Drug Interactions

Question 1

drug interactions in vitro commonly occur from

Answer 1

formulation or combination of drugs in IV bags in hospital settings

Question 2

facotrs which impact absorption in the intestines (2)

Answer 2

• pH changes
  
  • alter ration of ionized: non-ionized forms of a drug
• motility
  
  • delayed gastric emptying and reduced gut motility delay absorption

Question 3

non-ionized drugs are more lipid soluble and therefore more readily absorbed True or false

Answer 3

true

Question 4

Factors affecting drug interactions in the intestines include

Answer 4

• ionic interactions
• drug drug absorption interactions
• effect of diet
• kitamin k
• enterohepatic shunt

Question 5

ionic interactions in the intestine impact drug interactions and reduce effectiveness by

Answer 5

• forming inactive complexes with divalent or triavlent ions
  
  • e.g. tetracycline and milk or antacids (Ca2+, Mg3+)
• interfering with absorption of aspirin, warfarin by acidic molecules

Question 6

warfarin is inhibited by

Answer 6

pentobarbitone

Question 7

high fat diets are an example of how diet can enhance solubility of lipid soluble drugs and cause

Answer 7

• can cause drug ineffectiveness if drug is not intended to be absorbed in GIT
• may cause systemic absorption causing more toxicity

Question 8

grapefruit juice is another example of the effect of diet on drug interactions and causes

Answer 8

agumented oral bioavailability of CYP3A4 drugs

Question 9

coumarin and indanedione anticoagulants are Vitamin K

Answer 9

antagonists

Question 10

interactions of drugs with vitamin K antagonists cna lead to what

Answer 10

bleeding episodes

Question 11

these drugs reduce the absorption of vitamin k

Answer 11

• chloramphenicol
• chlortetracycline
• neomycin

Question 12

use of antibiotics with people on coumadin are challegning as they

Answer 12

reduce the microbial synthesis of vitamin K which causes plasma levels to drop potentiating the anticoagulant activity of warfarin

Question 13

the enterohepatic shunt allows for

Answer 13

• the recirculation of drug secreted into the bile back into the intestine where it re-enters circulation
• this causes increased persistence of drug and increased duration of action

Question 14

these drugs inhibit the enterohepatic shunt and may cause failure of contraceptives

Answer 14

antimicrobials

Question 15

what is the hERG channel

Answer 15

• human ether-agogo related gene
• cardiac potassium channel

Question 16

what is the major difference b/t hERG and normal potassium channels

Answer 16

• gating kinetics
• hERG channel target for Class III antidysrhthmic drugs

Question 17

individuals with genetic abnormalities in hERG channels predispose them to

Answer 17

Long QT syndrome

Question 18

Long QT syndrome is

Answer 18

• long QT interval
• ventricular dysrythmia
  
  • torsades de Pointes (sudden ddeath)

Question 19

what is acquired long QT syndrome caused by

Answer 19

• electrolyte imbalances (potassium and magnesium)
• hERG channel drug use

Question 20

what are some examples of drugs which target hERG as their mechanism of action

Answer 20

• antidysrhythmic drugs
  
  • amiodarone
  • quinidine
  • procainamide
• chlorpormazine
• haloperidol
• erythromycin
• clarithromycin

Question 21

enzyme induction related drug interactions occur when

Answer 21

one drug has the ability to induce enzymes responsible for the metabolism of other drugs

Question 22

chronic administration of a drug can cause tolerance by

Answer 22

inducing enzymes responsible for the metabolism of the drug

Question 23

what are two drugs that are examples of enzyme induction and drug interaction, and what happens

Answer 23

• barbituates and anticoagulants
• enzyme induction by the administration of barbituates causes the metabolism of vitamin K anticoagulants reducing their effectiveness

Question 24

True/False: drug interactions can occur when two structurally similar drugs compete for the same enzyme

what is an example

Answer 24

• True
• trycylic antidepressants and phenothiazine tranquilizers
  
  • e.g. amytriptyline and phenotiazine

Question 25

in the case of amitryptiline and phenothiazine tranquilizers, what happens when enzyme inhibition via competion occurs

Answer 25

* the activity of the tricyclic can be inhibited * the drug is not metabolized * antidepressants inhibitors of catecholamines which increase sympathetic effects * increased hypertension, cardiac events

Question 26

Monoamine oxidase inhibitors (MAOIs) can

Answer 26

* reduce sympathetic drive * enhace parasympathetic drive * interact with many foods

Question 27

after treatment with an MAOI there is a build up of noradrenaline in the nerve terminal and a greater release of noradrenaline which causes

Answer 27

hypertensive crisis, hemorrhage and cerebral bleeding/stroke

Question 28

these drugs are contraindicated with MAOIs as their affect can be enhanced

Answer 28

* amphetamine * ephedrine, pseudoephedrine (cough syrups)

Question 29

many drug interactions occur because of mixed function oxidase system

Answer 29

cytochrome P450

Question 30

CP450 metabolism mainly occurs in the

Answer 30

liver

Question 31

CP450 enzymes also exist in

Answer 31

intestines, lungs, orther organs

Question 32

poor metabolizers of drugs are at risk because

Answer 32

* drug may accumulate to toxic levels due to inability to metabolize * cannot change a prodrug into its active form * or have less response

Question 33

what are some of the different types of cytochome P450 isoforms

Answer 33

* CYP2D6 * CYP1A2 * CYP2E1 * CYP3A * CYP3A4

Question 34

drugs which are bound to albumin are active or inert

Answer 34

inert

Question 35

True/False: drug interactions can commonly occur due to displacement of drugs bound to plasma proteins increasing the soluble concentraton

Answer 35

True

Question 36

how is the effect of drug displacement from binding sites calculated

Answer 36

=1+ (% bound + % Displaced)/ (1500 x % unbound)

Question 37

drug interaction at binding sites can occur as a result of

Answer 37

* competitive antatognism * physiological antagonism * physiological addition/augmentation * drug synergism * drug interaction at nerve terminal

Question 38

drug interaction by competitive antagonism occurs when

Answer 38

* an agonist and antagonist are competing for the same receptor site

Question 39

why is drug interaction by competitive antagonism unlikely to occur

Answer 39

* the clinician would be prescribing drugs to do opposite things

Question 40

physiological antagonism is when

Answer 40

the action of one drug at a recoptor site opposes the actions of a drug at a different receptor site

Question 41

thiazide diuretics promote loss of K+ and convert a normal dose of cardiac glycosides to a fatal toxic dose. this is an example of what type of drug interaction

Answer 41

physiological augmentation

Question 42

effect produced by a combination of two or more drugs is greater than the effect of each on its own

Answer 42

drug synergism e.g. alcohol and antihistamines