Medication Dosing, Forms & Interactions

Learning Objectives

By the end of this chapter, you should be able to:

Interpret and convert between metric, apothecary, and household units of measure.

Calculate the correct dose, days' supply, and quantity to dispense for various dosage forms.

Identify the defining characteristics of solid, semi-solid, liquid, and parenteral dosage forms.

Apply the principles of pharmacokinetics (absorption, distribution, metabolism, excretion) to predict drug interactions.

Classify major drug-drug, drug-food, and drug-disease state interactions.

Recognize high-alert medications and the safety standards applied to their dispensing.

Distinguish between generic and brand-name drugs, and apply the FDA's therapeutic equivalence ratings.

1.1 Foundational Measurement Systems

Pharmacy practice in the United States relies primarily on the metric system, but you must be fluent in converting from the apothecary and household systems because prescribers and patients still use them.

Metric System (Primary)

Weight: 1 kilogram (kg) = 1000 grams (g); 1 gram = 1000 milligrams (mg); 1 milligram = 1000 micrograms (mcg).

Volume: 1 liter (L) = 1000 milliliters (mL).

Length: rarely used in dosing, but 1 meter = 100 centimeters.

Household System (Patient-facing)

1 teaspoon (tsp) = 5 mL

1 tablespoon (tbsp) = 15 mL

1 fluid ounce (fl oz) = 30 mL

1 cup = 8 fl oz = 240 mL

1 pint = 16 fl oz = 480 mL (often rounded to 480 mL in pharmacy)

1 quart = 32 fl oz = 960 mL

Apothecary System (Legacy)

1 grain (gr) = 60 mg (used for thyroid medications, nitroglycerin, and phenobarbital)

1 ounce (oz) = 30 g (apothecary weight) or 30 mL (apothecary volume)

1 minim = approximately 0.06 mL (rarely used today)

Common Conversions to Memorize

1 kg = 2.2 pounds (lb)

1 inch = 2.54 cm

1 mg = 1000 mcg

1 g = 15.4 grains (round to 15 grains for practical purposes)

Dosing Weight

Pediatric and some adult doses are calculated per kilogram of body weight. Always verify whether the prescriber intends the patient's actual weight or an ideal body weight (IBW). For obese patients, using actual weight can lead to toxicity; using IBW can lead to underdosing. The prescription will usually specify which weight to use.

1.2 Dosage Forms: Characteristics and Handling

Dosage forms are designed to deliver the active ingredient in a predictable manner. Your role includes understanding how each form behaves so you can counsel patients and detect dispensing errors.

Solid Dosage Forms

Tablets: May be immediate-release (IR), extended-release (ER/XR/XL), or delayed-release (DR, enteric-coated). Never crush or split ER or DR tablets unless the manufacturer's labeling explicitly permits it. Sublingual tablets (e.g., nitroglycerin) dissolve under the tongue for rapid absorption; buccal tablets dissolve between cheek and gum.

Capsules: Hard gelatin capsules contain powder or granules; soft gelatin capsules contain liquids or semi-solids. Some capsules are designed to be opened and sprinkled on food, but never for extended-release products.

Chewable tablets: Must be chewed thoroughly before swallowing; they are not meant to be swallowed whole.

Semi-Solid Dosage Forms

Ointments: Oil-based, 80% oil to 20% water. They form a barrier and are used for dry, scaly conditions. They are occlusive.

Creams: Water-based, 50% water to 50% oil. They are cosmetically elegant, easily absorbed, and used for weeping or moist lesions.

Lotions: Suspensions or emulsions with high water content; used for large body surfaces.

Pastes: Thick ointments with a high powder content; used for protection (e.g., zinc oxide).

Gels: Semi-solid systems with a liquid phase; they dissolve in the application area.

Liquid Dosage Forms

Solutions: Homogeneous mixtures (drug fully dissolved). Examples: oral solutions, ophthalmic drops.

Suspensions: Drug particles dispersed in a liquid vehicle. They require shaking before use. "Shake well" is a critical auxiliary label.

Emulsions: Mixtures of oil and water stabilized by an emulsifying agent (e.g., milk of magnesia).

Elixirs: Sweetened hydro-alcoholic solutions; used for drugs that are poorly water-soluble.

Syrups: Concentrated sugar solutions; may mask unpleasant tastes.

Parenteral and Inhalation Forms

Ampules: Single-dose glass containers; once opened, any unused portion must be discarded.

Vials: Multi-dose or single-dose; multi-dose vials have a rubber stopper that can be punctured multiple times.

