Pharmacokinetics Tutorial MCQs PT2201 ./BB
7. If the volume of distribution (VD) for a drug is 12 litres, how is it mainly distributed in the body? Note: See slide 33 of PK1 lecture for reference. a. In the blood b. In the blood and interstitial fluid c. In the blood, interstitial fluid and intracellular fluid d. None of the above
b. In the blood and interstitial fluid [intracellular aka cyptoplasm—-> small percentage may get in there] If the volume of distribution (VD) for a drug is 12 litres, it is mainly distributed in the blood and interstitial fluid. This is because a VD value of 12 litres indicates that the drug is distributed throughout the body's extracellular fluid, which includes the plasma (intravascular fluid) and the interstitial fluid surrounding cells, but not the intracellular fluid within cells. Therefore, the correct answer is "In the blood and interstitial fluid".
8. Some drugs with a large Vd act on intracellular receptors. Provide examples of intracellular receptors that drugs can act on.
—thyroid receptors —Ah receptors —glucocorticoid receptors (found within cell) —hormone receptors (sex steroid hormones) ++++
18. In relation to adverse drug reactions (ADRs), which of the following statements is/are TRUE? a. ADRs are always related to the primary pharmacological mode of action of the drug. b. ADRs are not a major clinical concern c. ADRs can occur at sub-therapeutic doses d. Options (a) and (b) e. Options (b) and (c)
c. ADRs can occur at sub-therapeutic doses exp: ADRs are NOT always related to the primary pharmacological mode of action of the drug.—> bizzaar (B) ones are not related to it.
1. What is the main mechanism by which drugs cross membranes? a. Active transport b. Facilitated diffusion c. Passive diffusion d. Pinocytosis e. Through gap junctions
c. Passive diffusion exp: Drug molecules travel passively across membranes, propelled by a concentration gradient, from a region of higher concentration to a region of lower concentration. This process is regarded as passive because it happens spontaneously and doesn't require energy input. The size, shape, polarity, and lipid solubility of the drug molecule, as well as the characteristics of the membrane, such as thickness and lipid composition, all have an impact on the rate of passive diffusion. Other mechanisms by which drugs can cross membranes include active transport, facilitated diffusion, and endocytosis/exocytosis. However, these mechanisms are generally less common and are often specific to certain drug molecules or transporters.
2. What is/are the main factor(s) that determine the rate of passive diffusion? a. Concentration gradient b. Surface area of membrane c. Metabolic energy d. Options (a) and (b) e. Options (a) and (c)
d. Options (a) and (b) exp: not Metabolic energy BC: Passive diffusion doesn't require energy. Metabolic energy is not a factor that determines the rate of passive diffusion, as this process occurs spontaneously without the need for energy input. The following parameters significantly influence the rate of passive diffusion, the primary mechanism by which medicines traverse membranes: Concentration gradient: The rate of diffusion increases as the concentration gradient increases. This implies that the drug will diffuse across the membrane more quickly the higher the concentration of the medication is on one side of the membrane relative to the other. Size and form of molecules: Smaller, more compact molecules diffuse more quickly than larger, more complicated molecules do. More spherical molecules also have a tendency to diffuse more quickly than elongated molecules. Lipid solubility: Molecules that are more lipid-soluble than water-soluble permeate across the membrane's lipid bilayer more easily. Membrane thickness: The rate of diffusion increases with membrane thickness. Surface area of the membrane: The potential for diffusion increases with membrane surface area. Membrane composition: The ease of diffusion may be impacted by the membrane's makeup. Faster diffusion is possible with membranes with more fluidity, such as those found in unsaturated lipid bilayers, as opposed to membranes with lesser fluidity, such as those found in saturated lipid bilayers.
17. In relation to drug interactions, which of the following statements is/are TRUE? a. Enzyme induction accelerates drug clearance b. Enzyme induction can increase the duration of action of a prodrug c. Enzyme induction can reduce the duration of action of a drug d. Options (b) and (c) e. All of the above
e. All of the above exp: (b) Enzyme induction can increase the duration of action of a prodrug. When an enzyme that activates a prodrug is induced, more active drug is produced, leading to higher plasma concentrations and a longer duration of action. For example, rifampicin induces the CYP3A4 enzyme, leading to increased activation of the prodrug oseltamivir to its active metabolite oseltamivir carboxylate, and higher plasma concentrations of the active drug.
