ANTIPARKINSONISM Dr Samah Gaafar Alshaygi Parkinson Disease Neurodegenerative

ﺑﺴﻢ ﺍﻟﻠﻪ ﺍﻟﺮﺣﻤﻦ ﺍﻟﺮﺣﻴﻢ ANTIPARKINSONISM Dr: Samah Gaafar Al-shaygi

Parkinson Disease � � � Neurodegenerative diseases. Dopamenergic neurones in substantia nigra. Environmental* genetic factors. Resting tremor, muscular rgidity & bradykinesia. Secondary parkinsonism.

� Therapy aim is to � minimize disability and side effects while maintaining quality of life. � restore dopamine in the basal ganglia & antagonize ACH. � The drugs are almost palliative ones.

Drugs used in parkinson Dx 1. � � � Levodopa & Carpidopa. L-dopa is a dopamine precursor. Very effective in the beginning of the dx. Carpidopa a dopa decarboxylase inhibitor. Decrease the dose of L-dopa needed (*4 -5). 2. Decrease side effects. 1.

� � � � Absorption & metabolism: On empty stomach 45 min before a meal. L-dopa is rapidly absorbed from the GIT. is absorbed primarily in the proximal duodenum by a saturable large neutral amino acid (LNAA) transport system. (Competition) Has short ½ life (1 -2 hrs). not bound to plasma proteins. It crosses the blood-brain barrier by saturable facilitated diffusion and competes with LNAA for transport into the brain.

� 1. ADVERSE EEFECTS: Peripheral effects: N&V. � Tachycardia & hypotension. � Mydriasis. � Brownish urine & saliva. � 2. 3. 4. CNS: anxiety, psychosis, depression. Wearing off. Dyskinesias and dystonias.

� Selegiline: � MAO-B inhibitor. � Lipophilic. � Reduces L-dopa dose. � Metabolized to amphetamine (insomnia). � COMT-inhibitors: � L-dopa COMT 3 -O-methyl dopa (competes with L-dopa for brain transport). � Entacapone reduces wearing off phenomena.

� Pharmacokinetics: � Plasma protein bound >98%. � Metabolized & excreted hepatically & renally. � Adverse effects: Diarrhea, postural hypotension, sleep disorders. Fulminant hepatic necrosis (tolcapone).

� Dopamine-receptor agonists: � In advanced dx with motor fluctuation & dyskinesia. � Have no effects on non-responders to L-dopa. � Bromocreptine. more nausea, hallucinations & less dyskinesias. � Worsen fibrosis. � MI, perepheral vascular dx, pulmonary Apomorphine as injections in advanced dx. � Delay the need for L-dopa in early parkinson & decrease the L-dopa dose in advanced dx. � No worsening of vasospasm & no fibrosis.

� Amanitidine: � An anti-viral drug. � Increases the release of dopamine & blocks the cholinergic receptors. � Less effective than L-dopa & readily developed tolerance. � Restlessness, hallucinations, toxic psychosis. � Little effect on tremor butmore the anticholinergic on rigidity & bradykinesia.

� Antimuscarinic agents: � Only adjuvant role. � Benztropin, procyclidine. � S. E: mood changes, xerostomia, urinary retention tachycardia. � Contraindicated in glucoma, BPH & pyloric stenosis.

Thank you