Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Nurs 572A Pharm
Chapter 4 pharmacokinetics
| Question | Answer |
|---|---|
| Pharmacokinetics definition | what the body does to the drugs |
| Four basic pharmacokinetic processes | ADME: absorption, distribution, metabolism, excretion |
| 3 mechanisms of cell membrane passage | *channels/pores (in capillaries MW < 200) *transport system - may require energy *direct penetration -requires lipid solubility |
| quaternary ammonium compounds | 4th bond confers permanent + charge --> not lipid soluble |
| tubocurarine | quaternary ammonium used in poisoned arrows; paralyzes muscles if injected. If ingested, can't cross membrane in stomach --> inactive |
| pH dependent ionization (acids) | tend to ionize in alkaline medium |
| pH dependent ionization (base) | tend to ionize in acid medium |
| Ionized/charged particles | water soluble, done pass through membrane well |
| will ASA be highly/poorly ionized in stomach | poorly ionized |
| will ASA be well or poorly absorbed from the stomach | well absorbed |
| how do acids ionize? | by giving up a proton (in alkaline media) |
| how do bases ionize? | by accepting a proton (in acidic media) |
| Ion trapping/pH partioning | *drug molecules will tend to accumulate on the side where pH most favors their ionization *helps us understand absorption, moving to SOA, metabolism and excretion |
| when there is pH gradient between two sides of membranes, on what side will acidic and basic drugs accumulate? | *acidic drugs will accumulate on basic side *basic drugs will accumulate on acidic side |
| ion trapping sets pH gradient by | drug can pass unionized in stomach (pH1), ionize once in plasma (pH 7.4). As it ionizes, drug becomes 'trapped' on serum side -can't pass back through. Reaction runs forward until = conc of UNIONIZED in stomach/plasma |
| factors affecting drug absorption (RSBLp) | *rate of dissolution *surface area (SI has more SA than stomach) *blood flow (higher blood flow -> more drug can enter -> concentration gradient established *lipid solubility *pH partioning (ion trapping) |
| two major routes of administration | *enteral - pass across epi cell, enterohepatic cycling *parentaral - outside GI |
| Three common routes of parenteral | IV, SQ, IM |
| IV administration advantages | faster, precise, large volume useful, avoids GI destruction, irritant drugs (anticancer, highly reactive)can be given |
| IV administration disadvantages | can't get drug back once given, drug must be water soluble, inconvenient, costly, possible fluid overload, infection, embolism |
| Factors influencing distribution- BEBP | *blood flow to tissue *exiting vascular system *BBB *placental drug transfer |
| definition of absorption | movement of drug from site of administration into the blood |
| IM/SQ barrier to absorption | capillary wall: ionized passes between cells, lipid soluble passes through membrane |
| advantage IM/SQ route | used for poorly soluble drugs, depot preparations (slow absorption over time) |
| disadvantage IM/SQ route | can't be given to anticoagulant tx, possible local tissue/nerve injury, painful, inconvenient |
| oral route barrier to absorption | *epi cells lining stomach/SI *capillary wall |
| GI absorption | stom->SI/LI -> portal vein/liver -> IVC ->heart ->gen circulation |
| enterohepatic recirculation | once drug in liver metabolizes, secreted into bile, re-enters SI bwo bile duct. Either reabsorbed into portal blood or excreted in stool |
| distribution definition | movement of drugs throughout the body |
| 2 pathological conditions affecting perfusion/distribution | abscesses (lack blood supply) tumors (limited blood supply) |
| 4 ways drugs exit vascular system | *capillary beds *BBB *placental drug transfer *protein binding |
| distribution - capillary beds | drugs pass between cells unimpeded to interstitial space |
| distribution - BBB | tight junctions & P-glycoprotein impede, must be lipid soluble or have transport system to pass |
| Distribution - BBB P-glycoprotein | transport molecule that pumps drug out of cell back to blood |
| distribution - placenta drug transfer | same factors allow for drugs to pass from maternal sinus to fetal circulation (lipid-soluble, unionized) |
| distribution - protein binding | albumin too big to leave bloodstream. Any drug bound for transport remains undistributed. Only unbound drugs free to leave vascular system |
| protein binding as source of drug interaction by | different drugs may compete for albumin binding -->one drug replaces another causing free concentration to rise |
| drug metabolism definition | biotransformation - enzymatic alteration of drug structure. Mostly in liver |
