antiparkinsonian drugs, antiepileptics & alcohol

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

10. Antiepileptic

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”

20. Alcohol

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.