chapter 2 basic principles Flashcards
agonist-cell receptor relationship
-fits like lock and key to produce pharmacological response
antagonist-receptor relationship (blockers)
- interferes with naturally occurring agonists or drugs
- incapable of producing biological effect
down-regulation/desensitization
- responsiveness decreases
- occurs when continually stimulated receptors
- due to decreased number of available receptors or change in existing receptors
- can ultimately result in lack of response to drug
up-regulation/hypersensitization
- receptor’s activity chronically reduced from antagonists
- if antagonists rapidly stopped receptors will exaggerate natural agonists response
therapeutic index
- relationship btwn therapeutic effects and adverse effects
- ratio of doses required to produce death/serious toxicity in 50% of pts versus doses required to produce effective treatment for 50% of pts.
- index is “wide”-drug safe and no need for close monitoring
- index is “narrow”-close monitoring needed
drug effect
- result of interaction between target cell/receptor to produce therapeutic effect
- usually temporary and reversible
- drug-receptor binding very specific (lock and key)
- usually graded-larger the dose the greater the effect
onset of action
- time needed for drug concentration to reach minimum level
- changes with manner of administration (i.e. IV, IM)
time to peak
-time required for maximum effect after administration
duration of action
- blood levels are above minimum effective concentration
- not effected by route of administration
termination of action
-drug level drops below minimum effective concentration
drug efficacy
-measured by maximum effect that drug can achieve
drug potency
- compares doses of two different drugs required to achieve same effect
- influenced by absorption, distribution, metabolism, and excretion
i. e 10mg rosuvarstatin = 20mg atorvaststin–rosuvarstatin is more potent
drug absorption
- passive diffusion-no energy, usually in GI tract, only nonionized lipid soluble drugs work well
- active transport-needs energy. usually opposite concentration gradient, uses absorption of electrolytes and pinocytosis (i.e. fat soluble drugs like vitamins)
- IV-begins distribution immediately
- IM/SQ-must undergo absorption from injection site; affected by blood flow@ site of injection
- PO: empty v. Full stomach;
- chelation-usually supplement that binds with drug and not free to be absorbed
first-pass metabolism
-ONLY FOR PO MEDS
-metabolism in liver of part of drug before it reaches systemic circulation
-IV and sublingual don’t use portal circulation
-PO-absorbed in stomach and then move to liver via portal vein
-the > amount of drug absorbed via first-pass the > dose
-drugs the large first metabolism:
dopamine, lidocaine, propanolol, imipramine, morphine, reserpine, nitro, isoproterenol, warfarin
enterohepatic recycling
- some drugs leave liver circulation and enter biliary tract to be excreted in bile eventually being available for reabsorption through intestinal wall
- bile reabsorbs every 80 days and therefore drug could re-circulate for a long time
bioavailability
- am’t of drug dose that reaches systemic circulation
- doesn’t take into account rate of absorption–only extent of absorption
- not usually important when taking meds chronically
- IV drug=1
drug distribution
- initial phase: distributes drug to high-flow areas-heart, liver, kidney, brain
- 2nd phase: areas of slower blood flow-fat, bone, skin
- influenced by body composition, cardiac output, regional blood flow, protein binding, lipid solubility
plasma protein binding
- protein bound drugs cannot cross over membrane to leave vasculature–inactive and unavailable to bind with receptor sites–unable for therapeutic effect to occur
- unbound drug–“free drug” able to pass membrane and bind with receptor sites
- %of free drug constant for any particular drug but differs btwn drugs
volume of distribution
- mathematically determined measure of size of compartment that would be filled by amount of drug in same concentration in blood/plasma
- larger volume of distribution indicates larger dose needed to achieve target concentration
- drug dependent on: lipophilicity–very large volume distribution needed
- protein binding: increased volume distribution with drug in circulation longer–only free drug is active form
- pt with hypoalbuminemia (cachectic, liver dz, elderly) risk for toxicity
drug metabolism
- chemically changing drug into metabolite
- increase of h2o solubility and decrease lipid solubility to be excreted in urine
- some drugs are inactive until turned into metabolite before any effect can occur (i.e.ACE inhibitors)
- drugs can undergo phase 1 or phase 2 or both reactions to be excreted into urine
- kidneys and liver major site
- other locations: skin, plasma, GI tract, lungs
phase 1 reactions
- oxidation-inserting oxygen atom into drug (i.e. CYP450)
- reduction
- hydrolysis
phase 2 reactions
- synthetic/conjugation reactions
- attachment of other chemical groups to become more water soluble and easily excreted
enzyme induction
- synthesize drug-metabolizing enzymes
i. e. alcohol, cigarette smoke - if coadministered with CYP450 enzymes will affect therapeutic level
enzyme inhibitors
-inhibit the metabolism of other drugs
variation in drug metabolism
- genetics
- age
- pregnancy
- liver dz
- time of day-station
- environment
- diet
- alcohol and nicotine
- drug interactions
drug elimination
- removal of drugs from tissues and circulation
- usually excreted through kidneys
- some through biliary
- others through lungs, skin, breast milk, and sweat
biological half-life
- amount of time takes to eliminate 1/2 of drug from body
- determines how often drug administered
- not dose dependent
- if pt has renal or hepatic disease could take longer
- used for: estimating time needed to reach steady state; time required to eliminate all/portion of drug; plasma initiation therapy; plasma concentration;
Pharmacokinetics
-what your body does to drug Absorption Distribution Metabolism Elimination
Drug concentration
Concentration (mg/dL) = amount (mg)/volume (V.D.) (dL)
-used for loading dose-to achieve target concentration right away
I.e. Phenytoin
Renal dysfunction
-estimating renal function: 24 hour urine (gold standard), Cockcroft-Gault, GFR
Steady-state
- kinetic principle that basically states am’t lost equals am’t gained in body
- when draw drug levels we will wait until steady-state achieved
- knowing the half life helps predict when steady-state will be reached
