Pharmacology test 1 WCU

Contraindication

situation(s) when a drug should NOT be used (ex. drug-drug interactions, pregnancy, etc.)

adverse effects

harmful effects

Pharmacodynamics

actions/effects a drug has on the body and the mechanisms of these actions

~What a drug does and how it does it~

How do drugs work?

Drugs 'work' by inhibiting enzymes, binding to proteins, or by binding to receptors

Receptors?

proteins that are located on the outer cell membrane or within the cell itself (intracellular)

-selective for a drug (like lock and key)

2 types of drug receptors

agonists and antagonist

Agonists

drugs that bind to specific receptors and produce an effect/action (cellular/physiological response)

antagonists

inhibit agonist drug action or cellular functions

efficacy

the "effectiveness" of a drug

Potency

a measure of the amount/concentration of a drug required to produce an effect

affinity

tendency of a drug to bind with its receptor

therapeutic index

measure of the safety of a drug

antagonists bind to their receptors so they have ____________

affinity

-have NO efficacy

full and partial agonists have _______

efficacy

competitive antagonist

Blocks binding by an agonist to its receptor BUT can be overcome by increasing the concentration of the agonist; reversible

noncompetitive antagonist

Binds covalently (strong bond) to the receptor & cannot be overcome by more agonist; irreversible

Time-Plasma Drug Concentration Curve

-Onset of Action: time from the drug's administration to the 1st observable effect

-Duration of Action: length of time that a drug continues to produce its effect

-Termination of Action: when plasma drug concentration falls below therapeutic range; effect is decreased

loading dose

an initial higher dose of drug (usually IV) given in order to rapidly reach therapeutic drug levels

maintenance dose

smaller doses that are calculated to maintain the desired drug level within the therapeutic range

drug tolerance

decreased effect of drug after repeated exposure; thus, must increase dose to attain 'original' effect.

parenteral administration

IV injection, inhalation, transdermal

-cant take it back if you overdose

Absorption

-Passage of a drug from the site of administration into the bloodstream (systemic circulation)

-To do so, need to cross cell membranes of GI tract, blood vessels, etc. (except IV admin.)

rate and efficiency of absorption depends on:

Route of admin. (surface area, blood flow, etc.),

The presence of food or other drugs

Size & form of the drug

Chemical property of the drug (lipid solubility, ionization)

Factors affecting absorption: lipid solubility

more lipid soluble a drug is, the more readily it will diffuse across the cell membrane (bc the membrane is lipid too)

Factors affecting absorption: Ionization

do not cross cell membrane very readily

Drugs that are acidic (ex. aspirin) are not ionized when in an acidic fluid (ex. stomach acid).... this is

favored drug absorption

*opposite for bases

Drugs that are acidic are ionized when in an alkaline fluid (ex. the lower GI tract).... this is

NOT favored drug absorption

*opposite for bases

Drugs are usually excreted (by kidneys) in an _____________

ionized form

in order to increase drug excretion, the pH of the urine can be altered (to prevent absorption)

~f it is an acidic drug ___________________

alkalinize the urine

in order to increase drug excretion, the pH of the urine can be altered (to prevent absorption)

~f it is a basic drug ___________________

acidify the urine

bioavailability

the amount of drug administered that is actually absorbed into the bloodstream

what happens after oral administration?

the drug is absorbed across the GI tract (small intestine) into the hepatic-portal circulation

During this 'first pass' through the liver, if the drug is significantly metabolized, then the amount of 'unchanged' drug that enters the systemic circulation is _________________

decreased

distribution is affected by:

-plasma protein binding

-blood flow

-presence of tissue barriers

Plasma protein binding

-Some drugs bind to plasma proteins (albumin), others remain unbound

-Only unbound exert a pharmacological effect

-Drugs can compete for plasma protein binding sites

Blood flow

-Organs differ in blood supply (amount) which can affect the amount of drug received

-Liver, kidneys, brain have large blood supply whereas muscle, adipose have lower supply

Presence of tissue barriers

Lipid barrier that restricts the passage of certain substances into an organ (ex., blood-brain barrier)

Volume of Distribution (Vd)

fluid volume required to contain the entire drug in the body at the same concentration measure in the plasma

If high mw or protein bound

then too large to pass through slit junctions of the capillaries & is thus "trapped" in the plasma

If low mw but hydrophilic

pass through capillaries but not across membranes

(extracellular fluid, plasma volume + interstitial fluid)

If low mw & lipophilic

pass into interstitium & through membrane into intracellular fluid

the main organ involved in drug metabolism

liver

how does the liver convert drugs into metabolites

uses cytochrome P-450 enzymes

what is the goal of drug metabolism by the liver?

Goal is to convert lipid-soluble drugs into water-soluble compounds (polar) so they can be excreted by kidneys (lipid-soluble are reabsorbed)

Enzyme induction

(drug increases metabolism of drug increases)

Enzyme inhibition

(drug decreases metabolism of drug decreases)

First Order Metabolism/Kinetics

constant percentage of drug eliminated per unit time

-ex., 50% of drug X eliminated every 1 hour

-Most drugs

Zero order metabolism/kinetics (capacity limited):

constant amount of drug eliminated per unit time

-ex., ~2 mg of drug Y eliminated every 1 hour

-alcohol! very few drugs

Alkalinize the urine to....

increase elimination of weak acids

Acidify the urine to.....

increase elimination of weak bases

Enterohepatic pathway:

liver -> bile -> intestines -> blood -> liver