Drug Interactions Block 4

Front 1

Describe, in general, pharmacodynamic mechanisms of drug-drug intrxns.

Back 1

includes examples of interaction at receptor level and interactions due to independent effect of 2 drugs

-two drugs act at the same receptor level
-two drugs cause different physiological results which may be additive

Front 2

Describe, in general, pharmacokinetic mechanisms of drug-drug interactions.

Back 2

involves a change in the availability of drug at the site of action; involves drugs that induce alterations in absorption, distribution, metabolism or excretion of another compound

-One drug changes the concentration of the other drug.

Front 3

Pharmacokinetic drug interactions alter drug delivery to site of action. What are the general mechanisms by which this occurs?

Back 3

alterations in absorption, distribution, metabolism or excretion

Front 4

4 Mechanisms that decrease delivery of drug to active site

Back 4

1. decrease GI absorption
2. Increase metabolic inactivation
3. decrease uptake taget
4. Increase urinary excretion

Front 5

4 Mechanisms that increase delivery of drug to active site

Back 5

1. Increase GI absorption
2.Decrease metabolic inactivation
3. Decrease plasma protein binding
4. Decrease urinary excretion.

Front 6

3 parameters can be altered in order to decrease GI absorption. What are they?

Back 6

(1) binding
(2) gut motility
(3) GI fluid pH

Front 7

Interaction btwn:
Cholestyramine + levothyroxine

Back 7

Decrease Levothyroxine GI absorption.
-due to binding of levothyroxine in GI tract.

Front 8

Antacids (Ca, Al, Mg) + tetracycline

Back 8

decreases tetracycline GI absorption.
-chelate formation --> binding

Front 9

Ferrous sulfate + tetracycline

Back 9

Decreases tetracycline absorption
-due to binding in GI

Front 10

2 compounds can decrease tetracycline absorption in the gut. What are they?

Back 10

Antacids and ferrous sulfate

Front 11

What bile acid sequestrant can decrease levothyroxine absorption?

Back 11

Cholestyramine

Front 12

Cimetidine (or ranitidine) + ketoconazole

Back 12

decreases ketoconazole absorption
-due to decreased dissolution of ketoconazole at increased gastric pH levels. Needs the acid in stomach to dissolve it.

Front 13

What drug can decrease ketoconazole absorption and how does it do it?

Back 13

Cimetidine raises the stomach pH which decreases ketoconazole absorption.

Front 14

What drug can decrease ketoconazole absorption and how does it do it?

Back 14

Cimetidine raises the stomach pH which decreases ketoconazole absorption.

Front 15

2 compounds can decrease tetracycline absorption in the gut. What are they?

Back 15

Antacids and ferrous sulfate

Front 16

What bile acid sequestrant can decrease levothyroxine absorption?

Back 16

Cholestyramine

Front 17

Cimetidine (or ranitidine) + ketoconazole

Back 17

decreases ketoconazole absorption
-due to decreased dissolution of ketoconazole at increased gastric pH levels. Needs the acid in stomach to dissolve it.

Front 18

What drug can decrease ketoconazole absorption and how does it do it?

Back 18

Cimetidine raises the stomach pH which decreases ketoconazole absorption.

Front 19

Tricyclic antidepressants + guanethidine

Back 19

Decreased guanethidine uptake by sympathetic nerve endings --> decreased antihypertensive effect

Front 20

Consider a patient who is on the anti-hypertensive drug, guanethidine. What 4 drugs, if also given to this patient, could decrease guanethidine's effects and how?

Back 20

(1) tricyclic antidepressants
(2) ephedrine
(3) amphetamines
(4) phenothiazines
They decrease guanethidine uptake by sympathetic nerve endings

Front 21

What are 3 general mechanims that can enhance elimination in order to decrease drug delivery to site of action?

Back 21

(1) induce CYP enzymes
(2) induce P-glycoprotein transporter
(3) increase renal elimination

Front 22

Name 5 examples of CYP inducers.

Back 22

(1) phenobarbital
(2) carbamazepine
(3) phenytoin
(4) rifampin
(5) St. John's Wort

Front 23

Phenobarbital + Warfarin

Back 23

Decreased anticoagulant effect of warfarin

Front 24

St. John's Wort can enhance the elimination of drugs by inducing (blank) and (blank).

Back 24

St. John's Wort can enhance the elimination of drugs by inducing CYP enzymes and P-glycoprotein transporter.

Front 25

Name the 3 drugs with which St. John's Wort interacts to decrease their delivery to their sites of action.

Back 25

(1) indinavir
(2) cyclosporine
(3) digoxin

Front 26

Alkalinization of urine + phenobarbital (or salicylates)

Back 26

Increases Excretion.

-non-ionized form is more likely to be reabsorbed in kidney so alkalinizing urine (basic) leads to decreased reabsorption and increased excretion.

Front 27

Acidification of urine + amphetamines

Back 27

Increases excretion

Front 28

Phenobarbital is a weak acid. How would changing the urine pH increase excretion of the drug?

Back 28

Alkalinization of urine would increase excretion of phenobarbital.

