Term
| Liver disease affects drug metabolism |
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Definition
- Liver is primary site for drug metabolism
- Enzymes in liver change drug to metabolites
- Cytochrome P-450 enzymes break the medication down to metabolites
- Result = lower concentration of active medication in bloodstream |
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Term
| Liver conditions that affect metabolism |
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Definition
- Alcoholic hepatitis
- Active or inactive alcoholic cirrhosis
- Hemochromatosis
- Chronic active hepatitis
- Biliary cirrhosis
- Acute viral or drug induced hepatitis |
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Term
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Definition
- can impair hepatic drug metabolizing enzymes
- half life of drug is increased which means there is a longer effect with a normal dose. May cause coma. |
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Term
| Cardiac disease and drug metabolism |
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Definition
- Cardiac disease may limit blood flow to liver and impair disposition of drugs whose metabolism is flow-limited
- These drugs are so readily metabolized by the liver that hepatic clearance is essentially equal to liver blood flow |
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Term
| Pulmonary dx and drug metabolism |
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Definition
a)Lung cancer - Results in increased half-life of antipyrine
b) Chronic respiratory insufficiency -
Results in impaired hydrolysis of procainamide and procaine |
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Term
| Renal disease and drug metabolism |
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Definition
drug effects can be greatly increased and dose needs to be adjusted with the following renal conditions:
- Acute Renal Failure
- Acute Renal Insufficiency
- Renal Artery Stenosis
- Diabetic Nephropathy |
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Term
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Definition
a) Hypothyroidism- Increase half-life of antipyrine, digoxin, methimazole and some beta-blockers
b) Hyperthyroidism - Has opposite effect, it decreases drug effect |
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Term
| US Food and Drug Administration (FDA) |
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Definition
- Scientific, regulatory, and public
- health agency
- Began in 1862 with a single chemist
- Oversees drug evaluation process
- Grants approval for marketing of new drug products |
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Term
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Definition
- FDA’s authority to regulate drugs is derived from legislation
- Must prove to be “safe and effective” through adequate testing |
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Term
| pure food and drug act of 1906 |
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Definition
| Prohibited mislabeling and adulteration of drugs |
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Term
| opium exclusion act of 1909 |
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Definition
| Prohibited importation of opium |
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Term
| 1912 amendment to the food and drug act |
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Definition
| Prohibited false or fraudulent advertising |
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Term
| Harrison Narcotic Act of 1914 |
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Definition
| Established regulations for use of opium, opiates, and cocaine (heroin added in 1924 and marijuana added in 1937) |
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Term
| Food, Drug, and Cosmetic Act of 1938 |
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Definition
- Required that new drugs be safe as well as pure (but did not require proof of efficacy). Enforcement by FDA.
- Sulfinamide poisoning caused deaths of over 100 individuals and then this law was put into affect |
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Term
| Durham-Humphrey Act of 1952 |
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Definition
- Allowed the FDA to determine which products could be sold without prescription
- Defined prescription and OTC categories |
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Term
| Kefauver-Harris amendments (1962) to the Food, Drug, and Cosmetic Act |
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Definition
- Required proof of efficacy as well as safety for new drugs and for drugs released since 1938
- established guidelines for reporting of information about ADRs(adverse drug rxn), clinical testing and advertising of new drugs
- know as “drug efficiency amendment”
- thalidomide: babies born w/o limbs |
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Term
| Comprehensive Drug Abuse prevention and control Act (1970) |
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Definition
- Outlined strict controls in the manufacture, distribution, and prescribing of habit-forming drugs
- established programs to prevent and treat drug addiction |
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Term
| Orphan Drug Amendements (1983) |
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Definition
Amended Food, Drug, and Cosmetic Act of 1938
- provided incentives for developing drugs that
a) treat a disease with less than 200,000 patients in USA
b) drug cost are not expected to be recouped by US sales |
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Term
| Drug Price Competition and Patent Restoration Act of 1984 |
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Definition
- Abbrev. new drug app for generic drugs
- Required bioequivalence data
- Patent life 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. |
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Term
| Nutrition Labeling and Education Act (1990) |
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Definition
- added ingredients & amounts to labels
- Reformulated the way food products convey basic nutritional information an
- added “herbs or similar nutritional substance” to “dietary supplement.” |
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Term
| Expedited Drug Approval Act (1992) |
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Definition
- Allowed accelerated FDA approval for drugs of high medical need
- Required detailed postmarketing patient surveillance. |
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Term
| Prescription Drug User Fee Act (PDUFA 1992)- reauthorized 1997 and 2002 |
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Definition
| - Attempts to make more FDA resources available to the drug approval process and increase efficiency through use of fees collected from manufacturers for certain new drug applications |
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Term
| Dietary Supplement Health and Education Act (DSHEA 1994) |
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Definition
- Amended the Federal Food, Drug, and Cosmetic Act of 1938 to establish standards with respect to dietary supplements.
