(9) Food-drug interactions

Food and Bioavailability

• Food can increase OR decrease bioavailability.

• There is no general rule for every drug

Food may increase bioavailability

→ ↑ dissolution/solubilization

Food may decrease bioavailability

→ delayed disintegration
→ binding
→ impaired diffusion.

Food and Bioavailability

foods talked about

• Grapefruit

• Dairy/chelation

• Vitamin K + warfarin

• Garlic

• Fermented foods/tyramine + MAOIs

• Alcohol

  • Alcohol + Benzodiazepines

  • Metronidazole + Alcohol

Grapefruit

Grapefruit inhibits:

• CYP3A4

• CYP1A2

• P-gp

→ for many affected drugs:

metabolism/efflux ↓ → drug exposure/AUC ↑

Grapefruit

example

Lovastatin example

Grapefruit caused about a 2–3× increase in lovastatin AUC in the professor's example.

Grapefruit

Management

Separating the doses may not prevent the grapefruit interaction → complete avoidance may be needed.

Dairy / Chelation

how it works?

Cation + drug → insoluble complex → absorption ↓ → AUC ↓

Dairy / Chelation

Important cations:

• Ca²⁺

• Mg²⁺

• Al³⁺

• Fe²⁺/Fe³⁺

• Zn²⁺.

Dairy / Chelation

Affected groups discussed:

• quinolones

• tetracyclines

• thyroid replacement

Dairy / Chelation

Management:

separate dosing / avoid coadministration when required

Dairy / Chelation (IDK, IF NEED TO MEMORIZE???)

Examples to recognize

• doxycycline

• ciprofloxacin

• levofloxacin

• levothyroxine

• alendronate.

Dairy / Chelation

How to take Levothyroxine?

take fasting → wait about 30 minutes → breakfast.

Vitamin K + Warfarin

Vitamin K is needed for…

coagulation-factor maturation.

Vitamin K + Warfarin

how they connected?

VKOR recycles vitamin K.

Warfarin inhibits VKOR → anticoagulation

Vitamin K therefore opposes/reverses warfarin's effect

Vitamin K + Warfarin

Excessive warfarin effect/bleeding → what reverses it?

Vitamin K.

Vitamin K + Warfarin

What food have vitamin K?

Know that vitamin K is found particularly in dark green leafy vegetables; professor mentioned broccoli.

Garlic

garlic can have what type of effects?

 additive pharmacodynamic effects.

Garlic

Know the three interaction patterns:

• Garlic + blood thinner → both reduce clotting → bleeding risk ↑

• Garlic + antihypertensive → both lower blood pressure → BP may drop too much

• Garlic + diabetes medication → both lower blood glucose → glucose may drop more

Fermented foods/tyramine + MAOIs

Monoamine oxidase (MAO) metabolizes…

monoamines such as:

• norepinephrine

• serotonin

• dopamine

Fermented foods/tyramine + MAOIs

MAO inhibition →

monoamine levels ↑

Fermented foods/tyramine + MAOIs

Tyramine is found in…

aged/fermented foods such as:

• aged cheeses

• cured meats

• some beers

Fermented foods/tyramine + MAOIs

Tyramine-rich food + MAOI →

norepinephrine surge → hypertensive crisis

Possible:

• severe headache

• palpitations

• dangerously high BP

Fermented foods/tyramine + MAOIs

Recommendation:

Tyramine restriction is required with drugs having MAOI effects.

Alcohol Interactions

Alcohol + Benzodiazepines

Metronidazole + Alcohol

Alcohol + Benzodiazepines

connection?

Alcohol and benzodiazepines both increase CNS-depressant effects involving the GABA system.

Combination → stronger CNS depression

Possible:

• excessive sedation

• coma

• death.

Alcohol + Benzodiazepines

Professor mechanism:

GABA receptor activation → Cl⁻ influx ↑ → hyperpolarization → neuron depressed

Alcohol Metabolism

Ethanol
→ ADH
→ Acetaldehyde
→ ALDH
→ Acetate

Alcohol Metabolism

What causes hangover-type symptoms?

accumulation of acetaldehyde

Metronidazole + Alcohol

Metronidazole can cause a…

 disulfiram-like effect.

Alcohol + metronidazole

mechanism?

→ ALDH inhibition

→ acetaldehyde accumulation

→ severe reaction.

• Symptoms discussed:

  • nausea/vomiting

  • tachycardia

  • flushing.

  
  

Alcohol + metronidazole

Professor counseling emphasis

 patients taking metronidazole should be counseled about alcohol, even if they do not specifically ask about the interaction.