Pharmacology: Terms and definitions

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pharmacology
the study of drugs

drug
any substance which can affect a biological system

pharmacodynamics
what the drug does to the animal

pharmacokinetics
what the animal does to the drug; the movement of drugs within the body (ADME process)

pharmacy
science of preparation of drugs

therapeutics
treatment of disease

toxicology
study of poisons

pharmacopoeia
official list of drug preparations

ADME
absorption, distribution, metabolism (a.k.a. biotransformation), elimination

absorption
of the drug from the site of administration into the blood circulation (it must dissolve in body fluids to be absorbed)

distribution
of the drug around the body including to the target tissue

metabolism
of the drug to something which can be excreted more easily (although some drugs are excreted unchanged)

elimination
of the drug from the body, usually via kidneys and urine

bioavailability
fraction of the dose given which finds its way into systemic circulation; “F”

pKa
dissociation constant; the pH at which the drug is 50% ionized and 50% nonionized

parenteral
any systemic route other than oral

inscription
names and amounts of drugs to be incorporated into prescription

subscription
instructions to the pharmacist

signa/transcription
instructions for administration of medication

C I
LSD and heroin, no therapeutic uses

C II
no refills, maximum supply 34 days, can’t order over phone

C III
can have refills and order over the phone, up to 5x within 6 mos.

dose
amount of drug given to animal to produce a certain effect

dosage
amount of drug per unit body weight (mg/kg or mg/lb)

minimal therapeutic dose
smallest amount of drug that has a therapeutic effect (threshold)

maximal therapeutic dose
largest amount of drug that can be tolerated without producing toxic effects

therapeutic dose
optimal dose, some place between minimal and maximal therapeutic doses

ED50
effective dose in 50% of animals

toxic dose
amount that produces undesirable clinical, hematological, biochemical or pathological alterations

lethal dose
dose that causes death

LD50
lethal dose that causes death in 50% of animals

TI
therapeutic index/therapeutic ratio: LD50/ED50 (the larger it is, the safer the drug)

SSM 100%
standard safety margin: (LD1 – ED99)/ED99 x 100 (the wider the margin between ED99 and LD1, the safer the drug) more accurate than TI

idiosyncracy
unpredictable abnormal reaction, not dependent on dose, genetic, caused by reactive drug metabolites

tachyphylaxis
acute form of tolerance because of down-regulation of receptors which causes desensitization

daytime
CNS stimulants more effective

nighttime
CNS depressants more effective

cumulation
rate of elimination slower than rate of absorption or distribution

summation
administer more than 1 drug with same effect

synergism
net effect is stronger than 2 individual effects of 2 drugs administered

chemical antagonism
drugs inactivate each other

physiological antagonism
drugs have opposite effects and cancel each other out

pharmacokinetic antagonism
one drug reduces the concentration of another drug at its site of action by interfering with the ADME process (inhibits absorption, competes for binding sites on plasma proteins, induces or inhibits enzymes, alkanizes or acidifies urine)

passive diffusion
bulk flow from osmotic or hydrostatic differences (high to low) across membranes, thru intercellular aqueous channels, or intercellular junctions; high lipid solubility, small, and nonionized gets thru easier

facilitated diffusion
carrier-mediated transport, can be saturable, selective, or neither; movement w/concentration gradient, no E required, into or out of cell

active transport
carrier-mediated transport, always saturable and selective, movement against concentration gradient, requires E

primary active transport
energy from ATP (Na+ K+ ATPase)

secondary active transport
energy stored in Na+ electrochemical gradient generated by using ATP (Na+ dependent glucose transport in GIT and kidney, Na+ Ca2+ exhanger)

