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
What kind of environment aids in renal clearance of weak bases?
an acidic environment because bases are ionized in acidic environments
Weak acid drugs
Aspirin, penicillin, cephalosporins, loop and thiazide diuretics, phenobarbital, methotrexate
“Please Don’t Make ACid”
Weak base drugs
morphine, local anesthetics, amphetamines, PCP
“Local Patrons Always Move”
How do you treat overdose with a weak acid?
bicarbonate
How do you treat overdose with a weak base?
ammonium chloride (NH4Cl)
Phase I metabolism
Reduction, oxidation, hydrolysis with cytochrome P450
- yields slightly polar, often still active metabolites
- geriatric patients lose phase I first
Phase II metabolism
“Attach something” or conjugation
glucorondidation, acetylation, sulfation
-yields very polar, inactive metabolite
-patients who are slow acetylators have greater side effects from certain drugs b/c have decreased rate of metabolism –> drug induced SLE
Therapeutic index
TI= TD50/ED50 “TITE”
- safer drugs have higher therapeutic indices
TD50: dose that 50% of the population experienced toxicity
ED50: dose that in 50% of the population was effective
LD50: TD for animal studies
Drugs with low therapeutic indices?
digoxin, lithium, theophylline, warfarin
- low TI means that its takes very little drug over optimal dosing to produce toxicity
Inducers of cytochrome P450 - Chronic alcoholic Mona Steals Phen-Phen and Never Refuses Greasy Carbs
Chronic EtOH Modafinil St. John's Wort Phenytoin Phenobarbitol Nevirapine Rifampin Griseofulvin Carbamezepine
Inhbitors of cytochrome P450- Acute Gentleman Cipped Iced Grapefruit Juice Quickly And Kept Munching on Soft Cinnamon Rolls
Acute EtOH Gemfibrozil Ciprofloxacin Isoniazid Grapefruit juice Quinidine Amiodarone Ketaconazole Macrolides- Erythro Sulfonamides Cimetidine Ritonavir
Substrates for cytochrome P450 interactions - Always Always Always Think When Starting Others
Anti-epileptics Antidepressants Antipsychotics Anesthetics Theophylline Warfarin Statins OCPs
