LE 1 Flashcards
Pharmacology –
study of drugs; their action on living organisms
Oral drugs - Three phases:
- Pharmaceutics
- Pharmacokinetics
- Pharmacodynamics
Pharmaceutics
a) Dissolution of drugs occurs, drugs must be soluble to be absorbed
b) Absorption, Distribution, Metabolism, Excretion
c) Alteration in cellular form/environment
a) Dissolution of drugs occurs, drugs must be soluble to be absorbed
Pharmacokinetics
a) Dissolution of drugs occurs, drugs must be soluble to be absorbed
b) Absorption, Distribution, Metabolism, Excretion
c) Alteration in cellular form/environment
b) Absorption, Distribution, Metabolism, Excretion
Pharmacodynamics
a) Dissolution of drugs occurs, drugs must be soluble to be absorbed
b) Absorption, Distribution, Metabolism, Excretion
c) Alteration in cellular form/environment
c) Alteration in cellular form/environment
Absorption: First-pass effect (3)
- drug absorbed by small/large intestine
- liver first metabolizes drug
- remaining drug not sufficient to produce
therapeutic effect
Factors affecting distribution:
- Protein binding (free/bound drug)
- blood flow
- solubility (lipid-soluble drugs/ water soluble
drugs
Sites of quick distribution:
o Heart
o Liver
o Kidneys
Sites of slow distribution:
o Internal organs
o Skin
o Muscle
Metabolism:
A) Absorption rate equals elimination rate
B) Body changes drug to a more or less active form for excretion
C) Elimination of drugs from the body
D) Time for drug to produce therapeutic effect
B) Body changes drug to a more or less active form for excretion
Excretion:
A) Absorption rate equals elimination rate
B) Body changes drug to a more or less active form for excretion
C) Elimination of drugs from the body
D) Time for drug to produce therapeutic effect
C) Elimination of drugs from the body
Difficulty in drug excretion:
A) Increases half-life
B) Decreases half-life
Increases half-life and
risk of toxicity
Onset of action:
a) absorption rate equals elimination rate
b) time between drug administration and beginning of therapeutic effect
c) time for drug to produce therapeutic effect
b) time between drug administration and beginning of therapeutic effect
Peak Concentration:
a) absorption rate equals elimination rate
b) time between drug administration and beginning of therapeutic effect
c) time for drug to produce therapeutic effect
a) absorption rate equals elimination rate
Duration of action:
c) time for drug to produce therapeutic effect
Pharmacodynamics:
a) desired or therapeutic effect
b) study of the drug mechanisms producing biochemical/physiologic changes in body
c) other desirable or undesirable effects
b) study of the drug mechanisms producing biochemical/physiologic changes in body
Primary effect of drug
a) desired or therapeutic effect
b) study of the drug mechanisms producing biochemical/physiologic changes in body
c) other desirable or undesirable effects
a) desired or therapeutic effect
Secondary effect of drug
a) desired or therapeutic effect
b) study of the drug mechanisms producing biochemical/physiologic changes in body
c) other desirable or undesirable effects
c) other desirable or undesirable effects
Two general MOA in pharmacodynamic phase:
a) Alteration in cellular form
b) Alteration in cellular environment
Which produces therapeutic response?
