Unit 2 - Pharmacokinetics Flashcards

Question

What is ion trapping?

Answer 1

movement of drug into a compartment where it changes from a hydrophobic state to a hydrophilic state, and stays in that compartment Ex. Asparin lipophilic, move across stomach wall-blood vessel walls-circulation. Once in plasma, has less similar enviro, becomes ionized and more hydrophilic. Aspirin trapped in plasma

Answer 2

P-glycoprotein is encoded by the MDR1 gene it is an active transport pump found in cells of the intestinal epithelium and BBB a genetic mutation of the MDR1 gene can lead to a lack of functional P-glycoprotein which leads to inc susceptibility to drug toxicosis drug lvls build up in CNS as pumps not pumping it out

Answer 3

many herding dogs like collies, shelties, border collie, australian sheperds and very young kittne Hetero mutation prods some functional pumps; less affected homo is more severely affected pump can also be inhib by certain drugs

Answer 4

Enzyme located in cells of intestinal wall metabolizes same drugs that P-glycoprotein removes from cell need to keep in mind if drugs or dz or other drugs inhib the func of these enzymes a correct dose will deliver a larger than expected quantity of drug alternatively, some drugs with long term use may induce these enzymes therefore dose may need to inc over time ex phenobarbital

Answer 5

1. degradation in saliva, stomach acid, sm int, GI flora(PO not common in ruminants bc of lg # of microbes in rumen will degrade most meds b4 can be absorbed) if peristalsis too fast, drug passed w/o chance to absorb - note that GI transit times in dogs/cats faster than humans, faster transit if diarrhea, oral drugs more if constipation First pass effect

Answer 6

yg anims may have poor oral absorption vomit and diarrhea dec oral absorption constipation inc oral absorption fever/heating sources in rate of absorption for IM, ID, SQ, transdermal routes Cold causes vasoconstriction and dec ID, SQ absorption BCS - fat poor perfusion; dec SQ absorption Ruminants - PO absorption typically poor

Answer 7

Acid drug in enviro of pH 9 Acid pH 2 Base pH 2 Base pH 9

Answer 8

describes the movement of drug from the plasma into the tissues a drug is only effective if it makes it to the target tissue There is a constant movement of drug btw plasma and the diff tissues

Answer 9

1. chemical nature of the drug; especially its solubility in aqueous solution vs fat-solubility 2. degree to which the drug binds to albumin and other plasma proteins 3. "volume of distribution" a pharmacological measure of how much of a drug leaves or stays in the plasma

Answer 10

sm molecules have inc ability to cross semi-permeable membranes by passive diffusion lg molecules cannot pass thru fenestrations of blood capillaries non-ionized (lipophilic) molecules will diffuse acoss lipid membranes. Ionized (hydrophilic) molecules will not

Answer 11

many drugs bind to plasma proteins, such as albumin and globulin, as soon as they reach the circulation protein bound drugs are not active - too big to leave circulation; only unbound drugs are active and can leave the circulation into tissues plasma protein binding is a dynamic equilibrium - constantly binding and detaching

Answer 12

what will happen if a patient is hypoproteinemia? how low lvls of plasma proteins causes of hypoproteinemia include: starvation, protein losing enteropathies/nephropathies, liver failure

Answer 13

if two highly protein bound drugs are given at the same time but one has more affinity for protein binding, it make preferentially bind to protein leaving more of the other drug free to be active, therefore see increased effects from the other drug

Answer 14

property of the drug determined in testing phase measure of how much drug leaves the circulation and enters the extracellular fluid Drugs with High Vd, leave the plasma more readily and enter the tissues drugs with a low Vd have a harder time leaving the circulation used to determine drug dosage

Answer 15

blood flow % body water - degree of hydration, affects the total conc of dissolved drug plasma, other extracellular fluids and intra cellular fluids Dehydrated and older anims have lower %BW and may req lower dosages of drugs to achieve a given plasma conc Tissue barriers and membrane permeability - some tissues easier for drugs to get into than others

Answer 16

Through passive diffusion thru sm gaps btw vascular endothelial cells

Answer 17

Capillaries in liver are very permeable neonatal blood vessels are more permeable inflam causes inc vas permeability - contraction of vascular endothelial cells that allows WBC to exit the caps and enter damaged tissue also allows more drug to exit

Answer 18

brain, heart, liver kidneys

Answer 19

drugs must be lipophilic to a degree to cross out of the blood vessels Lipophilic drugs have inc ability to leave vessels and only these ones can enter the BBB, choroid and prostate Body fat acts as a drug depo for lipophilic drugs act differently in thin vs fat animals

