Exam 1 Flashcards
What is the definition of a drug?
ANY substance, that when administered to living organisms, produces a change in function.
What is toxicology?
The study of the adverse effects of chemical, physical or biological agents on living organisms and the ecosystem.
What is pharmacology?
The study of the uses, effects, and modes of action of drugs.
What was the 1906 pure food and drug act?
First attempt to protect consumers in manufacture of drugs and foods.
Drugs must label dangerous ingredients.
Drugs must meet minimal standards of strength, purity, and quality.
Established two references of officially approved drugs (US Pharmacopeia ‘USP’, National formulary ‘NF’).
What was the 1938 federal food, drug, and cosmetic act?
Passed after a drug company distributed a sulfa (very similar to antifreeze) to pediatric patients, icing those kids. This authorized the FDA to demand evidence of safety for new drugs, issue standards for food, and conduct factory inspections.
What was the 1951 Durham-Humphrey Amendment?
Defined drugs that could only be purchased if the patient had a prescription from a licensed practitioner.
What was the 1958 Food Additives Amendment?
Approval of new food additives was required and safety determined by manufacturer before they could be marketed.
What are some of the Food Additive Amendment exemptions?
GRAS substances (deemed safe by experts).
Substances that were approved for use PRIOR to the passage of the amendment.
What was the FD&C Kefauver-Harris Amendment?
Required drug manufacturers to use standard labeling, listing adverse reactions and contraindications.
Required drug companies to prove their drugs safety and effectiveness.
What was the 1970 Drug Abuse Prevention and Control Act?
AKA “controlled substances act”
Regulation of drugs with “abuse potential” (controlled substances)
Substances categorized into 5 “schedules”
What was the 1994 Dietary Supplements Health and Education Act?
FDA responsible for taking action against any unsafe dietary supplement.
Generally, manufacturers are NOT required to register their products with FDA or get FDA to approve them.
What was the 1996 Food Quality Protection Act?
Reinvestigated pesticide tolerance levels
Development of stricter pesticide safety standards.
Who is the FDA and what do they oversee?
Food and Drug Administration.
Food labeling/nutrition, food ingredients/ packaging, pharmaceuticals, supplements, medical devices, vaccines, animal foods, tobacco, cosmetics
Who is the DEA and what do they oversee?
Drug Enforcement Administration
Controlled substances only, enforces laws against drug activity, changes schedules of abused drugs
Who is the USDA and what do they oversee?
US Department of Agriculture
Food distribution, school lunch programs.
Who is the EPA and what do they oversee?
Environmental Protection Agency
Agriculture and industrial chemicals, water.
Who is OSHA and what do they oversee?
Occupational Safety and Health Administration
Workplace chemical exposure
What are the 6 sources of drugs?
Plants Minerals Animals Microorganisms Synthetic/chemical Recombinant DNA
What are the 3 aspects of drug nomenclature?
Chemical name (e.g. N-acetyl-p-aminophenol)
Generic (e.g. acetominophen)
Brand or Trade (e.g. Tylenol)
What is the therapeutic affect of a drug?
The intended physiological effect of the drug
What does “indication” refer to?
Medical conditions or diseases for which the drug is meant to be used.
What does “contraindication” refer to?
Conditions/circumstances for which the drug should not be used
What does “caution” refer to?
Conditions or types of patients that warrant closer observation for specific side effects
What is a side effect?
Unintended effects other than therapeutic effect (may or may not be negative).
What is are adverse effects and what body system is most affected by them?
A side effect that is negative. GI system.
What do plasma proteings (albumin and globulins) in the blood, transport?
Hormones and vitamins. Many drugs are also attracted to proteins, especially albumin
What molecules can exert a pharmacological effect
Only unbound (free) drug molecules can exert a pharmacological effect
T/F
Some drugs are in competition
True
What systems usually receive the largest exposure to drugs
Organ that receive the greatest blood flow: liver, kidneys, and brain.
What tissues do not have much of an accumulation of drugs?
Adipose tiessue. However, highly lipid soluble drugs can enter adispose tissue where they accumulate and stay for a long time.
What conditions of blood flow may prevent drug from reaching tissue
Anything that impairs blood flow.
What does the BBB stop from passing into brain? What does it allow?
Blocks water soluble substances. Lipid soluble drugs pass readily into the brain.
T/F All drugs cross the placenta?
False
What is selective distribution?
An affinity, or attraction, of a drug to a specific organ or cells (e.g. amphetamines selectively distribute to CSF, hCG to ovaries)
What is half life (t 1/2)?
Time required for blood/plasma concentration of the drug to fall to 50% of the original level.
Metabolism, or AKA
Detoxification or biotransformation
What is metabolism?
Whenever a drug or other foreign substance is taken into the body, the body attempts to eliminate it. Some drugs are excreted in the same chemical form in which they were administered.
