Side effects

Question 1

Levodopa ADR

Answer 1

• ADRs

– Nausea / vomitting 
– Orthostatic hypotension 
– Drowsiness, sudden sleep onset 
– Hallucinations, psychosis 
– Dyskinesias  
        • Usual onset : within 3-5 years of initiating treatment with levodopa 

Dyskinesias
– Involuntary, uncontrollable 
– Twitching, jerking 
– Not tremor 
– Peak dose dyskinesia 
– Dystonia

Question 2

Levodopa DDI

Answer 2

• Pyridoxine
– Cofactor for dopa decarboxylase
– Generally not a problem if levodopa is administered with a DCI but…
– unless on ?High dose B6 for haematological problems or in high potency vit B6 —-> need do med review to confirm

• Iron
• Protein
Both can bind to LD and decrease absorption. need space 2 hr apart. Move protein to night time.

• Antidopaminergic drugs 
–Metoclopramide, prochlorperazine 
– Antiemetic of choice in PD = domperidone 
– 1st generation antipsychotics 
– Risperidone --> ~2mg can exhibit EPSE

• Volatile general anaesthetics – Sevoflurane, halothane • Nonselective MAOis

Question 3

Dopamine agonists – adverse effects

Answer 3

Dopaminergic - peripheral
• Nausea, vomitting
• Orthostatic hypotension
• Leg oedema

Dopaminergic - central
• Hallucinations (usually visual > auditory)
• Somnolence, day-time sleepiness
• Compulsive behaviours – Gambling, shopping, eating, hypersexuality

Non-dopaminergic adverse effects
• Fibrosis
– Pulmonary, pericardiac, retro-peritoneal
– May be partially reversible upon withdrawal
– Lower risk with non-ergot agents

• Valvular heart disease
– Incidence appears to be greater with ergot-derived agents

Question 4

• MAOI Drug interactions

Answer 4

• MAOI Drug interactions
– SSRIs, SNRIs, TCAs
• Washout periods recommended

– Pethidine , tramadol, 
– Linezolid 
– Dextromethorphan 
– Dopamine  
– Sympatomimetics : nasal decongestants e.g. pseudoephedrine, phenylephrine 
– Another MAOi

Question 5

MAOI FDI

Answer 5

Food interactions

• Chemical of concern = tyramine
– Metabolised by both MAO-A and MAO-B
• No firm guidelines regarding the necessity for dietary restrictions
– Europe AND SIngapore – no restriction
– US – absolute restrictions hold for aged cheeses & meats, draft beer, fermented food (sauerkraut, kimchi), Marmite, banana peel.

• In practice, patients should be advised to avoid such foods

Question 6

Entacapone • Drug interactions and ADR

Answer 6

– iron, calcium,
– Avoid concurrent nonselective MAOi (but safe with MAOBi, caution with selective MAO-Ai)
– any catecholamine drug
– Enhance anticoagulant effect of warfarin

• Diarrhoea, urine discolouration (orange)
• May cause dyskinesia upon initiation
– May require a DECREASE in levodopa dose

• May also potentiate other dopaminergic effects
– Orthostatic hypotension, nausea/vomitting

Question 7

Amantadine • Adverse effects

Answer 7

– Nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis

Question 8

Drug - induced parkinsonism

Answer 8

• Dopamine depleting drugs
– Tetrabenazine

• Others (?MOA) 
– Sod valproate 
– Lithium  
– Lamotrigine 
– Cinnarizine