E1: Parkinsons Flashcards
(42 cards)
What are the 4 major features of Parkinson’s disease?
- Bradykinesia
- Muscular rigidity
- resting tremor
- Impairment of postural balance and gait
What is the pathophysiology behind Parkinson’s disease?
- Loss of dopamine neurons in the Substantia Nigra pars compacta
- Symptoms develop when 70-80% loss of the DA neurons
How does L-Dopa treat Parkinson’s?
- “replacement”therapy
- Increases DA levels, dopamine does not cross the BBB, but L-Dopa does and si then converted to DA in the neuron
How long can L-Dopa treat the symptoms of Parkinsons?
- Improvement of PD symptoms for 3-4 years, and then the effectiveness will decrease
- Does not affect progression of disease and not effective in drug-induced Parkinsonism
Why Is Carbidopa often given with L-Dopa?
L-Dopa can be converted to DA in the periphery and Carbidopa inhibits Dopa-decarboxylase but doesn’t cross the BBB. Therefore conversion of L-Dopa to DA is inhibited in periphery but not in the brain
What are the side effects of L-Dopa/Carbidopa?
- N/V
- Postural hypotension, Arrhythmias, HTN
- dyskinesias
- Depression, anxiety, agitation (treat with atypical antipsychotics)
What is the “On-Off Phenomenon?”
- Fluctuations in the clinical response in patients on successful L-Dopa therapy
- “On” is improved mobility
- “Off” is Akinesia due to falling drug levels
What drug can be used as a rescue during an Off phase on L-Dopa therapy?
Apomorphine
What drugs cannot be given with L-Dopa and why?
- MAOI: may cause hypertensive crisis
- Pyridoxine: increases peripheral metabolism of L-Dopa thus decreases effectiveness
What are the contraindications of L-Dopa?
- Psychosis
- closed angle glaucoma
- Cardiac disease
- active peptic ulcer disease
- malignant melanoma
What kind of drugs are Selegiline, Rasagiline, and Safinaminde?
MAOIs
What is the MOA of MAOIs?
- Inhibits DA metabolism
- Inhibits MAO-B in the CNA and reduces striata metabolism of DA, does not affect peripheral metabolism of DA by MAO-B
** may inhibit progression of PD by decreasing free radicals produced during DA metabolism
What are the Adverse effects of MAO-BIs?
- Insomnia
- Severe HTN if combined with other MAOIs
- increase side effects of L-DOPA
- Do NOT combined with Meperidine: can lead to stupor, rigidity, agitation, serotonin syndrome
- Serotonin syndrome if combined with TCAs or SSRIs
What kind of drugs are Tolcapone and Entacapone?
COMT inhibitors: inhibits DA and L-Dopa metabolism
What is the MOA of tolcapone?
-Inhibits COMT in CNS and periphery, prolongs action of DA in the CNA, increases pool of L-Dopa for transport into the brain
What is the MOA of Entacapone?
-Inhibits COMT in periphery only, increases pool of L-Dopa for transport in the brain
What are the side effects of COMT inhibitors?
-Dyskinesia, confusion, nausea, hypotension, abdominal pain, sleep disturbance, and orange color to urine
What kind of drug is Stalevo?
A combination of L-Dopa, Carbidopa, and Entacapone
What is the MOA of DA receptor agonists?
- Stimulates DA receptors
- acts directly on receptors, Primarily DA D2
- because thy act directly on receptors, they continue to be effective as the disease progresses
What kind of drug is Bromocriptine, Ropinirole, Pramipexole, and apomorphine
-DA receptor agonist
What are the side effects of Bromocriptine?
Vasospasm, erythromelagia
Which drugs can be used as Monotherapy in mild PD and has a soothing response to L-Dopa in late PD?
Ropinirole and Pramipexole
What is the DOC of restless leg?
Ropinirole, a relatively pure DA D2 agonist
Since Apomorphine causes nausea, you should pretreat with an antiemetic. Which one should you use, and which should you avoid?
- Use trimethobenzamide
- avoid antiemetic that target the serotonin system (ondansetron) because it can cause HTN and LOC
- Avoid antiemetics that blocks DA D2 receptors (Prochlorperazine)