Prefilled syringes: Contain a single dose; common for vaccines and anticoagulants.

Transdermal patches: Deliver drug through the skin at a controlled rate. Rotate application sites to prevent irritation. Remove old patch before applying a new one.

Inhalers: Metered-dose inhalers (MDIs) require coordination of actuation and inhalation; dry powder inhalers (DPIs) require a rapid, deep inhalation.

1.3 Pharmacokinetics and Pharmacodynamics

Understanding how drugs move through the body is essential to predicting interactions and counseling patients.

Absorption

The movement of a drug from the site of administration into the bloodstream. Factors affecting absorption include:

Route of administration (IV bypasses absorption).

Blood flow to the absorption site.

Gastrointestinal pH.

Presence of food in the stomach.

Drug formulation (ER vs. IR).

Distribution

The movement of drug from the bloodstream into tissues. Drugs that are highly protein-bound (e.g., warfarin, phenytoin) have a low free fraction. If two highly protein-bound drugs are given together, one can displace the other, increasing the free concentration of the displaced drug and leading to toxicity.

Metabolism

Primarily hepatic, via the cytochrome P450 (CYP450) enzyme system. Key isoenzymes include CYP3A4, CYP2D6, CYP2C9, and CYP1A2. Enzyme inhibitors (e.g., ketoconazole, grapefruit juice) increase the concentration of the substrate drug. Enzyme inducers (e.g., rifampin, carbamazepine, phenytoin) decrease the concentration of the substrate drug.

Excretion

Primarily renal. In patients with renal impairment, drugs that are renally cleared accumulate, requiring dose reduction. Creatinine clearance (CrCl) is the standard measure used to adjust doses.

Half-life

The time required for the plasma concentration of a drug to decrease by 50%. Steady state is reached after approximately 4–5 half-lives.

1.4 Drug Interactions: Mechanisms and Major Examples

Drug-Drug Interactions

Additive/synergistic: Two drugs with similar effects produce an exaggerated response. Example: an opioid plus a benzodiazepine causes profound respiratory depression.

Antagonistic: One drug reduces the effect of another. Example: naloxone reverses opioid effects.

Pharmacokinetic: One drug alters the absorption, distribution, metabolism, or excretion of another.

CYP3A4 inhibition: Grapefruit juice, clarithromycin, ketoconazole, and ritonavir increase levels of simvastatin, leading to rhabdomyolysis.

CYP3A4 induction: Rifampin and St. John's Wort decrease levels of oral contraceptives, leading to unintended pregnancy.

CYP2C9 inhibition: Fluconazole increases warfarin levels, increasing bleeding risk.

CYP2D6 inhibition: Paroxetine increases tamoxifen's active metabolite levels, potentially reducing efficacy.

Drug-Food Interactions

Grapefruit juice: Inhibits intestinal CYP3A4, increasing levels of calcium channel blockers, statins, and certain immunosuppressants.

Vitamin K-rich foods (leafy greens): Antagonize warfarin, reducing its anticoagulant effect.

Tyramine-containing foods (aged cheese, cured meats): Can precipitate a hypertensive crisis in patients taking MAO inhibitors (e.g., phenelzine).

Calcium-rich foods (milk, yogurt): Chelate with fluoroquinolones (ciprofloxacin) and tetracyclines (doxycycline), reducing their absorption. Separate administration by 2 hours.

High-fat meals: Increase absorption of fat-soluble drugs (e.g., griseofulvin) but decrease absorption of others (e.g., some antibiotics).

Drug-Disease State Interactions

NSAIDs in patients with peptic ulcer disease or chronic kidney disease: Increased risk of bleeding and renal failure.

Beta-blockers in patients with asthma: Can cause bronchospasm.

Metformin in patients with renal impairment: Risk of lactic acidosis.

Potassium-sparing diuretics (spironolactone) in patients with hyperkalemia: Dangerous elevation of potassium.

1.5 High-Alert Medications and Safety Standards

The Institute for Safe Medication Practices (ISMP) maintains a list of high-alert medications that bear a heightened risk of causing significant patient harm when used in error. You must recognize these and apply extra safeguards.

Key High-Alert Classes

Anticoagulants: Warfarin, heparin, enoxaparin. Errors cause bleeding or thrombosis.

Insulin: All formulations. Errors cause severe hypo- or hyperglycemia. Always verify the concentration (U-100 vs. U-500).

Opioids: Morphine, hydromorphone, oxycodone, methadone, fentanyl. Errors cause respiratory depression.

