Pharmacokinetics Flashcards
Cmax
Maximum concentration of drug following administration
Tmax
Time at which maximum concentration of drug occurs
AUC
Area under the curve (of a concentration vs time curve)
What measures total systemic exposure to a drug?
AUC
Are the large majority of drugs eliminated by zero order or first order processes?
First order (concentration dependent)
Semi-log plot
Plotting log(concentration) against time
Relationship between half life and k
T1/2 = 0.693/k
Formula to calculate the concentration at any given time for first order drug
Ln C = -kt + ln C0
What percentage of a first order drug is eliminated by 4 half lives?
93.75%
How do you calculate half life for a zero order drug?
T1/2 = 0.5 A0/k0 (A0 is initial drug in system, k0 is the zero order rate constant (mass/time))
What effect does eating before taking an oral medication have on the pharmacokinetics of that drug?
Cmax is reduced and Tmax is delayed (because food inhibits gut housekeeper waves and thus slows absorption)
Why is it recommended that penicillin be taken on an empty stomach?
Because penicillin is degraded in acidic environments, and food presence slows absorption (increasing amount of drug degraded while in stomach)
Calculation for bioavailability
(Div * AUCoral) / (Doral * AUCiv)
Factors affecting oral availability of a drug
Solubility, polarity, size, lumen alterations of drug, first pass metabolism, drug transporters, pH
What type of drug best avoids being altered in the gut lumen when given orally?
Small, non-peptide molecules
Two examples of multi-drug transporters in the gut
P-glycoprotein and ABC cassette binding proteins
How do basic conditions in the stomach affect absorption of aspirin?
None will be absorbed in the stomach (requires acidic environment), but the small intestine will almost entirely make it for it
What types of medications can be taken sublingually?
Lipid soluble molecules (nitroglycerin, buprenorphine)
Why do rectally administered drugs have less first pass metabolism?
Venous drainage here is partially portal and partially systemic
When drugs are administered IM or SubQ, how are they absorbed?
Large molecular weight drugs (100,000 and up) are drained by lymphatics, smaller are taken up by capillaries
Is penicillin a good choice for treating meningitis? Why or why not?
No. Large and polar, does not cross BBB well
Calculation for volume of distribution
(Amount of drug in body at equilibrium) / (Plasma drug concentration)
Give the effects of tissue protein binding and plasma protein binding respectively on volume of distribution
Tissue protein binding - increases volume of distribution, plasma protein binding - decreases volume of distribution
What are the two main plasma binding proteins and what type of molecule does each bind?
Albumin - binds acidic drugs, a1-acid glycoprotein - binds basic drugs
Calculation for clearance
Elimination rate / (Plasma Concentration)
Calculation for a loading dose
D = Vd*C (volume of distribution times desired concentration)
The classic example of a drug that is freely filtered and not secreted
Inulin
Which form of acids and bases tend to be reabsorbed from the kidney tubule, ionized or non-ionized?
Non-ionized (remember, lipophilic (i.e. non-polar non-ionized) substances can cross membranes easily
When dosing drugs, what measurement do we use as a proxy for kidney function?
Creatinine clearance
In two compartment models, what do the alpha and beta half lives represent respectively?
Alpha half life - distribution phase, beta half life - terminal elimination phase
What effect does grapefruit juice have on the activity of p-glycoprotein?
Inhibits it (leading to an increase in drug levels)
Give two examples of drugs with huge volumes of distribution and state whether this indicates greater distribution of drug in plasma or tissue
Greater in tissue. Nortriptyline (1300 L), Digoxin (440 L)
Give two examples of drugs with small volumes of distribution and state whether this indicates greater distribution of drug in plasma or tissue
Greater in plasma (possibly only in plasma). Theophylline (35 L), Gentamicin (18 L)
In two compartment models, what determines the elimination rate and biologic half-life
The beta (elimination) phase
What two factors primarily determine elimination rate?
Blood flow to the eliminating organ and efficiency of the organ in eliminating the drug
Relationship of clearance to volume of distribution
Cl = Vd*Ke (volume of distribution times elimination constant)
Formula for estimating creatinine clearance
(140-age) * (Body weight in Kg) / (72 * Serum Creatinine) (applies to males, multiple by 0.85 for females)
What system is used to classify patients with hepatic impairment?
Child-Pugh Score for Cirrhosis (takes into account serum bilirubin, albumin, ascites, INR)
What effect does CHF have on drug pharmacokinetics
Decreases elimination (due to decreased blood flow to eliminating organs)
What effects can pregnancy have on drug pharmacokinetics?
Decrease protein binding, increase renal excretion, variable effects on metabolism
Approximately how many half lives are required to achieve steady state
4-5 half lives
