Drug excretion and clearance Flashcards
What is the equation for net excretion of a drug?
The equation for net excretion of a drug is:
Net Excretion = Glomerular Filtration - Reabsorption + Tubular Secretion.
What are the different sites of drug excretion in the body?
Drugs can be excreted through various sites, including:
Fluids: Urine, bile, sweat, tears, breast milk.
Solids: Faeces, hair.
Gas: Exhaled breath.
How does renal pathology affect drug excretion?
Any pathology that reduces glomerular filtration (such as kidney disease) can reduce drug excretion. Less than 90% of renally excreted drugs rely on active secretion. Reduced glomerular filtration leads to slower or less efficient elimination of drugs.
What factors determine the filtration of drugs at the glomerulus?
The filtration of drugs at the glomerulus is influenced by:
Molecular Size: Molecules with a molecular weight greater than 20 kDa (or a diameter < 4 nm) pass through easily.
Charge: The negatively charged glomerular capillary wall repels anions, so they are filtered less efficiently.
Protein Binding: Only free drugs (not bound to proteins) can be filtered. For example, warfarin has significant protein binding, so its filtration is low.
How does the distal tubular reabsorption process affect drug excretion?
Most water is reabsorbed by the time the filtrate reaches the distal tubule, leading to high drug concentration in the tubule. Lipid-soluble drugs tend to be reabsorbed through the concentration gradient, while polar drugs are less likely to be reabsorbed and thus remain in the tubule for excretion.
What role do the kidneys play in maintaining systemic pH?
The kidneys help maintain systemic pH through the reabsorption of bicarbonate and the excretion of acid, which also involves the production of new bicarbonate. The major buffer system in the human body is bicarbonate, and the kidneys help regulate its balance by excreting acid (e.g., ammonium ions) to produce new bicarbonate.
How can urine pH influence drug excretion?
Urine pH can be manipulated to alter drug excretion. For example, drugs can be excreted more rapidly or in greater amounts if the urine is made more acidic or alkaline. This is commonly done in cases of overdose or poisoning. The normal urine pH range is 4.5–7.8.
What factors influence renal excretion of drugs?
Several factors influence renal excretion, including:
Urine Flow: Increased urine flow reduces the time the drug spends in the kidney and the concentration gradient, affecting excretion.
Diuretics/Water Intake: These can increase urine flow but usually have minimal clinical effects on drug excretion.
Disease States: Conditions like sepsis increase renal clearance due to increased cardiac output and renal blood flow.
Drug Interactions: Drug-drug interactions can alter the efficiency of active transporters involved in excretion.
How does metabolism aid in renal drug excretion?
Metabolism, particularly Phase 2 reactions (conjugation), transforms lipophilic (fat-soluble) drugs into polar (water-soluble) molecules, making them easier to excrete through the kidneys. The conversion to more polar forms helps increase the renal excretion of these drugs.
What is biliary excretion, and how does it affect drug elimination?
Biliary excretion involves the transport of drugs or their metabolites into the bile by hepatic transporters. Hydrophilic conjugates are concentrated in bile and can be excreted into the intestines. If the drug or metabolite is reabsorbed in the intestine, it undergoes enterohepatic circulation, which prolongs the drug’s duration of action.
What factors can affect biliary or hepatic excretion?
Factors affecting biliary or hepatic excretion include:
Disease States: Acute or chronic liver disease can impair the efficiency of metabolic processes, leading to reduced drug elimination.
Drug Interactions: Drug interactions may induce or inhibit the CYP450 enzyme system, affecting the metabolism and elimination of drugs through the liver.
What is the impact of glomerular filtration on drug excretion?
Glomerular filtration plays a crucial role in drug excretion. The process involves the movement of drugs from the bloodstream into the renal tubules for elimination. Drugs with smaller molecular sizes and those not bound to plasma proteins are more easily filtered. Reduced glomerular filtration, such as in kidney disease, decreases drug excretion, leading to prolonged drug effects and possible toxicity.
How do lipid-soluble and polar drugs differ in terms of renal excretion?
Lipid-soluble (lipophilic) drugs tend to be reabsorbed in the renal tubules due to the concentration gradient, which means they are less likely to be excreted in urine. In contrast, polar drugs, which do not easily pass through the lipid membrane, are less reabsorbed in the distal tubules and are more likely to remain in the urine for excretion. This makes polar drugs more efficiently eliminated through the kidneys.
What role does the enterohepatic circulation play in drug elimination?
Enterohepatic circulation extends the duration of action of certain drugs by reabsorbing the drug or its metabolites from the intestines back into the bloodstream. After being excreted into the bile, hydrophilic conjugates are concentrated in bile and transferred to the intestines. In the intestine, the drug may be reabsorbed, which can prolong its presence in the body, thereby prolonging its effect.
How do changes in urine flow affect drug excretion?
Changes in urine flow can influence the excretion of drugs. Faster urine flow, often caused by diuretics or increased water intake, reduces the time drugs spend in the kidney and may lower the concentration gradient, potentially leading to increased drug excretion. However, in most clinical settings, the effect of altered urine flow on drug excretion is minimal unless there are specific conditions or overdose situations that require manipulation of drug elimination.
