Flashcards in Pharmacology I Deck (150):
Chinese developed drugs in 2700 BC in Doctrine of Signatures. The oldest prescription is on a Sumerian Tablet around 3000 BC.
Hippocrates big insight was that disease is from natural causes.
What was the 1st specific drug used to treat a specific disease?
Quinine from Peruvian Tree bark used to treat Malaria
What is the single most important drug discovery in medicine?
Acetylsalicylic Acid - aspirin - 1890's
What treatment/drug for Congestive Heart Failure is still isolated from the Foxglove plant?
How are arsenicals made?
Arsenic to Carbon atom attachment
What 2 Alkaloid substances were isolated from Atropa belladonna?
Atropine (pupil dilator)
Scopolamine (motion sickness)
Penicillin was used in WWI
not until WWII
How long does it take to develop and bring a new drug to market?
How much does it cost?
____ out of 10 compounds that are developed reach market.
Of those, ___ out of 10 have ROI.
How long does a Patent for a new drug last?
Define Margin of Safety:
LD50 divided by ED50
(lethal dose/effective dose)
What is an acceptable Margin of Safety?
2000 or more
Animal Testing and Margin of Safety (LD50/ED50) are part of ______ Testing
What is another name for Long-term toxicity studies?
Chronic Toxicity Studies
Chronic Toxicity Studies involve daily dosing of dogs/rats from 3 months to 2 years, than animals are killed and histopathology is studied
What are 2 Specialized animal studies done for Safety?
What can be submitted if drug has adequate margin of safety in rats, there are no long-term toxicities, no carcinogenic effects, non-teatogenic?
What is the Approval Time?
IND - Investigational New Drug Application
In what phase are drugs evaluated in humans for the 1st time?
When does it begin?
Clinical Studies - Phase 1
Immediately after IND approval
Who is studied in Phase 1?
20-80 healthy male humans
What is determined in Clinical Studies - Phase 1?
At what clinical phase of the study are new drugs given to patients that have the condition for which the drug is intended?
How many subjects are in Phase 2 studies?
What is determined?
Phase 1 establishes therapeutic efficacy, dose response/range, metabolism, and adverse drug events.
What Phase studied Long Term Efficacy?
How many subjects are in a Phase 3 study?
1000 - 3000
Phase 3 clinical studies are to confirm drug safety/efficacy and to try to detect adverse effects that are undetected in prior studies.
Phase 3 studies are always _____
Name 2 potential limitations in Phase 3 testing.
More Short term than Long term participants
Toxicities occurring less than 1 in 1000 will not be revealed
If Phase 3 testing is successful, what can be submitted (this is after 8 years of animal/human testing)?
NDA - New Drug Application process
If an NDA (New Drug Application) is accepted by the FDA, it can be sold exclusively and have a 17 year patent.
When are Phase 4 Studies done?
After FDA approval
***Drug pulled off market if new toxicities are uncovered
Often the result of Phase 4 study/surveillance is relabeling with new warnings and precautions
4 Phases Drug Testing Summary:
20-80, test for safety in "normals"
hundreds, Safety and Effectiveness
thousands, safety, dose, effectiveness, adverse events
Define Chemical, Generic, and Trade name of drugs:
Chemical: structure (combo letters/numbers)
Generic: lower case, official name
Trade: marketed commercially
*all drugs have on generic name and many trade names
The active ingredient in Generic Drugs must enter the blood at the _____ rate as the Trade brands
Name 8 pieces of legislation that regulate drug marketing and safety:
What do each do?
1906 Pure Food and Drug Act
(created FDA, standards purity/quality, correct/truthful labels)
Federal Food and Drug Cosmetic act of 1938
(Requires proof of safety/purity)
FDA Modernization Act of 1997
Durham-Humphery Act of 1952
(FDA authorized to determine what drugs can be sold w/o prescription)
Kefauver-Harris Amendment of 1962
(requires proof efficacy/safety of new drugs)
Controlled Substances Act of 1970
(abuse - DEA)
Dietary Supplement Health and Education Act of 1994
(FDA must demonstrate supplement unsafe before taking action against)
Federal Food, Drug, and Cosmetic Act of 2006
(supplement industry must report side effects)
The FDA controls OTC drugs, reviews for misbranding and adulteration, sets guidelines for safety/efficacy, and can prevent the sale and withdraw a drug from market
The Orphan Drug Amendments of _____ provides incentives to treat orphan diseases.
The Expedited Drug Approval Act of _____ allows accelerated FDA approval for drugs of significant need with detailed post-marketing _______.
The Harrison _______ act of 1914 first established regulations governing opiates and cocaine and preceded the Controlled Substances Act of 1970
A drug is a ______ substance
The are used for what 4 things?
Diagnosis, Prevention, Treatment, Prego prevention
What is the study of how drugs enter the body, circulates, changes, and leaves?
What are the 4 steps the body takes a drug through?
For the following describe how it influences passing a lipid bilayer:
Solubility: more soluble, passes easier
Charge: cannot pass if charged
Size: Small crosses easily
Shape: must fit through membrane
What is the study of biochemical and physiologic actions, and the mechanism of drug action at cell/sub-cell level?
