Pharm Flashcards
Michaelis-Menten Kinetics Equation Vmax Km Curve
v = (Vmax[S])/(Km + [S])
Vmax directly proportional to enzyme concentration
Km inversely related to the affinity of the enzyme for its substrate
At 1/2 Vmax, Km=[S]
Hyperbolic
What kind of enzymatic reactions do not follow Michaelis-Menten Kinetics?
Enzymes that show cooperative kinetics (hemoglobin) have sigmoid curves
Lineweaver-Burk Plot y axis x axis slope y intercept x intercept
1/V 1/[S] Km/Vmax 1/Vmax. As y-intercept ↑, Vmax ↓ -1/Km. As x-intercept moves further to the right, ↑Km (lower affinity)
Lineweaver-Burk Plot
Competitive inhibitor
Noncompetitive inhibitor
Vmax stays the same as Km moves closer to the right. ↑Km (lower affinity)
y-intercept increases (↓Vmax) but Km (x-intercept) stays the same
Competitive Inhibitors Resemblance to substrate Over come by ↑[S] Bind active site Effect on Vmax Effect on Km Pharmacodynamics
Resemble substrate Overcome by ↑[S] Binds active site Vmax unchanged Km ↑ ↓ potency
NonCompetitive Inhibitors Resemblance to substrate Over come by ↑[S] Bind active site Effect on Vmax Effect on Km Pharmacodynamics
No resemblance to substrate Not overcome by ↑[S] Doesn't binds active site Vmax ↓ Km unchanged ↓ efficacy
Bioavailability
Variable
What is it?
When is it 100%
F
Fraction of administered dose that reaches systemic circulation unchanged
IV dose
Volume of distribution Variable What is it? When can it be altered? Equation
Vd
Theoretical fluid volume required to maintain the total absorbed drug amount at plasma concentration
Vd of plasma-protein bound drugs can be altered by liver and kidney disease (↓ protein binding, ↑ Vd)
(Amount of drug in body)/(plasma drug concentration)
Low Vd
Volume
Distribution
Drug types
4-8L
Blood
Large/charged molecules; plasma protein bound
Medium Vd
Distribution
Drug types
ECF
Small hydrophilic molecules
High Vd
Distribution
Drug types
All tissues
Small lipophilic molecules, especially if bound to tissue protein
A drug infused at a steady state takes how many half lives to reach steady state?
4 to 5
Half Life
Property of…
Equation
First Order Elimination
(.7Vd)/CL
Clearance Variable What is it? Impaired with defect in what organ functions? Equation (2)
CL
Relates rate of elimination to the plasma concentration
Impaired with defect in cardiac, hepatic, or renal function
(Rate of elimination)/(Plasma drug concentration) = Vd x Ke (elimination constant)
Loading dose
Cp x (Vd/F) Cp = target plasma concentration
Maintenance dose
Cp x (CL/F) Cp = target plasma concentration
What happens to loading dose and maintenance dose in liver or renal disease?
Loading dose remains the same
Maintenance dose ↓
Time to steady state depends primarily on
Half life
Independent of dosing frequency or size
Zero-Order Elimination
What is it?
How does Cp change?
Examples
Rate of elimination is constant regardless of Cp. Constant amount of drug eliminated per unit time
“PEA looks like a 0”
Phenytoin, EtOH, Aspirin (at high concentrations)
First-Order Elimination
What is it?
How does Cp change?
Description
Rate of elimination is directly proportional to the drug concentration. Constant fraction of drug eliminated per unit time
Cp ↓ exponentially with time
Flow-Dependent Elimination
Ionized vs non-Ionized species in the urine?
Weak Acids? What happens? Examples
Weak Bases? What happens? Examples
Ionized species trapped in the urine and cleared quickly. Neutral forms can be reabsorbed
Trapped in basic environments so treat OD with bicarb. Phenobarbital, Methotrexate, Aspirin
Trapped in acidic environments. Treat OD with Ammonium chloride. Amphetamines
Drug Metabolism Phase 1 Reactions Mediator Metabolites Lost in what kind of pt
RedOx or hydrolysis
Cytochrome P450
Usually yields slightly polar water soluble metabolites (often still active)
Lost in geriatric pts
Drug Metabolism Phase 2 Reactions Metabolites Excretion Decreased in what kind of pt
"GAS" Conjugation (Glucuronidation, Acetylation, Sulfation) Very polar inactive metabolites Renally excreted Slow acetylators
Efficacy
Definition
Examples
Maximal effect a drug can produce
Analgesics, Antibiotics, Decongestants
