PARKINSONISM Flashcards
What are the four signs of Parkinsons?
Rigidity of skeletal muscles
Akinesia
Flat facies
Tremor
(RAFT)
Give the two types of Parkinsons
Naturally occurring - unknown cause
Drug induced - usually reversible.
Give three types of drugs that cause drug induced parkinsonism
1) Butyrophenone and phenothiazine
2)Reserpine at high doses
3)MPTP a byproduct of attempted synthesis of meperidine that causes irreversible Parkinson’s
Give three ways in which Parkinsons is treated.
Increasing dopamine activity in brain
Decrease muscarinic cholinergic activity.
Both
Give the drugs that enhance dopaminergic activity in the brain.
1) Dopamine precursor such as levodopa
2) Dopamine agonists such as bromocriptine
3)MAO inhibitors such as selegiline
4) COMT inhibitors such as entacapone
5) Amantadine
(LABSE)
Give the muscarinic antagonist
benztropine
Why is levodopa given instead of dopamine
Levodopa is a precursor of dopamine that can readily cross the BBB unlike dopamine then converted to dopamine via dopa carboxylase /L-amino decarboxylase
Since dopa decarboxylase is found in many peripheral tissues it can cause adverse effects such as hypotension . To prevent this levodopa is administered with
carbidopa - an inhibitor of dopa decarboxylase in peripheral tissues but does not cross BBB
Although levodopa shows improvement in the first few years and slows mortality , it is limited due to three main things
Cannot cure parkinsonism.
The responsiveness fluctuates.
Patients experience decline in 3-5yrs due to progression of disease.
Levodopa experiences a phenomena known as
on-ff
The A/E of Levodopa may be grouped into Peripheral and CNS . Give examples of each
Peripheral
1) GIT problems - tolerance to the emetic action occurs after several months
2) Postural hypotension
3) Mydriasis
4) Blood dyscrasias
5) Positive Coombs test
6) Saliva and urine a brownish colour
CNS
1) Dyskinesia and psychosis that show overactivity of dopamine neurons.
2)Mood changes such as anxiety and depression
Levodopa has a short half life of
1-2 hrs
Give the relationship between levodopa and meals
Should be taken on an empty stomach
Give three main drug interactions with levodopa
1) Vb6 that causes its breakdown thus reducing effectiveness
2) MAOIs that can cause a hypertensive crisis
3) Antipsychotics that inhibit dopamine neurons thus worsening of the Parkinsons
Give the C/I of Levodopa
Patients with a history of psychosis
Wich two groups of patients should be monitored closely when taking Levodopa
Antipsychotic patients
Cardiac patients due to development of arrhythmias
The Dopamine receptor agonists can be grouped into
1) Ergot derivatives - bromocriptine
2) Non ergot derivatives - ropinirole , pramipexole , rotigotine and apomorphine
Dopamine receptor agonists are preferred to Levodopa as
They have a longer duration of action
They are effective in patients who experience flactuations with levodopa
Between Levodopa and Bromocriptine , which is more common in
1) Dyskinesia
2) Hallucination , confusion , postural hypotension , nausea
1) Levodopa
2) Bromocriptine
Bromocriptine acts on which dopamine receptor
It is a partial agonist at D2 receptors in the brain
Give three clinical uses of bromocriptine
1) As an individual drug
2) In combination with levodopa
3) Patients unable to tolerate levodopa
Give three types of patients that need to be monitored with use of Bromocriptine
In psychotic patients
History of vascular disease and MI
Can cause pulmonary and retroperitoneal fibrosis
Bromocriptine as an ergot derivative has 2 unique A/E
Erythromelalgia
Pulmonary infiltrates - pulmonary and retroperitoneal fibrosis
Give the classification of the non ergot Dopamine receptor agonists
Oral - Paramipexole and Ropinirole
Transdermal - Rotigotine
Injectable - Apormophine
Unlike bromocriptine , the non ergot Dopamine receptor agonists di nit cause
Pulmonary and retroperitoneal fibrosis
Vascular disease
Pramipexole has a high affinity for which dopamine receptor
D3
Pramipexole is termed as neuroprotective due to
Neuroprotective as it is a scavenger for hydrogen peroxide
Pramipexole is excreted renally , which drug may inhibit tubular secretin and increase its plasma kevels.
Cimetidine
Give the C/I of pramipexole
PUD , MI and psychotic illness
Ropinirole has an affinity for which dopamine receptor
D2
Ropinirole is metabolised by
CYP1A2
Apomorphine is mainly used for and what is the duration and onset of action
Temporary relief during off period of akinesia and has an onset of 10 min and a duration of 1-2hrs
Give an A/E of Apomorphine
Severe nausea , antiemetics given 3 days befre treatment
Give two examples of MAOIs
Selegiline
Rasagiline
Selegiline undergoes hepatic metabolism to give
Desmethylselegiline and amphetamine
Give the DDI of MAOIs
1) When given with Mepiridine it can cause mortality , agitation and delirium
2) Selegiline when combined with ssris can cause serotonin syndrome
Give examples of COMT inhibitors
Entacapone and Tolacapone
Give the MOA of COMT
COMT is an enzyme found in the brain and peripheral tissues that coverts L-dopa to 3-O-methyldopa (3-OMD)
COMTIs increase on time
true
What should be monitored with Tolacapone
LFTS
