NBME Pharmacology
Define Km in MM kinetics: - ANSWER The concentration of substrate [S] at which
1/2 Vmax is reached
Km is _________ related to affinity of the enzyme for its substrate - ANSWER
inversely
Vmax is directly proportional to what? - ANSWER to the enzyme concentration
What characterizes MM kinetics? - ANSWER a hyperbolic curve when Vmax is
plotted against [S]. Most enzymes follow MM kinetics.
Enzymatic reactions demonstrated a sigmoid curve usually denote: - ANSWER
cooperative binding / kinetics, ie hemoglobin
In the lineweaver-burk plot, how is the y-intercept related to Vmax? What does the
slope of the line equal? The y-intercept? The x-intercept? - ANSWER They're
inversely related. The slope of the line is equal to Km/Vmax while the y-intercept is
equal to 1/Vmax. The x-intercept is equal to 1/-Km.
In the L-B plot, if the x-intercept is closer to 0, what does that mean? - ANSWER x-
intercept = 1/-Km. So if it is closer to 0, Km is greater and affinity is lower
In the L-B plot, how are competitive and non-competitive inhibitors expressed with
respect to one another? - ANSWER competitive inhibitors' lines cross eachother
competitively whereas non-competitive do not.
What are some key differences between competitive and non-competitve inhibitors?
- ANSWER competitive=reversible or irreversible. non-competitive=irreversible.
competitive may be overcome by a higher [S] whereas noncompetitive or irreversible
competitive may not be overcome. Noncompetitive inhibitors do not resemble
substrate, and they do not bind the active site like the other two. Reversible
competitive has no effect on Vmax whereas the other two lower it. Conversely,
reversible competitive increases the Km whereas the other two have no effect on
Km. pharmacodynamically, reversible competitive inhibitors lower potency whereas
the other two lower efficacy.
Define pharmacokinetics: - ANSWER The effects of the body on the drug. ADME.
Define pharmacodynamics: - ANSWER Effects of the drug on the body. Includes
receptor binding, drug efficacy, drug potency and drug toxicity
,Define Bioavailability (F): - ANSWER The fraction of the administered drug which
reaches systemic circulation unchanged. For an IV dose, the F=100%. Orally it is
typically less because of incomplete absorption and / or FPHM.
Define Volume of Distribution (Vd): - ANSWER The theoretical volume occupied by
the total absorbed drug amount at the plasma concentration.
Apparent Vd of plasma protein: - ANSWER bound drugs can be altered by liver and
kidney disease (low protein binding, high Vd). Vd=amount of drug in body / plasma
concentration of drug
Where is Vd low? - ANSWER In blood. 4-8L. Drug types: large / charged molecules,
plasma protein bound.
Where is Vd medium? - ANSWER ECF. Small hydrophilic molecules.
Where is Vd high? - ANSWER All tissues including fat. Small lipophilic molecules,
especially if bound to tissue protein.
What is the equation for half-life? - ANSWER T1/2= .693 x Vd / CL.
T1/2 is a property of _______ order elimination - ANSWER first
How many half lives does it take for a drug administered as a constant infusion to
reach steady state? - ANSWER 4-5
How many half lives does it take for a drug administered as a constant infusion to
reach 90% of steady state? - ANSWER 3.3
Define clearance (CL): - ANSWER The volume of plasma cleared of a drug during a
given time unit.
Under what circumstances may clearance be impaired? - ANSWER cardiac, hepatic
or renal defects
What is the equation for clearance? - ANSWER CL=rate of elimination of drug /
plasma drug concentration. This is = Vd x Ke (elimination constant)
How do you calculate loading dose? - ANSWER = Cp x Vd / F (where Cp=target
plasma concentration at steady state)
How do you calculate maintenance dose? - ANSWER = Cp x CL x T / F
(T=tau=dose interval, or time between doses, if it is not administered continuously)
What happens to loading and maintenance doses during renal and liver disease? -
ANSWER maintenance dose is lowered whereas loading dose remains unchanged
Time to steady state depends primarily on _____ and is _____ of dose and dosing
frequency - ANSWER T1/2 ; independent
, Zero order elimination: Definition and examples of drugs that follow - ANSWER Rate
of elimination is constant regardless of Cp. (constant AMOUNT of drug). Cp
decreases linearly with time. Phenytoin, ethanol, aspirin (at high or toxic
concentrations). **Capacity-limited elimination**
First-order elimination: - ANSWER rate of elim directly proportional to the drug
concentration. (constant FRACTION of drug per unit time). Cp lowers exponentially
with time. **flow-dependent elimination**
What forms of drugs are trapped in urine and cleared quickly? - ANSWER ionized
species
What forms of drugs may be reabsorbed? - ANSWER neutral species
What are some examples of drugs that are weak acids? What are the implications of
a drug being a weak acid on its elimination via urine? How can you treat an overdose
of these drugs? - ANSWER phenobarbital, mtx, aspirin. These are trapped in basic
environments. Treat overdose with bicarbonate.