T/F
Drugs must be chemically altered before they are excreted
True
What is the name for the process of chemically altering drugs for excretion (in vivo)?
Metabolism (detoxification or biotransformation).
What is needed for metabolism, where are they found?
Cytochrome P450. Referred to as the drug microsomal metabolizing system (DMMS). Mostly found in the liver (also kidneys, small intestine and most cells).
What kind f reactions does the cytochrome P450 enzyme use for metabolism?
Oxidation and reduction
How are water solube and lipid solube drugs excreted?
Water soluble (kidneys) Lipid soluble = repeatedly absorbed into blood to do/ be utilized for other stuff
T/F
Most drugs are activated?
False,
Most drugs are inactivated. A few are returned to circulation.
What is enzyme induction?
With drugs like barbiturates and other sedative-hypnotic drugs, when they are taken repeatedly they stimulate the DMMS, increasing the amount of cytochrome P450’S in the system. With an increase in the aount of enzymes, there is a faster rate of drug metabolism, the the duration of the drug action is decreased.
What does enzyme inhibition do?
Increases the duration and intensity of the drugs inhibited.
What are 2 common causes of adverse drug interactions?
Enzyme induction and enzyme inhibition
What is first pass metabolism?
After oral administration, all drugs are absorbed into the portal circulation. Some drugs are metabolized significantly as they pass through the liver this first time. Can significantly reduce bioavailability and the amount of active drug that reaches the general circulation.
What is the most significant route of excretion?
Urine
What are the steps to unrinary excretion?
Filtration form blood through pores in glomerulus
Diffusion from blood to tubules
Active transport into tubular fluid
What happens to drug excretion with age?
As age increases renal drug excretion decreases. At age 80, clearance is typically reduced to half of what it was at age 30.
What happens with excretion with acidic urine?
Acid drugs reabsorbed, basic drugs excreted.
What happens with excretion with alkaline urine
Basic drugs reabsorbed, acidic drugs excreted.
Where are bile acids made and stored?
Made in liver stored in gallbladder
What do gut bacteria do to compounds?
Metabolizes them.
What is enterohepatic circulation (cycling)
Drugs enter body, go to liver, bile, intestines, blood.
What does biliary excretion of a drug mean concerning enterohepatic cycling?
That enterohepatic cycling is incomplete
What are the three ancillary excretion mechanisms?
Lungs (passive diffusion of volatile metabolites form blood)
GI tract (passive diffusion of weak bases into intestinal lumen
Breast milk
What are some important aspects of patient variation?
Age Weight Gender & % body fat Genetics Emotional state Placebo effect Comorbidities Compliance (with treatment and stuff)
What is the pharmacodynamic phase?
“What the drug does to the body”. The action of the drugs on living tissue affected by the form of the drug and the route of administration.
Drugs work by attaching themselves to…
A cell receptor or chemical structure in or on a cell.
What are agonists and antagonists?
Drugs that bind to a specific receptor and produce an action (e.g. morphine). Antagonists do the same but inhibit (e.g beta blockers)
What is competitive antagonism?
when both agonist and antagonist drugs bind to the same receptor and are administered together
T/F
Most drugs have antidotes (antagonists) for reversing toxicity
False
What is the strength of a drug action determined by?
Dose and frequency
What 2 things define frequency?
How often the drug is given
Time-response relationship
What is drug response proportional to?
The dose
What is the ED50?
Effective dose 50. Dose necessary to produce half of the maximum response. Used to compare potency of drugs
What is the loading dose?
Initial high dose used to
quickly elevate blood
levels of the drug
What is the maintenance dose?
Dose required to keep
the drug blood levels steady in order to maintain the desired effect
What are the 3 ranges of the time-response curve?
Ineffective range, therapeutic range, toxic range
What is the pharmaceutic phase?
• Occurs after the drug is given and involves
disintegration and dissolution of the dosage
form
• Affected by the form of the drug and the
route of administration
What is a troche?
A lozenge. Dissolves in mouth (zinc, cough drops).
What is the route of administration for 80% of drugs?
80%
What route of administration is inhalation?
Parenteral
What is the acronym for the pharmacokinetic phase
ADME
Absorption
Distibution
Metabolism
Excretion
T/F
Drugs need to be dissolved into body
fluids prior to absorption
True
What needs to happen to drugs before they enter the blood?
• Must pass through membranes (lipids
and proteins) of skin, GI lining and blood
vessels before gaining access to blood
(unless IV or intra-arterial administration)
In what molecular form do drugs need to be in order to be absorbed
Non-ionic form
How do you increase the excretion of a drug?
Change the pH of the urine
How does food affect absorption?
Slows it down
What kind of drugs absorb the fastest?
Lipid-soluble, non-ionized liquids
What are the 3 major sites of absorption?
GI (MC)
Lungs
Skin
How are drugs MC absorbed in the 3 major sites of absorption?
Passive diffusion
What kind of compounds does the skin absorb via passive diffusion?
