Levodopa

Question 1

What is Levodopa?

Answer 1

immediate precursor of dopamine, but can be taken orally and crosses the bbb

Question 2

What class of compounds does levodopa belong to?

Answer 2

movement disorders

Question 3

What are other drugs in the same class as levodopa?

Answer 3

apomorphine hydrochloride
ropinirole
selegiline HCl
Benztropine mesylate
Entacaope
Orphenadrine HCl

Question 4

What is levodopa indicated for?

Answer 4

• Parkinson’s disease
• postencephalitic parkinsonism
• symptomatic parkinsonism which may follow injury to nervous system by CO intoxication and manganese intoxication
• for the reduction of ‘off’ fime in patients previously treated with standard formulations

Question 5

What is the mechanism of levodopa?

Answer 5

Replenishes dopamine levels in the striatum, the neurotransmitter depleted and thought to be responsible for parkinson’s symptoms

Question 6

What is the role of levodopa in parkinson’s therapy?

Answer 6

• gold standard for parkinson’s, and still considered most efficacious.
• can also be used as adjuvant therapy particularly in early onset where it can be added later in life

Question 7

What is the dose of levodopa given in parkinson’s?

Answer 7

Oral immediate release: Adult initially 100mg (with carbidopa 25mg) tds, increased by 100mg daily or on alternate days according to response and tolerability. Max 800mg (with carbidopa 200mg) daily in divided doses. If higher doses are required, change to 250mg(with carbidopa 25mg) formulation and increase dose by 250mg daily or on alternate days up to max 2g (with carbidopa 200mg)

Modified release:
initially 200mg (with 50mg carbidopa) OD adjusted at intervals of 3 days according to response and tolerability. 
Usual maintenace = 200mg (with carbidopa 50mg) every 4-12 hours. Max 2.4g (with carbidopa 600mg) daily

Question 8

What are the relevant PK/PD parameters with levodopa?

Answer 8

PD: used to replace dopamine lost in Parkinson’s because dopamine cannot cross the bbb. Often administered with carbidopa which is 90% metabolised so that levodopa wont be metabolised.

PK:
rapidly absorbed from proxmial SI
High protein binding
Half life of 50-90 minutes

Question 9

What are the precautions associated with levodopa use?

Answer 9

• severe pulmonary/CVD
• psychiatric illness
• endocrine disorders (incl hyperthyroidism, Cusing’s syndrome, diabetes mellitus,)
• history of convulsions or peptic ulcer
• patients susceptible to glaucoma
• hepatic/renal impairment
• avoid abrupt withdrawal,
• be aware of potential for excessive drowsiness/sudden onset of sleep.

Use with caution in pregnancy and may suppress lactation.

Question 10

What are the adverse reactions associated with levodopa use?

Answer 10

• nausea, vomiting, taste disturbances, dry mouth
• anorexia
• arrhythmias, palpitations, postural hypotension
• syncope, drowsiness, fatigue,
• dementia, psychosis, confusion, euphoria, abnormal dreams, depression

Question 11

What are the drug interactions associated with levodopa use?

Answer 11

avoid when taking with deserpdine, rescinnamine, reserpine

aluminium and magnesium hydroxide in antacids may reduce bioavailability of levodopa in MR prerparations.

Metoclopramide may increase rate of levodopa absorption, and antagonise effects or aggravate symptoms of parkinson’s disease.

Tryptophan can reduce levodopa concentration

Question 12

What are the alarm bells associated with levodopa use?

Answer 12

may cause sudden sleep onset- do not drive or operate machinery if affected
avoid high protein intake
report impulse disorders (such as pathological gambling, increased libido, hyper sexuality, compulsive spending, binge eating) to a doctor.