Lipid solubility, degree of ionization (charge), size, and shape are all characteristics of drug molecules
The lower the pKa, the _____ the acid
Weak Acid in Acidic =
Weak Acid in Basic =
Weak Base in Acidic =
Weak Base in Basic =
***Like with like = Lipid `
_____ is administered into the GI tract and ______ bypasses via injections, inhalation, topical administration
Enteral drug administration is the cheapest and is poorly/irregularly absorbed
Inhalation, IV, IM, Topical, Subgingival, SubQ, Sublingual, and transdermal are all...
IV is the most _____ and ______.
IM has the most ______ effect.
Transdermal is more _______ than others.
What route goes into the spinal or subarachnoid space?
Tablets and Capsules are _____ and _____-
Solution, syrup, suspension, emulsion, tincture, elixir all have a ______ control rate
Ointments and Creams have problematic dosage controls
What has slow, continuous delivery and must be changed?
Inhalants have slow onset
What are 3 mechanisms by which drugs penetrate biological membranes?
Diffusion - passive
Filtration - through pores
Specialized Transport - Facilitated/Active
Topical drugs cause systemic effects
*can be local or systemic, depending on dosage
Local anesthetics are usually delivered by what route?
What are 3 fast and 3 slow onset drug delivery methods?
Fast: IV, Sublingual, Inhalation
Slow: IM, Patch, Subcutaneous
Drug dissolved in aqueous solution:
Drug dissolved in saturated aqueous solution of sugar:
Drug dissolved in sweetened water/alcohol solution:
Drug dissolved in pure alcohol:
Drug dissolved in oil phase:
Drug not dissolved but...
IV faster than IM faster than Oral
What does the following pathway describe?
Oral - Stomach - Intestines - Portal veins - Liver
First Pass Effect
What is the fraction of administered drug that becomes available in the plasma?
***Frequently influenced by the "vehicle" of the drug
What is the only type of drug administration that gives 100% bioavailability?
The FDA mandates that generics have 90% bioavailability
What 2 forms do drugs take in the body?
*What can pass across membranes?
Bound to Plasma Proteins = Inactive
*Free = Active (passes membranes)
What are 2 potential barriers to drug distribution in the body?
BBB - blood brain barrier (only small, lipid soluble drugs pass through)
Placenta - most drugs pass, lipid soluble cross easiest
What must happen for a drug to terminate its activity?
***off site of action
What is the term for drug metabolism so it can be excreted by the kidneys?
Biotransformation converts _____ soluble drugs to ______ soluble metabolites.
Where does biotransformation take place?
What are the 2 Phases of Biotransformation?
Phase 1 - Liver modification (redox/hydrolysis)
Phase 2 - Conjugation. Pharmacologically inactive
What does LMOES stand for?
Liver Microsomal Oxidation Enzyme System
LMOES usually occurs in what phase of biotransformation?
An electron transport system requiring NADPH and Oxygen, present in the Liver (primarily), GI tract, and kidney.
LMOES - Liver Microsomal Oxidation Enzyme System
What 3 factors control the rate of drug metabolism in LMOES?
NADPH-cytochrome C reductase
What are the 2 general (descriptive) ways to eliminate drugs from the body?
Zero Order - constant (alcohol)
First Order - constant fraction (exponential)
6 routes of Drug excretion:
What is the time needed for the plasma concentration of a drug to fall to one half its blood level?
Biological Half Life
If a constant fraction of drug is eliminated over time, this is _____
If the rate of Intake = rate of Elimination of a drug, it has reached...
Plasma steady state concentration
At a regular dosing frequency, a drug reaches a steady state or equilibrium because the process of elimination is concentration dependent.
Drugs only interact with receptors covalently
Covalent, ionic, hydrogen, hydrophobic, Van der Waals
What are the 2 most common ways drugs bind to receptors?
The affinity of a drug for a particular receptor and the type of binding is intimately related to the drug's chemical structure.
How long does it take for a drug to be cleared from the body?
4 to 5 half lives
A drug that causes a conformational change in protein is the ______ model
Drug receptors are proteins that recognize selected molecules at the external surface and transmit information to inside the cell.
Membrane spanning protein receptors communicate with both sides of the cell, which allows drug to act without entering
A hormone, neurotransmitter, GF, or drug that binds a receptor protein/glycoprotein is called a...
A conformational change that causes a signal in response to a ligand is known as...
Name 4 Cell Signaling substances in the body:
What are 4 examples of cellular responses that occur following cell signaling?
Ion channel opening/closing
2nd Messenger formation
Gene expression alters
Drug interaction with receptors that control ion channels are found in excitable tissues
A drug that binds a receptor that controls ion channels will increase permeability to _____ and _____, that will determine _____ of the nerve.
Ligand gated ion channels, G proteins, Intracellular receptors, and Tyrosine Kinase receptors are all involved in Signal Transduction
Parasympathetic - Acytylcholine - muscarinic cholinergic receptors
Sympathetic - Norepinepherine - Adrenergic receptors
*these generate second messengers
Ligand binding causes events that generate 2nd messengers that pass message from inside the cell to effector organ
What in the internal membrane regulates the generation of 2nd Messengers?
