Pharmacokinetics Flashcards
Cmax
Maximum concentration of drug following administration
Pharmacokinetics
What the body does to the drug. Quantitative characterization of time-dependent processes.
Major concepts: drug disposition (absorption, distribution, metabolism, excretion), dose, route of administration, timing.
Tmax
Time at which max concentration (Cmax) is observed
AUC (Area under the curve)
Measure of total systemic exposure to drug
First order process
Exponential, amount processed is concentration dependent. Time of process is independent of concentration. Consistent volume of blood cleared per unit time
Zero order process
Linear, amount/mass processed is constant. Time of process is dependent upon total amount of drug in body, independent if concentration. Seen in saturated systems, phenytoin, alcohol
t1/2 = 0.5A0/K0
What is the equation to calculate the half life of a first order process drug?
t1/2 = 0.693/k where k is the rate at which the drug is processed
How many half lives does it take to get rid of a majority of a drug?
93.75% of a first order drug is removed after 4-5 half lives.
Zero order depends on initial amount of drug
How is transportation of drugs affects by P-glycoprotein?
P-glycoprotein is found in the lining of the gut and excretes drugs back into the lumen. It reduces the amount of drug absorbed. Blockage of PGP (eg: with grapefruit juice) will increase the amount of drug absorbed.
PGP also found in kidneys, increases secretion/excretion
Albumin
Negatively charged. Good for binding positive/acidic drugs
Volume of distribution (Vd)
Theoretical volume that measures distribution. Higher if drug binds tissue, lipophilic; lower if binds in plasma, hydrophilic
Vd = amt of drug put into body / amt of drug measured in blood
Large Vd use actual body weight, small Vd use ideal body weight
Biotransformation
Liver converts drugs to be more polar to be excreted in kidneys.
Phase I: expose a functional group (chemical structural change) @ ER
- by CYP450, CYP3A4…
Phase II: conjugation, covalent addition of group @ cytosol
- UDPGT -> glucuronate, acetyl group, TPMP -> methyl
What kind of drugs are more likely to be reabsorbed?
Non-ionic/non-polar drugs
1st order clearance equation
Cl = Vd x Ke Ke = rate of elimination, 1st order elimination constant Vd = volume of distribution
When is a loading dose useful?
When the half life of a drug is very long and you want to reach steady state
Loading dose = C desired x Vd
When is steady state achieved?
Takes 4-5 half lives to reach state when absorption = elimination. Want drug to be relatively stable in blood above ED50 but below LD50
Maintenance dose
Maintenance dose = t’ (desired peak)(Vd)(Ke)(1-e^-kT) / (1-e^-kT)
How does grapefruit juice affect drug levels?
Blocks PGP and CYP, therefore increases absorption and reduces metabolism. Overall increase of drug levels in body.
What are the types of drug interactions?
- Additive 1+2=3
- Synergistic (potentiation) 1+2=7
- Antagonistic 1+2=1.5
What are the labels used for risk categories for pregnant moms?
A- safe
B- no evidence
C- risk in animals, no evidence in people
D-
How are acetaminophen and aspirin different/similar?
Acetaminophen is closely related to NSAIDs. Is an antipyretic and analgesic. Only inhibits COX3 (found only in CNS)
Aspirin is prototype NSAID and is antipyretic, analgesic, ant inflammatory and anticoagulant. Inhibits COX1 and COX2
What are concerns with acetaminophen (Tylenol)?
Main adverse effect: liver hepatotoxicity
Treat with acetylcysteine.
