Drugs for Inflammatory Disease
Need a base line measurement of disease process so that you can monitor the effectiveness of disease
Monitoring is important so that toxic drugs can be terminated if ineffective
Always trading off toxicity for desired result
Often it is better to hit the disease early and hard even at the expense of some toxicity because later may be too late.
Always be open to the possibility that diagnosis is wrong and treatment plan must be reassessed
Drug Interventions in Inflammatory Disease
Quick acting Anti Inflammartories (aspirin Steroid)
Immune suppressors of inflammatory disease (cyclophosphamide)
Inhibitors (even remitters) of disease progression (gold compounds, penicillarine)
Cancer Drugs that alter the immune response
Azathiprine: metabolized to 6-mercaptapurine Þ made into nucleotides that acts as GTP analog
Cyclophosphamide: nitrogen mustard that kills rapidly proliferating cells (due to Ý immune system)
- Interferes with nucleic acid metabolism and biosynthesis
- Not selective for rapidly proliferating cells
Steroid: alters immune response, especially in lymphoid tissue.
Methotrexate: folic acid antagonist so inhibits all one carbon transfer reactions in body.
- Alkylates DNA thus inhibiting replication
- Most effective inhibitor of lymphocyte proliferation
Þ inhibition of DNA synthesis
Especially effective in lymphocyte tissue and GI tract due to ready access.
- Consequently inhibits thymidine biosynthesis
Inhibitors (even remitters) of disease progression
Gold compounds: used the longest, most effective
Drugs of 2nd and 3rd choice because of toxicity and weak evidence of effectiveness
Penacillamine: metabolite of penacilline
- Gold covalently links to compound (e.g. sugar) via thio linkage and is lowly delivered to the body
- Probable mechanism: inhibition of mononuclear phagocytosis
- Can be very effective
- Very toxic
- Orally administered form less toxic than the injected form
Þ dermatological, hematological and collagen disorders. + X-sensitivity to penacillin.
Chloroquine: anti inflammatory
- Likely acts as a metal chelating agent
- Short term use non toxic
- Long term use
- Unknown mechanism
- Unclear whether it induces remission