Prescription Medication Information

• Prescribing information inserts in prescription medications contain drug development information.
• The prescribing information is for physicians but is generally understandable.

Prescribing Information Insert Structure

• The insert has two parts: highlights and full information.
• The full information section includes:
  • Indications and usage (therapeutic effect)
  • Dosage and administration (how to take the drug)
  • Dosage forms (pill, capsule, lotion, nasal spray, etc.)
  • Contraindications (when to avoid, often allergy info)
  • Adverse reactions (reactions in clinical trials)
  • Drug interactions (drugs to avoid taking together)
  • Use in specific populations (effects based on gender, age, health, etc.)
  • Description (chemical structure)
  • Clinical pharmacology (target, pharmacodynamics, pharmacokinetics)
  • Nonclinical toxicology (animal data)
  • Clinical studies (charts, graphs, data)

Lipitor (Atorvastatin) Prescribing Information: Clinical Pharmacology (Section 12)

• Lipitor is a trade name for atorvastatin, a drug to lower LDL cholesterol.

12.1 Mechanism of Action

• Lipitor is a selective, competitive inhibitor of HMG-CoA reductase.
  • HMG-CoA reductase: Lipitor's target enzyme.

12.2 Pharmacodynamics

• Pharmacodynamics refers to what a drug does at its site of action.
• Information in this section mostly reiterated from the mechanism of action.

12.3 Pharmacokinetics

• Lipitor is rapidly absorbed after oral administration.
  • Maximum plasma concentrations occur within 1 to 2 hours (Tmax).
• The absolute bioavailability of atorvastatin (parent drug) is approximately 14%.
  • F = 0.14 (very low absorption)
• Mean volume of distribution of Lipitor is approximately 381 liters.
• In vitro studies suggest Lipitor metabolism by cytochrome P450 3A4.
  • P450 3A4: A liver enzyme, indicating Lipitor undergoes hepatic clearance (liver clearance).
• Lipitor and its metabolites are primarily eliminated in bile.
• Less than 2% of a dose of Lipitor is recovered in urine.
  • Renal clearance of Lipitor is approximately equal to 0.

Controlled Substances Act (1970)

• Was passed due to widespread drug use observed at the time
• Established the Drug Enforcement Administration (DEA) to regulate drugs likely to be abused
• Initially targeted drugs causing physical addiction, but broadened to include drugs with abuse potential, like anabolic steroids
• The DEA operates under the US Department of Justice, separate from the FDA
• Categorized controlled substances into five schedules based on their potential for dependency or abuse and therapeutic usefulness

DEA Registration and Prescription Rules

• Physicians, dentists, and other prescribers of controlled substances must register with the DEA and obtain a DEA number
• Prescriptions for schedules 2 through 5 controlled substances are valid for six months from the date they are written
• Anyone can fill out prescriptions, but a licensed prescriber must sign them

Schedule One Controlled Substances

• Are illegal in the United States
• They are not listed in the United States Pharmacopeia (USP)
• Considered to have a high potential for dependency and no accepted therapeutic use
• Examples include heroin and LSD
• Heroin is a controlled substance (but can be prescribed) in Canada, unlike in the United States

Schedule Two Controlled Substances

• Can be prescribed but have a high potential for dependency
• Have accepted therapeutic uses in the United States
• Require a special prescription form known as a security or tamper-resistant prescription form

Features of Security or Tamper-Resistant Prescription Forms

• The DEA number is pre-printed on the form
• "Void" appears upon photocopying or faxing
• The first line of the prescription contains the drug name and dosage
• The second line includes the number of pills, with a checkbox indicating the quantity range
• Refills are not allowed for schedule 2 substances

Regulations for Schedule Two Controlled Substances

• A new prescription is required for each refill
• The quantity prescribed cannot exceed a 30-day supply
• Prescriptions cannot be phoned or faxed in

Examples of Schedule Two Controlled Substances

• Narcotic pain relievers/analgesics: morphine, codeine, and Demerol
• Stimulants such as cocaine, Dexedrine, and Adderall (used for ADD)
• Sedatives: barbiturate sedatives like pentobarbital and Seconal
• Stimulants are "uppers", while sedatives are "downers"

