Pharm/clin Pharm Review 10.6 10.7.07--Gutierrez

Front 1

What is pharmacokinetics (PK)?

Back 1

PK describes "what the body does to the drug"
--absorption, distribution, metabolism and excretion of drugs

Front 2

What is pharmocodynamics (PD)?

Back 2

PD describes "what the drug does to the body"?
-biochemical and physiologic effects of drugs and their mechanism of action.

Front 3

What are 3 important pharmacologic properties that are necessary for good absorption with psychotropic medications?

Back 3

a. lipophillic
b. small molecular size
c. non-ionized

Front 4

What is the bioavailability of drugs administered by intravenous route?

Back 4

F = 1.0 (100% bioavailability).

Hint 4

F =

Front 5

A drug administered by oral route has F less than 0.1 (less than 10% bioavailability). Is this drug effective via the oral route?

Back 5

No, most of the drug will be metabolized before it is distributed to systemic system for drug effects.

Front 6

What is the first pass metabolism for orally administered drugs?

Back 6

Biotransformation by the liver that occurs before the drug reaches its site of action.

Front 7

What is the elimination half-life (t1/2) of a drug?

Back 7

The time it takes to eliminate half of the concentration of the drug in the body.

Hint 7

t1/2

Front 8

The half-life of lithium is 24 hours. If you discontinue lithium for your patient with toxic lithium level of 2.0mEq/L, what would the estimated lithium level be 24 hours later?

Back 8

1.0 mEq/L (half of the body's concentration is eliminated after 24 hrs.)

Front 9

If the half-life of the active metabolite of Prozac (fluoxetine) is at least 7 days. How long will it take to wash out Prozac and its metabolite from the body?

Back 9

5 x half-life = 5 x 7 days = 35 days

Front 10

If clearance (CI) of a drug is increased, the half-life of the drug will be _________.

Back 10

decreased

Front 11

If a highly lipid soluble psychotropic drugs like Valium have an increased volume of distribution (Vd) with advanced age (due to an increased fat/lean body ration), the half-life of the drug will be __________.

Back 11

increased

Front 12

Decreased albumin in the system can cause _________ effect of highly protein bound drugs from increased free drug.

Back 12

increased

Front 13

Metabolism of drugs is to make the chemical compound more ______ for elimination.

Back 13

Polar (hydrophylic)

Front 14

What is enterohepatic recirculation?

Back 14

Insufficient hydrophilicity chemicals unable to be eliminated by the kidneys may undergo elimination via the bile in the unchanged or conjugated form. Drugs eliminated in the bile are available for reabsorption in the GI tract. This re-entry into the body after 'elimination' via the bile results in the "recycling" of drug and prolongs the time required for the drug to be irreversibly eliminated from the body.

Front 15

Why do renally eliminated drugs (e.g. lithium) need increased dose adjustments in pregnant patients?

Back 15

Pregnancy increased the glomerular filtration rate (GFR) in the kidneys leading to an increased clearance of the renally eliminated drugs. Need to increase the drug dose to compensate for increased elimination.

Front 16

What are the 3 areas of the body that have specialized barriers to protect these areas from the effects of exogenous chemicals (e.g. drugs)?

Back 16

a. Brain (blood brain barrier)
b. Testicles (blood testicular barrier)
c. Placenta (blood placenta barrier)

Hint 16

blood _______ barriers

Front 17

Drugs like lithium and the tricyclic antidepressants (e.g. Elavil) have low therapeuic index (TI). What determines TI?

Back 17

a. LD50/ED50
b. LD50 (lethal does 50) is the lethal dose in 50% of animal tested subjects. ED50 (effective dose 50) is the dose that produces the desired therapeutic response in 50% of patients.

Front 18

Trazodone has a (high or low) therapeutic index?

Back 18

a. high
b. HighTI = safe with overdose.

Front 19

Sustained released formulations of drugs have _______ peaks and _______ trough drug levels compared to the immediate released formulations.

Back 19

a. lower peak and higher trough drug levels.

Front 20

Amphetamines are weak bases. Acidifying the system with high does of Vitamin C can lead to higher or lower ampetamine concentration.

Back 20

lower concentration

Front 21

What pharmacologic properties does Valium (diazepam) have that leads to a quick onset of action?

Back 21

Highly lipd soluble.

Front 22

Name 2 psychotropic medications that have increased absorption when taken with food.

Back 22

a. Geodon (ziprasidone) - increase by 100%
b. Zoloft (sertraline) - increase by 40%.

