ANTI-PARKINSONIAN

DRUGS

DRUGS FOR ALZHEIMER”S

DISEASE
 ANTI-PARKNSONIAN DRUGS
PARKINSONISM
1. Selective loss of dopaminergic neurons in the
nigro-striatal fibres.
2. Clinical picture is rigidity, bradykinesia,
tremor and postural instability.
DRUGS
1. Levodopa 5. Amantadine
2. Dopamine Agonists 6. Acetylcholine
3. MAO Inhibitors Blocking Drugs
4. COMT Inhibitors
 LEVODOPA
MECHANISM
1. Levodopa crosses blood brain barrier and is
decarboxylated to dopamine in the CNS.
2. Dopamine stimulates postsynaptic D2
receptors in the nigro-striatal neurons
PHARMACOKINETICS
Carbidopa (a dopa decarboxylase inhibitor) is
given with levodopa. It reduces peripheral
metabolism of levodopa, so more levodopa is
available for entry into the brain. Sinemet
contains carbidopa 25mg+Levodopa 100 mg.
ADVERSE EFFECTS
1. Anorexia, nausea, vomiting
2. Tachycardia, ventricular extra-systoles, atrial
fibrillation, postural hypotension, hypertension
3. Dyskinesias like chorea, ballismus,
athetosis dystonia, myoclonus, tics,
tremor.
4. Depression, anxiety, insomnia, somnolence,
delusions, hallucinations, euphoria.
5. On-off phenomenon ( fluctuations in clinical
state). “On” means improved mobility
with
marked dyskinesia. “Off” means marked
DRUG INTERACTIONS
1. Pyridoxine (B6) increases extracerebral
metabolism of levodopa.
2. MAOIs with levodopa will cause hypertensive
crisis.
CLINICAL USES
1. Parkinsonism
CONTRAINDICATIONS
1. Psychosis
2. Angle closure glaucoma
3. Malignant melanoma
4. Peptic ulcer
5. Cardiac arrhythmias
 DOPAMINE AGONISTS
1. Bromocriptine 3. Pramipexole
2. Pergolide 4. Ropinirole
This group directly stimulates dopamine receptors
Bromocriptine a D2 receptor agonist, is excreted
in bile and feces. Pergolide stimulates both D1 &
D2 receptors. Pramipexole has more affinity for
D3 receptors. Ropinirole is a D2 receptor agonist.
ADVERSE EFFECTS
GIT upsets, peptic ulcer with bleeding, postural
hypotension, painless digital vasospasm, oedema

dyskinesias, hallucinations, delusions, erythro-

-myalgia, retroperitoneal fibrosis.
CONTRAINDICATIONS
1. Psychotic illness
2. Recent myocardial infarction
3. Active peptic ulceration
4. Peripheral vascular disease
MAOIs
1. Selegiline 2. Rasagiline
Selegiline inhibits MAO-B which metabolizes
dopamine, so dopamine is increased in the CNS.
It has also neuroprotective effect.
Rasagiline is more potent than selegiline. MAOIs
are not used with levodopa to avoid hypertensive
crisis.
 COMT INHIBITORS
1. Tolcapone 2. Entacapone
They prolong the actions of levodopa by
decreasing its peripheral metabolism.
ADVERSE EFFECTS
Dyskinesias, nausea, confusion, diarrhea,
abdomonal pain, orthostatic hypotension,sleep
disturbances, orange colored urine.
AMANTADINE
It potentiates dopaminergic function by influenc-
-ing the synthesis, release or reuptake of
dopamine. Side effects are acute toxic psychosis
postural hypotension, heart failure.
 ACETYLCHOLINE BLOCKING DRUGS
1. Benztropine 4. Procyclidine
2. Biperiden 5. Trihexyphenidyl
3. Orphenadrine
They block the muscarinic receptors in the
striatal cholinergic fibres. They improve tremor &
rigidity but have little effect on bradykinesia.
ADVERSE EFFECTS
Drowsiness, confusion, dry mouth, blurred vision,
mydriasis, urinary retention, constipation,
cardiac arrhythmias.
CONTRAINDICATIONS: Prostate hyperplasia,
pyloric stenosis, paralytic ileus.
 DRUGS FOR ALZHEIMER”S
DISEASE
ALZHEIMER”S DISEASE
This disease is characterized by progressive
impairment of memory and cognitive functions. It
may lead to complete vegetative state and death.
PATHOPHYSIOLOGY
1. Marked decrease in choline acetyltransferase
2. Eventually cholinergic neurons are destroyed
3. Changes in the activity of glutamate, dopamine,
norepinephrine, serotonin & somatostatin occur.
DRUGS
CHOLINESTERASE INHIBITORS
1. Tacrine
2. Donepezil
3. Rivastigmine
4. Galantamine
TACRINE: It is a long acting cholinesterase
inhibitor, thus increasing the concentration
of acetylcholine. It has complex inhibitory
effects on M1 & M2 receptors. It increases
the release of acetylcholine from the nerve
endings.
Tacrine inhibits MAO, decreases the release of
GABA. It increases the release of norepinephrine,
dopamine & serotonin from the nerve endings.
ADVERSE EFFECTS
Cholinomimetic adverse effects, hepatocellular
necrosis with jaundice.
DONEPIZIL, RIVASTIGMINE & GALANTAMINE
Action limited to inhibition of acetylcholinesterase
only.
These newer drugs improve cognitive function.