Parkinson’s disease is an extrapyramidal motor disorder characterized by rigidity, tremor and hypokinesia with secondary manifestations like defective posture and gait, mask-like face and sialorrhoea; dementia may accompany.
Symptoms of Parkinson’s disease
Parkinson’s has four main symptoms:
- Tremor in hands, arms, legs, jaw, or head
- Muscle stiffness, where muscle remains contracted for a long time
- Slowness of movement
- Impaired balance and coordination
Causes
In idiopathic parkinsonism, there is degeneration of the dopamine-containing neu- rons in the substantia nigra, resulting in dopamine deficiency. Hence, the balance be- tween inhibitory dopaminergic neurons and excitatory cholinergic neurons is disturbed resulting in relative cholinergic overactivity.
CLASSIFICATION
Dopamine Precursor: Levodopa
.svg.png)
Dopamine Precursor: Levodopa
L-Dopa is the main drug for the treatment of idiopathic parkinsonism. Dopamine does not cross BBB; hence, its immediate precursor L-Dopa (prodrug) is used. It is converted to dopamine by decarboxylase enzyme in the dopaminergic neurons of the striatum. Dopamine produced then interacts with D2-receptors in the basal ganglia to produce antiparkinsonian effect. In early stages of the disease, improvement is almost complete.
Pharmacokinetics.
On oral administration, L-Dopa is rapidly absorbed from the small intestine by an active transport system. Amino acids present in food may interfere with the absorption of L-Dopa; hence, it should be given 30–60 minutes before meal. Active transport of L-Dopa into the brain may be inhibited by competition from dietary amino acids. The main metabolic products of L-Dopa are homovanillic acid (HVA) and 3,4- dihydroxyphenylacetic acid (DOPAC) The metabolites are excreted in urine.
MOA
source: https://quizlet.com/gb/497662590/parkinsons-disease-flash-cards/
Adverse Effects
1.GIT: Nausea, vomiting and anorexia are common during initial treatment with.L-Dopa. Tolerance to emetic effect develops slowly.
2. CVS: The commonest cardiovascular side effect is postural hypotension, which is usually asymptomatic. It can also cause tachycardia, palpitation and rarely cardiac arrhythmias.
3. Dyskinesias (abnormal involuntary movements): Tics, tremors and choreoathe-toid movements may occur. Tolerance does not develop to abnormal movements.
4. Alteration in taste sensation.
5. Mental changes like insomnia, confusion, delusions, euphoria, depression, anxiety, hallucinations and nightmares.
Peripheral Decarboxylase Inhibitors: Carbidopa and Benserazide
Carbidopa and benserazide are peripheral decarboxylase inhibitors. These drugs do not cross BBB. L-Dopa is always given in combination with carbidopa/benserazide. The cur- rently used combinations are as follows:
L-Dopa ! carbidopa (4:1 or 10:1 ratio).
L-Dopa ! benserazide (4:1 ratio).
The advantages of these fixed-dose combinations are as follows:
1.Increased bioavailability of dopamine in the basal ganglia . Hence, the dose of L-Dopa can be reduced by 75%.
2. Prolongation of plasma half-life of L-Dopa.
3. Reduction in the incidence of GI side effects like nausea and vomiting.
4.Cardiovascular side effects like tachycardia, hypotension and cardiac arrhythmias are minimized.
5.Better patient compliance.
6.Sustained release preparation of L-Dopa –carbidopa helps to reduce on/off phe-nomenon.
