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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
A.Drugs influencing brain dopaminergic system
Levodopa Bromocriptine, Pramipexole,
Ropinirole Amantadine Selegiline Tolcapone, Entacapone Carbidopa, Benserazide
B. Drugs affecting brain cholinergic system
Centrally acting anticholinergics : benztropine, benzhexol, procyclidine
Antihistaminics (H1 blockers) with anticholinergic activity : promethazine, diphenhydramine
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
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
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
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
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
Antiepileptic drugs
Epilepsy - neurological abnormality characterized by recurrent episodes of seizures
Seizures – paroxysmal abnormal discharge at high frequency from aggregate of neurons in cerebral cortex
Types of seizuresA.Generalized seizures - Grand Mal / Tonic-clonic seizures Aura
Tonic phase with epileptic cry
Clonic convulsions
Prolonged sleep and Postictal depression
Repeated occurrence of grand mal
seizures with no recovery of consciousness in between the attacks
“Status epilepticus”- clinical emergency
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
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
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
4. Simple partial seizures - carbamazepine, phenytoin, sodium valproate, lamotrigine
5. Complex partial seizures - carbamazepine, phenytoin, sodium valproate, lamotrigine
6. Status epilepticus – diazepam, fosphenytoin,
phenobarbitone
Adverse effects of phenytoin • Gingival hyperplasia Oral hygiene
• Megaloblastic anemia Folic acid supplements
• Vitamin K deficiency – hypoprothrombinaemia and haemorrhage
• Rickets and osteomalacia• Acne, hirsutism, coarsening of facial features• Hyperglycemia• Hypersensitivity reactions• Contraindicated in pregnancy – “fetal hydantoin syndrome”
Alcohol
Methanol poisoning – Methanol
Formaldehyde
Formic acid respiratory acidosis retinal
damage depression
alcohol dehydrogenase
aldehyde dehydrogenase
Signs & symptoms – • Nausea, vomiting, abdominal pain• Headache, vertigo, confusion• Metabolic acidosis • Dimness of vision, retinal damage &
blindness• Hypotension• Convulsions• Coma
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.