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| Basic Pharmacology | |||||||||||||||
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| Drug excretion Kidneys Most drugs and metabolites are excreted by the kidneys. Small drug or metabolite molecules may be transported by glomerular filtration into the tubule. This, however, only applies to free drugs and not drugs bound to plasma proteins. Active secretion of some drugs into the lumen of the nephron will also occur. This process however, requires membrane carriers and energy. Several factors may affect the rate at which a drug is excreted by the kidneys. These include:
Bile Several drugs and metabolites are secreted by the liver into bile. These then enter the duodenum via the common bileduct, and move through the small intestine. Some drugs will be reabsorbed back into the bloodstream and return to the liver by the enterohepatic circulation (Figure 1). The drug then undergoes further metabolism or is secreted back into bile. This is referred to as enterohepatic cycling and may extend the duration of action of a drug. Drugs secreted into bile, will ultimately pass through the large intestine and be excreted in faeces. Figure 1 - The enterohepatic circulation
Lungs Anaesthetic gases and small amounts of alcohol undergo pulmonary excretion.
Breast milk Milk-producing glands are surrounded by a network of capillaries, and drugs may pass from maternal blood into the breast milk. The amounts of drug may be very small, but may affect a suckling infant who has less ability to metabolise and excrete drugs.
Perspiration, saliva and tears Drugs may be excreted passively via these body secretions if the drugs are lipid-soluble.
The processes of drug metabolism and drug excretion will ultimately determine the drug’s half-life. This is the time taken for the concentration of drug in the blood to fall by half (50%) its original value. Standard dosage intervals are based on half-life calculations. This helps in the setting up of a dosage regime which produces stable plasma drug concentrations, keeping the level of drug below toxic levels but above the minimum effective level. There are occasions when an effective plasma level of drug must be reached quickly. This requires a dose of the drug which is larger than is normally given. This is called a loading dose. Once the required plasma level of drug has been reached, the normal recommended dose is given. This is then continued at regular intervals to maintain a stable plasma level and is called the maintenance dose. Determining plasma levels of a drug at frequent intervals is undertaken when clients are prescribed drugs with a narrow therapeutic index eg. digoxin and lithium. The therapeutic index is the ratio of the drug’s toxic dose to its minimally effective dose. Monitoring plasma levels can also be used to assess a client’s compliance to drug therapy. |
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