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PHAR 300 > Lec. 22 - Drug Interactions > Flashcards

Lec. 22 - Drug Interactions Flashcards

1
Q

Describe the case study of the 39 year old woman mentioned at beginning of lecture

A

Admitted to hospital with torsades de pointed

10 days prior prescribed anti-histamine + anti-biotic

Self medicated with anti-fungal

Drug-drug interaction

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2
Q

What is the risk of drug reactions (ADR)?

A

Adverse Drug Reactions (ADRs):

  • Leading cause of morbidity and mortality in health care
  • ADR is responsible for 1/5 of hospitalized patient’s deaths
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3
Q

Name 4 cases when drug-drug interactions occur

A
  1. Multiple drugs to treat 1 disorder
  2. Multiple disorders necessitating drugs
  3. OTC meds + caffeine/alcohol/nicotine
  4. Elderly patients (multiple conditions, need multiple drugs, slower clearance due to age)
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4
Q

Name 4 types of drug interactions

A

Additive:
1+1=2

Antagonism:
1+1=0.5

Synergistic:
1+1=3

Potentiation:
0.1+1=2

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5
Q

What do drug interactions depend on?

A

Pharmacokinetic:

ADME:
Absorption
Distribution
Metabolism
Excretion
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6
Q

Name 4 ways drug-drug interactions can occur during absorption

A
  1. Drug complexes:
    - Drugs binding can prevent/influence absorption
  2. Transit time in intestines:
    - Drugs influencing motility of GI (speed up/slow) will affect amount of time other drugs have to be absorbed
  3. Altering P glycoprotein and organic anion transporters:
    - P glycoprotein mediates uptake and efflux of many drugs
    - Drug A influencing P glycoprotein will cuz Drug B not to be absorbed well
    - Ex. antacids
  4. Altering vasoconstriction:
    - Things affecting vasoconstriction (ex. beta-blockers, epinephrine) will reduce topically applied absorption
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7
Q

Describe 2 ways drug-drug interactions can occur during distribution

A
  1. Competitive binding on plasma proteins:
    - ex. antibacterial sulfonamides displace warfarin, methotrexate, etc…
    - exception rather than rule
  2. Alter size of physical compartment in which drug distributes:
    - ex. diuretic decreases plasma level, increases concentration of other drugs (ex. lithium) and can lead to toxicity
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8
Q

Name 2 types of liver enzymes that aid in metabolism

A
  • Cytochrome p450s

- flavin monooxygenase (FMO3)

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9
Q

Name 2 important P450s

A
  • CYP2D6

- CYP3As

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10
Q

Describe CYP2D6:

Metabolizes? (3)

Inhibited by? (4)

Particularities

A

Metabolizes:

  • Codeine (into morphine)
  • β-blockers
  • Tri-cyclic antidepressants

Inhibited by:

  • Fluoxetine (SSRI)
  • Haloperidol (anti-psychotic)
  • Paroxetine (SSRI)
  • Quinidine

Particularities:

  • Absent in 7% of caucasians, 1-2% non-caucasian
  • Overactive in 30% of East Africans
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11
Q

What do CYP3As metabolize (7)?

A
  • Calcium channel blockers
  • (most) Benzodiazepines
  • (most) HIV protease inhibitors
  • (most) HMG-CoA-reductase inhibitors
  • Cyclosporine
  • (most) non-sedating histamines
  • Cisapride
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12
Q

What’s a common CYP3A inhibitor?

A

Grapefruit juice

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13
Q

Name 4 ways drug-drug interactions can occur during metabolism

A
  1. Reduction of hepatic blood flow
    - Reducing blood flow to liver (ex. propanolol) can reduce metabolism of other drugs (ex. morphine)
  2. Enzyme induction
    - Increasing activity of certain enzyme leads to more drug breakdown of said enzyme
    - ex. chronic administration of alcohol, barbiturates, carbamazepine
  3. Enzyme inhibition
    - Metabolism of certain drugs can be decreased by inhibition of certain enzymes
    - ex. disulfiram, furanocoumarins (grapefruit juice)
    - CYP3A4 particularly sensitive to this
  4. Competitive substrates
    - When two drugs are metabolized by the same enzyme, competitive binding to the enzyme occurs and increases metabolic clearance for the drugs
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14
Q

Explain the example of certain drug users avoiding wine, cheese, pickles.

