Parkinson's Flashcards
CATECHOL-O-METHYLTRANSFERASE INHIBITORS
- Inhibition of COMT by tolcapone and entacapone leads to:
- Decreased metabolism of levodopa
- Decreased plasma levels of 3-O-methyldopa
- Increased uptake of levodopa
- Higher dopamine levels in the brain.
AMANTADINE AE
- May cause restlesness, agitation, confusion, hallucinations.
- At high doses: acute toxic psychosis.
- Peripheral edema: not accompanied by signs of cardiac, hepatic or renal disease; responds to diuretics.
- Amantadine should be used with caution in patients with a history of seizures or heart failure.
AMANTADINE
- Antiviral drug with antiparkinsonian actions.
- Increases synthesis, release or re-uptake of dopamine from the surviving neurons.
- Less efficacious than levodopa and tolerance develops more readily, but it has fewer side effects.
What is Livedo reticularis?
• Livedo reticularis sometimes occurs in patients taking amantadine. Usually clears within a month of withdrawing the drug.
Strategy of tx. for PD
Therapy is aimed at restoring dopamine in the basal ganglia and antagonizing the excitatory effect of cholinergic neurons, thus reestablishing the correct dopamine/ACh balance
drugs used in PD:
DRUGS THAT RESTORE
DOPAMINE ACTIONS
- DOPAMINE PRECURSORS - DOPAMINE RECEPTOR AGONISTS - INHIBITORS OF DOPAMINE METABOLISM - AMANTADINE
Miscellaneous Adverse Effects of dopamine agonists?
- Ergot dopamine agonists: Headache, nasal congestion, increased arousal, pulmonary infiltrates, pleural and retroperitoneal fibrosis, and erythromelalgia.
- Pramipexole, ropinirole and rotigotine: Uncontrollable somnolence. This requires discontinuation of the medication.
Dopamine agonists: CI
- Dopamine agonists are contraindicated in patients with a history of psychotic illness or recent MI.
- Best avoided in patients with peripheral vascular disease or peptic ulceration
CATECHOL-O-METHYLTRANSFERASE INHIBITORS AE
- Tolcapone and Entacapone
- Fulminating hepatic necrosis is associated with the use of tolcapone
- Entacapone is not hepatotoxic and is therefore preferred.
DOPAMINE RECEPTOR AGONISTS:
- ERGOT DOPAMINE AGONIST
- NON ERGOT DOPAMINE AGONISTS
ERGOT D2 AGONIST:
- BROMOCRIPTINE
NONERGOT D AGONIST:
- Pramipexole AND ropinirole, rotigotine
ANTIMUSCARINICS
- Adjuvant therapy.
- May improve tremor and rigidity but have little effect on bradykinesia.
- Can produce mood changes, xerostomia, pupillary dilation, confusion, hallucinations, and urinary retention.
- Cannot be used in patients with glaucoma, prostatic hypertrophy or pyloric stenosis.
DOPAMINE AGONISTS AE?
GI Effects •Anorexia, nausea and vomiting, constipation, dyspepsia. •Bleeding from peptic ulceration. Cardiovascular Effects •Postural hypotension. •Cardiac arrhythmias. •Peripheral edema. •Ergot derivatives may cause painless digital vasospasm Dyskinesias • Abnormal movements. Mental Disturbances • Confusion, hallucinations, delusions.
DOPA levels in the brain are low because?
how is this used to our advantage when adminisitering substrate?
DOPA decarboxylase turns over so rapidly that DOPA levels in the brain are negligible under normal conditions.
-It is therefore possible to enhance the formation of dopamine by providing this enzyme with increased amounts of substrate
The On-Off Phenomenon
What drug is administered to help?
•
Fluctuations in response unrelated to the timing of doses.
•
The exact mechanism is unknown.
•
For patients with severe off-periods who are unresponsive to other measures, apomorphine SC may provide benefit
NONERGOT DOPAMINE AGONISTS: RESCUE THERAPY
- Rescue therapy for treatment of “off” episodes of akinesia in patients on dopaminergic therapy.
- Emetogenic; pretreatment with an antiemetic is recommended.
- Other adverse effects: QT prolongation, dyskinesias, drowsiness, sweating, hypotension and bruising at the injection site.
