Kinetics Final (Conceptual Questions)

Response is a pharmacodynamic process.

Dialysate is aqueous in nature therefore water soluble drugs more readily removed.

Neonates and infants have thinner and less developed skin compared to adults. This makes their skin more permeable, meaning that substances can more easily pass through their skin and be absorbed into their bodies. This increased permeability is due to the immaturity of their skin barrier function and the higher water content in their skin. As a result, neonates and infants are more susceptible to the absorption of chemicals and substances through their skin, which is why caution must be exercised when applying products or medications to their skin.

Physiologic-based Pharmacokinetic Models categorize organs into non-eliminating organs and eliminating organs. This classification is based on the organ's ability to eliminate drugs from the body. Non-eliminating organs do not play a significant role in drug elimination, while eliminating organs are responsible for drug metabolism and excretion. Therefore, the statement is true.

Pharmacodynamics refers to the study of the effects of drugs on the body and how they interact with the body's systems. It focuses on understanding the mechanisms of action of drugs, including how they bind to receptors, alter biochemical pathways, and produce therapeutic or adverse effects. Therefore, the correct answer is "what the drug does to the body."

Heart disease is the most common cause of death in adults over age 65. This is because as people age, their risk factors for heart disease, such as high blood pressure, high cholesterol, and obesity, increase. Additionally, the aging process itself can lead to changes in the heart and blood vessels, making them more susceptible to disease. Heart disease encompasses a range of conditions, including coronary artery disease, heart failure, and arrhythmias, which can ultimately result in heart attacks or sudden cardiac death. Therefore, it is not surprising that heart disease is the leading cause of death in this age group.

Dialysis is a medical procedure used to remove waste products and excess fluids from the blood when the kidneys are unable to perform this function adequately. Since drugs are typically eliminated from the body through the kidneys, dialysis can help remove drugs from the bloodstream, leading to a decrease in serum drug concentration. Therefore, the statement "In general, dialysis decreases serum drug concentration" is true.

In a continuous or intermittent IV infusion, it takes approximately 5 half-lives to reach steady state. Steady state refers to a point where the rate of drug administration equals the rate of elimination, resulting in a constant concentration of the drug in the body. Each half-life represents the time it takes for the drug concentration to decrease by half. By the time 5 half-lives have passed, the drug concentration will have reached a relatively stable level, indicating steady state.

The explanation for the given correct answer is that the Mean Residence Time (MRT) is a pharmacokinetic parameter that represents the average time a drug molecule spends in the body before being eliminated. It assumes that drug elimination primarily occurs on the primary constitutive element in a system, which refers to the main organ or tissue responsible for drug metabolism and excretion. Therefore, the statement that MRT assumes drug elimination occurs on the primary constitutive element is true.

An accountant is unlikely to be involved in a multidisciplinary approach to individualizing drug therapy because their role primarily revolves around financial management and record-keeping rather than patient care or medical decision-making. In a multidisciplinary approach, healthcare professionals like physicians, nurses, and pharmacists collaborate to tailor drug therapy to each patient's specific needs and circumstances. The involvement of an accountant is not necessary for this process.

Premature infants have decreased biliary function compared to older children and adults. This means that their ability to produce and secrete bile, a substance that aids in digestion, is lower than that of older individuals. This could be due to the immaturity of their liver and biliary system, which may not have fully developed at the time of birth. As a result, premature infants may have difficulties with proper digestion and absorption of nutrients.

lecture 19, slide 25

As we age, the amount of total body water in our bodies tends to decrease. This is because as we get older, our muscle mass tends to decrease and our body fat tends to increase. Since muscle tissue contains more water than fat tissue, the overall percentage of water in our bodies decreases. Additionally, as we age, our kidneys may become less efficient at conserving water, leading to a further decrease in total body water. Therefore, the correct answer is "decreases".

A substitution of one nucleotide for another nucleotide in a sequence of DNA is called a Single Nucleotide Polymorphism. This refers to a genetic variation that occurs when a single nucleotide (A, T, C, or G) in the DNA sequence is changed. SNPs are the most common type of genetic variation and can have various effects on gene function and protein production. They can be associated with increased susceptibility to certain diseases or have no effect at all.