a) agonist
b) antagonist
agonist
Drugs administered during the ____ may cause teratogenic effects
a) first trimester
b) second trimester
c) third trimester
a) first trimester
Risks of smoking and drinking:
- Low birth weight
- premature birth
- fetal alcohol syndrome
6 clinical problem areas
- Drug Interactions
- Pharmacogenetics
- Drug allergy
- Dosing modifications
- Monitoring plasma drug concentrations
- Evidence-based therapeutics
Drug Interactions
Change in the magnitude or duration of pharmacological response to a drug because of
the presence of another drug
Drug interaction of Ethanol
speeds metabolism of phenytoin,
tolbutamide, warfarin
Drug interaction of Chloramphenicol
inhibits metabolism of
hexobarbital, tolbutamide
Drug interaction of
Cimetidine
inhibits metabolism of
benzodiazepines, propranolol
Common Mechanisms of Drug Interactions
a. Acceleration/ Inhibition of drug metabolism
b. Displacement of plasma protein-bound drug
c. Impaired/Improved uptake of drug from the GI tract
d. Altered renal clearance
Example of Displacement of plasma protein-bound drug
- Salicylates
- NSAIDs
- oral hypoglycemics
___
each may be displaced by other drugs that bind on same region of the plasma protein
Renal clearance
measures the volume of plasma that is cleared of drug with time
Examples of drugs with altered renal clearance
- Probenecid
- Salicylates
Probenecid decreases clearance of ___ by
indomethacin (inhibit renal secretion)
Salicylates decreases clearance of ___ by
phenylbutazone, sulfinpyrazone, indomethacin, probenecid (inhibit renal secretion)
Example of drugs that irritate stomach can cause nausea, vomiting, epigastric distress, and should be given with meals
- anti-inflammatory drugs
- salicylates
Example of drugs combine with a drug
forming an insoluble food
tetracycline administered with dairy
products
Be especially careful of drug interactions with what types of drugs? (3)
- oral anti-coagulants
- anti-diabetics
- anti-convulsants
Study of variation in drug responses resulting from genetic differences in drug disposition
a) Pharmaceutics
b) Pharmacodynamics
c) Pharmacogenetics
d) Pharmacokinetics
c) Pharmacogenetics
Name one of the mechanisms by which the liver renders all the things you take in the body to become water-soluble so they get excreted; to detoxify
Acetylation
Asians are more likely to be
a) Fast Acetylators
b) Slow Acetylators
a) Fast Acetylators
Which population is more evenly split between fast and slow acetylators?
a) Americans
b) Asians
a) Americans
55% - Fast
45% - Slow
What are the variations in drug responses that can result from genetic differences in drugs disposition? (4)
a. Acetylation polymorphism
b. Pseudocholinesterase polymorphism
c. Cytochrome P450 monooxygenase
polymorphism
d. G6PD deficiency
Drugs with Acetylation polymorphism (4)
- INH (isoniazid; TB drug) → peripheral
neuropathy - Procanaimide & Hydralazine (anti-
hypertensive) → lupus - Sulfalazine → haemolytic anemia
- Environmental benzidine (pollutant,
petroleum) → urinary bladder cancer
Toxic effect and toxic mechanism of
INH
- INH (isoniazid; TB drug) → peripheral
neuropathy
-
Toxic effect and toxic mechanism of
Procanaimide & Hydralazine
Procanaimide & Hydralazine (anti-
hypertensive) → lupus
Mechanism: Acetylation polymorphism
Toxic effect and toxic mechanism of
Sulfalazine
Sulfalazine → haemolytic anemia
Mechanism: Acetylation polymorphism
Toxic effect and toxic mechanism of
Environmental benzidine
Environmental benzidine (pollutant, petroleum) → urinary bladder cancer
Mechanism: Acetylation polymorphism
Pseudocholinesterase is an enzyme that ____or_____ [______}
Pseudocholinesterase – enzyme that destroys or inactivates succinylcholine
{succinylcholine, which is a depolarizing muscle relaxant given to patients about to undergo surgery}
What is the importance of succinylcholine?
