Exam 1 Flashcards
What was the 1st attempt to protect consumers in the manufacture of food and drugs?
Food and drug act 1906
What did the food and drug act require?
All drugs meet minimal standards of strength, purity and quality
MUST label container if drug contains dangerous ingredients
What are the 2 references the food and drug act established?
USP- United States pharmacopeia
NF- national formulary
What are the 3 published drug references?
USP/NF
PDR
AHFS- American hospital formulary service
What are the 4 internet drug and supplement references?
Medscape
Natural medicine databases
Medline plus
WebMD
What are the 4 definitions of a drug according to the food, drug and cosmetic act?
1 a substance recognized in an official pharmacopeia of formulary
2 a substance intended for use in the diagnosis, cure, mitigation, treatment or prevention of a disease
3 a substance other than food intended to affect the structure or function of the body
4 a substance intended for use as a component of a medicine
Which amendment established that drugs need a prescription from a licensed practitioner?
FD & C Durham Humphrey- 1951
What established that new food additives be approved and determined for safety before being marketed?
FD&C food additives amendment- 1958
What are the 2 food additives amendment exceptions?
GRAS- generally recognized as safe
Substances which FDA or USDA approved as safe prior to amendment
What was used as a sleep aid and for morning sickness that caused birth defects in 1960?
Thalidomide
What is the official name for the controlled substances act?
Comprehensive drug abuse prevent and control act- 1970
What was created to regulate the dispensing of drugs with potential for abuse and created the 5 schedules to classify drugs?
Comprehensive drug abuse prevent and control act AKA
Controlled substances act
What schedule has high potential for abuse and no medical use?
Schedule 1- heroine, LSD, marijuana, ecstasy, methaqualone and peyote
Which schedule has high abuse potential but has a medical use?
Schedule 2- Vicodin, cocaine, dilaudid, Demerol, OxyContin, Dexedrine, adderall, Ritalin
Which schedule has moderate abuse potential and accepted medical use?
Schedule 3- Tylenol with codeine, ketamine, anabolic steroids, testosterone
Which schedule has low abuse potential and accepted medical use?
Schedule 4- xanax, soma, darvocet, Valium, Ativan, ambien, tramadol
Which schedule has limited abuse potential and accepted medical use?
Schedule 5- robitussin AC, lomotil, motofen, lyrica
What established that the FDA is responsible for taking action against any unsafe dietary supplement after it reaches market?
Dietary supplements health and education act- 1994
Which act reinvestigated pesticide tolerance levels and developed stricter standards especially for children?
Food quality protection act- 1996
Who regulates agricultural and industrial chemicals and water?
EPA
Who recalls unsafe consumer products?
CPSC- consumer products safety commission
Who regulates workplace chemical exposure?
OSHA- occupational safety and health admin.
What are the 2 requirements for FDA to approve a drug for use in humans?
Efficacy
Safety
What is the pharmaceutical development and approval process?
1 discovery and development- 1-2 years
2 pre-clinical research and development- institutional review boards, testing etc. 3-6 years
3 clinical trials- 3 phases; 6-7 years
4 FDA review NDA (new drug application) 1-2 years
5 manufacturing
What is the therapeutic index
TI= LD50/ED50
Used to establish dosage levels in animal trials
What is the highest dose without any adverse effect?
NOAEL- no observed adverse effect level
What is the lowest dose found by experiment or observation at which there was a statistically significant observed adverse effect?
LOAEL- lowest observed adverse effect level
What is unique about supplements?
There is no FDA approval required to market it is only the FDA’s job to prove it is unsafe
Adverse side effects are typically
Dose dependent
What are the 6 pregnancy FDA categories?
A- no study has been able to measure risk
B- no studies done in humans, but animals show no risk
C- no studies on humans or animals or if there were on animals, there is some teratogenic potential
D- drug has revealed adverse effect to effect, benefit to risk ratio must be assessed
X- studies have shown teratogenic effect in animals and women; contraindicated in pregnancy
NR- not yet rated by FDA
What are the common drugs that have shown teratogenic effect on fetus?
Androgens Carbamazepine (anti-seizure) Diethylstillbesterol (estrogen) Estrogen Lithium Phenytoin (Dilantin)- anti-seizure Retinoic acid Thalidomide (immune modulator; leprosy and MM) Warfarin Depakote (anti-seizure)
What are the 4 unexpected adverse drug effects?
Idiosyncrasy
Tolerance
Paradoxical
Dependence
What is the term to describe an unusual, unique or unexpected response to a drug that can cause genetic variations in enzymes or alter metabolism?
Idiosyncrasy
What is the term to describe an adverse effect with the opposite effect of what was intended?
Paradoxical
What is a decreased response that develops from a drug after repeated doses given?
Tolerance
What are the 5 types of toxic responses?
