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Pharmacokinetics > Drug Adjustment in Drug Interactions > Flashcards

Drug Adjustment in Drug Interactions Flashcards

1
Q

What is a DDI?

A

Modification of the action of one drug by another drug or food

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2
Q

What are the types of DDI?

A
  1. DDI
  2. Food-drug
  3. Chemical-drug
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3
Q

What is unintentional DI?

A

Produce adverse reactions in the patient

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4
Q

What is intentional DI?

A

Provide improved therapeutic response or decrease adverse drug effects

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5
Q

How is the potential for DDI large?

A

Polypharmacy is common practice

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6
Q

What are the 3 mechanisms of drug interactions?

A
  1. Pharmaceutical interactions
  2. Pharmacodynamic interactions
  3. Pharmacokinetic interactions
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7
Q

What is pharmaceutical interactions?

A

Occur when physical and/or chemical incompatibilities arise when drugs are mixed during extemporaneous pharmaceutical coumpounding

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8
Q

What are pharmacodynamic interactions?

A

Occur when different drugs bind to the same or similar physiological or biochemical receptor results in additive, potentiation, synergistic, or antagonistic actions

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9
Q

Describe additive?

A

1+1 = 2

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10
Q

Describe potentiation?

A

1+0 > 1

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11
Q

Describe synergistic?

A

1+1 > 2

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12
Q

Describe antagonistic?

A

1 + (-1) < 0

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13
Q

What are examples of pharmacodynamic interactions?

A
  1. Alcohol increases sleepiness caused by benzodiazepine
  2. Opposing actions of ß-agonists
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14
Q

What are pharmacokinetic interactions?

A

Occur when one drug alters the ADME of another drug, thereby changing its concentration in plasma and at the targeted site of action

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15
Q

Why is PK based DI difficult to predict?

A
  1. Because PK behavior of a drug is determined by drug structure and each patented drug structure is different
  2. Significant differences in plasma proteins binding, Vd, and CL are different even with drugs the closely related in pharmacodynamic effects
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16
Q

What are most clinically significant DIs mostly caused by?

A

PK alterations

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17
Q

What dietary supplements decrease drug absorption in GI?

A
  1. Antacids containing Mg2+ and Al3+
  2. Cholestryamine
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18
Q

What are the effects of antacids on absorption?

A

Interfere with absorption of many drugs leading to decreasing plasma concentration

Causes the formation of chelate complexes and facilitates the absorption of aluminum hydroxide gel

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19
Q

What are examples of antacids that affect absorption?

A
  1. Iron containing products
  2. Antacids or milk on tetracyclines -> reduced absorption of tetracyclines
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20
Q

What is chlolestryamine?

A

An anion-exchange resin that binds to bile acid and many drugs in the GIT including digoxin -> reducing absorption

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21
Q

How do drug the effect gastric emptying affect absorption as well?

A

Alters the rate or completeness of absorption of other drugs (metoclopramide, propantheline)

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22
Q

What drugs reduce the absorption of acidic drugs?

A
  1. Acid reducing agents (antacids)
  2. H2 blockers (Famotidine)
  3. Proton pump inhibitors (Omeprazole)
23
Q

What is NOT an important source of important DIs, under normal circumstances?

A

Displacement from plasma proteins

24
Q

How are clearances affected by low albumin?

A

Drug accumulation and toxicity

Special care is required if the displacing drug also impairs the CL of the displaced drug

25
Q

What are examples of drugs that affect distribution?

A
  1. Salicylates displace methotrexate (anti-cancer drug), and also compete for renal anion secretory carrier.
  2. Quinidine, verapamil & amiodarone displace digoxin from tissue binding sites, simultaneously they reduce renal excretion.
26
Q

What is the urinary pH?

A

4.8 - 7.5

27
Q

What do changes in urinary pH affect?

A

Ionization and reabsorption of weak electrolyte drugs

28
Q

Describe the effect salicylates have on urinary pH?

A
  1. Increase ionization in basic pH reduces drug reabsorption in tubule, increasing excretion
29
Q

What type of drugs are most affected by urinary pH?

A

Drugs with a pKa value within the urinary pH range

30
Q

How is probenicid affects by urinary pH?

A

Probenecid bloks excretion of anionic drugs (penicillins) by inhibiting anion transporter protein (OATP transporters) responsible for secretion of penicillin

31
Q

How are nephrotoxic drugs affects by urinary pH?

A

Amioglycoside antibiotics (Gentamicin) and lower GFR leading to accumulation of other drugs cleared renal such as digoxin

32
Q

What is the source of PK DI through metabolism?

A

Induction by inducer
Inhibition of an enzyme responsible for the metabolism of substrate drugs by another drug

33
Q

What are the inducing agents and effects with warfarin?

A
  1. Barbituates
  2. Ethanol
  3. Rifampicin

Decreased anticoagulation

34
Q

What are the inducing agents and effects with oral contraceptives?

A

Rifampicin

Pregnancy

35
Q

What are the inhibiting agents and effects with warfarin?

A
  1. Allopurniol
  2. Metronidazole
  3. Phenylbutazone

Hemmorahage

36
Q

What are the inhibiting agents and effects with theophylline?

A
  1. Cimetidine
  2. Erythromycin

Theophylline toxicity

37
Q

What are the inhibiting agents and effects with Cisapride?

A
  1. Erythromycin
  2. Ketaconzole

Ventricular tachycardia

38
Q

What are 2D6 Inducers?

A

Rifampin

39
Q

What are 3A4 inducers?

A
  1. Carbamazepine
  2. Rifampin
40
Q

What are 2D6 inhibitors?

A

Cimetidine

41
Q

What are 3A4 inhibitors?

A
  1. Ketoconazole
  2. Grapefruit juice
  3. Cimetidine
42
Q

What are common inducing agents?

A
  1. Barbiturates
  2. Ethanol
  3. Rifampicin
  4. Anticonvulsants
  5. Smoking
43
Q

What type of drugs are susceptible to DDI?

A
  1. Narrow TI
  2. Nonlinear PK
  3. Steep dose-response curves
  4. Enzyme or transporter inhibiting or inducing drugs
44
Q

What is a minor DI?

A

Limited clinical consequences and don’t require change in therapy -> disregarded

45
Q

What is moderate interactions?

A

Require an alteration in dosage or increased monitoring

46
Q

What is a severe interactions?

A

Should be avoided whenever possible, severe toxicity

47
Q

What are the common approaches of dealing with DDI?

A
  1. Avoid interacting combos by choosing alternative drugs
  2. Dosage adjustment
  3. Treatment
  4. Additional monitoring to maintain therapeutic effect or to prevent adverse outcomes may be required
48
Q

What is dosage adjustment based on?

A

PK and therapeutic considerations of interacting drugs

49
Q

How is a PK based dose adjustment base on?

A

CL or elimination t1/2 of drug

50
Q

What happens when t1/2 is increased by DIs?

A
  1. Dosing interval may be extended
  2. Dose could be reduced
51
Q

What are examples of inhibiting drugs?

A

Cimetidine

52
Q

What lexicomp categories are minor DIs?

A

A,B

53
Q

What lexicomp categories are moderate DIs?

A

C,D

54
Q

What lexicomp categories are severe DIs?

A

X

Pharmacokinetics (29 decks)

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