| P450 System in liver | hepatic microsomal enzyme system bwo cytochrome P450 |
| Cytochrome P450 comprised of | 12 related enzyme families. |
| CYP1, CYP2, CYP3 | metabolize drugs, others metabolize edogenous compounds (steriods/fa) |
| Nomenclature example CYP3A4 | CYP =cytochrome P450 3=family A=subfamily 4=isoenzyme within that subfamily |
| Special considerations - metabolism | age, drug metabolizing enzymes, first-pass effect, nutritional status, competition between drugs |
| First-pass effect | liver metabolizes/inactivates drug --> no/decreased therapeutic effect |
| First-pass effect drug (inactivated) | NTG |
| Therapeutic consequences of drug metabolism | *accelerated renal excretion *drug inactivation *increased therapeutic action *activation of 'prodrugs' *increased toxicity *decreased toxicity |
| metabolism - most important consequence | promotion of renal drug excretion bwo increasing drug polarity |
| metabolism - drug inactivation example | procaine --> PABA |
| metabolism - increased effectiveness example | codeine --> morphine |
| metabolism - activation of prodrug example | prazepam --> desmethyldiazepam |
| metabolism - increased or decreased toxicity example | acetaminophen --> N-acetyl-p-benzoquinone (metabolic byproduct, hepatotoxic, that causes injury with overdose. |
| drug excretion definition | removal of the drug from the body - primarily by renal routes, also by non-renal routes |
| 3 Steps of renal drug excretion | *glomerular filtration *passive tubular reabsorption *active tubular secretion |
| 3 classes of transport systems tubular secretion | *organic acid pumps *organic base pumps *P-glycoprotein |
| Factors that modify renal drug excretion | *pH dependent ionization *competition for active tubular transport *age (infants have limited capacity first few months) |
| Renal excretion pH dependent example | ASA poisoning: tx with agent to elevate urinary pH --> ASA ionization --> less ASA passively absorbed/more ASA excreted |
| Renal excretion - competition active tubular transport example | PCN alone rapidly cleared. Administer with probenecid, which competes for transport pumps -->PCN excretion delayed |
| Non-renal routes of excretion | *Breast milk *bile (part clears in feces, part reabsorbed by enteropathic recirculation) *lungs (volatile anesthetics) *sweat/saliva |
| Plasma drug levels correlation | direct correlation between therapeutic and toxic responses and amount of drug present in plasma |
| 2 plasma drug levels | *MEC - minimum effective concentration *toxic concentration |
| therapeutic range | range above MEC and below toxic concentration. |
| objective of drug dosing | maintain plasma drug levels within therapeutic range |
| Which is safer - wide or narrow therapeutic range | wide is safer, narrow likely requires intervention for drug-related complications |
| rate of absorption determines (time dose curve) | latency period between administration and reaching MEC |
| Drug half-life definition | time required for the amount of drug in body to decrease by 50% |
| Half-life determines | dosing intervals |
| Multiple dosing leads to | drug accumulation until plateau acheived |
| plateau definition | when the amount of drug eliminated between doses equals the dose administered (average drug levels remain constant) |
| Assuming constant dosage, is the time required to reach plateau dependent / independent of dosage size | Independent. Takes roughly 4 half-lives to reach administration/excretion balance in plateau |
| peak concentration | highest level as drug fluctuates between doses (must be kept below toxic concentration) |
| trough concentration | lowest level as drug fluctuates between doses (must be kept above MEC) |
| 3 techniques to reduce fluctuations | *continuous infusion *depot preparation *reduce both - size of dose, dosing interval |
| loading dose | when plateau must be achieved quickly |
| maintenance dose | given every half-life to maintain constant serum levels |
| Discontinuation of drug results in | essentially non-existent levels in 4-5 half-lives |
| Example of drug with long half-life | digoxin (toxin, half-life 7 days) takes weeks for clearance. During that time, excess drug remains in body and requires significant effort to keep pt alive. |
| most common way for drugs to cross membrane | direct penetration of membrane |
| minimum time over which IV drug should be injected to minimize risk | 60 seconds - all blood in body is circulated once per minute; this allows drug to be diluted in largest volume of blood possible |
| x | x |
Created by:
lorrelaws
Popular Nursing sets