14. How does advanced age affect the pharmacokinetics of a drug? a. GFR decreases with age b. Activity of hepatic microsomal enzymes declines slowly with age c. Drug distribution alters with age d. Cardiac output reduces with age e. All of the above
e. All of the above exp: -->GFR (glomerular filtration rate) decreases with age: GFR is the rate at which drugs are filtered out of the blood by the kidneys. As age increases, GFR decreases, which can result in a longer half-life and higher plasma concentrations of drugs that are eliminated renally. -->Activity of hepatic microsomal enzymes declines slowly with age: The liver plays a key role in drug metabolism, and hepatic microsomal enzymes are responsible for the metabolism of many drugs. As age increases, the activity of these enzymes can decline, which can result in slower drug metabolism and higher plasma concentrations of drugs that are metabolized hepatically. -->Drug distribution alters with age: The body composition of elderly individuals can be different from younger adults, with more body fat and less muscle mass. This can affect drug distribution in the body, resulting in changes in drug volume of distribution and plasma concentrations. -->Cardiac output reduces with age: Cardiac output is the amount of blood pumped by the heart per minute, and it can decrease with age. This can affect the absorption and distribution of drugs in the body, resulting in changes in drug plasma concentrations.
15. In relation to genetic polymorphisms of drug metabolising enzymes, which of the following statements is/are TRUE? a. Polymorphisms always result in decreased drug metabolism. b. Polymorphisms have only been observed with cytochrome P450 enzymes. c. Polymorphisms are especially important for drugs that are mainly metabolised by one isoform of an enzyme. d. Options (a) and (b) e. Options (a) and (c)
c. Polymorphisms are especially important for drugs that are mainly metabolised exp: (a) Polymorphisms do not always result in decreased drug metabolism. Depending on the specific polymorphism, drug metabolism may be increased, decreased, or remain unchanged. (b) Polymorphisms have not been observed only with cytochrome P450 enzymes. Polymorphisms can occur in many drug metabolizing enzymes, including UDP-glucuronosyltransferases, N-acetyltransferases, and thiopurine methyltransferase, among others. (c) The statement that is true is that polymorphisms are especially important for drugs that are mainly metabolized by one isoform of an enzyme. Polymorphisms can result in reduced or absent enzyme activity, which can lead to decreased drug metabolism and higher plasma concentrations of the drug. This can increase the risk of toxicity, particularly for drugs that have a narrow therapeutic index or are mainly metabolized by a single enzyme isoform.
5. What is/are the main reason(s) that some drugs cannot be administered orally? a. Poorly absorbed from the digestive tract b. Excessive first pass metabolism c. Highly lipophilic d. Options (a) and (b) e. Options (b) and (c)
d. Options (a) and (b) The main reasons that some drugs cannot be administered orally are poorly absorbed from the digestive tract and excessive first-pass metabolism. Therefore, the correct answer is (a) and (b). Explanation for step 5 Inadequate absorption can be caused by a number of things, such as insufficient solubility in the stomach's acidic environment, unstable pH levels, or being too big to be adequately transported over the intestinal epithelium. A drug's rapid breakdown or conversion by the liver into inactive or less active metabolites before it enters the systemic circulation is referred to as excessive first-pass metabolism. This may happen as a result of the considerable processing that medications go through in the liver after being absorbed through the digestive system. High lipophilicity does not preclude oral administration of some medications. In actuality, several lipophilic medications absorb effectively when taken orally. High lipophilicity, however, can reduce a medicine's clinical use by altering drug distribution and excretion and raising the risk of toxicity.
11. Where does the active secretion of drugs mainly take place? a. Distal tubule b. Glomerulus c. Loop of Henle d. Proximal tubule e. All of the above
d. Proximal tubule exp: (organic anion transporters + organic cation transporters) --The active secretion of drugs mainly takes place in the Proximal tubule of the nephron in the kidneys. This is because the proximal tubule has a high concentration of transporters and enzymes that are involved in the active secretion of drugs from the blood into the urine. The transporters in the proximal tubule can move drugs against a concentration gradient, allowing for the elimination of drugs that are not filtered by the glomerulus. --The other options - distal tubule, glomerulus, and loop of Henle - do not play a significant role in the active secretion of drugs. The distal tubule and loop of Henle are primarily involved in the reabsorption of water and electrolytes, while the glomerulus is involved in the filtration of small molecules such as drugs. However, some drugs can also be reabsorbed in the distal tubule and loop of Henle, which can affect their elimination from the body.
