9

Nonmessenger Targets for Drug Action III

Exogenous pathogens and toxins

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9.1 EXOGENOUS PATHOGENS AS TARGETS

FOR DRUG DESIGN

The fundamental mechanistic causes of human disease and pathology are multiple, but
they can be comprehensively categorized into the following ten groups:

1. Traumatic (pathology from injury)


2. Toxic (pathology from poisons)


3. Hemodynamic/vascular (pathology from disorders of blood vessels)


4. Hypoxic (pathology from inadequate supply or excessive demand for oxygen by
   a tissue)


5. Inflammatory (pathology from abnormal inflammatory response in the body)


6. Infectious (pathology from microbes or infectious agents)


7. Neoplastic (pathology from tumors, cancer)


8. Nutritional (pathology from too much/too little food intake)


9. Developmental (pathology in the chemistry of heredity)


10. Degenerative (pathology from age-related tissue breakdown)

When designing therapeutics for a specific disease, the medicinal chemist must consider
the pathological mechanism of the underlying disorder and then design the drug accord-
ingly. For example,anti-neoplasticagents are designed to treat malignancies like colon
cancer, whilst anti-inflammatory agentswould be designed to treat diseases such as
rheumatoid arthritis. Of these ten fundamental pathological mechanisms, most represent
errors or imbalances in endogenous mechanisms. Developmental diseases, for example,
arise from inborn errors in metabolism or from genetic disorders. Many common human
diseases may be understood in terms of these endogenous pathological mechanisms: a
myocardial infarction (heart attack), for instance, usually arises from an occluded coro-
nary artery—occlusion of this artery may be the product of traumaticdamage to the
artery (from years of untreated high blood pressure), leading to degenerativeathero-
sclerotic changes in the arterial wall, resulting in reduced hemodynamicblood supply