1.5 drug interactions

Question 1

Please give examples of pharmaceutical drug-drug interactions. What precautions can be taken to prevent those interactions?

Answer 1

Physicalchemical interactions on BA before or during apllication like compatibility (pH, ions), concentration (solubility), adsoprion of material in total parental nutrion or application via gastric tube

Question 2

Please give an overview of the most important pharmacokinetic interactions. Explain the underlying mechanisms in detail and discuss possibilites to reduce the risk of adverse effects due to those interactions.

Answer 2

Direct effects on bioavailability:

• absorption: activated charcoal, cholestyramine (unspecific with almost every drug)
• gastral increase of pH: PPI, H2-antihistamines –> unintended dissolution of other drugs in the stomach (loss of stomach protection (ulcerogenic) or loss of MRD mechanism (dose dumping)), absorption of Vit B12
• decelerated GI transit: antidiarrheals (loperamide), opioids –> delayed onset of other drugs, incerased BA of other drugs
• accelerated GI transit: laxatives, prokinetics –> faster onset of other drugs, decreased BA of other drugs

Indirect effects on bioavaibalility:

• toxic damage of GI mucosa/epithelium: cytostatic drugs –> faster onset, elevated Cmax and decreased BA of ther drugs
• interruption of the enterohepatic circulation: antibiotics –> interaction with oral contraceptives

Interacting via Plasma protein binding: deprescription is just as dangerous as prescription

CYP metabolsim interaction: competetion, induction inhibtion: clopidogrel and CYP 3A4 (inhibited by PPI), tamoxifen and CYP2d6, phytochemicals like (induction of CYP)

Question 3

What are pharmacodynamic interactions? Please give appropriate examples.

Answer 3

Interaction at the same receptor: eg. 2 opiods = overdose, 1 opioid + naloxone = overdose treatment

Interaction at the same physiological system:
- electrolyte metabolsim (laxative + diuretic)
- intestinal mucosa (NSAID + glucotricoid)
- sometimes inteneded: eg. Diabetes –> Metformin and SGLT-2I, same system, but different targets
or - eg. Hypertension: ACE inhibitors and diuretics

Question 4

Please give examples of phytotherapies that can cause relevant drug interactions. Discuss the underlying mechanisms in detail.

Answer 4

Oral contraceptive: Interaction with St. Johns ward (hypericum perforatum), Hyperforin –> Induction of CYP3A4 –> faster estrogen metabolism

In transplantation: Therapy with cyclosporin after transplantation –> Cyclosporin underlies CYP3A4 metabolism –> decreased plasma level –> graft rejection

Gingko and NSAID = higher bleeding risk
Ginseng + Vit K antagonists = higher bleeding risk
Valerian + paracetamol = higher hepatotoxicity