Answer 20

animals should always be dosed to lean body weight - est. weight if anim were to have BCS 3/5 or 5/9 Dec risk of toxicity - fat has low extra-cellular fluid content; no influence body water content drugs designed to move in and around body water dosing to fat weight inc conc of drug in both plasma and tissues

Answer 21

Drug in tissues > in blood = Vd high Drug in plasma > tissues = Vd low

Answer 22

amoutn of body water in circulation and extra-cellular fluid compartments stay the same even tho anim weighs more, had same distribution V as animal with BCS 3/5(5/() that weights less therefore, dose to lean body weight to reduce risk of OD

Answer 23

the way drugs interact with the body to produce their effects

Answer 24

most drugs work by altering func of cells via binding to receptors on/in cells and turning receptors on/off drugs can bind to enzymes and turn them on/on Drug must reach target cells in target tissue to have desired effect not all cells have same receptors/effects Drugs cannot be directed to only affect target tissue receptors we want to influence also exists elsewhere in body and may cause "side effects" mild-severe

Answer 25

All receptors are saturated meaning there is no more space to bind and thus, have no effect

Answer 26

ability of a drug to bind or fit with the receptor one drug may have "more affinity" for a given receptor than another Drugs do not bind to a receptor, prod an effect and just sit there. They combine, pop off, recombine multiple times. each time they combine they stim the cell to react

Answer 27

the ability of a drug molecule to prod a cellular effect when it combines with the cell's receptors

Answer 28

drug with both a good affinity for the receptor and ability to produce intrinsic activity

Answer 29

drug with good affinity but little or no intrinsic activity can be either a reversal agen or a blocker

Answer 30

combine with receptors to block the site from exogenous agonist drugs

Answer 31

Reversal for opioid analgesics Occupies receptor on cell preventing opioid such as hydromorphone frm attaching to the receptor Inhib or reversing the effect of the hydromorphone

Answer 32

Combine with receptors to prevent ENDOgenous agonist compounds such as hormone or neurotransmitters from combining with receptor and stimulating the cell

Answer 33

Propranolol - "b-blocker" as it occupies the b receptor on the heart and prevents norepinephrine from combining with the receptor which would cause an inc in the heart rate

Answer 34

competes with another drug for attachment to the receptor site determination as to whether drug A or B will occupy receptor depends on which of these 2 drugs is most abundant in the system

Answer 35

Drug that has a high affinity for the receptor site so other drugs can't access the receptor or drug that modifies the receptor so other drug cannot attach - not determined by amount of drug in system

Answer 36

some drugs prod an effect without attaching to an receptor

Answer 37

mannitol is an "osmotic" diuretic Chelators - combine with ions ex. penicillamine chelates (therefore removes) lead in lead toxicity Antacids - reduce gastric acidity by binding with HCl therefore reduce stomach irritation/ulcers

Answer 38

Biotransformation when drugs in body are chemically altered Usually a chem reaction done by enzymes. Diff enzymes mediate diff reaction types like oxidation, reduction or hydrolysis of drug molecules. it may add or remove diff func groups to/from the drug molecule biotransformation can turn drugs on or can inactive drugs prior to elimination

Answer 39

biotransformation can activate pro-drugs prodrug is the precursor form of a drug that has no biological activity, but mus the activated thru some enzymatic reaction to turn into the active form of the drug

Answer 40

required for activation of prednisolone Prednisone is a prodrug w/ no activity that needs hydroxysteroid dehydrogenase to make prednisolone which is active drug Cats + horses have very low lvls of this enzyme and cannot effectively transform prednisone->prednisolone, must give prednisolone direct or use diff steroid doves, bovids have normal lvls of enzyme, so can cheaply dose w/ pred

Answer 41

enzymatic alteration of drug can change its molecular structure so that its not longer biologically active Often this enzymatic reaction will alter drug to become less lipid soluble. -> more likely to stay trapped in plasma, can be eliminated from plasma via kidneys Resulting chemical is called a metabolite

Answer 42

90% in the liver Next is the GI tract > lungs, skin, kidney > other tissues (most tissues have some ability to metabolize drugs

Answer 43

Ingested products may have 1st pass effect

Answer 44

Bigger risk with patient with liver dz

Answer 45

found in liver group of related enzymes; among most important for drug detoxification (also activates some drugs)

