P. M. is admitted to the coronary intensive care unit (ICU) with atrial fibrillation (AFib) and rapid ventricular rate. After controlling the ventricular rate with metoprolol, it is decided to initiate procainamide by intravenous (IV) infusion. P. M. weighs 80 kg. How much of a loading dose would be required to target a level of 8 μg/L? The average steady-state volume of distribution (Vd ) for procainamide is 2 L/kg. The bioavailability of the IV formulation is 100%, whereas the oral (PO) form is only 83%.
b.1,300 mg. To determine the loading dose of a one-compartment drug, three items are needed: (a) the drug’s Vd (L/kg), (b) the desired steady-state concentration (Cpss [mg/L]), and (c) the patient’s weight. Loading dose = Vd × Cpss. Kilograms and liters cancel, and you are left with the loading dose in milligrams.
L. M. has been receiving digoxin 0.25 mg PO tablets daily. Her serum drug level is 1.8 ng/mL. She is no longer able to take PO medications and needs to receive digoxin IV. By what percentage do you need to decrease the dose to maintain the current digoxin level?
b. 25%. The bioavailability of digoxin tablets is 75%. Therefore, when converting from PO to IV administration (bioavailability of 100%), there is a 25% increase in bioavailability. Without altering the dose of digoxin, this patient would most likely have an increase in digoxin level to approximately 2.4 ng/mL. This could lead to potential digoxin toxicity.
What two pharmacokinetic parameters alter the half-life of medications?
c. Vd and clearance. Half-life is a function of both clearance (Cl) and Vd . The elimination-rate constant (kel ) is determined by two independent factors: Cl and Vd . kel = Cl/Vd . Half-life is determined by the equation 0.693/kel . Therefore, as the apparent Vd and Cl change, the half-life of a drug may change.
What is the relationship between drug concentration and pharmacologic effect known as?
d. Pharmacodynamics. Pharmacodynamics has been defined as the study of the biologic effects resulting from the interaction between drugs and biologic systems. Pharmacokinetic principles consider drug distribution, metabolism, clearance, and bioavailability, whereas pharmacodynamic principles take this one step further and relate these factors to pharmacologic response. Pharmacogenetics is the study of heredity on variations in drug response among individuals and populations. Pharmacogenetic studies have established that genetics play an important role in the dose–concentration– response relationships of medications, whereas pharmacology is simply the study of drugs.
Each line in Figure below
Relationship between drug concentration and effect.
represents a β-blocker in development. Which βblocker is the most potent?
a. Drug A is the most potent agent. This is based on the fact that at any given concentration of this agent, the effect is greater than that of the other drugs at similar concentrations. Drug B has the same maximal effect; however, it occurs at a higher concentration. Drug C is similar to drug B; however, it is less efficacious, because its maximal effect occurs at a concentration that is 50% lower than that of drug B.
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