Define antivitamins. Give examples with their mechanisms and clinical significance.

Definition

Classification BY Mechanism

Therapeutically Useful Antivitamins

• Methotrexate — inhibits dihydrofolate reductase; used in cancer, rheumatoid arthritis, psoriasis. Rescued with folinic acid
• Trimethoprim — selective for bacterial dihydrofolate reductase, which is why it is antibacterial and not cytotoxic to man
• Sulphonamides — compete with PABA, so bacteria cannot make folate. Man absorbs preformed folate and is unaffected — the basis of selective toxicity
• Warfarin — blocks vitamin K epoxide reductase; the standard oral anticoagulant

Clinically Harmful Antivitamins

• Isoniazid forms a hydrazone with pyridoxal phosphate → peripheral neuropathy; prevented by routine pyridoxine
• Avidin in raw egg white binds biotin irreversibly → dermatitis, alopecia and neurological signs in those who eat many raw eggs. Cooking denatures avidin
• Thiaminase in raw fish and betel nut chewing contributes to beri-beri in some populations
• Nitrous oxide irreversibly oxidises the cobalt of B12 → megaloblastic anaemia and neuropathy after repeated or prolonged anaesthesia
• Phenytoin and phenobarbitone induce hepatic enzymes → accelerated breakdown of vitamin D and folate

Applied Aspects

• The concept underlies much of chemotherapy and antibiotic action — exploiting a pathway that the pathogen or tumour needs more than the host does
• Selective toxicity is the key — sulphonamides and trimethoprim work because bacteria must synthesise folate while man absorbs it
• Prophylactic vitamin supplementation is standard practice where an antivitamin drug is unavoidable — pyridoxine with isoniazid, folinic acid with methotrexate
• A vitamin deficiency in the presence of a normal diet should always prompt a search for an antivitamin, a malabsorption state, or an increased requirement