1 direct toxic action- tissue lesions 2 pharmacological, physiological and biochemical effects 3 teratogenesis 4 immunotoxicity 5 mutagenesis 6 carcinogenesis
What direct toxicity- tissue lesion what happens and what is targeted?
Cell death- reversible or irreversible
Target organ toxicity- any organ but some are more susceptible
most susceptible: Liver, Lung, Kidneys
What % of adverse drug effects the liver?
9%
What percent of CO does the liver receive?
25%
What are the types of liver toxicity?
Steatosis Cytotoxic damage Cholestatic damage Cirrhosis Vascular lesions Tumors Proliferation of peroxisomes
What does liver damage look like on blood work?
Increased: AST, ALT
Decreased: bilirubin
What % CO for kidneys?
25%
What does blood work show with kidney damage?
Increased: BUN, creatinine
Urine volume, pH and specific damage abnormal with damage
Y-glutamyltransferase/ N-acetylglucosaminidase present in urine with damage
What are the types of lung damage?
Irritation Allergic response Cell damage Fibrosis Pulmonary cancer
No biochemical tests with lungs but what do we look at?
Decreased FEV- forced expiratory volume/ forced VC
A pharmokinetic based toxic effect is an increase in?
Concentration of the compound or active metabolite
A pharmodynamic based toxic effect is?
An altered responsiveness to target site
When is a fetus most susceptible to gross anatomical abnormalities?
Organogenesis 18-55 days
When drug interacts directly with DNA and causes damage?
Mutagenesis
What is clastogenesis?
Chromosomal damage
What is an acquisition or loss of complete chromosomes?
Aneugenesis
What is unrestrained cell replication and what are the steps?
Carcinogenesis
Initiation- DNA mutation
Promotion- altered gene expression and regulation
Progression- another mutation leading to proliferation
Chemical carcinogens may cause?
Unusual tumors or increased incidence of typical tumors
What are the 3 phases of drug activity?
Pharmaceutic
Pharmokinetic
Pharmodynamic
What phase involves disintegration and dissolution of the dosage form?
Pharmaceutic phase
What is the pharmaceutic phase affected by?
Form of drug and route of administration
Which phase is described as what happens to the drug as it moves through the body?
Pharmokinetic- ADME
Absorption
Distribution
Metabolism
Excretion
What are the 4 ways drugs can be absorbed?
Passive diffusion
Active transport
Pinocytosis
Filtration
Ionized molecules do not readily cross membranes so what needs to be done?
Needs to be un-ionized for absorption to occur
Acid drugs in acidic fluid
Basic drugs in alkaline fluid
What can we do in cases of toxicity to increase excretion?
Change pH of urine
Most drugs are water soluble what is an example of lipid soluble?
Anesthesia, marijuana
GI tract and lung absorption occurs mostly as?
Passive diffusion
Both have large surface area
What limits absorption of foreign compounds through skin?
Keratin rich epidermis
Passive diffusion may occur with skin absorption but only certain compounds, what are they?
Lipophilic- often use carriers
The % of a dose that reaches the bloodstream is called?
Bioavailability
How much of oral meds typically reach blood?
20-40%
How much drug reaches an organ or area depends on?
Plasma protein binding
Blood flow
Specific tissue barriers
Selective distribution
With plasma binding only ______ drug molecules can exert a pharmacological effect
Unbound, free;
some drugs are in competition and if one displaces another concentration of free drug increases and can lead to overdose
What are the 2 tissue barriers?
BBB
Placental barriers
What is the affinity or attraction of a drug to specific organ or cells?
Selective distribution
Ex. Amphetamines have selective distribution to CSF
What is the time required for blood/plasma concentration of drug to fall to 50% of original level?
Half life t1/2
What are the metabolism AKAs?
Biotransformation and detoxification
Whenever a drug or other foreign substance enters the body, it tries to eliminate it. This chemical alteration is known as?
Metabolism, biotransformation, detoxification
Why do we metabolize?
Make more polar/ water soluble for excretion
Decrease half-life
Prevent accumulation
Change bio activity
What is cytochrome P450 referred to as?
Drug microsomal metabolizing system
When a drug is taken repeatedly, the DMMS increases and leads to faster rate of drug metabolism and drug action is decreased. What is this phenomenon called?
Enzyme induction
What happens when the DMMS enzymes are inhibited thus increasing the duration and intensity of a drug?
Enzyme inhibition
What is first pass metabolism?
After oral administration all drugs are absorbed into the portal circulation; some metabolized significantly as they pass the 1st time
First pass metabolism can significantly reduce what?
Bioavailability and amount of drug that reaches general circulation
What are the major excretion sites?
Urine, bile, lungs, GI, breast milk
What are the minor excretion sites?
Sweat, tears, saliva, semen
What are the 3 methods of urinary excretion?
