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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 effects
To 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
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 brain
Advantages of combining carbidopa with levodopa :
1. Increased BA of dopamine in the brain - dose of
levodopa can be reduced
2. Prolongation of plasma half-life of levodopa
3. Systemic concentration of dopamine is reduced - less
GI and cardiovascular side effects
4. Better patient compliance
Antiepileptic
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 seizures
A.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 –
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.
13.antiparkinsonian drugs, antiepileptics & alcohol

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13.antiparkinsonian drugs, antiepileptics & alcohol

  • 1.
  • 2.  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
  • 3. A.Drugs influencing brain dopaminergic system  Levodopa  Bromocriptine, Pramipexole, Ropinirole  Amantadine  Selegiline  Tolcapone, Entacapone  Carbidopa, Benserazide
  • 4. B. Drugs affecting brain cholinergic system Centrally acting anticholinergics : benztropine, benzhexol, procyclidine Antihistaminics (H1 blockers) with anticholinergic activity : promethazine, diphenhydramine
  • 5. 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 effects To minimize this…………….. Levodopa + Carbidopa/Benserazide
  • 6. 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
  • 7. 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
  • 8. 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
  • 9.  Inhibits peripheral conversion of levodopa to dopamine  Do not cross BBB no effect on levodopa in brain Advantages of combining carbidopa with levodopa : 1. Increased BA of dopamine in the brain - dose of levodopa can be reduced 2. Prolongation of plasma half-life of levodopa 3. Systemic concentration of dopamine is reduced - less GI and cardiovascular side effects 4. Better patient compliance
  • 11. Epilepsy - neurological abnormality characterized by recurrent episodes of seizures Seizures – paroxysmal abnormal discharge at high frequency from aggregate of neurons in cerebral cortex
  • 12. Types of seizures A.Generalized seizures -  Grand Mal / Tonic-clonic seizures Aura Tonic phase with epileptic cry Clonic convulsions Prolonged sleep and Postictal depression
  • 13. Repeated occurrence of grand mal seizures with no recovery of consciousness in between the attacks “Status epilepticus”- clinical emergency
  • 14.  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
  • 15. 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 –
  • 16. 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
  • 17. 4. Simple partial seizures - carbamazepine, phenytoin, sodium valproate, lamotrigine 5. Complex partial seizures - carbamazepine, phenytoin, sodium valproate, lamotrigine 6. Status epilepticus – diazepam, fosphenytoin, phenobarbitone
  • 18. Adverse effects of phenytoin • Gingival hyperplasia Oral hygiene • Megaloblastic anemia Folic acid supplements
  • 19. • Vitamin K deficiency – hypoprothrombinaemia and haemorrhage • Rickets and osteomalacia • Acne, hirsutism, coarsening of facial features • Hyperglycemia • Hypersensitivity reactions • Contraindicated in pregnancy – “fetal hydantoin syndrome”
  • 21. Methanol poisoning – Methanol Formaldehyde Formic acid respiratory acidosis retinal damage depression alcohol dehydrogenase aldehyde dehydrogenase
  • 22. Signs & symptoms – • Nausea, vomiting, abdominal pain • Headache, vertigo, confusion • Metabolic acidosis • Dimness of vision, retinal damage & blindness • Hypotension • Convulsions • Coma
  • 23. 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.