Front 23

Name 2 commonly used benzodiazepines that can increase in concentration and effects when taken with grapefruit juice (CYP450 3A4 inhibitor)?

Back 23

a. Xanax (alprazolam)
b. Halcion (triazolam)

Front 24

Your patient asked if he can drink grapefruit juice in the mornings and take his Xanax at night to avoid the drug interaction. Is this OK?

Back 24

No, it takes more than 24 hours to regenerate P450 3A4 enzymes in the GI tract.

Front 25

Your patient was prescribed a commonly used antibiotic Cipro (ciprofloxacin) for an infection. What over-the-counter (OTC) product will cause this antibiotic to be ineffective when taken concurrently?

Back 25

antacid ---> significantly decreases the absorption of ciprofloxacin

Front 26

Many patients are on statin drugs for treatment of high cholesterol. Drints and medications that inhibit CYP450 _____ enzymes can lead to excessive concentrations and myopathy with patients c/o muscle tenderness and pain.

Back 26

3A4 (e.g. grapefruit juice, cimetidine, diltiazem)

Front 27

Your patient on Viagra asked if he should take it with food. What is effect of taking Viagra with a high fatty meal?

Back 27

Decreased absorption by approximately 30%.

Front 28

What dring can increase the concentration of viagra.

Back 28

Grapefruit juice (canned/concentrated or squeezed?)

Front 29

What is the maximum daily dose of Tylenol (acetaminophen) for patients who dring alcohol regularly? Why?

Back 29

a. 2 gm/day (usually max is 4gm/day)
b. Increased toxic metabolites from induction of metabolism of acetaminopohen to toxic metabolites that are hepatoxic.

Front 30

What OTC agent can cause patients to have insomnia when taken at night?

Back 30

Sudafed (pseudophredrine) -- oral decongestants.

Front 31

Name 2 atypical antipsychotics that need an increase in dose adjustments for smokers?

Back 31

a. Zyprexa (olanzapine)
b. Clozaril (clozapine)

Front 32

What CYP450 enzyme can be induced with the polycyclic aromatic hydrocarbons in smoke (smoking and charbroiled/BBQ foods)?

Back 32

a. 1A2

Front 33

Does smoking marijuana increase the metabolism of Zyprexa and Clozaril?

Back 33

Yes.

Front 34

Your patient on clozapine quits smoking without informing his medical team. What is the danger of quitting smoking on the higher dose of clozapine?

Back 34

a. Increased risk of seizures and other side effects with less metabollism of clozapine.

Front 35

What is the onset and offset of enzyme induction?

Back 35

a. Weeks for onset (takes time to make more enzymes)--how is onset different than offseet if both occur within weeks?
b . Weeks for offset (takes time to get rid of the excessive enzymes).

Front 36

What is the usual onset of enzyme inhibition?

Back 36

Hours to a day (block enzymes from working).

Front 37

Name a commonly used antibiotic that can inhibit CYP450 3A4 enzymes leading to increased side effects for your patient on Seroquel.

Back 37

Etythromycin

Front 38

Why does it take erythromycin 5 - 7 days before enzyme inhibition occurs?

Back 38

It is the metabolite of erythromycin that inhibits the 3A4 enzymes. It takes 5 - 7 days to accumulate the metabolites to cause the enzyme inhibition.

Front 39

Patients of Coumadin (warfarin) should not eat excessive leafy green vegetables due to an increase in vitamin ____.

Back 39

Vitamin K inhibits anticoagulation making warfarin less effective.

Front 40

Your patient has a higher risk of lithium toxicity if he increases or decreases his salt intake?

Back 40

Decrease: restricted sodium diet can increase the body's reabsorption of the sodium and lithium back to the body --> increase concentration and risk for lithium toxicity.

Front 41

Many patients take OTC pain medication Motrin IB (ibuprofen) and Aleve (naproxen) for minor to moderate pain. What medical conditions can be worsened with high doses of these pain medications?

Back 41

a. High blood pressure and congestive heart failure (increased sodium and water retention).
b. Gastrointestinal reflux or peptic ulcer disease (increased GI irritation & bleeding).

Front 42

What antidepressant has multiple CYP450 enzyme pathways (1A2, 2D6, 3A4) for its metabolism and does not have any enzyme inhibitory properties (with little potential for signficant drug interactions)?

Back 42

Remeron (mirtazapine)

Front 43

Which antidepressant has serotinin-3 (5HT-3) antagonistic effects and is the antidepressant of choice for patients with nausea or chemotherapy?

Back 43

Remeron (mirtazapine)

Front 44

What is the effect of adding CYP450 2D6 enzyme inhibitor (e.g. Paxil) toa 2D6 substrate (e.g. Risperdal)?

