Pharmacokinetics | Drug Excretion
Excretion of Drugs
In this section, the speaker discusses the different ways drugs can be excreted from the body and the organs involved in this process.
Organs Involved in Drug Excretion
- The kidneys are the primary way drugs are excreted from the body via urine.
- Drugs can also be excreted through bile, which is then eliminated through feces.
- Certain inhaled gases can be exhaled out of the lungs to eliminate drugs from the body.
Methods of Drug Excretion
In this section, the speaker explains how drugs can be eliminated from the body through various methods.
Methods of Drug Excretion
- Drugs can be eliminated through urine via kidney function.
- If a drug is not absorbed by the gastrointestinal tract, it may be eliminated through feces.
- Some drugs are absorbed into bile and then eliminated through feces.
- Certain inhaled gases can also be exhaled to eliminate drugs from the body.
Importance of Kidney Function in Drug Excretion
In this section, the speaker emphasizes how crucial kidney function is for drug elimination and discusses factors that affect drug excretion by kidneys.
Factors Affecting Kidney Function in Drug Excretion
- Filtration, secretion, and reabsorption are key factors affecting drug excretion by kidneys.
- Glomerular filtration rate (GFR) plays a critical role in filtration. Decreased GFR leads to less filtered drug and potentially higher blood drug concentration.
- Patients with chronic kidney disease or acute kidney injury may have decreased ability to filter particular things such as drugs. This leads to an increase in serum concentration of that drug and more toxic side effects.
Filtration Process for Drug Excretion
In this section, the speaker explains the filtration process for drug excretion by kidneys.
Filtration Process for Drug Excretion
- The filtration process occurs when a drug moves through the afferent arterial to the glomerulus and then across the glomerular hydrostatic pressure into Bowman's capsule.
- Filtration is primarily dependent on GFR. Decreased GFR leads to less filtered drug and potentially higher blood drug concentration.
Proximal Convoluted Tubule in Drug Excretion
In this section, the speaker discusses how drugs move from Bowman's capsule to proximal convoluted tubule during excretion.
Proximal Convoluted Tubule in Drug Excretion
- After moving from Bowman's capsule, drugs enter the proximal convoluted tubule.
- Secretion and reabsorption are key factors affecting drug excretion in this stage.
Ion Trapping in Drug Excretion
In this section, the speaker introduces ion trapping as a concept that can modify drug excretion.
Ion Trapping in Drug Excretion
- Ion trapping is a process where drugs with certain properties can be trapped inside cells due to differences in pH between extracellular fluid and intracellular fluid.
- This can lead to increased elimination of acidic or basic drugs depending on their properties.
Protein Binding and Filtration
This section discusses the relationship between protein binding and drug filtration across the glomerulus.
Importance of Protein Binding
- Drugs that are heavily protein-bound have decreased filtration across the glomerulus.
- Increased protein binding leads to less excretion of drugs, increasing their serum concentration and potential toxicity.
- Decreased protein binding can lead to more drug elimination from the body, potentially decreasing drug efficacy.
Importance of Glomerular Filtration Rate (GFR)
- GFR is heavily dependent on filtration. A decrease in GFR means less plasma and drug filtered across the glomerulus.
- Good kidneys with a normal GFR and decent protein binding allow for good amounts of drugs to be filtered across.
Secretion
This section explains how secretion works in moving drugs from peritubular capillary blood into kidney tubules for excretion.
Process of Secretion
- Some drugs remain in peritubular capillary blood after filtration.
- Solubility and concentration gradient determine whether a drug can be moved from low concentration in blood to high concentration in tubules for excretion.
Drug Excretion in the Kidney
In this section, we learn about the different ways drugs are excreted from the body through the kidneys.
Concentration Gradient and Transporters
- Drugs that are polar, water-soluble, and large require special transporters to move across the basolateral membrane into the kidney tubules.
- Organic anion transporters and organic cation transporters require ATP to pump drugs from low to high concentration areas.
- Nonpolar, lipid-soluble, small drugs can easily move across the phospholipid membrane without requiring ATP because they move from high to low concentration areas.
Drug Interactions with Transporters
- Many drugs can interact with these transporters and inhibit their function. For example, cimetidine and trimethoprim sulfamethoxazole can directly interact with these transporters and prevent drug secretion into tubular lumens.
- This step of excretion is highly dependent on solubility, concentration gradient of the drug, as well as drug interactions working against these transporters.
Reabsorption
- Reabsorption is when a drug gets back into circulation after being filtered or secreted out of the body.
- The solubility, weight, charge of a drug determine how much it will be reabsorbed back into circulation.
Drug Excretion and Reabsorption
In this section, the speaker discusses how drugs move down their concentration gradient and which types of drugs can easily passively diffuse across into the bloodstream. The speaker also explains how drugs can be excreted from the body and how reabsorption affects drug excretion.
Passive Diffusion of Drugs
- Drugs that are small, non-polar, and hydrophobic can easily move down their concentration gradient without any type of transporter.
- Low molecular weight and highly lipid-soluble drugs won't require any type of transport proteins or active transport process to passively diffuse across into the bloodstream.
Drug Excretion
- To excrete a drug, it needs to be sent to the liver where it can go through phase one metabolism (e.g., adding an OH group).
- Phase two metabolism involves adding a conjugate like glucuronate to make it more polar.
- More polar molecules are more water-soluble and will not be able to be reabsorbed when they get back into the blood.
Reabsorption Affects Drug Excretion
- Reabsorption decreases drug excretion because these drugs will be reabsorbed when they get back into the blood.
- The characteristics of a drug affect its reabsorption process. Non-polar, small, hydrophobic drugs are easily reabsorbed.
- Weak acids like phenobarbital or aspirin have a proton that disassociates into protons and conjugate base. The nonpolar form is easily absorbed while the polar form is not.
Preventing Reabsorption
- To prevent reabsorption, the drug needs to be in a charged and polar form.
- Alkalinizing the urine decreases the concentration of protons, which shifts the reaction towards making more of the charged and polar form.
- Making more of this form will not allow it to be reabsorbed and effectively excreted from the body.
Modifying Reabsorption and Enhancing Excretion
In this section, the speaker explains how to modify the reabsorption process and enhance the excretion process by changing the acidity or alkalinity of urine.
Alkalizing Urine
- Alkalinizing urine can drop the amount of proton shift, shift the reaction to the right, make more of a nonpolar molecule, and prevent its absorption.
- To convert a weak base into a polar molecule that cannot be absorbed, increase proton concentration by acidifying urine.
Acidifying Urine
- Ammonium chloride is given to patients to acidify urine and increase proton concentration.
- Bicarb is given in situations like weak acid overdoses because it decreases protons and traps ions inside kidney tubules.
Clearance Half-Life and Enzyme Kinetics
In this section, the speaker discusses clearance half-life and enzyme kinetics.
Clearance Half-Life
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Enzyme Kinetics
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