What are some examples of drugs that are weak bases? What are the implications
for elimination? How do you treat an overdose? - ANSWER amphetamines. These
are trapped in acidic environments. Treat with ammonium chloride.
Phase I of drug metabolism: - ANSWER redox, hydrolysis with cytp450 yielding
SLIGHTLY polar, water-soluble metabolites (still active usually)
What patients first lose phase I? - ANSWER geriatric patients
Phase II of drug metabolism: - ANSWER CONJUGATION (glucuronidation,
acetylation, sulfation) usually yielding VERY POLAR, INACTIVE metabolites (renally
excreted). Geriatric patients have phase II.
What happens in patients who are slow acetylators? - ANSWER greater side effects
from drugs because of lowered rate of metabolism of drugs.
Define efficacy: - ANSWER the maximal effect a drug can produce
What drugs have high efficacy? - ANSWER analgesics, abx, antihistamines,
decongestants.
Do partial or full agonists have greater efficacy? - ANSWER full agonists have more
efficacy than partial agonists
Define potency: - ANSWER The amount of drug needed for a given effect. High
potency means high affinity for receptor. A lower EC50 indicates higher potency.
High potency drug classes: - ANSWER chemotherapeutics, antihypertensives and
lipid lowering drugs (cholesterol drugs)
Define Km in MM kinetics: - ANSWER The concentration of substrate [S] at which
1/2 Vmax is reached
Km is _________ related to affinity of the enzyme for its substrate - ANSWER
inversely
Vmax is directly proportional to what? - ANSWER to the enzyme concentration
What characterizes MM kinetics? - ANSWER a hyperbolic curve when Vmax is
plotted against [S]. Most enzymes follow MM kinetics.
Enzymatic reactions demonstrated a sigmoid curve usually denote: - ANSWER
cooperative binding / kinetics, ie hemoglobin
In the lineweaver-burk plot, how is the y-intercept related to Vmax? What does the
slope of the line equal? The y-intercept? The x-intercept? - ANSWER They're
inversely related. The slope of the line is equal to Km/Vmax while the y-intercept is
equal to 1/Vmax. The x-intercept is equal to 1/-Km.
In the L-B plot, if the x-intercept is closer to 0, what does that mean? - ANSWER x-
intercept = 1/-Km. So if it is closer to 0, Km is greater and affinity is lower
In the L-B plot, how are competitive and non-competitive inhibitors expressed with
respect to one another? - ANSWER competitive inhibitors' lines cross eachother
competitively whereas non-competitive do not.
What are some key differences between competitive and non-competitve inhibitors?
- ANSWER competitive=reversible or irreversible. non-competitive=irreversible.
competitive may be overcome by a higher [S] whereas noncompetitive or irreversible
competitive may not be overcome. Noncompetitive inhibitors do not resemble
substrate, and they do not bind the active site like the other two. Reversible
competitive has no effect on Vmax whereas the other two lower it. Conversely,
reversible competitive increases the Km whereas the other two have no effect on
Km. pharmacodynamically, reversible competitive inhibitors lower potency whereas
the other two lower efficacy.
Define pharmacokinetics: - ANSWER The effects of the body on the drug. ADME.
Define pharmacodynamics: - ANSWER Effects of the drug on the body. Includes
receptor binding, drug efficacy, drug potency and drug toxicity
,Define Bioavailability (F): - ANSWER The fraction of the administered drug which
reaches systemic circulation unchanged. For an IV dose, the F=100%. Orally it is
typically less because of incomplete absorption and / or FPHM.
