What are inactive components of drugs?
Components that are added during manufacturing process and do not increase or affect therapeutic action of the active ingredient
What do inactive ingredients do?
- Solvents dissolve drug substance
- Flavors and sweeteners make product more palatable
- Colorants enhance appeal
- Preservatives prevent microbial growth
- Stabilizers, such as antioxidants and chelating agents, prevent decomposition
- Diluents or fille
What are differences between generic and brand name drugs?
Generic drugs are drugs created to be the same as the brand name drug, must be bioequivalent (within 20% of name brand)
generics are much less expensive d/t competition between companies and no need for ads
disadvantages of generic drugs
may have several manufacturers
may look different
may see differences in amount or rate of dissolution
bioequivalence
same rate and extent of absorption
Acts on same target, ie receptor, as the brand-name
Same amount of active drug is delivered to target site
how long does drug development typically take?
10-15 yrs
5 stages of drug development
1. Discovery and development
2. Preclinical research
3. Clinical research
4. FDA review
5. FDA post-marketing safety monitoring
discovery & development
random screening, molecular designing, investigating drug metabolites, chance discovery --> mechanism of action, pharmacokinetics, potential side effects, toxicity risk
preclinical research
toxicity risk, in vitro studies and animal testing, figure out how to make large quantities, file applications with FDA to test on humans
phases pic
4 phases of clinical trials: who and how long?
phase 1: healthy volunteers, several months
phase 2: larger # with condition, 2 yrs
phase 3: more people with condition, 1-4 yrs
phase 4: post-market safety monitoring with FDA after being approved
clinical trial phase 1: questions
how does drug interact with human body? dose adjustments with humans, acute side effects, how best to admin drug
clinical trial phase 3: questions
most safety data!
(uncommon side effects)
clinical trial phase 2: questions
establish efficacy and side effects, gather safety data
benefits of controlled release, sustained release, and extended release drugs
o Reduced dose frequency compared with conventional dosage forms
o Maintenance of therapeutic effect overnight
o Decreased incidence and intensity of undesired effects through dampening of peaks in drug levels
o Reduction in nontherapeutic blood levels of
drawbacks to CR/SR/ER
o More expensive
o Dose dumping possible
o Patient education: don't break/chew tablets
FDA mission statement
The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of our nation's food suppl
What is regulated by FDA?
OTC drugs, prescribed drugs
not herbal products or vitamins
Pure Food and Drug Act of 1906
prohibited mislabeling and adulteration of drugs
Opium Exclusion Act of 1909
prohibited importation of opium
Amendment (1912) to the Pure Food and Drug Act
prohibited false or fraudulent advertising claims
Harrison Narcotic Act of 1914
established regulations for use of opium, opiates, and cocaine (marijuana added in 1937)
Food, Drug, and Cosmetic Act of 1938
requires that new drugs must be as pure (but did not require proof of efficacy). Enforcement by FDA.
Durham-Humphrey Act of 1952
Vested in the
FDA
the power to determine which products could be sold without
prescription
Kefauver-Harris Amendments (1962) to the Food, Drug, and Cosmetic Act
Required proof of efficacy as well as safety for new drugs released since 1938; established guidelines for reporting of information about adverse reactions, clinical testing, and advertising of new drugs
Abuse Prevention and Control Act (1970)
schedules and programs to prevent and treat drug addiction
Orphan Drug Amendment of 1983
Provided incentives for development of drugs that treat diseases with fewer than 200,000 patients in the USA
Drug Price Competition and Patent Restoration Act of 1984
Abbreviated new drug applications for generic drugs. Required bioequivalence data. Patent lief extended by amount of time drug delayed by FDA review process. Cannot exceed 5 extra years or extend to more than 14 years post-NDA approval
Prescription Drug User Fee Act (1992, reauthorized 2007, 2012)
manufacturers must pay user fees for certain new drug applications. "Breakthrough" products may receive special category approval after expanded phase 1 trials (2012).
Dietary Supplement Health and Education Act (1994)
Established standards with respect to dietary supplements but prohibited the FDA from applying drug efficacy and safety standards to supplements and botanicals. Required the establishment of specific ingredient and nutrition information labeling that defi
Bioterrorism Act
enhanced controls of dangerous biologic agents and toxins. Seeks to protect safety of food, water, and drug supply
Food and Drug Administration Amendments Act of 2007
Granted FDA greater authority over drug marketing, labeling, and direct-to-consumer advertising; required post-approval studies, established active surveillance systems made clinical trial operations ad results more visible to the public
Biologics Price Competition and Innovation Act of 2009
Authorized the FDA to establish a program of abbreviated pathways for approval of "biosimilar" biologics (generic versions of monoclonal antibodies, etc)
FDA Safety and Innovation Act of 2012
Renewed FDA authorization for accelerated approval of urgently needed drugs; established new accelerated process, "breakthrough therapy," in addition to "priority review," "accelerated approval," and "fast-track" procedures
metered-dose inhalers basics
contains pressurized inactive gas that propels a dose of med in each puff
advantages of MDI inhalers
o Wide range of medication can be delivered
o Relatively low costs
o Portable, multi-dose, quick and easy to use
o Suitable for emergencies
o lower doses d/t extra fine particles
common user errors for MDI
inhaling too fast, failure to tilt head to correct position, failure to empty lungs prior to inhalation, and failure to hold breath following inhalation
limitations to MDI
not suitable for young children (without a spacer), doesn't always have dose counter, needs to be shaken and primed, propellant required
dry-powdered inhalers: basics
breath-activated; don't contain pressurized inactive gas to propel med. Breathe in fairly hard to get powder into your lungs
advantages of DPI
small and portable, breath actuated, less coordination required, short tx time
disadvantages of DPI
moderated to high inspiratory flow required, not suitable for young children, may not be suitable for emergencies, partly sensitive to humidity, need proper dose prep and loading
common errors for DPI
not keeping device in correct position while loading dose, failure to tilt head in correct position, insufficient inspiratory effort, not emptying lungs before inhalation
doses for DPI
either general, single-dose capsule-based, multi-unit, or multiple dose
spacers: basics
holds med like a reservoir when inhaler is pressed. Breathe in, open; breathe out, valve closes.
use of spaers
commonly used in children to reduce need for actuation and breathing coordination
used with pressurized MDIs
what would you instruct a patient about transdermal patches?
o Longer on, longer absorption
o Hydration helps, and TDDS helps hydration (doesn't let sweat out)
o works by passive diffusion, so absorption depends on surface area applied and lipid solubility of drug. absorption increases with abraded skin
benefits of transdermal patches
o Avoids first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acid media, drug fluctuations, GI irritation, and disease transmission risks
o Can achieve local and systemic effects
o May help overcome poor patient c
def: pharmaceutics
science of drug delivery and disposition
def: bioavailability
fraction of med that makes it to general circulation
in vitro
in lab
in vivo
in animals
generics must have the same...
active ingredient, intended use, dosage form, strength, route of administration, pharmacodynamics, and stability
form for generic
ANDA: abbreviated new drug application
be aware of generics for...
warfarin, thyroid, digoxin, AEDs