Back 44

Increased effect of the substrate drug with less metabolism leading to increased drug concentration.

Front 45

What is the effect on adding an enzyme inhibitor (e.g. Prozac) to a prodrug (e.g. codeine)?

Back 45

Decreased effect of the prodrug since decreased metabolism leads to a decreased

Front 46

Why is Prozac (fluoxetine) and Paxil (paroxetine) contraindicated with Mellaril (thioridazine)?

Back 46

Prozac and Paxil are potent CYP450 2D6 enzyme inhibitors ---> increased concentration
of Mellaril ---> increased risk for QTc prolongation.

Front 47

What is the effect adding a CYP450 enzyme inducer to a CYP450 metabolized drug?

Back 47

Decreased effect of the CYP450 metabolized drug from an increased metabolism and a
decreased drug concentration.

Front 48

What is the effect of adding a CYP450 enzyme inducer to a prodrug?

Back 48

Increased effect of the prodrug – increased metabolism of the prodrug to its active metabolite ---> increased concentration/effects of the active metabolite (e.g. losartan to
active metabolite).

Front 49

True or False: The CYP450 enzymes are only found in the liver.

Back 49

False – also found in GI tract, lungs, kidneys, blood vessels, and almost every cell of the
body.

Front 50

True or False: The CYP450 enzymes are used only for drug metabolism.

Back 50

False – also acts as catalysts for activation and synthesis of endogenous chemicals such
as fatty acids, steroids, and cholesterol.

Front 51

What CYP450 enzymes are important for drug metabolism?

Back 51

a. 1A2 (e.g. Zyprexa)
b. 2B6 (e.g. Wellbutrin)
c. 2C9 (e.g. Coumadin)
d. 2C19 (e.g. Klonopin)
e. 2D6 (e.g. Risperdal)
f. 2E1 (e.g. Tylenol)
g. 3A4 (e.g. Seroquel)

Front 52

Which CYP450 enzyme is not inducible?

Back 52

2D6

Front 53

Which CYP450 enzyme used in drug metabolism has no polymorphism (no poor or rapid
metabolizers among any ethnic groups)?

Back 53

3A4

Front 54

What is the effect of adding Tegretol (carbamazepine) to Klonopin (clonazepam)?

Back 54

Decreased effect of Klonopin from an increased metabolism and decreased drug
concentration.

Front 55

What are the common CYP450 enzyme inducers that can increase metabolism of drugs?

Back 55

b. Dilantin (phenytoin) – anticonvulsant
c. Phenobarbital – anticonvulsant
d. Mysoline (primidone) – anticonvulsant – metabolized to phenobarbital
e. Rifadin, Rimactane (rifampin) – antimicrobial agent for TB

Front 56

What is the effect of adding Equetro (recently approved for Bipolar disorder) to your patient on
oral contraceptives?

Back 56

Equetro (carbamazepine) can induce the 3A4 enzymes ---> subtherapeutic levels of the
oral contraceptives.

Front 57

Can your patient on oral contraceptives be prescribed Depakote?

Back 57

Yes, Depakote does not have enzyme induction properties like many other
anticonvulsants.

Front 58

What is the effect of adding Cipro (ciprofloxacin) to Zyprexa (olanzapine)?

Back 58

Increased effect of Zyprexa from decreased metabolism and an increased drug
concentration.

Front 59

List 3 benzodiazepines that are not affected by CYP450 enzyme inhibitors or inducers?

Back 59

a. Ativan (lorazepam)
b. Serax (oxazepam)
c. Restoril (temazepam)

Front 60

Why is Serax (oxazepam) not prescribed for PRN use?

Back 60

Slow onset (3-6 hours) with low lipophilic properties making it difficult to cross the
blood brain barrier.

Front 61

Which ethnic group has a higher incidence of increased side effects with the CYP450 2C19
drugs (e.g. Klonopin)?

Back 61

Asians – 18-25% are poor metabolizers of CYP450 2C19

Front 62

Which ethnic group has a higher incidence of decreased effects to codeine (e.g. Tylenol #3) and
hydrocodone/acetaminophen (Vicodin)?

Back 62

Caucasians – 5-14% are poor metabolizers of CYP450 2D6

Front 63

Your schizophrenic patient on high therapeutic doses of Seroquel and Lipitor for his
hyperlipidemia. He developed hypertension. He was prescribed Cardizem (diltiazem) for his
hypertension. Any potential problems?

