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?

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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. 1

st, 2nd, and 3rd degree AV blocks

i. 1

st degree HBcards consult

ii. 2

nd 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

rd degree/ complete HB: PPM; tele and transcutaneous pace if 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)

c. Atrial fibrillation:

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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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