Chapter 1 · Module 6
Section 1
The Five Elements of Rational Prescribing
1
Right Drug
Evidence-based selection for this specific indication
2
Right Dose
Individualized by weight, organ function, age, genetics
3
Right Route
Matched to urgency and bioavailability
4
Right Duration
Defined endpoint; not open-ended
5
Right Patient
Contraindications, interactions, and adherence all assessed
Therapeutic drug monitoring is indicated when: a drug has a narrow therapeutic index AND significant interpatient pharmacokinetic variability AND a well-established concentration-effect relationship. Classic examples: aminoglycosides, vancomycin, digoxin, lithium, phenytoin, cyclosporine, tacrolimus.
Section 2
High-Yield Teratogens
| Drug | Fetal Risk | Clinical Action |
|---|---|---|
| Isotretinoin | Severe craniofacial, cardiac, central nervous system malformations | Absolutely contraindicated. Mandatory iPLEDGE program required. |
| Warfarin | Embryopathy (1st trimester); fetal bleeding (later) | Switch to heparin (does not cross placenta). |
| Valproic acid | Neural tube defects, cognitive impairment, autism spectrum disorder | Highest-risk antiepileptic. Avoid if alternatives exist. |
| Angiotensin-converting enzyme inhibitors / angiotensin receptor blockers | Fetal renal dysgenesis, oligohydramnios (2nd and 3rd trimester) | Switch to methyldopa, labetalol, or nifedipine. |
| Methotrexate | Fetal death, limb and central nervous system malformations | Contraindicated. Washout required before conception. |
| Tetracyclines | Fetal tooth and bone dysplasia | Avoid after week 14. Use safe alternatives. |
Section 3 — Evidence Appraisal
Absolute vs. Relative Risk Reduction
Same trial — two ways of presenting the result
Drug reduces myocardial infarction: placebo group 4% event rate → treated group 2% event rate
50%
Relative Risk Reduction
What marketing uses. Sounds impressive.
2%
Absolute Risk Reduction
Actual probability of benefit per patient treated.
50
Number Needed to Treat
49 of 50 receive no benefit; all 50 bear risks and cost.
Always ask for the absolute risk reduction and number needed to treat. The relative risk reduction alone cannot tell you whether the absolute benefit is clinically meaningful. Low baseline event rates produce small absolute benefits even with impressive relative reductions.
Hierarchy of Evidence (highest to lowest)
Section 4
Medication Errors and Prevention
Most common category
Wrong drug, dose, route, or omission of indicated drug. Decimal place errors, weight-based calculation errors, look-alike/sound-alike name errors (hydroxyzine vs. hydralazine; vinblastine vs. vincristine).
Pharmacy stage
Wrong drug selected, wrong strength, misread handwriting. Substantially reduced by electronic prescribing.
Point of patient care
Wrong patient, wrong time, wrong rate. Barcode administration systems and independent double-checks for high-risk drugs (insulin, anticoagulants) reduce risk.
Failure to track response or toxicity
Missing drug levels for narrow therapeutic index drugs, not checking renal function after starting nephrotoxic agents, missing early toxicity signals.
Individual Prescriber Safety Habits
Never abbreviate drug names · Always specify complete route and frequency · Double-check unusually high or low doses · Verify weight-based calculations independently · Confirm renal function before prescribing renally cleared drugs · Review the complete medication list for interactions before adding any new drug