A

Monoamine Oxidase (MAO) inhibitors cross-react with tyramine (present in wine, cheese, pickles).

People taking MAO inhibitors (anti-depressants) can have severe hypertensive reaction to cold remedies, decongestants and appetite suppressants.

Ex. of drug-drug interaction during metabolism

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15
Q

Name 3 ways drug-drug interactions can occur during excretion

A
  1. Reduction of renal flow
    - Drugs that reduce blood flow to kidneys (ex. beta-blockers) reduces elimination rate
  2. Inhibit renal transport mechanisms
    - ex. aspirin on uric acid secretion in proximal tubule
  3. Specific interactions (ex. influencing inflammation) reducing elimination rate
    - ex. penicillin and probenecide
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16
Q

What are4 ways pharmacodynamic drug-drug interactions can occur?

A

Antagonistic

Additive
+Supradditive/synergistic
(+Potentiation)

17
Q

Give 2 examples of pharmacodynamic antagonism

A
  1. Beta-blocker will decrease bronchodilating effects of beta2 adrenoreceptor activators (for asthma)
  2. Catecholamine on heart rate (-> beta adrenoreceptor activation) antagonized by inhibitor of acetylcholinesterase
18
Q

Give an example of pharmacodynamic antagonism that does not act on receptor

A

NSAIDs reducing renal elimination of sodium

Decreases antihypertensive action of angiotensin (which converts ACE enzyme inhibitors)

19
Q

Give 2 examples of pharmacodynamic additive effects

A
  1. Asprin anti-platelet (ie anti-coagulant) activity + Warfarin (anticoagulant) can cause bleeding
  2. trycyclic antidepressants + antihistamines (ex. promethazine, diphenhydramine) -> excessive atropine-like effects
20
Q

Give example of synergistic/superadditive pharmacodynamic interaction

A

Therapeutic effect of anti-biotics

ex. sulfonamides + dihydrofolic acid reductase inhibitiors

21
Q

Give an example of an interaction that a herbal remedy may have with a certain type of drug

A

Many herbal remedies have anti-coagulant capabilities, so taking them with anti-coagulants can be dangerous

22
Q

Explain a positive and negative example for synergism

A

Good - Aminoglycosides + penicillins:
Penicillins break bacterial cell wall, enhancing aminoglycosides entry and antibacterial activity

Bad - Barbiturates + opioids:
CNS depressants (with different targets) that enhance each other's dangerous effects (sedation and respiratory depression)
23
Q

Explain a positive and negative example for summation

A

Good - Aspirin + acetaminophen:
Acetaminophen adds to anti-pyretic and analgesic effects of aspirin (no anti-inflammatory though)

Bad - Macrolides + quinolones:
Both antibiotic groups can elicit heart arrhythmia

24
Q

Explain 2 positive and 1 negative example for antagonism

A

Good - Naloxone + opiates:
Naloxone -> opiod receptor blocker
Can reverse opiate effect in acute poisoning

Good - Copper + penicillamine:
Penicillamine binds copper and reduces copper poisoning

Bad - Warfarin + Vitamin K:
Vitamin K dependent synthesis of anti-coagulants can disrupt anti-coagulant therapy maintained by warfarin

25
Q

Name 6 diseases bacteria can cause

A
  • Gastritis
  • Gonnorhea
  • Meningitis
  • Food poisoning
  • Pneumonia
  • Strep throat
26
Q

How do anti-biotics work?

A

Different mechanisms, but basically target bacteria mechanisms for reproduction

27
Q

What is a strategy to deal with antibiotic resistance

What’s a caveat?

Give an example

A

Administer 2 anti-biotics concurrently (making it harder for target bacteria to adapt to both), allowing for synergism to occur

Avoid giving drugs with similar effects, as it might lead target bacteria to adapt to both

Penicillin + aminoglycosides -> penicillin breaks cell wall, aminoglycosides stop gene expression

PHAR 300 (9 decks)

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