NRNP 6566
Key Concepts Week 1
to 5
Week 1
1. Describe the cytochrome P450 system. Describe how inducers and inhibitors
affect the cytochrome system and how that affects the half-life of
medications.
a. Cytochrome p450 system is a series of enzymes used to metabolize
medications.
b. Drugs that cause CYP450 metabolic drug interactions are referred to as
either inhibitors or inducers. Inducers increase CYP450 enzyme activity by
increasing enzyme synthesis
c. Inhibitors block the metabolic activity of one or more CYP450 enzymes
2. Describe the affect on low and high albumin levels on active drug levels
especially for drugs that are highly protein bound.
a. Albumin is the plasma protein with the greatest capacity for binding drugs.
i. Binding to plasma proteins affects drug distribution into tissues,
because only drug that is not bound is available to penetrate tissues,
bind to receptors, and exert activity. As free drug leaves the
bloodstream, more bound drug is released from binding sites.
b. Highly protein bound drugs, low albumin levels (w/ malnutrition, or chronic
illness) may lead to toxicity because there are fewer than the normal sites
for the drug to bind
3. Describe ways to lessen the hepatic first pass effect: metabolism during first pass
through the liver
a. Alternative routes (suppository, intravenous, intramuscular, inhalational
aerosol, transdermal, and sublingual) avoid the first-pass effect allow drugs
to be absorbed directly into the systemic circulation
4. Be able to calculate creatinine clearance using the Cockgraft Gault equiation:
a. Male = ([140-age] × weight in kg)/(serum creatinine × 72)
b. Female = CrCl (male) × 0.85
5. Describe what determines the frequency of drug administration:
a. Drug half-life, plasma concentration
6. Be familiar with the Beers criteria and how to use it:
a. Potentially Inappropriate Medication Use in Older Adults
i. to call attention to medications that are commonly problematic, and
thus should be avoided in most older adults
7. Describe factors that affect absorption, distribution, metabolism and excretion:
a. Absorption low blood state (shock or arrest); contact time with GI tract too
fast (diarrhea = can’t absorb); delayed stomach emptying (large meal =
delayed absorption); drug-drug or drug-food interactions
b. Metabolism genetics, age, organ function
,c. Distribution low albumin levels, body composition, cardiac decomp (HF), and
age
d. Excretion affected by abnormal kidney or liver function; age, drug
interactions
, 8. Define narrow therapeutic index How would you monitor a patient with a narrow
therapeutic index?
a. Therapeutic index: dose range where efficacy of med is optimized while
side effects minimized
b. Narrow therapeutic index (NTI) drugs are defined as those drugs where
small differences in dose or blood concentration may lead to dose and
blood concentration dependent, serious therapeutic failures or adverse
drug reactions.
c. Blood tests to monitor blood concentrations and dose adjustments
accordingly
9. Describe how aging affect absorption, distribution, metabolism, and excretion
a. Decreased organ function, poorly tolerate drugs that require metabolism,
lower rates of excretion
b. decrease in small-bowel surface area, slowed gastric emptying, and an
increase in gastric pH, changes in drug absorption
c. With age, body fat generally increases and total body water decreases.
Increased fat increases the volume of distribution for highly lipophilic drugs
(eg, diazepam, chlordiazepoxide) and may increase their elimination half-
lives.
d. Serum albumin decreases and alpha 1-acid glycoprotein increases
i. Phenytoin and warfarin are examples of drugs with a higher risk of
toxic effects when the serum albumin level decreases
e. hepatic metabolism of many drugs through the cytochrome P-450 enzyme
system decreases with age. For drugs with decreased hepatic metabolism
clearance typically decreases 30 to 40%.
i. Drugs metabolized in phase 1 reactions likely prolonged
ii. First-pass metabolism (metabolism, typically hepatic, that occurs
before a drug reaches systemic circulation) decreasing by about
1%/yr after age 40.
1. Thus, for a given oral dose, older adults may have higher
circulating drug concentrations.
f. Decreased renal elimination
Week 2 and 3
1. Identify and describe 12 lead EKGs that demonstrate:
a. 1st, 2nd, and 3rd degree AV blocks
i. 1st degree HBcards consult
ii. 2nd degree HB type 1 & 2
1. Type 1: Echo (r/o structural dx), Thyroid levels, meds, lytes to
identify and treat cause
2. Type 2: PPM, continuous tele with transcutaneous pacing if
needed, determine cause; IV atropine if poor perfusion s/s q 3-
5m with max 3mg if s/s poor perfusion;
3. If no response to atropine dopa, epi, isoproterenol
iii. 3 degree/ complete HB: PPM; tele and transcutaneous pace if
rd
, neded; identify cause; IV atropine if s/s poor perfusion; If no
response to atropine dopa, epi, isoproterenol
b. STEMI in any lead (know what area of the heart is affected based on lead
location)
Key Concepts Week 1
to 5
Week 1
1. Describe the cytochrome P450 system. Describe how inducers and inhibitors
affect the cytochrome system and how that affects the half-life of
medications.
