Drugs for Inflammatory Disease

Introduction

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)

Steroid: alters immune response, especially in lymphoid tissue.

Methotrexate: folic acid antagonist so inhibits all one carbon transfer reactions in body.

Especially effective in lymphocyte tissue and GI tract due to ready access.

Inhibitors (even remitters) of disease progression

Gold compounds: used the longest, most effective

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

Drugs of 2^nd and 3^rd choice because of toxicity and weak evidence of effectiveness

Penacillamine: metabolite of penacilline

Likely acts as a metal chelating agent

Short term use non toxic

Long term use Þ dermatological, hematological and collagen disorders. + X-sensitivity to penacillin.

Chloroquine: anti inflammatory