Useful drugs, attributes

Critical for predictivity in a recent comprehensive study was the number and choice of parameters measured [4]. Early, sublethal effects on cell proliferation, cell morphology and mitochondria occurred consistently and ubiquitously with toxicity and when used collectively were most diagnostic. It is noteworthy that the toxicity of many drugs is attributable to various mitochondrial targets, including oxidative phosphorylation, fatty acid oxidation, Krebs cycling, membrane transport, permeability transition pore, proliferation and oxidative stress (Table 14.4). 

All test methods used for each of the drug product attributes need to be qualified to demonstrate adequacy and reliability. 

Drugs that form strong bonds with their receptors do not readily dissociate from the receptor when their concentrations in the extracellular fluid fall. Consequently, drugs that act in this manner will often have a long duration of action. This is a useful attribute for drugs used in the treatment of cancers, where it is particularly desirable that the drug forms irreversible bonds to the receptors of tumour cells. 

The role that dopamine plays in regulating mood and emotional stability can be at least partially grasped by examining dopamine s role in schizophrenia and drug addiction. Schizophrenia is a disorder characterized by delusions, hallucinations, withdrawal from external reality, and emotional unresponsiveness. The dopamine theory of schizophrenia, proposed in 1965, attributes the disorder to elevated brain concentrations of dopamine or to a hypersensitivity of dopaminergic receptors, especially the D2 and D4 receptor subtypes. Several drugs used to treat schizophrenic patients bind to D2 and D4 receptors and block the dopaminergic response. 

Reuschel and Smith conducted a study in which they measured the concentration of benzoylecgonine in black, brown, blond, and red hair collected from jail detainees. They tested 48 hair samples for drug and 22 tested positive. The concentration of benzoylecgonine in black and brown hair was 5.6 + 5.2 ng/mg of hair in comparison to that in blond and red hair, which was 1.39+ 1.34 ng/mg of hair. However, Reuschel and Smith did not elicit information about prior drug use from individuals, and these results could be attributable to differences in the frequency and extent of drug use. 

Restlessness, irritability, and headache are withdrawal effects attributable to caffeine. These and other sjmp-toms can occur with lower doses of caffeine than generally supposed (30). The caffeine withdrawal headache may be responsible for the widespread practice of taking caffeine-containing analgesics habitually, since a withdrawal headache could create a vicious cycle of drug use (SEDA-5, 6). 

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