01- Intro to Pharmacology Flashcards
Henderson-Hasselbalch equation of Weak Base
pH= pKa + log ([non-ionized]/[ionized])
pH= pKa + log ([B]/[BH+])
Pharmacology
study of how drugs (medications) affect biological systems
Pharmacy
production, compounding, and distribution of drugs (medications)
Toxicology
study of toxic effects of drugs and other chemicals on biological systems
Therapeutics
treatment of disease
Pharmacotherapeutics
treatment of disease with a drug
Pure Food and Drug Act- 1906
Required manufacturers to put active ingredients on drug labels
-first pharma law passed
Harrison Narcotic Act- 1914
Made it illegal to sell drugs of abuse over the counter but were made available with a perscription
Food, Drug, and Cosmetic Act- 1938
Had to demonstrate product was safe before you could market it and had to label both active and inactive ingredients on content labels
Durham-Humphrey Amendments to Food, Drug, and Cosmetic Act- 1951
Created two drug categories:
Legend Drugs- prohibited from dispensing without a prescription (drugs that can cause significant side effects
OTC Drugs- drugs can be received over the counter and considered relatively safe
Kefauver-Harris Amendments to Food, Drug, and Cosmetic Act- 1962
Required manufacturers to demonstrate that product had to be as effective or more effective than any current drug on the market
Controlled Substances Act- 1970
- Created strict outlines for distribution of drugs with addictive potential
- created DEA in dept. of justice
- required prescribers to be licensed
- required prescription limits
- Schedules (I- no medical use, II- highest addictive potential, on down)
Dietary Supplement Health & Education Act- 1994
Removed vitamins, minerals, herbals, botanicals, etc. from FDA control
pH Partition Hypothesis
For Weak Organic Acids or Weak Organic Bases, the Non-Ionized, more lipid-soluble form crosses biomembranes much more readily than does the Ionized, more Water-Soluble form
HA H+ + A- (weak acid) BH+ B + H+ (weak base)
ABC Transporters
Primary active transporters with ATPase activity
-MRPs (MDR, P-Glycoproteins)
SLC Transporters
Secondary active transport
- Co-transporters using indirect energy, usually anti-porters
- Organic Anion transporters- wide variety of organic acids
- organic cation transporters- wide variety of organic bases
Receptor Mediated
most drugs act via interactions with receptors
Non-Receptor Mediated
Drugs that do not act by interaction with receptors.
- usually produce direct chemical effect or binds a molecule
- produces a direct effect
Quantal Response
all or none response
Graded Response
Continually increasing or decreasing
ED50
amount of drug that produces a response in 50% of the population
TD50
amount of drug that is toxic to 50% of population
LD50
amount of drug that is lethal to 50% of the population
Efficacy
refers to how big of a response you can produce with a particular drug
- change in Emax (y-axis)
- ED50 remains the same (x-axis)
Potency
how much drug does it take to produce a response
- ED50 will change (x-axis)
- Emax will remain the same (y-axis)
Potency Ratio
reflects the difference in potencies of two drugs and is used to measure how much of one drug would you need to get the same effect as the other drug
Potency Ratio= ED50 Drug A/ ED50 Drug B
Therapeutic Index
-unitless number that characterizes the safety of a drug by describing the difference between the ED50 and TD50
-drugs with high T.I. will produce therapeutic effects with low risk of toxicity
T.I.= TD50/ED50
Agonist
a drug that, by itself, produces a response
Antagonist
a drug that, by itself, produces no response but prevents the agonist response
Full Agonist
drugs that produce the highest response in a drug class (highest Emax)
Partial Agonist
Agonist that produces a response lower then full agonist
-will never have as high of an Emax because doesn’t stimulate receptors as effectively
Inverse Agonist
by itself is producing a response but the response is inhibitory
-need some sort of basal response for this to suppress
Competitive Antagonists
interferes with the agonist response by competitively binding to a receptor
- simple competition so is not permanent and can be competed off by giving more agonist
- will see change in ED50 but not in Emax
Non-Competitive Antagonist
covalently bind to receptor irreversibly
- will see change in Emax but not ED50
- cannot be reversed by giving more agonist
Chemical Antagonists
inhibit agonist by chemically interacting with it which neutralizes its ability to bind to a receptor and produce a response
Physiological Antagonist
two agonists that act at their own receptor and produce opposite physiological responses
-ACh and Epi
Receptor SPECIFIC Drug
interacts with only a single receptor sub-type
Receptor SELECTIVE Drug
interacts with several receptor sub-types but has a preference for one of them
Additive Response
response of two drugs together is sum of response to each
Synergistic Response
response to two drugs together is greater than the sum of response to each
Idiosyncratic Drug Response
unusual or atypical response in small % of individuals
Hypersensitivity
allergic response
Tolerance
decreased response (takes hours to develop)
Tachyphylaxis
decreased response that develops in minutes
Refractoriness
decreased response to no response
Biotransformation
metabolism of drugs
- usually converts to more hydrophilic compound for excretion