Chemotherapeutic agents: Vincristine (must never be given intrathecally), methotrexate.

Electrolytes: Concentrated potassium chloride (must be diluted before IV administration), magnesium sulfate.

Hypoglycemics: Sulfonylureas (glyburide, glipizide).

Neuromuscular blocking agents: Succinylcholine, vecuronium.

Safety Standards

Tall man lettering: Used to differentiate look-alike drug names (e.g., DOBUTamine vs. DOPamine, hydrOXYzine vs. hydrALAZINE).

Independent double-checks: Required for high-alert medications, especially insulin and anticoagulants, before dispensing.

ISMP error-prone abbreviations: The use of "U" for units, "QD" for once daily, and trailing zeros (e.g., 5.0 mg) is prohibited because they cause misinterpretation. Always write "units," "daily," and "5 mg" without a trailing zero.

1.6 Prescription Processing and Calculations

Sig Code Interpretation

q.d. = every day (once daily) — ISMP recommends writing "daily" to avoid confusion with q.i.d.

b.i.d. = twice daily

t.i.d. = three times daily

q.i.d. = four times daily

q.h.s. = every hour of sleep (at bedtime)

p.r.n. = as needed

a.c. = before meals

p.c. = after meals

ad lib = as desired

stat = immediately

Days' Supply Calculation

The formula is: Quantity dispensed ÷ (dose per administration × administrations per day) = days' supply.

Example: Dispense 60 tablets, take one tablet twice daily. Days' supply = 60 ÷ (1 × 2) = 30 days.

Quantity to Dispense Calculation

The formula is: Dose per administration × administrations per day × days' supply = quantity to dispense.

Example: Take 2 tablets three times daily for 10 days. Quantity = 2 × 3 × 10 = 60 tablets.

Dose Calculation Based on Weight

Dose = (weight in kg) × (dose per kg).

Example: A child weighs 44 lb. Convert to kg: 44 ÷ 2.2 = 20 kg. If the dose is 5 mg/kg, the dose is 20 × 5 = 100 mg.

Flow Rate Calculation (IV)

Flow rate (mL/hr) = Total volume (mL) ÷ Total time (hr).

Example: 1000 mL over 8 hours = 125 mL/hr.

Drops per Minute (gtts/min)

Gtts/min = (Volume in mL × Drop factor) ÷ Time in minutes.

Common drop factors: 10 gtts/mL (macro), 15 gtts/mL, 20 gtts/mL, and 60 gtts/mL (micro).

1.7 Regulatory Framework and Drug Standards

DEA Controlled Substances Act and 21 CFR

The Controlled Substances Act (CSA), enforced by the DEA, classifies drugs into five schedules based on accepted medical use and abuse potential.

Schedule I: No accepted medical use, high abuse potential (heroin, LSD, marijuana).

Schedule II: High abuse potential, severe dependence liability, written prescription required (oxycodone, fentanyl, amphetamine, methylphenidate).

Schedule III: Moderate to low abuse potential (codeine-containing products with acetaminophen, testosterone).

Schedule IV: Low abuse potential (alprazolam, diazepam, zolpidem, tramadol).

Schedule V: Lowest abuse potential (cough preparations containing small amounts of codeine).

Key Rules for C-II Drugs

No refills permitted.

Prescriptions must be written (electronic or paper) and signed by the prescriber; oral emergency prescriptions are limited to a 72-hour supply in most states.

Records must be maintained separately from other prescriptions.

FDA Drug Labeling and REMS

The FDA requires standardized labeling for all approved drugs. The package insert contains prescribing information, contraindications, warnings, and clinical pharmacology. Some drugs have a Risk Evaluation and Mitigation Strategy (REMS) , which may require restricted distribution, patient registries, or special prescriber certification. Examples include isotretinoin (iPLEDGE REMS) and clozapine (monitoring for neutropenia).

USP <795> and <797> Compounding Standards

USP <795> covers non-sterile compounding (e.g., creams, suspensions, capsules). It requires the use of a beyond-use date (BUD) based on the water content of the preparation.

USP <797> covers sterile compounding (e.g., IV admixtures). It requires an ISO Class 5 environment (laminar airflow hood), garbing, and hand hygiene. Sterile preparations have BUDs ranging from 12 hours (highest risk) to 45 days (lowest risk, sealed).

HIPAA Privacy Rule

The Health Insurance Portability and Accountability Act (HIPAA) protects patients' protected health information (PHI). In the pharmacy, this means you cannot discuss a patient's medications with unauthorized individuals, you must use private counseling areas, and you must not leave prescriptions or labels visible to other customers.

ISMP Recommendations

The ISMP recommends that all high-alert medications be stored with auxiliary labels, separated from look-alike products, and verified by a second person. ISMP also maintains a list of confused drug names (e.g., "Tegretol" vs. "Trandate").

1.8 Generic Substitution and Bioequivalence

When a brand-name drug loses patent protection, generic versions may be approved by the FDA. A generic must be pharmaceutically equivalent (same active ingredient, strength, dosage form, and route) and bioequivalent (same rate and extent of absorption). The FDA assigns an "A" rating to drugs that are considered therapeutically equivalent and can be substituted. A "B" rating indicates that bioequivalence has not been demonstrated, and substitution is not recommended.

Narrow Therapeutic Index (NTI) Drugs

For drugs like warfarin, digoxin, levothyroxine, and phenytoin, small changes in blood concentration can cause toxicity or therapeutic failure. Many states restrict automatic generic substitution for NTI drugs, requiring the prescriber's approval.

Common Exam Traps

1. Confusing q.d. and q.i.d.

Students often misread "q.d." (once daily) as "q.i.d." (four times daily). This error leads to a fourfold overdose. On the exam, always count the number of "i"s. If you see "q.i.d.," it has two "i"s and means four times daily.

2. Mixing Up DEA Schedules

A common error is classifying tramadol as Schedule III or alprazolam as Schedule II. Tramadol is Schedule IV, and alprazolam is Schedule IV. Remember: Schedule II drugs are the most restricted that can be prescribed; Schedule III–V have decreasing restrictions. Hydrocodone combination products were moved to Schedule II in 2014.

3. Incorrect Metric Conversions

Students frequently convert 1 gram to 100 mg instead of 1000 mg, or 1 liter to 100 mL instead of 1000 mL. Always check the number of zeros. A microgram is 1/1000 of a milligram, so 0.5 mg = 500 mcg, not 50 mcg.

4. Days' Supply Errors with "Take as Needed"

If a prescription says "take 1–2 tablets every 4–6 hours as needed for pain," you cannot calculate a precise days' supply. You must use a reasonable estimate based on the maximum or expected frequency, but the exam will usually provide a specific instruction such as "take one tablet every 6 hours as needed." In that case, the maximum is 4 tablets per day.

5. Forgetting to Convert Pounds to Kilograms

A pediatric dose question may give a child's weight in pounds. If you skip the conversion (divide by 2.2), your dose will be 2.2 times too high. Always convert to kg before multiplying by the mg/kg dose.

6. Confusing "Injection" Routes

The routes are: IV (intravenous, into the vein), IM (intramuscular, into the muscle), SC/SQ (subcutaneous, under the skin), and ID (intradermal, into the dermis). Insulin is subcutaneous; most vaccines are IM; epinephrine for anaphylaxis is IM.

7. Misidentifying Extended-Release Abbreviations

ER, XR, XL, SR, CR, and TR all indicate extended or controlled release. If a patient is instructed to crush an ER tablet, the entire dose may be released at once, causing toxicity. On the exam, if a question asks whether a tablet can be crushed, the answer is "no" for any ER/DR formulation unless the label states otherwise.

8. Overlooking the "Shake Well" Label

For suspensions, if the patient does not shake the bottle, the first doses will be concentrated and subsequent doses will be subtherapeutic. Always attach a "Shake Well" auxiliary label to suspensions.

9. Confusing Brand and Generic Names

Look-alike/sound-alike pairs are a favorite exam topic. Examples: Celebrex (celecoxib, an NSAID) vs. Cerebyx (fosphenytoin, an anticonvulsant) vs. Celexa (citalopram, an SSRI). These are not interchangeable.

10. Misapplying the "Right Patient" Check

When verifying a prescription, you must confirm the patient's identity using at least two identifiers (name and date of birth). Using only the room number or the medication name is an error.

Summary

Mastering medication dosing, dosage forms, and interactions requires fluency in conversions, a clear understanding of pharmacokinetic principles, and the ability to apply regulatory standards. Always double-check your calculations, verify the dosage form before dispensing, and remember that high-alert medications demand extra vigilance. On the PTCE, the most common errors are not due to lack of knowledge but to careless reading of sig codes and unit conversions. Read every question twice, and confirm that your answer is reasonable in the clinical context.

Medication Dosing, Forms & Interactions