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

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 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 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.