Back 63

a. 2 calcium channel blockers (diltiazem and verapamil) are CYP450 3A4 inhibitors
b. Can increase the concentrations of 3A4 drugs ---> increased side effects of patient’s
Seroquel and Lipitor

Front 64

Name an OTC antidepressant that can induce CYP450 3A4 enzymes.

Back 64

St. John’s wort

Front 65

Among the atypical antipsychotic agents, which ones can have decreased drug concentrations
with concurrent use of St. John’s wort?

Back 65

a. Seroquel (quetiapine) – metabolized by 3A4
b. Abilify (aripiprazole) – metabolized by 3A4 & 2D6
c. Geodon (ziprasidone) – 33% metabolized by 3A4

Front 66

Your patient on multiple CYP450 metabolized psychotropic and cardiovascular medications
was switched from Prozac to Celexa. The concentration and effects of these medications are
likely to be __________________.

Back 66

Decreased – discontinuation of an enzyme inhibitor can lead to increased metabolism of medications ---> decreased concentrations and side effects.

Front 67

Your patient on multiple CYP450 metabolized psychotropic and cardiovascular medications
was switched from Dilantin to Depakote. The concentration and effects of these medications
are likely to be __________________.

Back 67

Increased – discontinuation of an enzyme inducer can lead to decreased metabolism of
medications ---> increased concentrations and effects.

Front 68

Your patient was admitted to a non-smoking psychiatric hospital and stabilized after weeks on
Zyprexa 20 mg po qhs. Upon discharge, he resumed his 1 ppd smoking habit. What is the
most likely effect of restarting smoking on Zyprexa?

Back 68

Increased metabolism of Zyprexa (1A2 drug) from smoking – may need to increase
dose to accommodate the 1A2 enzyme induction.

Front 69

What psychotropic medications can have increased concentrations when patients stop smoking?

Back 69

1A2 psychotropic drugs – Zyprexa (olanzapine), Clozaril (clozapine), Luvox
(fluvoxamine), and Cymbalta (duloxetine).

Front 70

Your patient is doing well on Luvox (fluvoxamine). She needs to be started on a statin drug for
her high cholesterol. The dose of the CYP450 3A4 statin drugs (e.g. Lipitor, Zocor) has to be
__________________ (higher or lower) than usual therapeutic doses.

Back 70

Lower doses to accommodate for the enzyme inhibition by Luvox.

Front 71

If you want a statin drug that is not affected by any CYP450 enzyme inhibitors or inducers,
what would you recommend?

Back 71

Pravachol (pravastatin) is not metabolized by any CYP450 enzymes.

Front 72

Your patient doing well on a low dose of Klonopin c/o increased side effects (cognitive
impairment and sedation) from her Klonopin (2C19 drug). What OTC agents can increase the
concentration of Klonopin?

Back 72

a. Tagamet HB (cimetidine) for heartburn
b. Prilosec (omeprazole) for gastrointestinal reflux

Front 73

Chronic alcohol consumption can _______________ (induce or inhibit) the CYP45 2E1
enzymes leading to increased toxic metabolites from Tylenol (acetaminophen).

Back 73

induce

Front 74

Your patient gets four 100 mg Viagra tablets per month with instructions to use ½ tablet (50
mg) an hour before sexual intercourse. He complains that he only gets 8 doses per month and
wants to know if he can use ¼ tablet to get 16 doses per month by drinking grapefruit juice to
increase Viagra’s concentration. Would you recommend this strategy to increase the number of
doses/month? Why?

Back 74

No, using grapefruit juice to increase Viagra’s concentration is highly variable among
individuals which may lead to insufficient increase by 100% to the equivalent of the
normal 50 mg dose, or to excessive concentrations (>> 100% increase) leading to excessive side effects.

Front 75

Which ethnic group has the highest risk of having the natural built-in Antabuse properties with
alcohol causing the facial flushing and throbbing headaches (i.e. lacks aldehyde dehydrogenase
leading to an increased acetaldehyde metabolite of alcohol)?

Back 75

Asians – up to 80% are deficient in aldehyde dehydrogenase enzyme

Front 76

What is the effect of Antabuse (disulfiram) reaction with alcohol?

Back 76

Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage. During alcohol
metabolism after disulfiram intake, the concentration of acetaldehyde occurring in the blood
may be 5-10x higher than that found during metabolism of the same amount of alcohol
alone. Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant
symptoms referred to as the disulfiram-alcohol reaction. Disulfiram plus even small
amounts of alcohol produces flushing, throbbing in head and neck, throbbing headache,
respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea,
hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, weakness, vertigo,
blurred vision, and confusion. The intensity of the reaction may vary with each individual
but is generally proportional to the amount of disulfiram and alcohol ingested. Ingestion of
alcohol may produce unpleasant symptoms 1 or even 2 weeks after a patient has taken his
last dose of disulfiram.