P-glycoprotein system
drug transporter associated w/multiple drug resistance family; removes drugs after being absorbed into specific cells or tissue sites (efflux pump)

pinocytosis
type of endocytosis; drug binds to membrane and gets invaginated and interiorized; requires ATP

small intestines
primary site of absorption for most drugs (nonionized)

sublingual
bypasses portal vein

enteroheptic recycling
drug goes from systemic circulation into bile into SI into blood; continuous opportunity for intestinal absorption; give w/food

first-pass metabolism
drugs that are absorbed distal to oral cavity proximal to rectum enter portal vein, then into liver for biotransformation (+/-) note: in dogs, rectal administration goes thru portal vein

presystemic metabolism
epithelial and bacterial biotransformation

administration IV
rapid onset, short duration (note: no absorption b/c already in blood)

administration PO
slow onset, longer duration

topical
transdermal, intramammary, intrauterine, onto cornea, nasal

stratum corneum
rate-limiting barrier for absorption through skin

high blood flow organs
brain, heart, kidney, endocrine glands

intermediate blood flow organs
liver, skin

low blood flow organs
muscle, fat, bone

thyroid gland
iodine has an affinity for this

kidney
aminoglycosides have an affinity for this

albumin
weak acids bind to this

glycoproteins
weak bases bind to this

globulin
some drugs, like steroids, bind to this

metabolites that are easily excreted
water-soluble, polar, ionized

liver
main organ for biotransformation

phase I reactions
oxidative, reductive, hydrolytic; production of more reactive molecules which then conjugate with a polar molecule

phase II reactions
conjugation w/glucuronide, sulphate, methyl, acetyl, glycine, glutamine, or ornithine

oxidative reaction
phase I reaction: microsomal (cytochrome P450) or nonmicrosomal enzymes (alcohol dehydrogenase from cytosol or mitochondria)

reductive reaction
phase I reaction: rare; microsomal or nonmicrosomal enzymes

hydrolytic reacion
phase I reaction: microsomal or nonmicrosomal enzymes (esterases, amidases, peptidases)

conjugation
phase II reaction: molecule w/reactive group capable of attaching to substituent group; can be reversed; deficient in neonates; glucuronidation is most common reaction (the only microsomal conjugation reaction)

enzyme induction
drugs that increases synthesis, decrease degradation, and activate preexisting compounds; only microsomal enzymes induced; can lead to tolerance or drug-drug interactions

enzyme inhibition
drugs that inhibit liver to produce metabolic enzymes; may lead to drug-drug interactions

OCTs: organic cation transporters
secretion of organic bases (endogenous and drugs)

OATs: organic anion transporters
secretion of organic acids (endogenous and drugs)

total renal excretion of a drug
filtration rate plus secretion minus reabsorption

cats
these animals are deficient in glucuronyl transferase and therefore hydroxilation and dealkylation processes; have sulfonic acid instead

dogs and cats
these animals lack acetyl coenzyme A

pigs
these animals lack sulphate conjugating enzymes

birds
these animals lack oxidative enzymes and are the only animals to use ornithine as a conjugating substrate

ruminants
these animals have less plasma pseudocholinesterases than horses, dogs, and cats

ruminants and horses
these animals have lots of oxidative enzymes

ionotropic receptors
4-5 proteins embedded in cell membrane forming a pore; allows/prevents Ca2+, Na+, K+ thru when drug is bound; very fast neurotransmission (milliseconds); ex: nicotinic ACh receptors

metabotropic receptors
a.k.a G protein-coupled-receptors & 7TM receptors; drug binds, G protein binds and takes up GTP, G proteins activate/inhibit target enzymes; slow (seconds) secretory and smooth muscle functions; ex: muscarinic ACh receptors

kinase-coupled receptors
directly activates enzymes; receptor/enzyme has kinase domain, phosphorylates and activates proteins which activates effectors; cell growth, very slow (minutes); ex: insulin receptors

nuclear receptors
receptors in cytoplasm’ alter gene transcription; new protein production; extremely slow (hours), then moves into nucleus; ex: steroids, thyroid hormones

receptor up-regulation
increase # of receptors and drug’s effect

receptor down-regulation
decrease # of receptors and drug’s effect

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