CHAPTER 1- INTRO TO DRUGS Flashcards
pharmacology is…
the study of biological effects of chemicals.
drugs are therapeutic/helpful/or potentially dangerous
pharmacokinetics
what the body does to the drug (absorption, etc…)
pharmacodynamics
what the drug does to the body
think Dynamics-Drugs (D-D)
what is a drug? how long to discover?
any substance that is used/intended to modify physiological systems or pathological states for the benefit of the recipient
15 to 20 yrs to develop
Drug evaluation: How many phases
preclinical trials, phase I studies, phase II, phase III, phase IV
Preclinical trials
chemicals are tested on lab animals
Phase I studies
chemicals tested on human volunteers, NOT those with the disease
testing safety of chemicals
Phase II studies
drug tried on informed patients WITH the disease
Phase III studies
drug used in vast clinical market
Phase IV studies
continual evaluation of the drug
generic drugs
-chemicals produced by companies involved only in manufacturing of drugs
-patent made on original drug eventually expires and leads to…
brand name drugs
other companies can make a bioequivalent drug that usually costs more
ex) acetaminophen v. tylenol
over the counter drugs (OTC)
available without prescription for self treatment
- many of these were “grandfathered”
drug names (4)
chemical, generic, official, brand
pharmacokinetics: ADME what is it?
ADME determines the onset, intensity, and duration of drug action
what does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
ADME- Absorption
The movement of drug from the site of administration into the systemic circulation
ADME- Distribution
movement of the drug from the bloodstream into various body tissues/organs.
this depends on blood flow through the tissue
- can trap in tissue or be moving in and out
ADME- Metabolism
biotransformation of a drug into more polar substances
ADME- Excretion
removal of a drug from the body (urine, bile, tears, breast milk, saliva, sweat, or feces)
Chemical Instability
some drugs cannot be taken by a certain route/moa (method of administration), therefore it is considered chem instability
- ex) insulin is destroyed by the stomach if taken orally
Excipients
ingredients/substances other than the active drug used in the drug product for binding/long term stabilization
Binders
used to hold together products in a drug (ex. in Tylenol tablets)
Pharmacokinetic curve:
MEC- minimum effective concentration
the amount of a drug needed to cause a therapeutic EFFECT
Cmax
MAX amount of drug that reaches the plasma after dose is given (concentration)
what is duration of drug action?
how long the patient will experience the drug’s effects
onset
how long it takes to see the beginning of therapeutic effect
bioavailability
fraction of administered dose of drug that reaches the systemic circulation
- think about how it changes between different routes (orally v. IV)
Factors that influence bioavailability
-route of administration
-first pass hepatic metabolism
-solubility of the drug
-chemical instability
-nature of the drug formulation
First-pass hepatic metabolism
the drug gets metabolized at a specific location, the liver, resulting in decrease concentration of the ACTIVE drug at the site of action.
- drug becomes less active as it passes through the liver
routes of drug administration: 3 main
enteral (mouth), parenteral (injection), and other
Enteral administration
by mouth
- oral, sublingual, buccal (lozenge)
Parenteral administration
Intravenous (IV), Intramuscular (IM), Subcutaneous (SC), Intradermal (ID)
OTHER administration
oral inhalation (inhaler), nasal (decongestants), topical, transdermal (patches), rectal (suppositories)
which route provides the highest plasma concentration and shortest onset?
IV. takes least time to reach concentration of the drug in the blood
IV- Intravenous
- absorption?
- onset?
- rapid absorption
- 100% bioavailability
- rapid onset (time till seeing effect)
- IRREVERSIBLE, causing tissue damage, fear, pain
- IV curve
PROS
- useful when unconscious, intubated, or need rapid onset
CONS
- poor compliance of patient
SC- Subcutaneous
- constant/slow absorption
- sustained effect
- not useful for skin/tissue irritating drugs
may cause pain/necrosis - short needle under the skin, pouch may form at site of injx.
IM- Intramuscular
- rapid absorption with AQ drug solution
- slow/sustained absorption with NON AQ drug solution
- dependent on BLOOD FLOW and the water solubility of the drug
intramuscular absorption depends on…
BLOOD FLOW!
