13.antiparkinsonian drugs, antiepileptics & alcohol
TRANSCRIPT
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Parkinson’s disease - slowly progressive neurodegenerative disease
Loss of dopaminergic neurons in substantia nigra
Balance between inhibitory dopaminergic neurons and excitatory cholinergic neurons is disturbed
Characterized by 4 cardinal features – Bradykinesia Muscular rigidity Resting tremors Loss of postural reflexes
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A.Drugs influencing brain dopaminergic system
Levodopa Bromocriptine, Pramipexole,
Ropinirole Amantadine Selegiline Tolcapone, Entacapone Carbidopa, Benserazide
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B. Drugs affecting brain cholinergic system
Centrally acting anticholinergics : benztropine, benzhexol, procyclidine
Antihistaminics (H1 blockers) with anticholinergic activity : promethazine, diphenhydramine
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Large amount of levodopa is converted to dopamine in the peripheral tissues by peripheral dopa decarboxylase enzyme –
a. Low bioavailability in the CNS b. Adverse effectsTo minimize this…………….. Levodopa + Carbidopa/Benserazide
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At the initiation of therapy : GIT : Nausea, vomiting, anorexia Antiemetic - Domperidone CVS : Postural hypotension, tachycardia, palpitation
Tolerance develops to these adverse effects
with continued treatment
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After prolonged therapy Abnormal movements : dyskinesia, tics,
tremors Behavioral effects : anxiety, insomnia, nightmares, depression, confusion
Fluctuations in response : a) Wearing off phenomenon – dose of levodopa improves the mobility for a period of time but rigidity and akinesia rapidly returns at the
end of dosing interval
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Smaller & frequent doses of l-dopa improves this condition
b. On-off phenomenon: Patient shows fluctuation in response - being “off” and being “on”
Sustained release preparations of levodopa &
carbidopa helps to reduce this phenomenon
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Inhibits peripheral conversion of levodopa to dopamine Do not cross BBB no effect on levodopa in brainAdvantages of combining carbidopa with
levodopa : 1. Increased BA of dopamine in the brain - dose of
levodopa can be reduced2. Prolongation of plasma half-life of levodopa3. Systemic concentration of dopamine is reduced
- less GI and cardiovascular side effects4. Better patient compliance
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Antiepileptic drugs
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Epilepsy - neurological abnormality characterized by recurrent episodes of seizures
Seizures – paroxysmal abnormal discharge at high frequency from aggregate of neurons in cerebral cortex
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Types of seizuresA.Generalized seizures - Grand Mal / Tonic-clonic seizures Aura
Tonic phase with epileptic cry
Clonic convulsions
Prolonged sleep and Postictal depression
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Repeated occurrence of grand mal
seizures with no recovery of consciousness in between the attacks
“Status epilepticus”- clinical emergency
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Petit Mal / Absence seizures• Prevalent in children• No aura, postictal confusion or amnesia• No/momentary loss of consciousness• During seizure – vacant stare, lack of
response, small clonic jerks Myoclonic seizures Sudden and brief skeletal muscle contraction
that may involve one part or the entire body
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B. Partial seizures – Simple partial seizures Clonic convulsions - group of muscles Somatosensory symptoms (auditory, visual or olfactory hallucinations)
Complex partial seizures (Psychomotor epilepsy) - originate in the temporal or frontal lobe, characterized by aura – amnesia – abnormal behavior & automatism
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Antiepileptic drugs (Clinical classification) 1. Generalized tonic-clonic seizures (grand
mal) – carbamazepine, phenytoin, sodium valproate, lamotrigine
2. Absence seizures (petit mal) – ethosuximide,
sodium valproate, lamotrigine
3. Myoclonic seizures – sodium valproate, lamotrigine
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4. Simple partial seizures - carbamazepine, phenytoin, sodium valproate, lamotrigine
5. Complex partial seizures - carbamazepine, phenytoin, sodium valproate, lamotrigine
6. Status epilepticus – diazepam, fosphenytoin,
phenobarbitone
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Adverse effects of phenytoin • Gingival hyperplasia Oral hygiene
• Megaloblastic anemia Folic acid supplements
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• Vitamin K deficiency – hypoprothrombinaemia and haemorrhage
• Rickets and osteomalacia• Acne, hirsutism, coarsening of facial features• Hyperglycemia• Hypersensitivity reactions• Contraindicated in pregnancy – “fetal hydantoin syndrome”
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Alcohol
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Methanol poisoning – Methanol
Formaldehyde
Formic acid respiratory acidosis retinal
damage depression
alcohol dehydrogenase
aldehyde dehydrogenase
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Signs & symptoms – • Nausea, vomiting, abdominal pain• Headache, vertigo, confusion• Metabolic acidosis • Dimness of vision, retinal damage &
blindness• Hypotension• Convulsions• Coma
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Treatment - Patient is kept in dark room to protect the eyes from light Maintain airway, breathing & circulation Gastric lavage i.v. NaHCO3 – to correct acidosis Ethanol (10%) i.v. Haemodialysis Fomepizole – alcohol dehydrogenase inhibitor Calcium leucovorin i.v.
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