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Lipophilic drug molecules are not directly excreted from the kidney. Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine. Drugs and their metabolites are also excreted into bile. This is usually mediated by protein transporters.
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Thus the kidney cannot actively excrete lipid-soluble substances. This means the kidneys cannot alter the plasma concentration of these substances. Water-soluble substances are effetively trapped in the tubules. This means the kidneys can selectively secrete or reabsorb water-soluble substances via channels etc.
Furthermore, the kidney is one of the major organs responsible for drug biotransformation and excretion. Thus drug-induced toxicity frequently occurs in the kidney. Renal uptake, accumulation, and biotransformation all contribute to susceptibility of kidneys to toxic damage.
Genetic variation and underlying acute or chronic comorbidities can also impact drug excretion. Impaired kidney function or hepatic diseases that compromise biotransformation pathways may decrease drug excretion, which can result in drug accumulation and potential toxicity.
Renal disorders, such as chronic kidney disease, can reduce renal function hindering drug excretion. As kidney function declines with age, drug excretion becomes less efficient, and dosing adjustments may be needed. Other than direct renal dysfunction, pathologies that impact renal blood flow or urine flow can affect drug elimination as well.
Drugs can be excreted in two forms: Unchanged drugs. Form of metabolites. The primary role of biotransformation is to convert lipophilic drugs into hydrophobic compounds or to convert non-excretable drugs into excretable forms. Being lipophilic is a property desirable for absorption and passage through the body, but not for excretion.
Lipophilicity of drug candidate molecules is a major concern in the development of its dosage form, because drug molecules must penetrate the lipid bilayer of most cellular membranes, including that of the enterocytes. Therefore, it is generally believed that drug molecules must be lipophilic to have good absorption.
The greatest proportion of drug excretion occurs through the kidneys.. The liver makes most drugs and remedies water soluble for removal via the kidneys (see Figure 17.1, p. 131).. One-fifth of the plasma reaching the kidney glomerulus is filtered through the pores in the glomerular cell membrane. The rest passes through the blood vessels around the renal tubules (Figure 18.1).
The kidneys are the principal organs for excreting water-soluble substances. The biliary system contributes to excretion to the degree that drug is not reabsorbed from the gastrointestinal (GI) tract. Generally, the contribution of intestine, saliva, sweat, breast milk, and lungs to excretion is small, except for exhalation of volatile anesthetics.
The kidney is the principal drug-excreting organ. The three components of renal excretion, i.e. glomerular filtration, secretion, and reabsorption, are introduced in a brief video from Handwritten Tutorials (see the Learning Resources at the end of this topic).All renally excreted drugs reach urine via glomerular filtration.Many drugs additionally are secreted into the proximal tubule through ...
Some drugs, notably insulin, are routinely administered SC. Drug absorption is generally slower SC than IM, due to poorer vascularity. Absorption can be facilitated by heat, massage or vasodilators. It can be slowed by coadministration of vasoconstrictors, a practice commonly used to prolong the local action of local anesthetics. As above, arm > thigh.