INC flow rate = INC absorption
PO- Oral
absorption
- absorption is VARIABLE
-convenient, economical, safe
CON: reduced conc. of drug in systemic circ (bloodstream)
OTHER routes: Rectal
- irregular and incomplete absorption
- 50% of drug absorbed bypasses liver
can cause irritation to mucous membranes
OTHER routes: oral inhalation
- rapid circulation in lungs bc of SURFACE AREA
- avoid of first pass loss
- local application= drug at desired site of action
OTHER routes: nasal inhalation
decongestants and corticosteroids
OTHER routes: topical
- 2 effects
- applied to skin of mucous membranes
- can have local OR systemic effect
(ex skin mycosis vs. nicotine patch)
OTHER routes: transdermal
type of topical
- sustained delivery of drugs
- absorption depends on nature of skin/ lipophilicity of drug into our membranes
ABSORPTION: how is it affected?
by route of administrtion, environment of where drug is absorbed, chemical characteristics of drug
GI tract absorption: 4 types
passive diffusion: move with the conc gradient, NO ATP
facilitated diffusion: transmembrane carrier proteins pass large molecules, NO ATP
active transport: carrier proteins, against conc gradient, YES ATP
endo/exocytosis: engulfing drug and transporting with vesicle (drugs with high MW), YES ATP
pH effect on drug absorption
drug passes through membrane easily if its UNCHARGED/NEUTRAL
Acids: weak acids in neutral form A- pass easily in ACIDIC enviro
Bases: weak bases in neutral form B pass easily in BASIC enviro
why is pH important when determining whether to use an ACIDIC or BASIC drug?
You want the drug to be in its neutral form, dissociated. If the drug is placed in its opposite environment, an acid-base reaction will occur resulting in protonated molecules and difficulties passing through membranes.
- weak acid thrives in stomach which has acidic pH
- weak base would not thrive in this enviro
acidic drugs stay neutral when the pH is..
less than the pKa (more acidic)
basic drugs stay neutral when the pH is…
larger than the pKa (more basic)
How does blood flow influence absorption?
inc blood flow, inc absorp
- ex) intestines receive from blood flow than the stomach
How does surface area influence absorption?
inc SA, inc absorp
- intestinal wall have microvilli
How does contact time influence absorption?
inc contact time, inc absorp
if drug passes too fast through the GI, it will NOT absorb well
ex of decreased contact time: vomiting, diarrhea
How does P-GP expression influence absorption?
P-GP is a transporter that pumps drugs out of the cell (efflux)
- if the drug is a substrate of P-GP, conc of drug that reaches blood DECREASES
- drug will be pumped OUT instead of going INTO bloodstream
DISTRIBUTION: depends on?
_the drug reversibly leaves the blood stream and enters the ECF and tissues (performs its effect)
- Cardiac output and local blood flow
- capillary permeability
- tissue volume (ICF)
- degree of binding the drug to plasma and tissue proteins
- relative lipophilicity of the drug
Distribution: capillary permeability
depends on capillary structure and chemical nature of the drug
Distribution: degree of binding of the drug depends on which protein?
albumin is major drug binding protein
- tissue reservoirs prolong drug actions
Volume of Distribution (Vd)
fluid volume required to contain the entire drug in the body at the same conc measured in plasma
- highly distributed in adipose=large Vd
- primarily retained in vascular compartment=low Vd
Drug Clearance (CL)
-Unit of volume
estimates volume of blood from which the drug is cleared per unit of time
- clearance through hepatic metabolism and kidney
Half life
time is takes to reduce the plasma drug conc by HALF
- tells us how long it takes for drug to be eliminated
Drug Metabolism occurs where
the liver.
- transformed into polar molecules to be easily eliminated by kidney
drug metabolism phase I and II
Phase I: P450 CYP enzyme, biotransformation and chemically changing structure
Phase II: conjugated drug with molecules (polar compounds) in our body for excretion
Drug metabolism: ISOFORMS
CYP Isoforms: drug can be specifically metabolism by one or more CYP enzymes
CYP inducer and inhibitor
inducer: induce CYP activity
inhibitor: inhibit CYP activity and slow down metabolism/production of metabolites
DRUG-DRUG Interaction
2 drugs, 1 is an inhibitor, resulting in slower metabolism
DRUG METABOLISM QUESTION:
Drug A is a CYP3A4 inducer while Drug B relies on CYP for its metabolism. If A and B are coadministered, what happens to the half-life of drug B?
The half-life of drug B is SHORTER
, the time to metabolize is REDUCED/faster metabolism bc of the inducer
Urinary Excretion
removal of drugs from the body through the kidneys
path of Urinary excretion
A) glomerular filtration (free drug through capillary slits)
B) active secretion through transporters (anions and cations/ acids and bases have their own system)
C) passive reabsorption: keeps drug in urine
- drug conc inc, uncharged drug diffuses out
- urine pH can alter excretion
