Pharmacology Flashcards
Enzyme kinetics- what is the Km? How is it associated with affinity?
Km: the substrate concentration at which the reaction progresses at 1/2 the maximal velocity
Km is inversely related to enzyme affinity–> the lower the Km, the higher the affinity
What do enzymatic reactions that exhibit a sigmoid curve indicate?
cooperative kinetics (eg. hemoglobin)
How is Vmax related to enzyme concentration?
Vmax is directly proportional to enzyme concentration
-the higher the enzyme concentration, the higher the Vmax
What is the equation for the lineweaver-burk plot?
1/V = (Km/Vmax)(1/[S]) + 1/Vmax or Y=mx + b
Lineweaver-burk plot: x-intercept?
x-intercept = -1/Km
-the smaller the x-intercept, the higher the Km= the lower the affinity
lineweaver burk plot: y-intercept?
y-intercept = 1/Vmax
-the higher the y-intercept, the lower the Vmax
Competitive inhibitors (irreversible)
:compete for active site and stay bound, decreases efficacy
- Vmax: decreased
- Km: unchanged
- lineweaver burk plot: y-intercept increases, x-intercept stays the same
Competitive inhibitors (reversible) actions
:compete for active site, causes a decrease in potency
- Vmax: unchanged (can be achieved with increased substrate)
- Km: increase
- lineweaver burk plot: y-intercept stays the same, x-intercept decreases
Pharmacokinetics
What the body does to the drug; Absorption Distribution Metabolism Elimination
Noncompetitive inhibitor actions
: bind to allosteric site, decreases efficacy
- Vmax: decreases
- Km: unchanged
- lineweaver burk plot: y-intercept increases, x-intercept unchanged
Pharmacodynamics
What the drug does to the body
-receptor binding, drug efficacy, potency, toxicity
Bioavailability
:F; the fraction of administered drug that reaches systemic circulation unchanged
-IV dose, F=100%
What route of drug administration has the highest absorption?
Inhalation
Recall: IV administration does not require absorption
Volume of distribution
:Vd; theoretical volume occupied by the total absorbed drug
- tells where the drug is distributed
- Vd= low; mostly in the blood, large/charge or plasma protein bound
- V=medium; in ECF, small hydrophilic
- Vd= high; mostly in tissues, small lipophilic or bound to tissue protein
Half-life
:the time it takes to lower the plasma concentration of a drug by 50%
1/2 life = 0.7 x Vd/CL
-characteristic of first order elimination
How long does it take to reach steady state?
4-5 half lives
What factors determine the time to steady state?
the half life ONLY
- frequency of dosage and dosage are independent factors, but increasing the dose, increases the plasma concentration achieved at steady state
Clearance (CL) of a drug
: the volume of plasma cleared of drug per unit time; may be effected by defects in cardiac, renal or hepatic function
CL= rate of elimination of drug/plasma drug concentration
CL= Vd x Ke, where Ke= the rate of elimination constant
Loading dose
:puts serum concentration of drug at target concentration within one dose
LD= Ctarget x Vd/F
Maintenance dose
MD= Ctarget x CL x T/F
where T is the time interval between doses
- In renal or hepatic disease, maintenance dose should decrease b/c of effect on CL
Zero-order elimination
:constant amount of drug eliminated per unit time; plasma concentration decreased linearly with time
PEA: Phenytoin, EtOH, Aspirin
First order elimination
:constant fraction of drug eliminated per unit time; plasma concentration decreases exponentially with time
What form of a drug is easily cleared in the urine?
the ionized form
What kind of environment aids in renal clearance of weak acids?
basic environment b/c weak acids are ionized in a basic environment