Front 77

Your patient c/o episodes of severe diarrhea when he takes OTC Imodium to try to stop the
diarrhea. What needs to be ruled out for this patient?

Back 77

a. R/O lactose intolerance where individuals cannot digest lactose in dairy products ---> diarrhea.
b. Management – avoid dairy products or use OTC Lactaid pills before consumption of
any dairy products.
77. Why is it important to have your

Front 78

Why is it important to have your patients on steroid therapy receive an eye exam q6-12
months?

Back 78

a. Steroid therapy can cause glaucoma and cataracts in patients on long-term treatments.
b. Also need to monitor for increase blood pressure, hyperglycemia, and bone density test
(osteoporosis).

Front 79

Which muscle relaxant medication should be avoided for patients with dry mouth, urinary
retention, chronic constipation, or memory impairment?

Back 79

Flexeril (cyclobenzaprine) is structurally similar to the tricyclic antidepressants (TCA)
with similar side effects (dry mouth, urinary retention, constipation, memory
impairment, etc).

Front 80

What is the common pharmacodynamic drug interaction with risperidone and trazodone?

Back 80

a. Increased alpha-1 blockade ---> increased risk of orthostasis.
b. Ask patients about any episodes of dizziness upon standing.

Front 81

What is the common pharmacodynamic drug interaction with OTC sleep aids (e.g. Unisom,
Tylenol PM) and Cogentin?

Back 81

a. Increased muscarinic blockade ---> additive anticholinergic effects ---> dry mouth, urinary
retention, constipation, memory impairment, etc).
b. Most non-herbal sleep aids are antihistamines (diphenhydramine and doxylamine).

Front 82

Your patient on Seroquel 300 mg po BID c/o daytime sedation and has problems sleeping at
night. He takes trazodone 200 mg po PRN insomnia. He c/o orthostasis when he takes the
trazodone nightly. What is the pharmacodynamic drug interaction in this case and what would
you recommend?

Back 82

a. Increased alpha-1 blockade ---> increased risk of orthostasis.
b. Management – consolidate Seroquel to nighttime to avoid daytime sedation and helps
with insomnia at night.

Front 83

Your patient on Zoloft 100 mg po qd c/o reemerging depressive symptoms. She did not want
to tell her doctor and she bought OTC St. John’s wort. What is the potential pharmacodynamic
interaction in this case?

Back 83

Additive serotoninergic effects ---> possible serotonin syndrome (symptoms of agitation,
diarrhea, dizziness, headache, tremor, etc).

Front 84

What other OTC products can increase the risk of serotonin syndrome with other serotonergic
agonists (e.g. SSRIs)?

Back 84

a. SAMe (S-adenosylmethionine)
b. Used for osteoarthritis and depression

Front 85

Your patient saw the advertisement for natural herbal remedy for constipation. She bought
senna and took it daily. What is the problem with using this herbal laxative daily?

Back 85

a. Senna is a stimulant type of laxative that has a quick onset of action by stimulating and
increasing the motility of the GI tract. Used daily for more than 7 days can lead to the
GI becoming dependent on the stimulant laxatives. Severe rebound constipation can
occur when the stimulant laxatives are discontinued.
b. Side effects include cramping and abdominal pain from the GI contractions. Can also
cause electrolyte imbalance (e.g. hypokalemia).

Front 86

Your patient on Zyprexa gained a significant amount of weight. She started drinking a lot of
dieter’s tea daily in an attempt to lose the weight. What is the danger of using some of these
dieter’s tea?

Back 86

Some dieter's teas containing senna, aloe, buckthorn, and other plant-derived laxatives
---> can cause diarrhea, vomiting, nausea, stomach cramps, chronic constipation,
fainting, electrolytes imbalance, and death. In recent years, FDA has received "adverse
event" reports, including the deaths of four young women, in which dieter's teas may
have been a contributing factor.

Front 87

What is the problem with switching from Trade to generic formulations for low therapeutic
index drugs (e.g. Dilantin to generic phenytoin)?

Back 87

a. Changes in bioavailability can result in significant changes in drug levels.
b. There is a + 20% difference in bioavailability compared to the Trade name formulation
allowed by the FDA for generic drugs ---> can be between 80-120% bioavailability of the
Trade formulation ---> can be a difference of 40% between 2 difference generic
formulations of the same drug.