Levodopa+carbidopa

Levodopa & Carbidopa fixed dos combination

1. LEVODOPA+CARBIDOPA Fixed Dose Combination Dr. Swarnank Parmar JR-1 Dept. Of Pharmacology GMC Nagpur

2. Introduction Pharmacokinetics Mechanism of Action Adverse reactions Contra-indications Drug interactions Summary Overview:

3. L-DOPA or L-3,4-dihydroxyphenylalanine Highly inert Carbidopa is inhibitor of L-aromatic amino acid decarboxylase (dopa decarboxylase) Introduction:

4. Pharmacokinetics:

5. Rate and extent of absorption of levodopa depends on- Rate of gastric emptying pH of gastric juice Length of time drug exposed to degradative enzymes

6. Carbidopa

7. Mechanism of Action:

8. Levodopa crosses Blood Brain Barrier, where it is converted to DA Only 1-3% of levodopa actually enters brain unaltered Mechanism of Action:

9. Addition of carbidopa lowers the dose requirement of levodopa, also reduces peripheral side effects associated with levodopa alone Two forms available 1:4 1:10 (carbidopa 25mg + levodopa 100mg) (carbidopa 25mg + levodopa 250mg)

10. Combination used for treatment of all types of parkinsonism, except one..?? Therapy started with smaller dose Dose raised gradually Dopamine agonist can be added

11. Fluctuations in response “Wearing off” effect “On & Off phenomenon” Dyskinesias Central side effects Cardiovascular side effects Adverse Reactions:

12. Chest pain, asthenia Agranulocytosis, Thrombocytopenia Leukopenia Hypersensitivity Dyspnoea, upper respiratory infection Contd..

13. Contraindications:

14. Pyridoxine (Vit. B 6 ) decreases therapeutic effects Mono Amine Oxidase-B inhibitors potentiates toxicity Tricyclic Anti-depressant decreases absorption Active peptic ulcer - Risk of bleeding Drug Interactions:

15. Combination allows levodopa to cross BBB & prevents peripheral degradation Lowers dose requirement & peripheral side effects of levodopa Tremors – Less responsive & duration of benefit shortens as therapy progresses Summary:

16. Goodman & Gilman’s 12 th edition, The Pharmacological basis of therapeutics S K Sharma 2 nd edition, Principles of Pharmacology S K Srivastava , Textbook of Medical Pharmacology References: