Chapter 2: Drug Testing, Drug Forms, and Drug Measurements

2.1 Describe the process of chemical and animal testing and clinical drug trials.
2.2 Name laws and federal agencies that control drug testing and marketing.
2.3 Name the forms in which drugs are manufactured.
2.4 Describe seven types of tablets and two types of capsules.
2.5 Describe the difference between an ointment, a cream, and a lotion.
2.6 Describe the difference between a solution and a suspension.
2.7 Describe the metric system of drug measurement.
2.8 Describe other drug measurements: units, milliequivalents, percentages, and ratios.
2.9 Demonstrate mastery of the chapter by completing the Chapter Review Exercises.

FDA Guidelines: All drugs must undergo rigorous testing by the producing company before they can be marketed, following the protocols established by the FDA.
Testing Focus Areas:
- Effectiveness
- Safety
Process Characteristics:
- Lengthy and costly, spanning development, testing, manufacturing, and marketing phases.
- Thousands of chemicals may be evaluated to arrive at one that receives FDA approval.

In Vitro Testing:
- Meaning: Latin for "in glass".
- Involves chemical analysis and laboratory tests conducted in test tubes.
In Vivo Testing:
- Meaning: Latin for "in living".
- Conducted using animal and human subjects.

Purpose: It precedes human testing to evaluate:
- Side effects
- Toxic effects
- Potential addictions
- Risk of cancerous tumors
- Possible fetal deformities
- Pharmacodynamics
Pharmacodynamics Definitions:
- Frequency Distribution Curve: A graphical representation of the number of animals that respond or do not respond to a drug at a specified dose.
- Half-Life: The duration required for the drug concentration in the blood to decrease from 100% to 50%.
- Note: This can be extended if liver or kidney function is impaired, affecting the drug's metabolism or excretion.
- Short half-life necessitates more frequent administration of the drug.
- Therapeutic Index (TI):
- Definition: The ratio that represents the margin of safety between a dose that offers therapeutic benefits and one that incurs toxicity. A higher TI signifies a more favorable therapeutic profile.

Submission: Sent to the FDA when animal studies conclude and seeks permission for human testing.
Contents: Information regarding animal study outcomes, safety data, drug chemistry, and manufacturing processes. If approved, human trials commence.

Phase 1:
- Subjects: Approximately 10 to 100 healthy volunteers.
- Purpose: Testing safe dosage ranges and side effects. Significant studies include the effect of pharmacokinetics and gender. Duration: about 1.5 years.
Phase 2:
- Subjects: 50 to 500 patients with the targeted disease.
- Purpose: Experimental administration to determine the therapeutic effect. Duration: typically 2 years.
Phase 3:
- Subjects: Hundreds to thousands of patients, reflecting the real-world use of the drug.
- Purpose: Comparison to existing treatments and double-blind studies with placebos. Usually lasts 3 years. Includes studies on pediatric dosing.
Post-Approval:
- Following FDA approval via New Drug Application (NDA), ingredients, dosage, and packaging are fixed. Manufacturers can expand drug usage post-approval.
- Example: Propranolol (Inderal) was initially approved for heart arrhythmias, later for other conditions like hypertension and migraines.

Historical Context: Historically, pharmacists compounded drugs manually; current manufacturing regulations prioritize quality, sanitation, and packaging.
Drug Types: Both generic and trade name drugs must have the same active ingredient and dosing but are exempt from similar bioavailability profiles.
Packaging: Drugs are sealed in appropriate containers, often with desiccants, to enhance stability and prevent tampering. Individual blister packs protect and identify drug dosage.
National Drug Code (NDC): A unique identifier for each drug product is required. Expiration dates are updated for new batches.

Regulations:
- Prescription drug advertising is regulated by the FDA.
- Over-the-counter advertising falls under the jurisdiction of the Federal Trade Commission (FTC).
Marketing Strategies:
- Use of medical journals for advertisement.
- Distribution of promotional material and direct healthcare provider engagement.
- Direct-to-consumer (DTC) advertising is prevalent through media channels.

Historical Laws: Key developments include the Pure Food and Drug Act of 1906, establishing the FDA's authority over approved substance regulation.
Drug Patents: Legally protected for 17 years following FDA approval. The exclusive manufacturing and marketing by the original company apply during the patent period, fostering a successful trade name. Upon patent expiration, generics can enter the market. Drugs may acquire multiple trade names based on various manufacturers.

Drugs can be manufactured in several forms to ensure efficacy and safety. Incorrect administration forms can lead to severe consequences.
Examples:
- Tablets, Capsules, Ointments, Creams, Lotions, Solutions, Suspensions, Powders, Suppositories, Transdermal patches, and Gases.

General Composition: Each tablet contains the active ingredient plus inert additives for bulk and uniformity.
Types Include:
- Scored: Tablets marked for easy splitting.
- Effervescent: Designed to dissolve in water for ingestion.
- Enteric-coated: Withstands stomach acid to dissolve in the small intestine.
- Caplets: Enteric-coated tablets shaped like capsules, allowing for controlled release.
- Lozenges: Dissolve in the mouth, releasing medication topically.
- Troches: Oval tablets that dissolve in the mouth.

Formulation: Can exist as one-piece gelatin shells (liquid-filled) or two-piece hard shells around powdered or granulated drug forms. Extended-release capsules provide sustained therapeutic effects.

Solution: Drug dissolved in a suitable solvent (e.g., sterile water or saline) for injection or oral administration.
Suspension: Contains undissolved particles dispersed in a liquid but settles over time; requires shaking.

Solid forms like powders, suppositories, or transdermal patches provide diverse administration routes.