Define Volume of Distribution (Vd): - ANSWER The theoretical volume occupied by
the total absorbed drug amount at the plasma concentration.
Apparent Vd of plasma protein: - ANSWER bound drugs can be altered by liver and
kidney disease (low protein binding, high Vd). Vd=amount of drug in body / plasma
concentration of drug
Where is Vd low? - ANSWER In blood. 4-8L. Drug types: large / charged molecules,
plasma protein bound.
Where is Vd medium? - ANSWER ECF. Small hydrophilic molecules.
Where is Vd high? - ANSWER All tissues including fat. Small lipophilic molecules,
especially if bound to tissue protein.
What is the equation for half-life? - ANSWER T1/2= .693 x Vd / CL.
T1/2 is a property of _______ order elimination - ANSWER first
How many half lives does it take for a drug administered as a constant infusion to
reach steady state? - ANSWER 4-5
How many half lives does it take for a drug administered as a constant infusion to
reach 90% of steady state? - ANSWER 3.3
Define clearance (CL): - ANSWER The volume of plasma cleared of a drug during a
given time unit.
Under what circumstances may clearance be impaired? - ANSWER cardiac, hepatic
or renal defects
What is the equation for clearance? - ANSWER CL=rate of elimination of drug /
plasma drug concentration. This is = Vd x Ke (elimination constant)
How do you calculate loading dose? - ANSWER = Cp x Vd / F (where Cp=target
plasma concentration at steady state)
How do you calculate maintenance dose? - ANSWER = Cp x CL x T / F
(T=tau=dose interval, or time between doses, if it is not administered continuously)
What happens to loading and maintenance doses during renal and liver disease? -
ANSWER maintenance dose is lowered whereas loading dose remains unchanged
Time to steady state depends primarily on _____ and is _____ of dose and dosing
frequency - ANSWER T1/2 ; independent
, Zero order elimination: Definition and examples of drugs that follow - ANSWER Rate
of elimination is constant regardless of Cp. (constant AMOUNT of drug). Cp
decreases linearly with time. Phenytoin, ethanol, aspirin (at high or toxic
concentrations). **Capacity-limited elimination**
First-order elimination: - ANSWER rate of elim directly proportional to the drug
concentration. (constant FRACTION of drug per unit time). Cp lowers exponentially
with time. **flow-dependent elimination**
What forms of drugs are trapped in urine and cleared quickly? - ANSWER ionized
species
What forms of drugs may be reabsorbed? - ANSWER neutral species
What are some examples of drugs that are weak acids? What are the implications of
a drug being a weak acid on its elimination via urine? How can you treat an overdose
of these drugs? - ANSWER phenobarbital, mtx, aspirin. These are trapped in basic
environments. Treat overdose with bicarbonate.
What are some examples of drugs that are weak bases? What are the implications
for elimination? How do you treat an overdose? - ANSWER amphetamines. These
are trapped in acidic environments. Treat with ammonium chloride.
Phase I of drug metabolism: - ANSWER redox, hydrolysis with cytp450 yielding
SLIGHTLY polar, water-soluble metabolites (still active usually)
What patients first lose phase I? - ANSWER geriatric patients
Phase II of drug metabolism: - ANSWER CONJUGATION (glucuronidation,
acetylation, sulfation) usually yielding VERY POLAR, INACTIVE metabolites (renally
excreted). Geriatric patients have phase II.
What happens in patients who are slow acetylators? - ANSWER greater side effects
from drugs because of lowered rate of metabolism of drugs.
Define efficacy: - ANSWER the maximal effect a drug can produce
What drugs have high efficacy? - ANSWER analgesics, abx, antihistamines,
decongestants.
Do partial or full agonists have greater efficacy? - ANSWER full agonists have more
efficacy than partial agonists
Define potency: - ANSWER The amount of drug needed for a given effect. High
potency means high affinity for receptor. A lower EC50 indicates higher potency.
High potency drug classes: - ANSWER chemotherapeutics, antihypertensives and
lipid lowering drugs (cholesterol drugs)
