Dermatology
Drug Interactions
Built from Dermatology, 5th Edition
What’s inside
15 sections · 114 slides
Understanding drug interactions
What a drug interaction is, who causes it, and how big the problem really is.
- Where a drug interaction can arise
- Two kinds of drug safety problem
- How common are drug interactions
- Potential risk is not the same as actual harm
- Narrow therapeutic index drugs need extra care
Assessing patient risk
The same drug pair is riskier in some patients than others - here is why.
- Patient risk factors for drug interactions
- Elderly patients
- HIV-infected patients
- Genetic differences in drug-metabolizing enzymes
- Disease state changes interaction risk
- Dose-dependent interaction: methotrexate and NSAIDs
- Sex and body weight affect metabolism
- How the precipitant drug is given matters
- Patient factors that raise risk
Evidence and prediction
Why the published lists of drug interactions are often unreliable.
- In vitro versus in vivo evidence
- Why prediction is hard in real regimens
- Confusing drug interaction literature
Absorption interactions
Interactions that happen before a drug even reaches the bloodstream.
- Three ways drugs block each other's absorption
- Complex-forming drugs bind and block absorption
- Drug interactions that reduce the efficacy of substrates
- Drug interactions that reduce the efficacy of substrates (continued)
- Drug interactions that reduce the efficacy of substrates (continued)
- Mycophenolate absorption and recirculation
- Gastric acid and drug absorption
- Enterohepatic recirculation and warfarin
P-glycoprotein transport
A cell-membrane pump that decides how much of a drug gets in - or stays out.
- What P-glycoprotein does
- PGP as a gatekeeper for CYP3A4
- PGP, the blood-brain barrier and sedation
- Substrates of P-glycoprotein
- Substrates of P-glycoprotein (continued)
- Inhibitors of P-glycoprotein
- Inhibitors of P-glycoprotein (continued)
Distribution interactions
What happens when one drug pushes another off its carrier protein.
- Protein-binding displacement
- Why displacement effects usually fade
- When displacement does matter clinically
- Interactions that raise the risk of substrate toxicity
Drug biotransformation
How the liver turns a drug into something the body can excrete.
- Two phases of drug metabolism
- The cytochrome P450 (CYP) enzyme family
- The six enzymes that matter most
- Substrate, inhibitor and inducer are different roles
- Influences on cytochrome P450 activity
- Limits of lab (in vitro) prediction
CYP3A4 in focus
The single busiest drug-metabolizing enzyme, and why it drives so many interactions.
- Why CYP3A4 matters so much
- CYP3A4 activity varies a lot between people
- Substrates of CYP3A4, CYP3A5 and CYP3A7
- Substrates of CYP3A4, CYP3A5 and CYP3A7 (continued)
- Substrates of CYP3A4, CYP3A5 and CYP3A7 (continued)
- CYP3A4 inhibitors, by class
- CYP3A4 inducers, by class
- How grapefruit juice raises cyclosporine levels
- Grapefruit juice: what and why
- Practical advice on grapefruit juice
Enzyme induction and inhibition
Two opposite ways a drug can change how fast another drug is broken down.
- What induction and inhibition each do
- Induction: slow to start, slow to stop
- Inhibition: fast to start, fast to stop
- Competitive vs non-competitive inhibition
- How an inhibitor raises a substrate's level
- Induction vs inhibition, side by side
Other key CYP isoforms
CYP1A2, 2C9, 2C19 and 2D6 - smaller than CYP3A4, but still clinically important.
- CYP1A2 - substrates, inhibitors and inducers
- CYP2C9 - substrates, inhibitors and inducers
- CYP2C19 - substrates, inhibitors and inducers
- Substrates and inhibitors of CYP2D6
- CYP2D6 metabolizer phenotypes
Interactions by drug class
Not every drug in a class carries the same risk - choosing wisely matters.
- Not all drugs in a class are equal
- Drugs and foods with differing interaction potential
- Terbinafine and CYP2D6
- Terbinafine's clinical interaction risks
- Azole antifungals as CYP3A4 inhibitors
- Azole antifungals: monitoring needed
- Azole-calcium channel blocker case: nifedipine edema
- Azole antifungals: other specific interactions
- Azathioprine metabolism
- Allopurinol/febuxostat plus azathioprine: avoid
- Colchicine: a double substrate
- Recognizing colchicine toxicity
- Cyclosporine, tacrolimus, everolimus, sirolimus
- Monitoring calcineurin/mTOR inhibitor levels
- Herbal remedies are not automatically safe
- Which drugs are most at risk from herbs
- St John's wort induces CYP3A4
- Herbal remedies: side effects and contraindications
- Herbal remedies: drug interactions
- Statins: not all equally risky
- Kinase inhibitors: BRAF/MEK and JAK drugs
- Choosing a macrolide antibiotic safely
- More macrolide interactions to know
- Quinolone antibiotics and cation binding
- Quinolones: QT risk and warfarin
- Pimozide and QT prolongation
Pharmacogenetics
Why the same drug dose can be too much for one patient and too little for another.
- Four metabolizer phenotypes
- Pharmacogenetics: impact of polymorphisms on drug metabolism
- TPMT and azathioprine dosing
- What TPMT deficiency does to azathioprine
Cytokines and viral interactions
Inflammation and viral infection can change drug metabolism too, not just other drugs.
- Cytokines can suppress CYP3A activity
- HHV-6/7 reactivation and DRESS
- HIV drug interactions
- Hepatitis C antiviral interactions
Reducing risk and resources
Practical habits and trusted tools for prescribing with confidence.
- A safer versus riskier choice, within one class
- How to lower the risk of drug-drug interactions
- Trusted resources for checking interactions
- 90%
- “
- Reporting new interactions
References
Sources cited in this chapter.
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- Dermatology, 5th Edition (2-Volume Set)