S1B5 - Pharmocokinetics Flashcards
In pharmacokinetics, is zero-order elimination capacity-limited or flow dependent?
Zero-order elimination: Capacity-limited elimination
In pharmacokinetics, how is t1/2 calculated?
How would you treat an overdose of amphetamines?
Weak bases
- Example: amphetamines.
- Trapped in acidic environments.
- Treat overdose with ammonium chloride.
Which phase of drug metabolism do geriatric patients lose first?
Phase I
In pharmacokinetics, what does “F” represent?
Bioavailability (F)
Which drugs are more likely to be reabsorbed in the kidney: ionized forms or neutral forms?
Ionized species are trapped in urine and cleared quickly. Neutral forms can be reabsorbed.
Reduction, oxidation, hydrolysis with cytochrome P-450 is part of which phase of drug metabolism?
Phase I
What is the word for the fraction of administered drug reaching systemic circulation unchanged?
Bioavailability (F)
What is the effect of renal or liver disease on maintenance dose and loading dose?
In renal or liver disease, maintenance dose decreases and loading dose is usually unchanged.
What does t1/2 represent in pharmacokinetics?
Half-life (t1/2)
How many half-lives does it take for a drug infused at a constant rate to reach steady state?
A drug infused at a constant rate takes 4–5 half-lives to reach steady state.
How would you treat an overdose of a weak acid drug?
Weak acids
- Examples: phenobarbital, methotrexate, aspirin, TCAs
- Trapped in basic environments.
- Treat overdose with bicarbonate.
What effects do dose and dose frequency have on time to steady state?
Time to steady state depends primarily on t1/2 and is independent of dose and dosing frequency.
What is the name for a theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration?
Volume of distribution (Vd)
Which has more bioavailability: IV drugs or oral drugs?
For an IV dose, F = 100%. Orally: F typically < 100% due to incomplete absorption and first-pass metabolism.
In pharmacokinetics, how many half-lives does it take for a drug to reach 90% of the steady-state level?
It takes 3.3 half-lives to reach 90% of the steady-state level.
In pharmacokinetics, is half-life a property of zero-order elimination or first-order elimination?
Half-life is a property of first-order elimination.
How is loading dose calculated?
Which order of drug elimination is flow-dependent?
First-order elimination is flow-dependent elimination.
Slightly polar, water-soluble metabolites that are often still active are products of which phase of drug metabolism?
Phase I
What order of drug elimination is shown?
What processes are involved in phase II of drug metabolism?
Conjugation (Glucuronidation, Acetylation, Sulfation)
Geriatric patients have GAS (phase II).
In pharmacokinetics, how is clearance calculated?
Why do patients who are slow acetylators have increased side effects from certain drugs?
Patients who are slow acetylators have side effects from certain drugs because of rate of metabolism.
How is volume of distribution (Vd ) calculated?
What order of drug elimination is shown?
zero-order elimination
How is maintenance dose calculated?
Very polar, inactive metabolites (renally excreted) are products of which phase of drug metabolism?
Phase II
a. about 1%
The percentage of the drug in the protonated form changes from 50% when the pH is equal to the pKa to 1% (1/100) at 2 pH units more alkaline.
d. particle size of the drug
Increasing the particle size decreases the surface area for dissolution and slows the rate of absorption.
intravenous
d. decreases the pharmacologically effective fraction
Only the unbound, FREE drug in the plasma can produce pharmacological effect(s).
c. extensive binding to plasma proteins
Which route of drug administration has the highest risk for toxicity, requires strict aseptic techniques, and is not suitable for self-administration?
Intravenous
Which route of administration provides slow and sustained drug delivery, convenient and painless, and bypasses first-pass effect?
transdermal
a. acetylation
Phase II is the GAS reactions:
- Glucuronidation involves addition of glucuronic acid by a glucuronosyltransferase.
- Acetylation involves addition of acetic acid by an acetyltransferase
- Sulfation involves addition of sulfate by a sulfotransferase.
(geritatric patients have “GAS”)
a. their activity is inducible
Metabolism of most drugs is mediated by microsomal enzymes located on the smooth surface of endoplasmic reticulum in hepatocytes and some cells in other tissues. Microsomal enzymes catalyze oxidation, reduction, hydrolysis and glucuronide conjugation reactions.
There are differences in levels of expression of each CYP amongst individuals due to the presence of genetic polymorphisms and differences in gene regulation.
b. decreased metabolism
a. daily ingestion of grapefruit juice
CYP3A4 is the most predominant CYP isoform in human drug metabolism, both in terms of the amount of enzyme and the variety of drugs that are substrates. It is present in the liver and the small intestine, where it is frequently co-expressed with P-glycoprotein and shares common substrates. CYP3A4 is responsible for more than 50% of all CYP-mediated drug oxidation reactions and is likely to be involved in the greatest number of drug-drug interactions.
Enzyme inhibition slows the rate of drug metabolism and can elevate a drug’s concentration, leading to increased toxicity. Examples of agents that inhibit CYP3A4 include erythromycin, ketoconazole, and grapefruit juice.
enterohepatic recycling
12 hours
It went through 2 half lives in a day.
constant IV infusion
IV infusion under strict control is the best route of administration for drugs with a narrow therapeutic index.
