Lecture 2 Drug Regulation, Development, etc.

Question 1

Established the FDA (for safety, efficacy, and security of human & veterinary drugs, biological products, and medical devices); and US Pharmacopeia (that establishes drug product standards for a drug’s chemical composition and analysis and how much variance in a drug is allowed for each drug product)

Answer 1

Food, Drug, and Cosmetic Act (1938) = FDCA

Question 2

Focuses on drug abuse and prevention of drug abuse
Classified drugs with abuse potential into 5 schedules
Enforced by the DEA

Answer 2

Comprehensive Drug Abuse Prevention and Control Act (1979) = CDAPCA
(aka Controlled Substances Act)

Question 3

Focuses on products taken orally for supplementing the diet: vitamins, minerals, herbs, amino acids, enzymes or metabolites, weight loss products.
FDA regulates it, but unlike drugs, dietary supplements are NOT evaluated by the FDA before they are on the market for public use. No proof is required to show they are effective (or safe) before marketing them.

Answer 3

Dietary Supplements Health & Education Act (1994)

Question 4

High abuse potential. May lead to severe dependence. NOT ACCEPTED FOR MEDICAL USE!
Examples: Heroin, Marijuana, and Peyote

Answer 4

Controlled Substances Schedule 1 (NOT ACCEPTED FOR MEDICAL USE!)

Question 5

High abuse potential. May lead to severe dependence.

Examples: Fetanyl, Cocaine, Codeine, Morphine, Amphetamine, Methadone, Hydrocodone, Oxycodone

Answer 5

Controlled Substances Schedule 2

Question 6

Abuse potential less than Schedule 1 and 2. May lead to moderate dependence.
Examples: Drugs with lower levels of codeine (<90mg), anabolic steroids, buprenorphine (pharmacotheraphy drug)

Answer 6

Controlled Substances Schedule 3

Question 7

Moderate abuse potential. May lead to limited dependence

Examples: Alprazolam (XANAX), Zolpidem (AMBIEN), Phenobarbital (LUMINAL), Modafinil (PROVIGIL)

Answer 7

Controlled Substances 4

Question 8

Small abuse potential. May lead to limited dependence

Examples: Cough medications with codeine, certain antidiarrheals

Answer 8

Controlled Substances 5

Question 9

What must an optometrist obtain in order to prescribe a drug that is a controlled substance?

Answer 9

DEA Certificate

Question 10

Describe the drug development process in the US.

Answer 10

Takes about 10-15 years with an average price of 1.3 billion dollars
Drug scientists identify a molecular target (ex: a receptor related to a disease) and design a drug to alter it via supercomputers, cell cultures, or animal tissues.
Once they find the drug, they start preclinical trials where they do lots of pharmacokinetics and pharmacodynamic studies on animals.

If all goes well, and they can develop a human formulation of the drug, the company will file an Investigational New Drug (IND) application to the FDA (with all their study information). Once approved, they can start human trials.

Question 11

When can a company submit a New Drug Application (NDA) to the FDA?

Answer 11

After phase 3 clinical trials where they’ve tested a large number of humans across the nation, and have proven safety and efficacy amongst the diseased. Upon approval, they can sell and market to the public in the US with the appropriate labeling (package insert).

Question 12

Describe the clinical trial stages: preclinical and phase 1-4 clinical trials.

Answer 12

Preclinical (Phase 0) = studies are done on cell-cultures and animals (no humans)
Phase 1 = small sample of healthy patients WITHOUT THE DISEASE where they determine the max. tolerated dose
Phase 2 = hundreds of patients WITH THE DISEASE
Phase 3 = thousands of patients WITH THE DISEASE across the nation
Phase 4 = studies continue upon FDA approval amongst the public

Question 13

Explain why a patient’s age, disease status, and pregnancy/lactation/fertility status must be considered when prescribing drugs

Answer 13

These are biological factors that can alter a drug’s safety and efficacy.
The very young and very old have differences in anatomy and physiology that can affect the pharmacokinetics / pharmacodynamics of the drug.
Kidney, liver, heart disease can alter the pharmacokinetics (ADME) resulting in a drug build up in the body or smaller amount.
Some drugs can cross the placenta and affect the developing fetus, or be excreted into breast milk.
Information about these special populations can be found on a drug’s label (package insert)
The Daily Med is a database of package inserts.

Question 14

What is a teratogen, and when are the eyes at a higher risk for teratogen damage?

Answer 14

Any drug that can cause adverse effects in a fetus or infant.
1st trimester when the eyes are developing.

