Week 2 Ch 2: Drug Action and Handling

dose-effect curve

x-axis increasing dose. y-axis increasing effect of the drug

log dose-effect curve

as dose increases (x-axis) the effect is “0” at first, then a quick increase effect - this range is the therapeutic effect

EC50

effective concentration of drug is needed to get half of maximum effect

potency

amount of drug to produce an effect - shown by the location along the log-dose axis (x-axis)

maximal effect

maximum intensity of effect that can be produced by a drug no matter the dose

LD50

death dose in 50% of test animals

ED50

dose required to produce desirable effect on 50% of tested animals

agonist drug

affinity for a receptor; combines with the receptor; produces an effect; naturally occurring neurotransmitters

competitive antagonist

affinity for receptor, combines with receptor, produces no effect

noncompetitive antagonist

binds to a different receptor site than agonist; reduces maximal response of agonist

physiologic antagonist

affinity for a different receptor than agonist; decreases the maximal response of the agonist by producing an opposite effect via different receptors

pharmacokinetics

amount and rate of drug passing through cell membrane are important in time course of action and individual response

active transport

substances transported against a concentration gradient or electrochemical gradient; locked by metabolic inhibitors; mediated by transport carriers with energy

facilitated diffusion

does not move against a concentration gradient

absorption, distribution, metabolism, excretion

what are 4 major steps that influence the movement of drugs?

absorption

process where drug molecules are transferred from administration site to circulating blood, passing through biological membranes

physiochemical factors, site of absorption, solubility

what are the influencing rate of absorption factors?

absorption: effect of ionization

weak electrolyte dugs dissociate in solution and break into un-ionized and ionized forms; pH site of administration and dissociation characteristics will determine the amount of drug present in ionized and un-ionized states

unionized

uncharged, non-polar, lipid soluble, easily crosses cell membrane

ionized

charged, polarized, less lipid soluble, difficult to cross cell membrane

disruption

of tablet coating or capsule shell

disintegration

contents of tablet or capsule

dispersion

concentrated drug particles must be spread throughout the stomach or intestine

dissolution

concentration dissolved in GI fluid

bound to plasma proteins, free drug

what are 2 forms that drugs occur on the blood?

distribution

passage of drugs into various body fluid compartments (plasma, interstitial fluids and intracellular fluids) for an action

biologic activity

related to the concentration of the free or unbound drug in the plasma

drug interaction

happens when one drug is bounded and another highly bounded drug displaces the first drug from plasma protein-binding site increasing the effect of the first drug

thiopental

highly lipid soluble, unionized drug easily penetrates the blood brain barrier to access cerebrospinal fluid and induce sleep within seconds after IV

enterohepatic circulation

metabolites are secreted via bile into intestine and continues with some drug being excreted in the cycle; allows for prolonged effect of the drug

metabolite

more polar and lipid insoluble, therefore, renal reabsorption will be reduced bc reabsorption favours lipid soluble

active to inactive

most common, disruption in metabolism will increase active drug in blood (ig. doxycycline active metabolized by liver becomes inactive metabolite)

inactive to active

the inactive compound is called the prodrug that metabolizes into an active drug; disruption in metabolism the harder the action drug to form (ig. acyclovir must be absorbed by the cell to form an active metabolite)

active to active

active forms another active metabolite and then converted to inactive; allows for action of the drug to be prolonged (ig. diazepam - antianxiety metabolized into desmethyldiazepam, therefore total effect of both drugs longer duration)

phase 1 reactions

carried out by microsomal or cytochrome P-450 enzymes in the liver; metabolism bind oxygen, hydrogen, water or amino acids to the lipophilic drug thus result in a modest increase in the parent drug's water solubility

phase 2 reactions

involve conjugation with any of the following agents - glucuronic acid, sulfuric acid, acetic acid, amino acid

transferases

enzyme that mediates the conjugation

phenobarbital

stimulates the production of microsomal enzymes that normally metabolize the anticoagulant warfarin

glomerular filtration

filtered through glomeruli and concentrated in the renal tubular fluid; depends on the amount of plasma protein binding and the glomerular filtration rate; bound drugs cannot be filtered and remain in systemic circulation

active tubular secretion

transports drug from the bloodstream across the renal tubular epithelial cells into the renal tubular fluid

passive tubular diffusion

regulates the amount of drug in the tubular fluid; more ionized, less lipid soluble metabolites difficult to absorb in renal cell membranes likely retained in tubular fluid and eliminated in urine

alkaline urine

tubular urine is more alkaline, weak acids are excreted more rapidly and weak bases excreted more slowly

acid urine

tubular urine is more acid, weak acids are excreted more slowly and weak bases are excreted rapidly

first order kinetics

drug eliminated from the body at a constant percentage per unit of time; plasma blood levels equals levels eliminated and proportional to the dose administered

zero order kinetics

aspirin, alcohol; rate of metabolism remains constant over time, same amount of drug is metabolized per unit of time regardless of dose

enteral route

via the human gastrointestinal tract (by mouth)

parenteral route

from routes outside the GI tract such as intravenous routes

oral route

most common, simplest; large absorbing surface area intestines; least expensive; slower onset of action; drug blood levels are less predictable

rectal route

used if pt is vomiting or unconscious; poorly absorbed; suppositories, creams or enemas

intravenous route

most rapid response; absorption phase bypassed it into the blood already; predictable response; route of choice for emergency situation

intramuscular

absorption through high blood flow in muscle; irritating drug may be given via this route; deltoid area

intradermal route

small amounts of drug LA in epidermis of skin; bleb (small bump) like tb test

intrathecal route

injection into spinal subarachnoid space; treat meningitis or give an epidural

intraperitoneal route

placing fluid in the peritoneal sac via mesenteric veins; peritoneal dialysis for renal disease