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...
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
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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 neded;
rd
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)
c. Atrial fibrillation:
, i. Stable Rate control vs rhythm control strategy (AV nodal blockers,
antiarrhythmics, anticoagulation); ablation if no response to meds;
ii. unstable DCC/CV
d. Atrial flutter
i. CV; rate control not as responsive as afib
e. Ventricular fibrillation:
i. Defibrillate and CPR
f. VT: stable
i. Stable/nonsustained BB
ii. Amiodarone, sotalol, mexiletine to reduce # shocks
iii. Mg if torsades
iv. EPS/ablation
v. Unstable CPR, epi vaso (2nd dose), amio, lidocaine, mg, airway management
g. Tachycardia:
i. Vagal maneuver, adenosine (6/12mg), BB or Ca channel;
ablation; antiarrhythmics if no response to BB or don’t want
ablation
h. Asystole: CPR
2. Distinguish between dihydropyridine and non-dihydropyridine calcium channel blocker.
Know what conditions each class would be used to treat.
a. dihydropyridine calcium channel blocker: (e.g., nifedipine, amlodipine) primarily act
on vascular smooth muscles
i. use for HTN
b. non-dihydropyridine calcium channel blocker: (diltiazem < verapamil) primarily act
on the heart
i. use for CP, SVT (verap); controlling irregular rapid HR and lowering
BP (Diltiazem)
3. Describe the medications to treat atrial fibrillation (rate, rhythm, and embolus
prevention). Know the side effects, needed monitoring, and interaction for each of these
medications.
a.
4. Calculate a CHADS2 score and describe treatment based on the score:
a. 1 point for the following h/o: HF, HTN, DM, stroke/TIA (2 pt) and age >/= 75
i. 0 = low risk, 1-2 = mod risk, >3 = high risk start anticoag
5. Calculate a HASBLED score and describe treatment based on the
score:
a. 1 point for each of the following:
i. Hypertension
ii. Uncontrolled, >160 mmHg systolic
iii. Renal disease (Dialysis, transplant, Cr >2.26 mg/dL or >200 µmol/L)
iv. Liver disease (Cirrhosis or bilirubin >2x normal with AST/ALT/AP >3x normal)
v. Stroke history
vi. Prior major bleeding or predisposition to bleeding
vii. Labile INR (Unstable/high INRs, time in therapeutic range <60%)
viii. Age >65
ix. Medication usage predisposing to bleeding (Aspirin, clopidogrel, NSAIDs)
x. Alcohol use (≥8 drinks/week)
b. Risk of major bleeding in one year:
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