depolarizing muscle relaxant given to patients about to undergo surgery
Toxic effect of Pseudocholinesterase polymorphism
Slow succinylcholine hydrolysis → prolonged
muscle relaxation → apnea (cessation of breathing)
Pseudocholinesterase polymorphism in Filipinos is
a) common
b) rare
2% worldwide, rare in Filipinos
Toxic effect of Cytochrome P450 monooxygenase
polymorphism
- Poor metabolism of debrisoquine,
dextrometorphan (for dry cough), phenytoin (for seizures), metoprolol (anti-hypertensive) - side effect is sedation
Dextrometorphan is used for
dry cough
Phenytoin is used for
seizures
Metoprolol is used for
anti-hypertensive
Drugs for the following conditions are susceptible to Cytochrome P450 monooxygenase
polymorphism EXCEPT FOR
a) anti-hypertensive
b) dry cough
c) seizures
d) A and B
e) NOTA
e) NOTA
a) anti-hypertensive - metoprolol
b) dry cough - dextrometorphan
c) seizures - phenytoin
Toxic effect of Glucose-6-phosphate dehydrogenase deficiency (G6PD)
Decreased “reduced glutathione” (oxidized
RBC) → haemolytic anemia
When you have G6PD deficiency, you lack reduced glutathione. So you have no antioxidants. Glutathione is needed in the reduced form
for it to function as an antioxidant.
Drugs that are contraindicated in pts with G6PD deficiency
Chloramphenicol Chloroquine
Primaquine
Sulfonamides
What is important to know about Chloramphenicol?
- contraindicated in pts with G6PD deficiency
- inhibit metabolism of
hexobarbital, tolbutamide
What is important to know about phenytoin?
- for seizures
- contraindicated in pts with Cytochrome P450 monooxygenase
polymorphism - metabolism is sped up by ethanol (along with tolbutamide, warfarin)
Salicylates are subject to which mechanism/s of drug interaction?
a. Acceleration/ Inhibition of drug metabolism
b. Displacement of plasma protein-bound drug
c. Impaired/Improved uptake of drug from the GI tract
d. Altered renal clearance
e. NOTA
f. AOTA
f. AOTA
True of drug allergies EXCEPT
a. Undesirable immunologic responses to drugs (as antigens)
b. Response occurs only with initial exposure
c. Inter-individual variation- genetic influence
d. NOTA
b. Response occurs only with initial exposure
Correct: Response occurs only after a previous exposure
Types of Drug Allergies (4)
a. Immediate/ Anaphylactic reaction
b. Cytotoxic/ Autoimmune responses
c. Immune complex – mediated reaction
d. Cell-mediated response
bronchiolar constriction, capillary dilatation, urticaria, sometimes anaphylactic shock are signs of what type of drug allergy?
a. Cell-mediated response
b. Cytotoxic/ Autoimmune responses
c. Immediate/ Anaphylactic reaction
d. Immune complex – mediated reaction
c. Immediate/ Anaphylactic reaction
cytolysis and cell
death are signs of what type of drug allergy?
a. Cell-mediated response
b. Cytotoxic/ Autoimmune responses
c. Immediate/ Anaphylactic reaction
d. Immune complex – mediated reaction
b. Cytotoxic/ Autoimmune responses
acute inflammatory reaction, serum sickness, arteritis, urticaria, and granulocytopenia are signs of what type of drug allergy?
a. Cell-mediated response
b. Cytotoxic/ Autoimmune responses
c. Immediate/ Anaphylactic reaction
d. Immune complex – mediated reaction
d. Immune complex – mediated reaction
induced hepatitis; and infiltration causes local inflammatory response are signs of what type of drug allergy?
a. Cell-mediated response
b. Cytotoxic/ Autoimmune responses
c. Immediate/ Anaphylactic reaction
d. Immune complex – mediated reaction
a. Cell-mediated response
Immune complex – mediated reaction involves
a) Drug-antibody complexes
b) Delayed type hypersensitivity involving T lymphocytes, macrophages, and neutrophils occurring primarily in skin
c) IgE antibodies produced by drugs that bind to the surface of mast cells and basophils
d) IgG and IgM antibodies
a) Drug-antibody complexes
Immediate/ Anaphylactic reaction involves
a) Drug-antibody complexes
b) Delayed type hypersensitivity involving T lymphocytes, macrophages, and neutrophils occurring primarily in skin
c) IgE antibodies produced by drugs that bind to the surface of mast cells and basophils
d) IgG and IgM antibodies
c) IgE antibodies produced by drugs that bind to the surface of mast cells and basophils
Cytotoxic/ Autoimmune responses involves
a) Drug-antibody complexes
b) Delayed type hypersensitivity involving T lymphocytes, macrophages, and neutrophils occurring primarily in skin
c) IgE antibodies produced by drugs that bind to the surface of mast cells and basophils
d) IgG and IgM antibodies
d) IgG and IgM antibodies
Cell-mediated response involves
a) Drug-antibody complexes
b) Delayed type hypersensitivity involving T lymphocytes, macrophages, and neutrophils occurring primarily in skin
c) IgE antibodies produced by drugs that bind to the surface of mast cells and basophils
d) IgG and IgM antibodies
b) Delayed type hypersensitivity involving T lymphocytes, macrophages, and neutrophils occurring primarily in skin
Possible drug allergy of Methyldopa via what response?