Warfarin is a highly protein bound drug because it binds extensively to plasma proteins, particularly albumin. This binding plays a crucial role in the drug's distribution and elimination from the body. Protein binding helps to keep the drug in circulation and prevents it from being rapidly metabolized or excreted. As a result, only the unbound fraction of warfarin is pharmacologically active. High protein binding also means that interactions with other drugs that also bind to proteins can occur, potentially affecting the therapeutic efficacy and safety of warfarin.

The statement is true because only free drugs, which are not bound to proteins or other molecules in the bloodstream, can be distributed to the tissues. Bound drugs are unable to interact with target receptors or exert their intended effects. Therefore, for a drug to be effective, it must be in its free form and able to reach the target tissues.

In a two compartment model, k21 does not describe drug elimination from a system. Instead, k21 represents the rate constant for drug distribution from the central compartment to the peripheral compartment. Drug elimination from the system is typically described by k10 or kel.

Serum Creatinine and Creatinine clearance are inversely related.

As people age, their baroreceptor reflex, which helps regulate blood pressure, tends to become less sensitive. This can result in orthostatic hypotension, a condition where blood pressure drops significantly when standing up from a sitting or lying position. This can cause symptoms such as dizziness, lightheadedness, and even fainting. Therefore, it is true that a decrease in the baroreceptor reflex can lead to orthostatic hypotension in the elderly.

Allometry is indeed the study of biological scaling, which examines how the size and shape of organisms influence their physiological processes. It specifically focuses on the relationship between the size of an organism and its various biological characteristics. A physiologic-based pharmacokinetic model, on the other hand, is a mathematical representation of how drugs are distributed and eliminated in the body. While allometry is not the only use of this model, it is one of the applications that can be explored to understand how drug metabolism and pharmacokinetics vary across different species and body sizes. Therefore, the statement that allometry is one use of a physiologic-based pharmacokinetic model is true.

Both hypertension and arthritis affect over half the population age 65 and older.

Protein Binding does not eliminate the active drug, it can still dissociate after it binds.

Extraction ratio describes the amount of drug extracted during first pass metabolism. A drug with high first pass metabolism will have a greater percentage change in bioavailability in a patient with liver disease.

Patients with renal disease have impaired kidney function, which can result in the accumulation of meperidine and its metabolite, normeperidine. Normeperidine has CNS stimulatory effects and can increase the risk of seizures. Additionally, meperidine is primarily eliminated through the kidneys, so its clearance is reduced in patients with renal disease. Therefore, meperidine will have less analgesic activity and more CNS stimulatory effects in patients with renal disease.

As people age, the lens of the eye becomes less flexible and loses its ability to change shape easily. This decreased accommodation of the lens leads to difficulty in focusing on nearby objects, resulting in farsightedness or hyperopia. Therefore, it is true that decreased accommodation of the lens in the elderly causes farsightedness.

The Child-Pugh Classification is a widely used system to grade the severity of liver disease. It assesses the severity based on five clinical and laboratory parameters: serum bilirubin level, serum albumin level, prothrombin time, presence of ascites, and hepatic encephalopathy. Each parameter is assigned a score, and the total score determines the severity of the liver disease, ranging from class A (mild) to class C (severe). This classification system helps in determining the prognosis and guiding treatment decisions for patients with liver disease.

From birth to nine months, the general trend is for body fat to increase with age. This is because during this period, infants experience rapid growth and development, and body fat plays a crucial role in providing energy, insulation, and protection. As they grow, their body composition changes, with an increase in body fat percentage. This is a natural and necessary process for their overall health and development.

Hepatic disease is most likely to affect the metabolism of drugs. The liver is responsible for metabolizing drugs and converting them into their active or inactive forms. When the liver is diseased, its ability to metabolize drugs may be impaired, leading to altered drug levels in the body. This can result in decreased drug effectiveness or increased drug toxicity. Therefore, metabolism is the pharmacokinetic parameter that would be most affected by hepatic disease.

The EC50 is the concentration at which half of the maximal effect of the drug occurs. This means that at the EC50 concentration, the drug is exerting its maximum effect on the target. It is an important pharmacodynamic parameter as it helps determine the potency of a drug and provides valuable information for dose-response relationships.

There is no good evidence to support this practice.