- Required the establishment of specific ingredients and nutrition info labeling that defines dietary supplements and classifies them as part of the food supply |
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Term
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Definition
- Enhanced controls on dangerous biologic agents and toxins
- Seeks to protect safety of food, water, and drug supply |
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Term
| 2006 Prescription drug info format |
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Definition
| - Implementing improvements in the prescription drug labels and inserts so they are less confusing and more concise with respect to info for patient and health care practitioner |
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Term
| Dietary Supplement and Nonprescription Consumer Protection Act of 2006 |
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Definition
| - Required FDA to establish systems to collect data on serious ADRs related to dietary supplements and nonprescription drugs |
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Term
| Amendment Act of 2007 to the Food, Drug, and Cosmetic Act |
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Definition
| These programs will ensure that FDA staff have the additional resources needed to conduct the complex and comprehensive reviews necessary to new drugs and devices |
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Term
| Preclinical Toxicity Testing |
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Definition
| Procedures are in place to estimate the risk associated with exposure to the drug candidate and to consider this in the context of therapeutic needs and duration of likely drug use |
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Term
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Definition
| Acute dose that is lethal in approximately 50% of the animals and the maximum tolerated dose |
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Term
| Subacute testing for toxicity |
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Definition
The longer the duration of expected clinical use, the longer the subacute test
- 4 weeks to 3 months |
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Term
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Definition
- 6 months or longer
- Required when drug is intended to be used in humans for prolonged periods |
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Term
| Effects on Reproductive (toxicology) |
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Definition
- Mating behavior
- Reproduction
- Birth Defects
- Postnatal Development |
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Term
| Carciogenic Potential (toxicology) |
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Definition
| Required when drug is intended to be used in humans for prolonged periods |
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Term
| Mutagenic Potential (toxicology) |
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Definition
- Effects on genetic stability
- Mutations in bacteria or mammalian cells in culture
- Dominant lethal test in mice |
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Term
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Definition
- Determine sequence and mechanisms of toxic action
- Discover the genes, proteins and pathways involved
Develop new methods for assessing toxicity |
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Term
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Definition
| The maximum dose at which a specific toxic effect is not seen |
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Term
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Definition
| The smallest dose that is observed to kill any experimental animal |
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Term
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Definition
| The dose that kills approximately 50% of the experimental animals |
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Term
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Definition
a)Placebo response - Patients tend to respond pos. to any therapeutic intervention
b)Open study - Trials are nonblinded
c)single-blind study - Uses a placebo or dummy medication
c)Double-blind study - Identity of medication is controlled by a third party (two identical bottles, different drugs) and not revealed until all clinical data is collected |
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Term
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Definition
1. In vitro studies (biological compound + chemical synthesis = lead compound)
2. animal studies done with lead compound to testing efficacy selectivity mechanism
3. clinical studies done
I - is it safe?
II - does it work in patients?
III - does it work (double-blind)?
4. marketing done with surveillance |
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Term
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Definition
Investigational new drug(IND) - b/w animal testing and clinical testing
New drug application(NDA)- once clinical trials are done, drug is safe for market |
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Term
| Drug development (patent) |
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Definition
| - patent expires 20 years after initial application, generics become available |
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Term
| Investigational New Drug(IND) |
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Definition
- files with FDA in order to be tested on humans
- 3 types of drug categories(Investigator, emergency use, and treatment)
- must wait 30 days before starting trials |
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Term
| Clinical Testing (phase I) |
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Definition
- Effects of a drug as a function of dosage in a small number (25-50) healthy volunteers (Exception: cancer/AIDS trials often conducted in volunteers with the disease)
- Non-blinded, open trials
- Find maximal tolerated dose and to avoid severe toxicity
- Pharmacokinetic measurements |
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Term
| Clinical Trials(phase II) |
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Definition
- To determine efficacy in modest number of patients (100-200) who have the target disease
- Single-blind design
- Detect a broader range of toxicities |
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Term
| Clinical Trials(phase III) |
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Definition
- To further establish safety and efficacy in large number of patients (100s-1000s) with target disease
- Double-blind, crossover technique
- Designed to minimize errors caused by placebo effects, variable course of disease, etc. |
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Term
| clinical trials(phase IV) |
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Definition
- Monitoring safety of a new drug under actual conditions of use in large # of patients
- Dependent on careful and complete reporting of events by physicians and patients
- Many important drug-induced events have an incidence of 1/10,000, so may not be detected until phase 4 trials |
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Term
| New Drug Application (NDA) |
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Definition
- If phase III results meet expectations an NDA, drug is submitted to FDA to request permission to market new agent in US
- Contains full reports of all preclinical and clinical data pertaining to the drug (chemistry, pharmacology, medical, biopharmaceutics, and statistics)
- In addition to safety and efficacy data, proposed labeling and manufacturing also included |
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Term
| Adverse Drug reactions(ADRs) |
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Definition
- Harmful or unintended response
- Preventable ADRs occur in hospitals
- All ADRs must be reported to FDA before approval
- Surveillance, evaluation and reporting continue to be required post FDA approval
- Event that are both serious and unexpected are required to be submitted within 15 days to the FDA |
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Term
| Abbreviated New Drug Application(ANDA) |
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Definition
- not required to inc. preclinical and clinical data to prove safety/effectiveness
- Used for review and approval of generic drug products
- Generic products are safe and effective, low cost alternatives for Americans(active ingredient, dosage, and strength) |
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