Schedule Three Controlled Substances

• Are less regulated than schedule two substances
• Still require special tamper-resistant prescription forms
• Refill instructions are allowed: up to five refills every six months, if noted on the prescription
• Prescriptions can be phoned or faxed in

Examples of Schedule Three Controlled Substances

• Combinations of a narcotic with a non-narcotic, such as codeine with Tylenol, or Vicodin
• Vicodin: a combination of hydrocodone (narcotic) with acetaminophen (Tylenol)
• Anabolic steroids
• Considered less likely to be abused than pure narcotics

Schedule Four Controlled Substances

• Regular prescription forms can be used, but tamper-resistant forms are also acceptable
• Valium-like drugs such as Xanax or Valium
• Ambien is used to help with sleep
• Meridia is used to promote weight loss

Schedule Five Controlled Substances

• The lowest level of controlled substance
• Viewed as drugs with little potential for abuse
• There are no refill limitations
• Regular prescription form is acceptable
• A DEA number is still required

Examples of Schedule Five Controlled Substances

• Robitussin AC (cough medicine with codeine): contains a small amount of codeine
• Lomotil (anti-diarrheal): used for severe diarrhea
• Contains a narcotic to cause constipation and decrease gastrointestinal motility
• Has minimal euphoric effects

Federal Law (1984) Regarding Generic Drugs

• Requires that all generic drugs meet the same standards of efficacy as brand-name drugs
• CVS brand atorvastatin must work as well as Lipitor atorvastatin
• Ensures that generics should work just as well as brand names after 20 years from the original drug being released

FDA vs. DEA Responsibilities: Examples of Drugs

• Overlapping responsibilities in terms of medications

Vicodin

• FDA: requires a prescription (legend drug)
• DEA: is a schedule three controlled substance, requiring a tamper-resistant prescription

Amoxicillin

• FDA: requires a prescription (legend drug) due to concerns about antibiotic resistance
• DEA: not a controlled substance

Advil

• FDA: over-the-counter drug
• DEA: not regulated; not a controlled substance

Types of Civil Actions (Torts)

• Civil actions = lawsuits taken by an individual

Misfeasance

• Making a mistake while doing something within one's license

Nonfeasance

• Failing to do something that should have been done within one's responsibility
• Example: Previously, failing to premedicate a patient with rheumatic heart disease

Malfeasance

• Doing something wrong that is not within one's licensed scope of practice
• Example: A dental hygienist performing a filling against their job description

Sources of Drug Information

• United States Pharmacopeia (USP): Official listing of legal drugs in the United States, identified by official or generic names
• Physician's Desk Reference (PDR): Compilation of package inserts provided to prescribers, not necessarily objective

Prescription Writing: Parts of a Prescription

• Heading:
  • Information about the prescriber (name, address, phone number)
  • Information about the patient (name, date, address, age)
• Body:
  • The most important part
  • Begins with RX (recipe, meaning "this is what you should do")
  • Three lines: name/dose of the drug, dispense amount, directions to the patient (Sig)
• Closing:
  • Prescriber's signature
  • DEA number
  • Refill instructions
  • Instructions for generic drug substitution

Prescription Writing Continued - Abbreviations

• Common Abbreviations
  • BID: twice a day (bis in die)
  • TID: three times a day (ter in die)
  • QID: four times a day (quarter in die)
  • Q6H: every six hours
  • AC: before meals (ante cibum)
  • HS: hour of sleep (hora somni)
  • PRN: as needed (pro re nata)
  • PO: by mouth (per os)

Important Notes

• Liquid prescription measurement
  • one teaspoon = 5 milliliters for prescription directions

Old Apothecary System: Grains

• Old-fashioned unit still used for some drugs like aspirin and codeine
  • If aspirin is five grains, converting each grain to 60 milligrams
  • Five grain aspirin tablet turns out to be: 5 * 60 = 300 milligrams
  • Codeine also uses grains
• One grain = 60 mg
• The value of one grain = 60 mg
  • This correlates to the size "number" of the pill

Numbered Pills

• One grain is also called a number four pill
• Codeine typically is used with Tylenol
  • Tylenol with Codeine number three = ½ grain (30mg) of codeine per tablet
• Think, you are taking about the hour of sleep at night = 60 minutes
  • There are four quarters in an hour
  • Thus, three = half of 60 = 30 mg of codeine