Question 15

Define the 5 FDA pregnancy/lactation categories that were in effect for all drugs from 1979-2015

Answer 15

Rating A = No fetal risks in controlled studies
Rating B = No risk to human fetus despite possible animal risk or no risks in animal studies but human studies lacking.
Rating C = Adverse effects on the fetus were found in animal studies, but no adequate human studies, OR there are no animal or human studies to determine the safety
Rating D = Evidence of human fetal risk, but the benefits of use outweigh the risks
Rating X = Human or animal studies have shown fetal abnormalities, and the risks are much more significant than the benefits

Most drugs are Category C!

Question 16

Explain why in 2015 the FDA changed the labeling requirements for pregnancy, lactation, and fertility.

Answer 16

In 2015, the FDA replaced the former pregnancy risk letter categories (1979-2015) on prescription & biological drug labeling with new information to make them more meaningful to both patients and healthcare providers. The new rating system helps doctors and patients make better risk-benefit assessments for taking a medication during pregnancy/lactating than the old system.

Question 17

Discuss what the FDA now requires drug labels to include regarding pregnancy, lactation, and fertility risk.

Answer 17

They now require narrative sections and subsections to include:
Narrative: Pregnancy, Lacatation, Females and Males Reproductive Potential

Subsection for Pregnancy: Pregnancy Exposure Registry, Risk Summary, Clinical Considerations, Data
Subsection for Lactation: etc.

Question 18

Define a Pregnancy Exposure Registry

Answer 18

study that collects health information from pregnant humans or newborn babies when they’re taking medications or vaccines. This information is compared with people who are not pregnant.

The new FDA labeling requires that if a drug is evaluating its use in pregnant humans via a Pregnancy Exposure Registry, it must state this on the label and provide enrollment, and a way to obtain information about the Pregnancy Exposure Registry.

Question 19

Define drug interaction

Answer 19

an interaction, if given concurrently with another drug or with food/drink, that changes its pharmacologic effect.

more likely to occur if the drug has a low therapeutic index = (effective dose / toxic dose)
more likely to occur in polypharmacy (use of multiple medications)–especially in the elderly

Question 20

Pharmacodynamic Drug Interaction: Additive Effect

Answer 20

combining the drugs evokes the same response compared to taking them separately

Question 21

Pharmacodynamic Drug Interaction: Synergistic Effect

Answer 21

combining the drugs evokes a stronger response compared to taking them separately

Question 22

Pharmacodynamic Drug Interaction: Antagonistic Effect

Answer 22

one drug inhibits the effect of another drug

Question 23

Pharmacodynamic Drug Interaction: Potentiation

Answer 23

a drug that has no effect alone but enhances the effect of a second drug

Question 24

Pharmacokinenetic Drug Interactions: Alterations in gastric emptying

Answer 24

The function or state (full vs empty stomach) of the GI tract can alter the absorption of the drug.

Question 25

Pharmacokinenetic Drug Interactions: Chelation

Answer 25

irreversible binding of a drug to another drug or mineral in GI tract–reducing the ability of it being absorbed.

Question 26

Pharmacokinetic Drug Interactions: Inducers and Inhibitors

Answer 26

Inducers: increase of liver CYP 450 enzymes–resulting in faster elimination of drug from body

Inhibitors: decrease of liver CYP 450 enzymes–resulting in a build up of drug concentration. DIET CAN AFFECT THIS TOO–like drinking grapefruit juice.

Question 27

Pharmacokinetic Drug Interactions: Alterations in renal excretion

Answer 27

decrease in renal excretion (like in kidney disease) can cause a build up of the drug

Question 28

Allergic Hypersensitivity Drug Reaction

Answer 28

immune system-related reaction to a drug

Ex. allergy to penicillin or sulfa antibiotic drugs

Question 29

Idiosyncratic Drug Reaction

Answer 29

unexpected effect caused by a genetic susceptibility. cant be explained by known mechanisms of the drug. not due to an immune response either

ex. type of glaucoma caused from sulfa based drugs (ex. topiramate, sulfa)

Question 30

Tachyphylaxis and Tolerance

Answer 30

tachyphylaxis: the rapid tolerance of a drug
tolerance: the gradual tolerance of a drug

Question 31

Define the 3 types of names a single drug can have.

Answer 31

Chemical name
Generic name (non-proprietary, US Adopted Name by the USAN council) = drug's official name, based on the mechanism of action. 
Brand name (proprietary name, trade name) 

Note: The patent protects the new drug for 20 years from the time the drug molecule is invented, and equates to about 10 years after the drug is finally out in the market. Once the patent expires, if other companies want to manufacture the drug, they can and they may come up with a different brand name to trademark and market to the public.

Question 32

Half-Life (t 1/2)

Answer 32

the time required to lower the concentration of the drug by half.

It generally takes 5 half-lives to remove a drug from the body.

3 half lives is 1/2 1/2 1/2 = 1/8