Lecture 2 Drug Regulation, Development, etc. Flashcards
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)
Food, Drug, and Cosmetic Act (1938) = FDCA
Focuses on drug abuse and prevention of drug abuse
Classified drugs with abuse potential into 5 schedules
Enforced by the DEA
Comprehensive Drug Abuse Prevention and Control Act (1979) = CDAPCA
(aka Controlled Substances Act)
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.
Dietary Supplements Health & Education Act (1994)
High abuse potential. May lead to severe dependence. NOT ACCEPTED FOR MEDICAL USE!
Examples: Heroin, Marijuana, and Peyote
Controlled Substances Schedule 1 (NOT ACCEPTED FOR MEDICAL USE!)
High abuse potential. May lead to severe dependence.
Examples: Fetanyl, Cocaine, Codeine, Morphine, Amphetamine, Methadone, Hydrocodone, Oxycodone
Controlled Substances Schedule 2
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)
Controlled Substances Schedule 3
Moderate abuse potential. May lead to limited dependence
Examples: Alprazolam (XANAX), Zolpidem (AMBIEN), Phenobarbital (LUMINAL), Modafinil (PROVIGIL)
Controlled Substances 4
Small abuse potential. May lead to limited dependence
Examples: Cough medications with codeine, certain antidiarrheals
Controlled Substances 5
What must an optometrist obtain in order to prescribe a drug that is a controlled substance?
DEA Certificate
Describe the drug development process in the US.
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.
When can a company submit a New Drug Application (NDA) to the FDA?
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).
Describe the clinical trial stages: preclinical and phase 1-4 clinical trials.
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
Explain why a patient’s age, disease status, and pregnancy/lactation/fertility status must be considered when prescribing drugs
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.
What is a teratogen, and when are the eyes at a higher risk for teratogen damage?
Any drug that can cause adverse effects in a fetus or infant.
1st trimester when the eyes are developing.
Define the 5 FDA pregnancy/lactation categories that were in effect for all drugs from 1979-2015
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!
Explain why in 2015 the FDA changed the labeling requirements for pregnancy, lactation, and fertility.
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.
Discuss what the FDA now requires drug labels to include regarding pregnancy, lactation, and fertility risk.
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.
Define a Pregnancy Exposure Registry
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.
Define drug interaction
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
Pharmacodynamic Drug Interaction: Additive Effect
combining the drugs evokes the same response compared to taking them separately
Pharmacodynamic Drug Interaction: Synergistic Effect
combining the drugs evokes a stronger response compared to taking them separately
Pharmacodynamic Drug Interaction: Antagonistic Effect
one drug inhibits the effect of another drug
Pharmacodynamic Drug Interaction: Potentiation
a drug that has no effect alone but enhances the effect of a second drug
Pharmacokinenetic Drug Interactions: Alterations in gastric emptying
The function or state (full vs empty stomach) of the GI tract can alter the absorption of the drug.
Pharmacokinenetic Drug Interactions: Chelation
irreversible binding of a drug to another drug or mineral in GI tract–reducing the ability of it being absorbed.
Pharmacokinetic Drug Interactions: Inducers and Inhibitors
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.
Pharmacokinetic Drug Interactions: Alterations in renal excretion
decrease in renal excretion (like in kidney disease) can cause a build up of the drug
Allergic Hypersensitivity Drug Reaction
immune system-related reaction to a drug
Ex. allergy to penicillin or sulfa antibiotic drugs
Idiosyncratic Drug Reaction
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)
Tachyphylaxis and Tolerance
tachyphylaxis: the rapid tolerance of a drug
tolerance: the gradual tolerance of a drug
Define the 3 types of names a single drug can have.
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.
Half-Life (t 1/2)
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