Lipophilic compounds only
T/F
Not all drug particles reach the circulatory system
True
What is the “bioavailability” of a drug?
The % of a dose that
reaches the bloodstream
T/F
Bioavailability is the same for drugs and supplements?
Defined slightly differently for drugs as
opposed to dietary supplements due to the
method of administration and FDA regulations
What factors determine how much drug
Reaches organs/area of the Body?
Plasma protein binding
Blood flow
Presence of specific tissue barriers
Selective distribution
For what 4 reasons do we metabolize?
Make more polar (and thus more water soluble) for urinary excretion Decrease half-life Prevent accumulation Change bioactivity
T/F
After metabolism A few drugs are initially
converted into pharmacologically
active metabolites
True
What is the breakdown for CYP3A4?
CPY3 = gene family A = subfamily 4 = gene coding
What are the two major criteria for drug safety?
Efficacy, safety (must provide evidence from multiple human and animal trials).
What kind of subject is tested to determine drug safety?
Animals
What is the LD50?
The dose that will kill 50% of the animals tested
What is the therapeutic index (TI) and what is it for?
LD50/ED50. Used to establish dosage levels in animal trials
What is NOAEL?
No Observed Adverse Effect Level
• Highest dose without an adverse effect
What is LOAEL
Lowest Observed Adverse Effect Level. • Lowest dose found by experiment or observation at
which there was a statistically significant observed
adverse effect
T/F
Adverse effects are not dose dependent?
False
Most are dose dependent
What are the 4 categories of non-dose dependent adverse effects?
1.) Idiosyncrasy
2.) Paradoxical: Opposite effect from what is
expected
3.) Tolerance
4.) Dependence
Types toxic reponses to a drug is determined by what factor?
Dose
How are toxic responses categorized?
According to the manifestation of toxic effect
What is direct toxic action?
Tissue lesions
What organs are most susceptible to toxic effects?
Liver
Kidneys
Lungs
What organ serves as the portal of entry to tissues?
Liver
T/F
In humans only a small percentage of of adverse affects from drugs affect the liver
True
What two compounds are going to be found to be more prominent upon blood work in the case of liver damage?
AST: aspartate transaminase
ALT: alanine transaminase
Bilirubin
What will be found upon blood work to be decreased in the case of liver damage?
Albumin
What are found to be increased in blood with kidney damage?
BUN: Blood Urea Nitrogen
Creatinine
What biochemical tests are available to determine lung damage?
None
What is decreased with lung damage?
Forced Expiratory Volume (FEV) (Forced Vital Capacity)
What are some consequences of clinical drugs?
Exaggerated or unwanted pharmacological responses
T/F
Drugs that have teratogenic effects often cause both embryotoxic and fetotoxic effects
False,
Selectively either embryotoxic or fetotoxic
When is the fetus most susceptible to gross anatomical abnormalities (form teratogenesis)?
During organogenesis (~18-55 days)
What are the two major things that drug toxicity can cause?
Immunosuppresion
Allergy
What is mutagenesis?
Genetic toxicity
Drug interacts directly with DNA
• DNA damage
• Base substitutions, additions or deletions
What is clastogenesis (associated with mutagenesis)
Chromosomal damage
What is aneugenesis (associated with mutagenesis)
Aquisition or loss of complete chromosomes
What is carcinogenesis and what are the 3 stages?
Unrestrained cell replication
• Initiation – DNA mutation
• Promotion – altered gene expression & regulation
• Progression – another mutation leading to
proliferation of initiated cells
What is the definition of a schedule I substance? What are some drugs that fall into this category?
Drugs with high abuse potential and no accepted medical use (heroine, hallucinogens, marijuana)
What is the definition of a schedule II substance? What are some examples?
Drugs with high abuse potential and accepted medical use (narcotics, cocaine, amphetamines, short acting barbiturates, nabilone).
What is the definition of a schedule III substance? What are some examples?
Drugs with a moderate abuse potential and accepted medical use (moderate and intermediate acting barbiturates, dronabinal, anabolic steroids, preparations containing codeine + another drug).
What is the definition of a schedule IV substance? What are some examples?
Drugs with low abuse potential and accepted medical use (phenobarbital, ambien, antianxiety drugs
What is the definition of a schedule V subtance? What are some examples?
Drugs with a limited abuse potential and accepted medical use (narcotic drugs used in limited quantities for antitussive, and antidiarrheal purposes).
What are the rules concerning prescription of schedule I substances?
They are not to be perscribed
What are the rules concerning prescription of schedule II substances?
No refills without a new, written prescription from the physician.
What are the rules concerning prescription of schedule III substances?
Prescription required. May be refilled 5 times in 6 months when authorized by the physician.
What are the rules concerning prescription of schedule IV substances?
Prescription required. May be refilled 5 times in 6 months when authorized by the physician.
Who is the CPSC?
Consumer products safety commission. Recalls unsafe consumer products