- hemolytic anemia
- Cytotoxic/ Autoimmune responses
Possible drug allergy of Quinidine via what response?
- thrombocytopenic purpura
- Cytotoxic/ Autoimmune responses
Possible drug allergy of sulfonamide via what response?
- Stevens Johnson
syndrome - Immune complex-mediated reaction
What is Stevens Johnson syndrome?
Drug allergy of sulfanamides due to immune complex-mediated reaction involving drug-antibody complexes
Possible drug allergy of halothane via what response?
- induced hepatitis
- cell-mediated response
Liver metabolism and renal elimination of drugs are usually increased at extremes of age.
True or False
False
What is MONITORING PLASMA DRUG CONCENTRATION
The quantitative determination of drug concentrations in small samples of patient blood
• Made possible by development of suitably sensitive assays
Define Single blind study -
a clinical trial in which the investigators, but not the subjects, know which subjects are receiving active drug and which are receiving placebo
What is “a clinical trial in which neither the subjects nor the investigators know which subjects are receiving placebo; the code is held by a third party”?
Double-blind study -
Define IND -
Investigational New Drug - application for FDA approval to carry out new drug trials in humans; requires animal data
What is “application for FDA approval to to market a new drug for ordinary clinical use”?
NDA - New Drug Application;
Define Placebo -
a dummy medication made up to resemble the active investigational formulation as much as possible
What is “three parts of a clinical trial that must be carried out before submitting an NDA to the FDA”?
Phases I, II and III of clinical trials -
Define Positive control -
a known standard therapy, to be used along with placebo, to fully evaluate the safety and efficacy of a new drug in relation to the others available
What is “having an effect on the heritable characteristics of a cell or organism - a mutation in the DNA; tested in microorganisms with the Ames test”?
Mutagenic -
Define Teratogenic -
having an effect on the prenatal development of an organism resulting in abnormal structure or function; not generally heritable
What is “having an effect of inducing malignant characteristics”?
Carcinogenic -
Define Orphan Drugs
- drugs developed for rare diseases in which the expected number of patients in the USA is less than 200,000; bestows certain advantages on companies that develop drugs for unusual diseases
What is “application for the FDA that enables patients not qualified for participation in ongoing studies to be treated using investigational drugs outside clinical trials”?
Treatment IND -
What is the GENERAL PROCESS OF DRUG DEVELOPMENT
- Synthesis / isolation
- Pre-clinical testing
- Clinical testing
- Review - efficacy and safety
- Marketing
- Post-marketing surveillance
The FDA approves approximately how many new compounds a year?
20-30
Federal Food and Drug Act
- 1906
- FDA designated authority
- Est standards for strength purity
- 1938
- Prohibited marketing new drugs unless with tested safety as labeled
Federal Food and Drugs and Cosmetics Act
Amendment to FFDCA
- 1962
- Required manufacturer to provide scientific proof of safety and efficacy
- 1970
- Control manufacture and prescribing of habit-forming drugs
Comprehensive Drug Abuse Prevention and Control Act
Orphan Drug Act
- 1983
- Facilitated drgu development for rare diseases
- 1984
- Encouraged new drug applications for generic drugs
Drug Competition and Patent Restoration Act