neuro pharmacology

Question 1

Idiopathic Parkinson’s Disease

Answer 1

• Neurodegenerative disorder
• Progressive clinical course
• Motor symptoms improve with levodopa
• Non motor symptoms: depression, hallucinations, sleep disorder, fatigue
Lewy bodies are present
reduced dopamine
• Tremor* • Rigidity* • Bradykinesia** • Postural instability

Question 2

levodopa

Answer 2

precursor to dopamine, this can cross BBB, (dopamine cannot and would have side effects, )
taken up by dopaminergic cells in the substantia nigra to be converted to dopamine.
Fewer remaining cells results in a less reliable effect of levodopa and motor fluctuations.

Question 3

levodopa pharma kinetics

Answer 3

oral, 90% inactivated in intestinal wall, short T1/2, high dose, short dose interval.

Question 4

levodopa and DOPA decarboxylase inhibitor

Answer 4

Co-careldopa*, Co-beneldopa
• Reduced dose required
• Reduced side effects
• Increased levodopa reaching brain

Question 5

levodopa #,

Answer 5

• Nausea/ anorexia
• Hypotension, tachycardia
• Psychosis
– Schizophrenia-like
effects Hallucination/ delusion/ paranoia

Question 6

levodopa interactions

Answer 6

Pyridoxine (vitamin B6) increases peripheral
breakdown of levodopa
• MAOIs risk hypertensive crisis
high dose)
• Many antipsychotic drugs block dopamine receptors and parkinsonism is a side effect

Question 7

Levodopa with COMT inhibitor

Answer 7

Entacapone

• Have levodopa ‘sparing’ effect • Prolongs motor response to levodopa

Question 8

Dopamine Receptor Agonists

Answer 8

Amantadine(improves dyskinesia#: hallucinations, confusion),
Apomorphine (sub.cut. for severe motor fluctuations),
Ropinirole,
Rotigotine(patch)

Question 9

Dopamine Receptor Agonists #

Answer 9

• Sedation • Hallucinations • Confusion • Nausea • Hypotension
• Impulse control disorders: • Pathological Gambling • Hypersexuality • Compulsive Shopping • More psychiatric s/e :• Dose limiting
• Expensive

Question 10

monoamine oxidase B inhibitors

Answer 10

• Rasagaline • Safinamide

• Metabolises dopamine • Predominates in dopamine containing regions in brain • MAOB inhibitors enhance dopamine
• Can be used alone • Prolong action of levodopa • Smooths out motor response

Question 11

anticholinergics

Answer 11

Orphenadrine, Procyclidine
• Treat tremor
No effect on bradykinesia
#:• Confusion • Drowsiness

Question 12

Myasthenia Gravis

Answer 12

autoimmune, antibodies to Ach receptors on post syneptic membrane
Fluctuating, fatiguable, weakness skeletal
muscle
– Extraocular muscles – commonest presentation – Bulbar involvement – dysphagia, dysphonia, dysarthria – Limb weakness – proximal symmetric – Respiratory muscle involvement

Question 13

drugs exacerbate Myasthenia Gravis

Answer 13

• Aminoglycosides
• Beta-blockers, CCBs, quinidine,
procainamide • Chloroquine, penicillamine • Succinylcholine • Magnesium • ACE inhibitors

Question 14

Myasthenia Gravis drugs Anticholinesterases

Answer 14

Neostigmine, Pyridostigmine 
Enhance neuromuscular transmission
– Skeletal and smooth muscle
– Excess dose can cause depolarising block – cholinergic crisis
– Muscarinic side effects

Question 15

Pyridostigmine

Answer 15

oral
Onset 30min; peak 60-120min; duration 3-6hr • Dose interval and timing crucial
• Muscarinic side effect –
– miosis and the SSLUDGE syndrome: