chapter 2 basic principles

Question 1

agonist-cell receptor relationship

Answer 1

-fits like lock and key to produce pharmacological response

Question 2

antagonist-receptor relationship (blockers)

Answer 2

• interferes with naturally occurring agonists or drugs

- incapable of producing biological effect

Question 3

down-regulation/desensitization

Answer 3

• 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

Question 4

up-regulation/hypersensitization

Answer 4

• receptor’s activity chronically reduced from antagonists

- if antagonists rapidly stopped receptors will exaggerate natural agonists response

Question 5

therapeutic index

Answer 5

• 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

Question 6

drug effect

Answer 6

• 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

Question 7

onset of action

Answer 7

• time needed for drug concentration to reach minimum level

- changes with manner of administration (i.e. IV, IM)

Question 8

time to peak

Answer 8

-time required for maximum effect after administration

Question 9

duration of action

Answer 9

• blood levels are above minimum effective concentration

- not effected by route of administration

Question 10

termination of action

Answer 10

-drug level drops below minimum effective concentration

Question 11

drug efficacy

Answer 11

-measured by maximum effect that drug can achieve

Question 12

drug potency

Answer 12

• 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

Question 13

drug absorption

Answer 13

• 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

Question 14

first-pass metabolism

Answer 14

-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

Question 15

enterohepatic recycling

Answer 15

• 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

Question 16

bioavailability

Answer 16

• 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

Question 17

drug distribution

Answer 17

• 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

Question 18

plasma protein binding

Answer 18

• 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

Question 19

volume of distribution

Answer 19

• 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

Question 20

drug metabolism

Answer 20

• 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

Question 21

phase 1 reactions

Answer 21

• oxidation-inserting oxygen atom into drug (i.e. CYP450)
• reduction
• hydrolysis

Question 22

phase 2 reactions

Answer 22

• synthetic/conjugation reactions

- attachment of other chemical groups to become more water soluble and easily excreted

Question 23

enzyme induction

Answer 23

• synthesize drug-metabolizing enzymes
  i. e. alcohol, cigarette smoke
• if coadministered with CYP450 enzymes will affect therapeutic level

Question 24

enzyme inhibitors

Answer 24

-inhibit the metabolism of other drugs

Question 25

variation in drug metabolism

Answer 25

- genetics - age - pregnancy - liver dz - time of day-station - environment - diet - alcohol and nicotine - drug interactions

Question 26

drug elimination

Answer 26

- removal of drugs from tissues and circulation - usually excreted through kidneys - some through biliary - others through lungs, skin, breast milk, and sweat

Question 27

biological half-life

Answer 27

- 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;

Question 28

Pharmacokinetics

Answer 28

``` -what your body does to drug Absorption Distribution Metabolism Elimination ```

Question 29

Drug concentration

Answer 29

Concentration (mg/dL) = amount (mg)/volume (V.D.) (dL) -used for loading dose-to achieve target concentration right away I.e. Phenytoin

Question 30

Renal dysfunction

Answer 30

-estimating renal function: 24 hour urine (gold standard), Cockcroft-Gault, GFR

Question 31

Steady-state

Answer 31

- 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