Filtration from blood through pores in glomerulus
Diffusion from blood to tubules
Active transport into tubular fluid
What are the 2 methods of biliary excretion?
Active transport into bile- can be saturated; liver toxicity
Gut bacteria metabolize compounds- increase liver toxicity
What is the cycle of enterohepatic circulation?
Blood -> liver -> bile -> intestines ->
Where does passive diffusion of volatile metabolites from blood occur?
Lungs
Where does passive diffusion of weak bases into intestinal lumen occur?
GI tract
Where does passive diffusion of fat-soluble compounds occur?
Breastmilk
What is the action of the drugs on living tissue?
Pharmacodynamic phase- affected by form and route of administration
Drug concentration -> Pharmacological effect -> clinical response -> toxicity or effectiveness
Pharmacodynamics
Dose administered -> absorption or distribution -> concentration in systemic circulation or elimination-> concentration at site of action
Pharmacokinetics
Number of patients who leave doc with at least 1 prescription
2/3
Percent of population that have 4 or more prescriptions
40%
When does the rate of adverse drug reactions increase dramatically?
After 4 or more prescribed
What drug reacts with NSAIDS, sulfa drugs, macrolides, quinolones, phenytoin, statins and thyroid meds?
Warfarin
What drug reacts with potassium and spironolactone?
ACE inhibitors
What drug recommends you check with doctor if taking tranquilizers, sedatives, HBP meds or antidepressants?
Antihistamines
What percent of adults use dietary supplements?
50% or more
What supplement is an inducer of CP450 and can reduce concentration of drugs in blood?
St. John’s wort
What can interfere with bleeding effects of Coumadin, heparin, aspirin and NSAIDs?
Ginseng
What can decrease effectiveness of anticonvulsant therapy (tegretol, depakote)
Ginkgo biloba
What may reduce effects of BP drugs and diuretics and increase risk of lanoxin toxicity?
Licorice
MAO inhibitors shouldn’t be consumed with excessive amounts of?
Chocolate
Calcium fortified orange juice interacts with
Fluoroquinolones (cipro)
Cranberry juice interacts with
Warfarin
Grapes with
Cyclosporine (immunosuppressant)
Pomegranate with
Carbamazepine (anticonvulsant)
Grapefruit, apple or orange juice with
Fexofenadine (Allegra)
What food increases effect of diabetes meds?
Carrot
Broccoli, cauliflower, watercress, spinach, tomato and avocado effect?
Warfarin
Patients taking MAOIs need to avoid
High tyramine foods
High tyramine foods also need to be avoided with
St. John’s wort
What foods induce CYP?
Alcohol Caffeine Garlic Grape seed Licorice St. John's wort Tobacco
What foods inhibit CYP?
Black cohosh Echinacea Feverfew Ginkgo Ginseng Goldenseal Grapefruit Milk thistle Peppermint
What depletes C, B12, D, Calcium, iron, zinc and folic acid?
Antacids
What depletes Vit K?
Antibiotics
What depletes B12, folic acid, thiamin, magnesium and COQ10?
Antidiabetics
What depletes zinc, COQ10, melatonin, copper, B6?
Antihypertensives
What depletes folate, iron, C, K and melatonin?
NSAIDs
What depletes sodium and melatonin?
SSRIs
What depletes COQ10?
Statins
What is an example of an absorbent?
Activated charcoal
What is the term for pumping the stomach?
Gastric lavage
What are the contraindications for inducing vomiting?
Ingestion of corrosive substances, volatile petroleum products, convulsants
If patient is semi-conscious, inebriated, in shock, convulsing or has no gag reflex
Patients less than 1 year
Patients with cardiac or vascular disease
History of poisoning/toxicity
1906- pure food and drug act, paved way for modern FDA
1910- radium, advertised as health cure
1918- Charles Norris appointed chief medical examiner
1920- prohibition
1924- lead added to gas, caused dementia, DC in 1996
1953- first poison control center in Chicago
What is the lethal amount of methanol?
2-8 oz
What does methanol poisoning lead to?
Liver ->formaldehyde ->formic acid -> leads to metabolic acidosis and tissue injury
Sx of methanol poisoning
Difficult breathing Blurred vision, blindness Agitation Coma Severe abdominal pain
What was sold as rejuvenating tonics and dial painters ingested large amounts leading to death?
Radium
Sx of radium poisoning
Anemia
Jaw necrosis
Osteogenic carcinoma
Malignancies
Deposits in bone similar to calcium
Handling of this substance lead to severe mental deterioration and some deaths, developed by GM as anti-Knock formula
Leaded gas
Stings by bees, wasps, scorpion or fire ant may require
Epinephrine or corticosteroids
Cleanse, remove stinger, apply ice
With a snake bite what must you not do?
Apply tourniquet or ice
