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ANTIPARKINSONIAN DRUGS - Coggle Diagram

- - - - Pharmacological Actions :check:
        1. CNS
        
        Marked symptomatic improvement
        
        Hypokinesia & rigidity resolve first, later tremor
        
        Improves 2° symptoms of posture, gait, speech, facial expression, mood, interest.
        
        Effect on behaviour : "General alerting response", may progress to excitement→frank psychosis in some.
        
        Disproportionate ↑ in sexual activity
        
        Dementia, if present, doesn't improve→ predisposes to psychiatric symptoms
        
        Non-specific 'awakening effect' in hepatic coma
        
        Cannot arrest progress of disease
        
        Not given for Drug induced PD
        
        2. CVS
        
        Peripherally formed DA→ tachycardia ( act on ß adr. ®)
        
        Postural hypotension is common
        
        Tolerance develops
        
        3. CTZ
        
        DA is excitatory to dopaminergic ® in CTZ
        
        Nausea & Vomiting
        
        Tolerance develops
        
        Domperidone can be admn. as it does not cross BBB & interfere with antiparkinsonian effect
        
        4. Endocrine
        
        On pituitary mammotropes→ inhibit PRL release
        
        On somatotropes→ increase GH release
        
        Pharmacokinetics :check:
        
        Rapidly absorbed from SI via active transport process meant for aromatic amino acids
        
        BA affected by
        ○ Gastric emptying- slow→ L dopa exposed to gut wall & liver for long time→ less drug available to penetrate BBB
        ○ Amino acids in food→ compete for same carrier for absorption
        
        High first pass metabolism in GI mucosa & liver
        
        Plasma T½=1-2hr
        
        Metabolism of Levodopa :check:
        Peripheral metabolism
        
        About 95% decarboxylated by DOPA decarboxylase(co factor-pyridoxine)→ Dopamine
        
        Also metabolised by COMT(Catechol-O-methyl transferase) to 3-O-methyldopa(3-OMD)
        
        After entering brain
        
        Levodopa→ DA by DDC
        
        Levodopa→ 3-OMD by COMT
        
        Finally metabolised by Monoamine oxidase-B(MAO-B) & COMT to final metabolites HVA(Homovanillic acid) & DOPAC (Dihydroxy phenylacetic acid)
        
        Adverse Effects :check:
        At initiation of therapy
        
        Nausea, vomiting: tolerance develops gradually
        
        Postural hypotension: tolerance develops with continued treatment& BP normalizes
        
        D/t ß adrenergic action of peripherally formed DA-
        ○ Cardiac arrhythmias
        ○ Exacerbation of angina
        
        Altered taste sensation
        
        After prolonged therapy
        
        Abnormal movements(dyskinesias)
        ○ Facial tics
        ○ Grimacing
        ○ Tongue thrusting
        ○ Choreoathetoid mvmts of limbs
        ○ No tolerance develops
        
        Behavioral effects
        ○ Mild anxiety
        ○ nightmares
        ○ depression, mania, hallucinations
        ○ mental confusion, frank psychosis
        ○ C/I in patients with psychotic illness
        
        Fluctuation in motor performance
        ○ 'End of dose effect' (Wearing off) gradually develops into rapid 'switches'or 'On-Off Effect'
        ○ With time,all or none response develops→ patient is alternately well & disabled.
        
        Cautious use of Levodopa is needed in
        ○ elderly
        ○ IHD
        ○ cerebrovascular, psychiatric, hepatic, renal disease
        ○ peptic ulcer, glaucoma, gout
        
        CLINICAL USE :check:
        
        Used alone→ only 1-2% enters brain
        
        Coadmn. with peripheral dopa decarboxylase inhibitors(carbidopa/ benserazide) +/- COMT inhibitors
        
        Drug Interactions :check:
        
        Pyridoxine
        ○ Abolishes therapeutic effect by ↑ peripheral decarboxylation
        ○ Combined with carbidopa for admn.
        
        Phenothiazines, butyrophenones, metoclopramide reverses therapeutic effect by blocking DA ®
        ○ Domperidone(anti-DA drug) blocks levodopa induced nausea→ does not abolish its antiparkinsonian effects
        ○ Reserpine abolishes Levodopa action→ prevent entry of DA into synaptic vesicles
        
        Non selective MAO inhibitors→prevent degradation of DA & NA synthesised in excess from administered levodopa at peripheral sites→ hypertensive crisis
        
        Antihypertensive drugs→ postural hypotension accentuated
        
        Atr. , & antiparkinsonian anticholinergics have additive therapeutic action with l-dopa but retart its absorption
        
        Contraindications :check:
        
        Psychotic patients
        
        Angle closure glaucoma
        
        Peptic ulcer
        
        Malignant melanoma