Pharmacokinetics – Excretion Flashcards
What are the various routes of drug elimination from the body?
The various routes of drug elimination from the body include excretion through renal/urine, bile (faeces), exhaled air, sweat, saliva, breast milk, nails, and hair.
What is drug clearance (CLtot)?
Drug clearance (CLtot) refers to the sum of all the drug-eliminating processes in the body, primarily determined by metabolic excretion/clearance (CLmet) and renal excretion/clearance (CLren), along with any additional significant routes of elimination. It can be defined as the theoretical volume of plasma from which a drug is completely removed in a given period of time.
What are the main organs involved in drug excretion?
The kidneys are the main drug-excreting organs. Drugs can be excreted unchanged or metabolized before excretion. The excretion process involves glomerular filtration (for unbound drugs), secretion in the proximal tubule (via passive/facilitated diffusion and active secretion), and reabsorption in the proximal and distal tubules. Factors such as pH and urine rate are important for renal clearance.
What is biliary excretion and entero-hepatic circulation?
Biliary excretion refers to the elimination of drugs or their metabolites via the bile into the gastrointestinal tract. Entero-hepatic circulation occurs when drugs are reabsorbed from the intestines back into the bloodstream via the portal vein, potentially leading to their prolonged presence in the body. Examples of drugs that undergo biliary excretion and entero-hepatic circulation include NSAIDs and oral contraceptives.
What are the factors that affect drug clearance in the body?
Factors that affect drug clearance include renal function (including renal blood flow and glomerular filtration rate), protein binding, urine flow rate and pH, concentration of the drug in plasma, size of drug complex, and age.
What are the causes of low drug clearance?
Causes of low drug clearance include renal impairment, liver impairment, enzyme inhibition, genetic poor metabolizer status, age (neonate or old age), and reduced blood flow (including normal variations).
What happens in patients with poor renal function?
In patients with poor renal function, several changes can occur, including increased renal blood flow, increased glomerular filtration rate (GFR), decreased protein plasma binding, genetic ultrarapid metabolism, and enzyme induction (including normal variations).
What are the causes of high drug clearance?
Causes of high drug clearance include factors such as increased renal blood flow, increased GFR, decreased protein plasma binding, genetic ultrarapid metabolism, and enzyme induction (including normal variations).
What precautions should be taken with renally excreted drugs?
Renally excreted drugs require caution, especially those that are excreted unchanged or produce active metabolites. Drugs with a narrow therapeutic window and those that may further reduce renal function should also be used with caution.
What is the significance of clearance in pharmacokinetics?
Clearance is a pharmacokinetic parameter that represents the rate at which a drug is eliminated from the body. It influences important aspects such as half-life, steady state, therapeutic window/range/index, area under the curve (AUC), ED50 (effective dose for 50% of the population), TD50 (toxic dose for 50% of the population), and more.
What are some important terms in pharmacokinetics?
Important terms in pharmacokinetics include Cmax (maximum concentration of a drug), tmax (time taken to reach Cmax), area under the curve (AUC) which represents overall drug exposure, half-life (t1/2) which is the time for plasma drug concentration to reduce by half, and the concept of steady state which is achieved after approximately 3-5 half-lives and is important for determining the therapeutic effect of a drug.
How is steady state achieved in drug administration?
Steady state is achieved when the rate of drug administration equals the rate of drug elimination. It typically takes about 3-5 half-lives of a drug to reach steady state. This is an important concept in determining the appropriate dosing regimen and assessing the therapeutic effect of a drug.
What is the therapeutic window/range/index?
The therapeutic window/range/index refers to the range of drug concentrations within which the drug exhibits maximum efficacy (desired effect) and minimum toxicity in the majority of patients. It is quantified by the therapeutic index (TI), calculated as TD50 (toxic dose for 50% of the population) divided by ED50 (effective dose for 50% of the population). A large TI indicates a wide therapeutic window, while a small TI indicates a narrow therapeutic window.
What is drug clearance (CLtot)?
Drug clearance (CLtot) represents the sum of all the drug-eliminating processes in the body, primarily determined by metabolic clearance (CLmet) and renal clearance (CLren), along with any additional significant routes of elimination. It can also be defined as the theoretical volume of plasma from which a drug is completely removed in a given period of time. CLtot relates the rate of elimination of a drug (in units of mass/unit time) to the plasma concentration (Cp).
What is the elimination rate of drugs?
Most drugs follow first-order elimination, meaning they are removed from the body at a rate that is proportional to the plasma concentration. This leads to a constant half-life, constant time to peak concentration, constant clearance, and proportional relationships between AUC (area under the curve), Cmax (maximum concentration), and steady-state concentration (Css) with the dose. As a result, drug monitoring is relatively straightforward.
