Pharmacology
In this section, we will describe some of the basic principles of how drugs work (pharmacology), how drugs are used (therapeutics) and how drugs are handled by the body (pharmacokinetics). We also need to remember that posology (drug doses) can be fundame
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Pharmacology Sue Hill
Introduction In this section, we will describe some of the basic principles of how drugs work (pharmacology), how drugs are used (therapeutics) and how drugs are handled by the body (pharmacokinetics). We also need to remember that posology (drug doses) can be fundamental in differentiating between benefits and toxicity. Mammalian cells consist of a cellular membrane surrounding groups of specialized organelles. It is these sub-cellular organelles that differentiate eukaryotes from prokaryotes like bacteria. The organelles also provide a variety of targets for poisons or drugs. In many cases, the same chemical is poisonous to healthy cells at high doses or produces therapeutic effects at lower doses. Cytotoxic chemotherapeutic agents lack even this distinction and rely on malignant cells that replicate rapidly and accumulate the agent and die before healthy cells suffer excess toxicity. Methotrexate is an antimetabolite cytotoxic drug that binds to the enzyme that activates folic acid in the synthesis of purine bases for DNA. In high doses, healthy human cells need folinic acid (an alternative pathway for purines) to rescue them from excess toxicity. Antimicrobials differ in their relative accumulation within microbes and mammalian cells. Sometimes, bacteria have different, simpler internal processes that lack alternative pathways for making essential nutrients such as the antifolate antibiotics trimethoprim or sulphonamides. In high doses, the species selectivity may be lost and folic acid may need to be given to avoid bone marrow suppression of the human host.
Within human tissue, drugs often exploit the differences between structures or groups of cells to have therapeutic uses. Blood flow is enhanced when platelets (non-nucleated) cannot synthesize thromboxane, because aspirin has irreversibly blocked the cyclo-oxygenase enzyme when they were formed. However, blood vessel cells (nucleated) can synthesize fresh enzyme and restore prostacyclin production. Thus aspirin has benefits at low doses, but these are diminished or lost as the dose increases. Unfortunately, as knowledge grows, the pharmacology of drugs appears to change. When I first learnt about sodium nitroprusside, its actions were explained by free cyanide ions poisoning the chain of electron transfer of cytochrome A in respiration. Later, we discovered that this was the toxicity pathway and the benefits came from the release of nitric oxide. Thus keeping up-to-date is essential to maintain safe and evidence-based practice. Mammalian cells are surrounded by a thin plasma membrane and this is often the site of drug action. Opening the pores in the cell and allowing, loss, gain or exchange of electrolytes or other intracellular components is a primary pharmacological effect. Understanding how this membrane functions is crucial to know whether chemicals will attach to, or pass through, the plasma membrane. The plasma membrane is a complex bipolar layer with an external hydrophilic (water loving) and internal hydrophobic/lipophilic (
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