Intracellular G-Protein Complex
What 3 responses can an Activated G-Protein Complex Induce?
Adenylyl Cyclase - generate cAMP
Phospholipase C - phosphorylates proteins
Membrane channel - changes ionic conductance
The amount of drug necessary to produce an effect is what?
The maximum intensity of a drug's effect is the...
*maximum response produced by the drug
Demerol and Morphine have similar ______, but differ greatly in ______.
A drug that is able to bind to a receptor to produce an effect is an....
A drug that binds to the same receptor as an agonist but is unable to Activate the receptor (produces to effect) is what?
If an agonist and antagonist are administered together, what binds the receptor first?
An Antagonist can be either competitive or non-competitive
A Competitive Antagonist is ______ and physically blocks the receptor
Administering additional agonist will displace the antagonist from the receptor
A Non-Competitive Antagonist will bind ______ and binds either the same or different sites. (both inhibit agonist)
*cannot be displaced - think botox
A Physiological Antagonist will oppose an agonist by ______.
A Pharmacologic Antagonist will oppose an agonist by ______.
Binding first and preventing pathway
The range of doses that elicit a therapeutic response without unacceptable side effects is known as the ______.
If the Therapeutic Window is small, the blood plasma level of a drug must be closely monitored
Receptor molecules include proteins and glycoproteins
Binding of ligand to receptor occurs through induced fit
Receptors recognize ligands at external cell surface and transmit info into the cell.
Cell signaling involves Conformational Change in receptor molecule due to ligand binding
Cell signaling substances can be hormones, neurotransmitters, growth factors, and drugs
TD50 (toxic) / ED50 (therapeutically effective), defines what?
Quantitative measure of Therapeutic Window
Cell and Tissue damage due to overdose that leaves permanent micro/macro and Intolerable effects is _____
Undesired effects that are tolerable, reversible, and dose related are.....
Multiple medications given to a pt (5 or more), is known as....
Taking multiple supplements is known as....
What report, in terms of percentage of population affected, is categorized by body/organ system for each drug?
*required by FDA
Hypersensitivity rxns manifest as skin rash, asthmatic rxns, rhinitis, and anaphylaxis
A person must have a previous exposure to a drug to have an allergic rxn
What are the 3 types of allergic rxns associated with drugs and what are the antibodies associated with them?
Type 1 - IgE
Type 2 - IgG, IgM
Type 3 - IgG
Type 1 IgE hypersensitivity rxns are the most severe and include what 4 symptoms?
Type 2 hypersensitivity (IgG, IgM) is manifested by what?
Hemolysis of RBC's
Type 3 hypersensitivity (IgG) rxs include these 3...
Causing defects in developing embryo
FDA pregnancy risk categories and what they mean:
A = failed to demonstrate risk to fetus
B = animal studies no risk demonstrated
C = animal studies reveal risk to fetus, no human data
D = positive data human fetal risk, but useful benefits
X = animal and human fetal risk demonstrated (contraindicated)
What sedative used to relieve morning sickness caused limb defects in the 1960's?
What is the modern use of Thalidomide?
Oral ulcers from AIDS
Multiple myeloma/other blood dyscrasias
Reverses wasting in AIDS
What field studies the genetic variability of drug effects?
*often by misspelled genes
Pharmacogenetic variability can alter pharmacokinetics seen by______, and pharmacodynamics seen by ______.
drug plasma levels
therapeutic effects of drugs
How do "misspelled genes" affect the following drug interactions:
Albuterol ineffective in dilating smooth muscle in bronchioles
Prozac metabolized so slowly becomes toxic
Isoniazid (TB drug) metabolized too rapidly to be effective
What 4 Factors greatly influence the effectiveness and safety of drugs?
Pediatric pts will have lower dose because of _______ kinetics
Geriatric pts will have lower dose because of _______ clearance
In Liver Disease, ____ is reduced, so _____ must be reduced.
In Renal Disease, drug excretion is inhibited
A rapid development of Tolerance (e.g. - local anesthesia wears off quickly) is knows as...
What 3 effects can drug interactions have?
What are the 4 basic mechanisms of Drug Interactions?
Synergistic (similar effects)
Metabolic (induction, inhibition)
Absorption (altered pH, binding in stomach)
Displacement of plasma proteins (more active free drug in circulation)
Name the components of the Heading, Body, and Closing of a prescription.
Heading: name, address, tele# of presciber and pt, DATE
Body: Name, dosage size/concentration, amount dispensed, directions to pt
Closing: Presciber signature, DEA number, Refill instructions
In prescription writing, define Rx:
Sig: How should be taken
What are the 4 factors that determine dosage?
Total body surface area
1 (one) 15 gm tube
Any Scheduled Drug, a prescription for a controlled substance, requires what?
Define Schedule 1:
CI: high potential for abuse
CII: high abuse, severe dependence
CIII: lesser abuse, moderate dependence
CIV: low abuse, moderate dependence
CV: low abuse, moderate dependence