- usually converts substances to less pharmacologically active compound
Phase I Reaction
introduction or unmasking of a functional group (-OH, -NH2, -SH)
- oxidations (CYPs, MAOs), reductions, hydrolysis
- product usually more polar
Phase II Reaction
conjugation of endogenous polar substance to functional group on substrate
- transferases
- products usually very polar
Probenecid
competitive inhibitor of organic anion transporter
Cimetidine
an Imidazole that acts as competitive inhibitor of organic cation transporter and also contributes to decrease drug metabolism which leads to higher drug plasma levels
Henderson-Hasselbalch Equation of Weak Acid
pH= pKa + log (ionized/non-ionized)
pH= pKa + log ([A-]/[HA])
Active Metabolite
drug metabolite that has significantly activity (sometimes greater than parent compound)
Reactive Metabolite
very toxic compound (e.g. carcinogen) produced by biotransformation of a relatively inert substance
Prodrug
inactive or relatively inactive precursor that is converted by metabolism to a more active compound
Detoxification
conversion of an active or toxic compound to a much less active, or inactive compound
Active secretion
secretion of a drug through use of active transporters
-requires energy and transporters can be saturated resulting in a maximal rate of secretion
Enterohepatic Circulation
when a drug travels from liver to bile duct to intestine and then is either reabsorbed back into blood stream or excreted
-some drugs can maintain therapeutic levels by being continuously reabsorbed from intestine
Side effects
minor, undesired effects of a drug that are not medically serious
Adverse effects
undesired effects of a drug that are major, and have serious medical consequences
Toxic Effects
very serious adverse effects produced by a drug
Hyperreactive
greater then expected response to a drug
Hyporeactive
less then expected response to a drug
Intrinsic Efficacy
the ability of a drug to interact with and stimulate the receptor
Protein Binding
Drugs may bind to plasma proteins
- protein binding sites are saturable
- drugs may competitively bind proteins leading to dangerous Drug-Drug interactions (one may become excessively free in plasma and cause toxicity)
- FROM REVIEW: will not generally effect the absorption of a drug
Enteral
oral, sublingual, rectal routes of admin
Paranteral
subQ, IM, IV, IA, intraspinal routes of admin
-usually any route involving a needle
Pulmonary Route
inhalation routes
Dermal
topical, transdermal routes
Blood-Brain Barrier
tight junctions between endothelial cells of brain capillaries
- lack aqueous channels so drugs must transit cells
- lipophilic drugs much more permeable then hydrophilic
Drug Receptors
normal endogenous components of cells that are present to recognize normal endogenous molecules but also happen to recognize and bind specific drugs.
-once activated, receptor produces observed effect of the drug
CYPs
P450 mixed function oxidases that metabolize a wide variety of endo and xenobiotics
SLC Transporter
sub-set of active transporters that uses an indirect energy source
-usually functions as co-transporter that transports Ion along with drug (usually anti-porters)
OAT Transporter
organic anion transporter
-transports a wide variety of weak acids
OCT Transporter
organic cation transporter
-transports a variety of weak bases
MRP Transporter
Sub-family of ABC transporters (MDR, P-glycoproteins) that uses active transport molecules (generally out of cell)
-FROM REVIEW: inhibition may cause SLC transporter to function poorly (pump drug into cell) and lead to higher plasma concentrations of drug
a1-acid glycoprotein
plasma binding protein located in blood plasma that can bind to plasma free drug
Redistribution
drug becomes inactive because it redistributes from an area containing receptors for the drug to an area that does not contain receptors for the drug
Monoamine Oxidase
enzymes that performs Phase I reactions by oxidizing agents, usually to expose functional group and create more polar compound
Acetylcholinesterase
enzyme that performs Phase 1 reaction (usually break down of ACh)
-found at
Plasma Cholinesterase
enzyme that performs Phase 1 reaction
Bioflavonoids
inhibitors of drug metabolism that lead to inc. levels of drug in the plasma
-common site of drug-drug interaction
Pharmacogenetics
genetic polymorphisms to specific enzymes that affect drug metabolism
-variants that decrease level or activity of enzyme so drug is metabolized more slowly
Excretion
a primary means of reducing drug concentration in tissues, and, thus, in terminating drug action
- drugs primarily excreted by one route
- deficiency in route will lead to inc. plasma concentration of a drug unless frequency or dose reduced
Filtration
a mechanism of drug excretion where drug is filtered out of blood and eliminated
-that takes place primarily in kidney but also in liver
ethanol
activator of drug metabolism that decreases plasma levels of a drug (can cause toxicity of reactive intermediates formed)
-common site of drug-drug interaction
erythromycin
macrolide antibiotic that acts as inhibitor of drug metabolism that lead to inc. levels of drug in the plasma
-common site of drug-drug interaction
phenobarbital
activator of drug metabolism that decreases plasma levels of a drug (can cause toxicity of reactive intermediates formed)
-common site of drug-drug interaction