Front 29

Amphetamines are weak bases. How would changing the urine pH increase excretion of the drug?

Back 29

Acidification of urine would increase excretion of amphetamines.

Front 30

What are 5 mechanims that can decrease elimination in order to increase drug delivery to site of action?

Back 30

1) inhibit xanthine oxidase
(2) inhibit CYP enzymes
(3) inhibit MAO - monoamine oxidase
(4) decrease renal excretion
(5) inhibit P-glycoprotein transporter

Front 31

Allopurinol + azathioprine (or 6-Mercaptopurine)

Back 31

Increased toxicity due to increased concentration of azathioprine (or 6-MP) due to inhibition of xanthine oxidase (which usually breaks down azathioprine and 6-MP)

Front 32

Allopurinol inhibits inactivation of (blank) and blocks formation of (blank)...see Fig. 1 on page 81

Back 32

Allopurinol inhibits inactivation of 6-mercaptopurine and blocks uric acid formation.

Front 33

What enzyme does allopurinol inhibit? What is the function of this enzyme?

Back 33

Allopurinol inhibits xanthine oxidase, which is responsible for production of uric acid.

Front 34

Allopurinol inhibits xanthine oxidase, which is responsible for production of uric acid.

Back 34

Allopurinol would inhibit xanthine oxidase, which then could not metabolize the drugs. The result would be increased drug toxicity.

Front 35

Name 4 inhibitors of CYPs.

Back 35

(1) amiodarone
(2) erythromycin
(3) ketoconazole
(4) grapefruit juice

Front 36

Amiodarone + Warfarin

Back 36

Decreases warfarin elimination by inhibiting CYP enzymes.

-Amiodarone = antiarrhythmic drug

Front 37

Ketoconazole + terfenadine

Back 37

decreases terfenadine elimination which can lead to ventricular arrhythmia.
-Ketoconazole Inhibits CYP enzymes

Front 38

Which CYP inhibitor discussed in the notes would decrease warfarin elimination?

Back 38

Amiodarone

Front 39

Which CYP inhibitor discussed in the notes would decrease terfenadine elimination? What is the EKG finding related to the drug-drug interaction?

Back 39

Ketoconazole decreases terfenadine elimination and causes prolonged QT interval & ventricular arrhythmia.

Front 40

Terfenadine is an anti-histamine and responsible for cardiac toxicity. It has been replaced with its active metabolite. Name it.

Back 40

Fexofenadine or Allegra

Front 41

Grapefruit juice + felodipine

Back 41

Increased plasma felodipine concentration
-due to inhibition of CYP enzymes

Front 42

If you had a patient on the calcium-channel blocker, felodipine, what liquid would you tell him/her NOT to drink and why?

Back 42

Grapefruit juice b/c it inhibits CYPs and increases the plasma concentration of felodipine

Front 43

MAO inhibitor + tyramine

Back 43

Leads to severe hypertensive crisis
-due to inhibition of monoamine oxidase

Front 44

MAO inhibitor + selective serotonin reuptake inhibitor (antidepressants such as prozac)

Back 44

Leads to Serotonin syndrome (increased temperature, HTN, coma, death)
-due to inhibition of monoamine oxidase

Front 45

Tyramine occurs widely in foods that we eat and acts as catecholamine releasing agent. Which class of drugs would inhibit the enzyme that metabolizes tyramine? What would be the side effect?

Back 45

MAO inhibitors (anti-depressants) would inhibit metabolism of tyramine. The build up of tyramine is converted to norepinephrine, and this leads to hypertension.

Front 46

Which 2 classes of anti-depressants, if taken together, could result in serotonin syndrome?

Back 46

MAO inhibitors and selective serotonin reuptake inhibitor

Front 47

Probenecid + penicillin

Back 47

decreased penicillin excretion

Front 48

Thiazide diuretic + lithium

Back 48

decreased lithium excretion

Front 49

What drug could be given to a patient taking penicillin so as to increase the levels of the antibiotic? How does the drug work?

Back 49

Probenecid decreases renal excretion of penicillin

Front 50

What drug could be given to a patient taking lithium so as to increase the levels of the drug? How does the drug work?

Back 50

Thiazide diuretic decreases renal excretion of lithium

Front 51

Quinidine + digoxin

Back 51

Increased digoxin concentration
-because decreases clearance by inhibiting P-glycoprotein-mediated digoxin transport

Front 52

What anti-arrhythmic agent would increase plasma concentrations of digoxin and how?

Back 52

Quinidine increases plasma concentrations of digoxin by inhibition of P-glycoprotein mediated transport

And possibly involves increased GI absorption, decreased biliary excretion and decreased renal excretion

Front 53

Probenecid decreases renal excretion of penicillin. Would renal clearance of penicillin, then, be increased or decreased? What about plasma half-life?

Back 53

Renal clearance: decreased
Plasma half-life: increased

Front 54

These 2 drugs have opposite effects in respect to changing drug concentrations of digoxin. Name them and how do they change the concentrations?

Back 54

2. Quinidine- inhibit P-glycoprotein transporter to increase digoxin levels