a. Cytochrome p450 system is a series of enzymes used to metabolize
medications.
b. Drugs that cause CYP450 metabolic drug interactions are referred to as
either inhibitors or inducers. Inducers increase CYP450 enzyme activity by
increasing enzyme synthesis
c. Inhibitors block the metabolic activity of one or more CYP450 enzymes
2. Describe the affect on low and high albumin levels on active drug levels
especially for drugs that are highly protein bound.
a. Albumin is the plasma protein with the greatest capacity for binding drugs.
i. Binding to plasma proteins affects drug distribution into tissues,
because only drug that is not bound is available to penetrate tissues,
bind to receptors, and exert activity. As free drug leaves the
bloodstream, more bound drug is released from binding sites.
b. Highly protein bound drugs, low albumin levels (w/ malnutrition, or chronic
illness) may lead to toxicity because there are fewer than the normal sites
for the drug to bind
3. Describe ways to lessen the hepatic first pass effect: metabolism during first pass
through the liver
a. Alternative routes (suppository, intravenous, intramuscular, inhalational
aerosol, transdermal, and sublingual) avoid the first-pass effect allow drugs
to be absorbed directly into the systemic circulation
4. Be able to calculate creatinine clearance using the Cockgraft Gault equiation:
a. Male = ([140-age] × weight in kg)/(serum creatinine × 72)
b. Female = CrCl (male) × 0.85
5. Describe what determines the frequency of drug administration:
a. Drug half-life, plasma concentration
6. Be familiar with the Beers criteria and how to use it:
a. Potentially Inappropriate Medication Use in Older Adults
i. to call attention to medications that are commonly problematic, and
thus should be avoided in most older adults
7. Describe factors that affect absorption, distribution, metabolism and excretion:
a. Absorption low blood state (shock or arrest); contact time with GI tract too
fast (diarrhea = can’t absorb); delayed stomach emptying (large meal =
delayed absorption); drug-drug or drug-food interactions
b. Metabolism genetics, age, organ function
,c. Distribution low albumin levels, body composition, cardiac decomp (HF), and
age
d. Excretion affected by abnormal kidney or liver function; age, drug
interactions
, 8. Define narrow therapeutic index How would you monitor a patient with a narrow
therapeutic index?
a. Therapeutic index: dose range where efficacy of med is optimized while
side effects minimized
b. Narrow therapeutic index (NTI) drugs are defined as those drugs where
small differences in dose or blood concentration may lead to dose and
blood concentration dependent, serious therapeutic failures or adverse
drug reactions.
c. Blood tests to monitor blood concentrations and dose adjustments
accordingly
9. Describe how aging affect absorption, distribution, metabolism, and excretion
a. Decreased organ function, poorly tolerate drugs that require metabolism,
lower rates of excretion
b. decrease in small-bowel surface area, slowed gastric emptying, and an
increase in gastric pH, changes in drug absorption
c. With age, body fat generally increases and total body water decreases.
Increased fat increases the volume of distribution for highly lipophilic drugs
(eg, diazepam, chlordiazepoxide) and may increase their elimination half-
lives.
d. Serum albumin decreases and alpha 1-acid glycoprotein increases
i. Phenytoin and warfarin are examples of drugs with a higher risk of
toxic effects when the serum albumin level decreases
e. hepatic metabolism of many drugs through the cytochrome P-450 enzyme
system decreases with age. For drugs with decreased hepatic metabolism
clearance typically decreases 30 to 40%.
i. Drugs metabolized in phase 1 reactions likely prolonged
ii. First-pass metabolism (metabolism, typically hepatic, that occurs
before a drug reaches systemic circulation) decreasing by about
1%/yr after age 40.
1. Thus, for a given oral dose, older adults may have higher
circulating drug concentrations.
f. Decreased renal elimination
Week 2 and 3
1. Identify and describe 12 lead EKGs that demonstrate:
a. 1st, 2nd, and 3rd degree AV blocks
i. 1st degree HBcards consult
ii. 2nd degree HB type 1 & 2
1. Type 1: Echo (r/o structural dx), Thyroid levels, meds, lytes to
identify and treat cause
2. Type 2: PPM, continuous tele with transcutaneous pacing if
needed, determine cause; IV atropine if poor perfusion s/s q 3-
5m with max 3mg if s/s poor perfusion;
3. If no response to atropine dopa, epi, isoproterenol
iii. 3 degree/ complete HB: PPM; tele and transcutaneous pace if
rd
, neded; identify cause; IV atropine if s/s poor perfusion; If no
response to atropine dopa, epi, isoproterenol
b. STEMI in any lead (know what area of the heart is affected based on lead
location)