4. At which of the following sites does active transport not occur? a. Renal tubule b. Biliary tract c. Blood brain barrier d. Gastrointestinal tract e. None of the above
e. None of the above exp: (=eg. bring in nutrients (ex. AAs) as well as drugs [normal system is used by drugs]) Active transport is a ubiquitous mechanism that occurs in various biological systems, including the renal tubule, biliary tract, blood-brain barrier, and gastrointestinal tract. Therefore, the answer is None of the above. Explanation for step 4 Several organs and tissues, such as the kidneys, liver, brain, and digestive system, depend on active transport to function properly. For instance, active transport in the renal tubule is essential for preserving the correct electrolyte balance and controlling the body's excretion of waste products. Similar to this, active transport is necessary for the absorption of nutrients and other crucial substances from the diet in the gastrointestinal system.
9. In relation to drug metabolism, which of the following statements is/are TRUE? a. Drug metabolism always involves a phase I reaction followed by a phase II reaction. b. Drug metabolism occurs only in the liver. c. Reduction is the main phase I reaction. d. Drug metabolism always results in formation of pharmacologically inactive metabolites. e. None of the above.
e. None of the above. exp: oxidation is the main phase 1 reaction --Drug metabolism does not always involve a phase I reaction followed by a phase II reaction. While many drugs do undergo both phase I and phase II reactions, some drugs only undergo one or the other, and some drugs may undergo additional metabolism steps. --Drug metabolism can occur in many different tissues and organs, not just the liver. The liver is a major site of drug metabolism, but other organs such as the kidneys, lungs, and gastrointestinal tract can also contribute to drug metabolism. --Reduction is one type of phase I reaction, but there are other types of phase I reactions such as oxidation and hydrolysis. The specific type of phase I reaction that a drug undergoes depends on its chemical structure and the enzymes involved in its metabolism. --Drug metabolism can result in the formation of both pharmacologically active and inactive metabolites. Some metabolites may have different pharmacological effects than the parent drug, while others may have no pharmacological activity at all.
6. In relation to the "blood brain barrier", which of the following statements is/are TRUE? a. Refers to reduced permeability of brain capillaries compared non-brain capillaries b. Prevents the entry of non-polar, lipophilic chemicals into the brain c. Can be disrupted by inflammation d. Options (a) and (b) e. Options (a) and (c)
e. Options (a) and (c) only chemicals that can get across ARE non-polar, lipophilic chemicals . —> BBB prevents polar, hydrophillic The blood-brain barrier refers to the reduced permeability of brain capillaries compared to non-brain capillaries, due to the presence of tight junctions between endothelial cells, pericytes, and astrocytes. This barrier is essential for protecting the brain from potentially harmful substances in the bloodstream, such as toxins and pathogens. Explanation for step 6 The blood-brain barrier is selective, which means that it lets certain molecules and nutrients, like oxygen and glucose, enter the brain while blocking most other substances from doing the same. This includes non-polar, lipophilic chemicals, which have trouble crossing the barrier because of their hydrophobicity. The blood-brain barrier can be damaged by inflammation and become more permeable, allowing chemicals and immune cells to enter the brain. This may happen as a result of illnesses, trauma, or other forms of brain damage.
10. What process(es) is/are involved in the renal elimination of drugs? a. Active Transport b. Diffusion c. Filtration d. Hepatotoxicity e. Options (a), (b) and (c)
e. Options (a), (b) and (c) exp: Active Transport: This is a process by which drugs are transported across the cell membrane against a concentration gradient using energy derived from ATP. In the renal tubules, active transport is used to eliminate drugs that are not lipid-soluble, such as certain organic acids and bases. Diffusion: This is a process by which drugs move from an area of higher concentration to an area of lower concentration. In the renal tubules, diffusion is involved in the elimination of lipid-soluble drugs, as these drugs can passively diffuse through the cell membrane. Filtration: This is a process by which substances are removed from the blood and enter the renal tubules via the glomerulus. The glomerulus acts as a filter, allowing small molecules such as drugs to pass through while retaining larger molecules such as proteins. The filtered drugs can then be eliminated in the urine. Hepatotoxicity is not involved in the renal elimination of drugs, as hepatotoxicity refers to liver damage caused by drugs or other substances.