CRRT: Continuous Renal Replacement Therapy

The term "coefficient" refers to a numerical value that quantifies the relationship between two variables. In the context of a dose response curve, the coefficient mentioned here is likely the slope or gradient of the curve. A higher coefficient indicates a steeper curve, meaning that there is a greater change in the response variable (e.g., drug effect) for a given change in the dose variable. Therefore, "Hill" is the correct answer as it best describes the concept of a coefficient determining the steepness of a dose response curve.

Drugs with anticholinergic side effects should be avoided in the elderly because they can cause mental confusion, memory impairment, delerium, constipation, BPH, incontinence, and glaucoma.

lecture 20, PK-PD models

In mutation notation, P34S means that the 34th amino acid in the gene sequence has undergone a change from a proline to a serine.

Lecture 19, slide 5

C-telopeptide is a product of bone turnover that is used to measure the pharmacodynamic response to ibandronate (Boniva). It is a marker of bone resorption and is released during the breakdown of collagen in bone. Measuring C-telopeptide levels can help assess the effectiveness of ibandronate in inhibiting bone resorption and treating conditions such as osteoporosis.

During the first year of life, glomerular function increases. This is because as an infant grows, their kidneys also develop and mature. The glomeruli, which are responsible for filtering waste products from the blood and forming urine, become more efficient and capable of higher filtration rates. This increase in glomerular function allows the kidneys to effectively remove waste and maintain fluid balance in the body as the infant grows and their metabolic demands increase.

In end stage renal disease, the kidneys are severely damaged and their function is significantly impaired. This can lead to decreased protein binding of acidic drugs like warfarin. Protein binding refers to the attachment of drugs to proteins in the blood, which affects their distribution and elimination from the body. In renal disease, the balance of protein binding may be disrupted, resulting in decreased binding of acidic drugs. Therefore, the statement that protein binding of acidic drugs is generally decreased in end stage renal disease is true.

Mean Residence Time (MRT) is a useful parameter in both normal modeling systems and non-compartmental analysis. In normal modeling systems, MRT helps in determining the time it takes for a substance to leave the system or be eliminated. In non-compartmental analysis, MRT is used to estimate the average time a drug or substance remains in the body. Therefore, the statement that MRT can be used in both normal modeling systems and non-compartmental analysis is true.

The formula for rate of excretion is rate of filtration + rate of secretion - rate of reabsorption.

Will be higher in adults due to higher body fat. Therefore the drug will have more volume to distribute in.

In chronic liver disease, the main issue is the alteration in hepatic blood flow. This can occur due to various factors such as cirrhosis, fibrosis, or inflammation of the liver. These conditions can lead to the development of scar tissue, which can obstruct the normal flow of blood through the liver. As a result, the liver may not receive enough oxygen and nutrients, leading to further damage and dysfunction. Therefore, chronic liver disease is characterized by long-term changes in hepatic blood flow, contributing to the progression of the disease.

lecture 19, slide 9.

If a drug is metabolized by CYP2D6 and the patient is homozygous for mutant variation that decreases the expression of CYP2D6, and they have a homozygous mutant receptor genotype that decreases the target receptor's affinity for the drug, the response seen will be one of low efficacy and high toxicity. This is because the decreased expression of CYP2D6 will result in slower metabolism of the drug, leading to lower efficacy. Additionally, the decreased affinity of the receptor for the drug will result in a reduced response, further contributing to low efficacy. On the other hand, the slower metabolism of the drug can lead to its accumulation in the body, increasing the risk of toxicity. Therefore, the response seen will be characterized by low efficacy and high toxicity.

The eGFR is multiplied by 0.742 if the patient is female and by 1.21 is the patient is African American.

Decrease in tissue blood perfusion and atrophy of the epidermis and dermis lead to a decrease in transdermal drug absorption and a decrease or variable rate in IM & SQ drug absorption.

The opposite is true.

It always takes 5 half lives for a drug to reach steady state. However, the half life of the drug would double, so it would take twice as long to reach steady state, and the steady state drug concentration would be twice as high. In terms of normal half lives, it would take 10 of the "normal" drug half lives (the half life listed on the package insert) to reach steady state, however, this is not what the question asks.

An DEcrease in active transport in the elderly will lead to a DEcrease in absorption of vitamin B12, calcium, and iron.