5453590
Description
Flashcards by Valentina Valenz, updated more than 1 year ago
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Created by Valentina Valenz
almost 8 years ago
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| Question | Answer |
| EXAMPLES | Aspirin (prodrug) --> salicylic acid (active agent) Phenacetin (prodrug) --> paracetamol (active agent) |
| TRANSPORT CHARACTERISTICS | prodrugs can interfere with transport (EXAMPLE: putting hydrophilic group may restrict gut to one specific area) |
| PHARMACEUTICAL PROBLEMS | - poor water solubility - aesthetic properties such as taste or tissue irritation - formulation problems |
| PHARMOKINETIC PROBLEMS | - incomplete absorption of the drug across biological barriers - too rapid absorption or excretion - poor site specificty |
| PHARMACEUTICAL SOLUTION 1 | improve flavour of drug by decreasing water solubility so drug does not dissolve on the tongue (CHLORAMPHENICOL = OH --> alkyl chain) |
| PHARMACEUTICAL SOLUTION 2 | reduce pain by improving water solubility. injections hurt, however when made more soluble they hurt less (CLINDAMYCIN phosphate ester addition) |
| PHARMACEUTICAL SOLUTION 3 | mask drug toxicity side effects (SALICYLIC ACID causes gastric bleeding, ASPRIN doesn't OH --> ester) |
| SULPHANOMIDE AS A PRODRUG | - antibacterial agents, active drug of PRONTOSIL (prodrug) - have a versatile synthesis with many derivates - competes with PABA, PABA is the enzyme active in DHF synthesis |
| GENERAL SYNTHESIS | |
| SIMILARITIES WITH PABA | 1º aryl amine Para substituents Similar charges Polar substituents Van der Waals b/c aromatic H-bonding Ionic factors in substituents Similar lengths (6.9 v. 6.7 Å) Similar widths (2.4 v. 2.3 Å) |
| ROLE OF DIHYDROFOLATE REDUCTASE DHF --> THF | |
| BIOSYNTHESIS OF FOLATES | - DHF plays ket role in synthesis of DNA bases - DHF introduces a methyl group into thymine - synthesis of DHF, THF, 10-fromylTHF -DHF not synthesised in HUMAN bodies -DHF pathway interrupted by Trimethoprim |
| INHIBITION OF DHF PATHWAY 1 | - Trimethoprim and a sulphadrug are combined to hit bacteria - high selectivity to DHF - sulphadrug -> inhibits PABA insertion - Trimethoprim inhibits (DHFR) - effective for bronchial adn urinary tract infections |
| INHIBITION OF DHF PATHWAY 2 | - methotrexate is another inhibitor of DHF - low selectivity for bacteria but block DHFR - used in acute childhood leukemia, does not differentiate between normal and malignant cells - v. toxic with serious side effects |
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