3. What is/are the main requirement(s) for active transport? a. Structural similarity to endogenous molecules b. Specific receptor c. Metabolic energy d. Options (a) and (c) e. Options (a), (b) and (c)
e. Options (a), (b) and (c) exp: [less common than passive diffusion because it does require specific receptors eg. Levodopa —> l-dopa mimics tyrosine (mimic endogenous molecules).] Explanation for step 3 Structural similarity to endogenous molecules and specific receptors are not requirements for active transport. Rather, active transport is driven by energy input and requires transport proteins to move molecules against their concentration gradient. Well, the main requirements for active transport are: 1. Energy: Active transport requires metabolic energy in the form of ATP or an electrochemical gradient to drive the movement of molecules against their concentration gradient. 2..Transport Proteins: Membrane-bound transport proteins are required to carry out active transport. These proteins use energy to move molecules against their concentration gradient and can be either primary or secondary active transporters. 3. Concentration Gradient: Although active transport moves molecules against their concentration gradient, there must be some initial concentration gradient to allow for active transport to occur. Active transport is able to create concentration gradients by pumping molecules out of or into the cell.
16. In relation to drug interactions, which of the following statements is/are TRUE? a. Enzyme inhibition accelerates drug clearance b. Enzyme inhibition can increase the duration of action of a drug c. Enzyme inhibition can reduce the duration of drug action of a prodrug d. Options (a) and (b) e. Options (b) and (c)
e. Options (b) and (c) exp: (=duration of action of a prodrug is dependant on its conversion.) (b) Enzyme inhibition can increase the duration of action of a drug. When an enzyme that metabolizes a drug is inhibited, the drug is metabolized more slowly or not at all, leading to higher plasma concentrations and a longer duration of action. For example, grapefruit juice inhibits the CYP3A4 enzyme, leading to increased plasma concentrations and prolonged effects of many drugs that are metabolized by this enzyme. (c) Enzyme inhibition can reduce the duration of drug action of a prodrug. A prodrug is an inactive compound that is metabolized into an active drug. If the enzyme responsible for activating the prodrug is inhibited, the prodrug will not be activated and the duration of drug action will be reduced. For example, the prodrug codeine is metabolized to morphine by the CYP2D6 enzyme. If a CYP2D6 inhibitor is co-administered with codeine, the duration of action of morphine will be reduced.
13. In relation to a first order one-compartment model, which of the following statements are TRUE? a. The rate of drug elimination declines linearly over time. b. The rate of elimination is independent of the plasma concentration of the drug. c. The half-life of a drug is independent of its plasma concentration. d. If the half-life of a drug is 2 hours, 8 hours after i.v. administration the plasma concentration will be reduced to 6.25% of the initial concentration. e. Options (c) and (d)
e. Options (c) and (d) exp: The rate of elimination is dependant of plasma conc. of drug!! The rate of drug elimination does not decline linearly over time in a first-order one-compartment model. Instead, the rate of elimination is proportional to the plasma concentration of the drug, which means that the rate of elimination declines exponentially over time as the plasma concentration decreases. (b) The rate of elimination is not independent of the plasma concentration of the drug in a first-order one-compartment model. As mentioned above, the rate of elimination is proportional to the plasma concentration, which means that the rate of elimination will decrease as the plasma concentration decreases. (c) The half-life of a drug is independent of its plasma concentration in a first-order one-compartment model. The half-life is a constant parameter that depends only on the rate constant of elimination, and is calculated as 0.693 divided by the rate constant. (d) If the half-life of a drug is 2 hours, 8 hours after i.e. administration the plasma concentration will be reduced to 6.25% of the initial concentration. This can be calculated using the equation for exponential decay: C = C0 x e-kt, where C is the plasma concentration at time t, C0 is the initial plasma concentration, k is the rate constant of elimination, and t is the time since administration. Substituting the values given, we get: C = 100% x e^(-0.693 x 8/2) = 6.25%.