine competitive inhibitor Tacrine--hepatotoxicTacrine--hepatotoxic
NMDA receptor antagonistNMDA receptor antagonist Antagonist of NMDA receptors are Antagonist of NMDA receptors are
neuroprotectiveneuroprotective Memantine—slows the rate of memory lossMemantine—slows the rate of memory loss Prevents loss of neuronsPrevents loss of neurons
DRUGS USED IN MULTIPLE DRUGS USED IN MULTIPLE SCLEROSISSCLEROSIS
MS is an autoimmune inflammatory MS is an autoimmune inflammatory demyelinating disease of the CNS.demyelinating disease of the CNS.
Corticosteroids for acute attacks have been Corticosteroids for acute attacks have been usedused
Cyclophosphamide and azathioprine can also Cyclophosphamide and azathioprine can also be triedbe tried
Newer drugs interferon beta 1a and 1bNewer drugs interferon beta 1a and 1b Mitoxantrone, Dalfampridine and fingolimod Mitoxantrone, Dalfampridine and fingolimod
are also used noware also used now