Anti Ian Drugs

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.