PARKINSONISM

• Most common example of a family of

neurodegenerative disorders.
• Parkinsonism, defined as a paucityand
slowness of movement (bradykinesia), tremor
at rest, rigidity, shuffling gait, and flexed
posture.
• result from a reduction of dopaminergic
transmission within the basal ganglia.
• Its peak age of onset is in the 60s.
• Familial clusters of autosomal dominant and
recessive forms of PD comprise 5% of cases.
• Characterized by an earlier age of onset.
• Three cardinal signs— rest tremor, rigidity, and
bradykinesia.
• Micrographia
• Hypophonia
• bulbar bradykinesia.
• Dystonia
• Gait disturbance.
• Non-Motor Features-depression and anxiety,
cognitive impairment, sleep disturbances, sensory
abnormalities and pain, anosmia and disturbances of
autonomic function.
• Neuropsychiatric Symptoms-Changes in mood,
cognition, and behavior in later stages of PD.
 Levodopa
• Crosses the blood-brain barrier and is
converted to dopamine in basal ganglia and
periphery.
• Absorbed from the small bowel.
• T max is 0.5 to 2 h and may be delayed in
presence of food.
• Rate of absorption is dependent upon rate of
gastric emptying, pH of gastric juice, and length
of time drug is exposed.
• Plasma t ½ is 1 to 3 h.
• Initial buffering and prolonged postsynaptic
effect.
 Indications and Usage
• Treatment of idiopathic, postencephalitic, and
symptomatic parkinsonism.
Unlabeled Uses
• Relief of herpes zoster (shingles) pain and
restless leg syndrome.
• Contraindications
Narrow-angle glaucoma; concomitant MAOI
therapy (excluding MAOI-type B agents) ;
history of or suspected melanoma.
 Adverse Reactions
• Cardiovascular-Cardiac irregularity, palpitation;
orthostatic hypotension; hypertension.
• CNS-Ataxia; headache; dizziness; numbness;
weakness; faintness; confusion; insomnia;
nightmares, psychosis, choreiform or dystonic
movements.
Induction of hallucinations and confusion.
• Dermatologic-Flushing; skin rash; sweating.
• EENT-Blepharospasm; diplopia; blurred vision;
dilated pupils; impaired taste perception.
• GI-Anorexia; nausea; vomiting; abdominal pain;
distress; dry mouth.
• Genitourinary-Urine retention; urinary
incontinence; priapism.
• Hematologic-Hemolytic anemia; anemia;
agranulocytosis; leukopenia.
• Hepatic-Elevated AST, ALT, LDH.
• Respiratory-Bizarre breathing patterns.
• activation of malignant melanoma.
• Miscellaneous-hot flashes; weight gain or loss;
dark sweat or urine.
• Management of drug-related motor fluctuations
in Parkinson's disease.
 Bromocriptine
• dopamine receptor agonist
• directly stimulating the dopamine receptors in
the corpus striatum.
• may permit a reduction of the maintenance
dose of levodopa.
• Patients unresponsive to levodopa are poor
candidates for Bromocriptine mesylate therapy.
• administered alone or concomitantly with
levodopa may cause hallucinations.
 Contraindications
• Uncontrolled hypertension.
• pregnancy
 ADRs
• nausea, abnormal involuntary movements,
hallucinations, confusion, "on-off“ phenomenon,
dizziness, drowsiness, faintness/fainting,
vomiting, asthenia, abdominal discomfort
• visual disturbance, ataxia, insomnia,
depression,
• hypotension, shortness of breath, constipation,
and vertigo.
• blepharospasm, dry mouth, dysphagia, edema
of the feet and ankles, erythromelalgia.
• epileptiform seizure, fatigue, headache,
lethargy, mottling of skin, nasal
stuffiness,nervousness, nightmares,
paresthesia, skin rash, urinary frequency.
• Exacerbation of Raynaud's Syndrome.
• elevations in blood urea nitrogen, SGOT,
SGPT, GGPT, CPK, alkaline phosphatase and
uric acid.
 Pergolide
• ergot derivative dopamine receptor agonist at
both D and D receptor sites.
• 10 to 1000 times more potent than
bromocriptine.
• inhibits the secretion of prolactin in humans; it
causes a transient rise in serum concentrations
of growth hormone and a decrease in serum
concentrations of luteinizing hormone.
• Pergolide sulfoxide and pergolide sulfone are
dopamine agonists.
 ADRs
• Cardiac Valvulopathy and Fibrotic
Complications.
• Falling Asleep During Activities of Daily Living.
• Symptomatic Hypotension.
• Hallucinosis.
• APCs and sinus tachycardia.
• neuroleptic malignant syndrome-with rapid
dose reduction, withdrawal.
• Dyskinesia.
• Peripheral edema, Anemia, Dry mouth
 Pramipexole
• Nonergot dopamine receptor agonist.
• Bioavailability is more than 90%.
ADRs