Answer 46

liver induction = more cytochrome P450 activity Inc enzyme activity -> drugs break down faster (less effective drug) may need higher dose or more frequent dosing certain drugs can inc lvls of cytochrome P450 activity Chronic penobarbital turns up cytochrome P450 -> same dose becomes less effective chronic opioids

Answer 47

enzyme activity is dec > drug is metabolized slower > can result in drug accumulation > inc risk of toxicity bc it just sits there Caused by grapefruit specifically inhibs cytochrome P450, ketoconazole (anti-fungal drug), liver dz (in very old patients, taking steroids and any other cause of hepatopathy), some species prod less cytochrome than others - dogs have less than cats

Answer 48

drug metabolism enzyme in liver adds a glucuronic acid molecule to the drug causes drug to be inactivated and inc renal emlimination

Answer 49

cats cannot prod glucuronic acid and have very low lvls of glucuronyl transferase; therefore, are susceptible to toxicity from drugs that are metabolized by this enzyme Ex. Tylenol, aspirin, meloxicam (metacam)

Answer 50

there will be competition for binding of drug to enzyme. One drug will be metabolized first; next drug does not bind as strongly to enzyme will be metabolized slower

Answer 51

can be active drug or inactivated drugs (metabolites( kidney - most important (urine testing in competition animals) Liver/GI tract - next important (biliary excretion) lungs - less important for elimination of inhalant anesthetics and gases Also skin, secretions (saliva, milk) - mamarry secretion is important in nursing animals and dairy cows

Answer 52

kidney dz - not being able to filter out drugs hypotension, dehydration, blood loss, increased sympathetic tone - anything that dec blood flow thru the kidneys, changes in urine pH

Answer 53

kidney dz'd - reduced reabsorption fluids + use of diuretics (both used to tx drug overdoses)

Answer 54

#2 most important route of drug elim (esp for large molecular sized drugs) drug enters liver via portal vein (small in) or hepatic vein (systemic circulation) -> may or may not undergo liver metabolism -> enters biliary ducts -> secreted in bile -> gall bladder -> bile enters intestines -> fecal elimination Decreased in patients with liver dz

Answer 55

onyl relates to drug NOT completely inactivated in liver and some (or all) of the drug is excreted via bile in ACTIVE FORM. when bile is secreted into sm in, active drug is reabsorbed (Liver)>some drug is active>bile acide>Gall bladder>bile duct>Sm int>absorption thru SI caps> portal vein>liver>systemic circulation>liver

Answer 56

cycle is continuous until all drug is either metabolized, degraded or defecated can occur with any route of admin; related to drug and how it is eliminated Will see the a rise to peak conc, a decrease as drug eliminated via biliary excretion, an increase when drug is reabsorbed through SI, a decrease, increase, gone

Answer 57

time required fro the amount of active drug in the body will be reduced by half of its original lvl

Answer 58

A measure of drug elimination that takes into account all methods of elimination AND metabolism can be mins, hrs, or days depending on drug/patient found on drug label

Answer 59

t1/2 = 1 = 50% drug remaining 2 = 25% drug remaining 4 = 6.25 drug remaining 7 = 0.8 (or 99.2 eliminated) 9 = 0.2 (or 99.9 eliminated)

Answer 60

of half lives = 1, # of hours after dose = 4hrs, amount of drug remaining 50% 2 = 8 = 25% 4 = 16hr = 6.25% 7 = 28hr = 0.8% 9 = 36hr = 0.2%

Answer 61

t1/2 is not affected by mg/kg dose but if you double a single dose you add one t1/2 to the time it takes to eliminate the drug can be affected by patient factors like with renal dz may be affected by route of admin if only referring to a single dose, like IV drugs elim'd faster than SQ drugs is used to calculate dosing frequency and WDT's

Answer 62

only applies to long-term dosage regiments point when drug accumulation and drun elim are balanced - once steady state is reached, therapeutic range is maintained by giving a dose that is equal to the amount of drug eliminated in same time period takes time to reach steady state

Answer 63

Peak - highest plasma conc of drug after single dose or while in steady state, occurs after giving a dose of drug, should stay below min toxic conc Trough - lowest plasma conc of drug ins steady state, occurs b4 next dose, should always be above min effective conc

Answer 64

measure plasma conc of drug after 5 elimination half lives (after drug has reached steady state) some drugs, blood collection must be done at certain # of hrs after doing - time of peak conc if monitoring for toxicity, time of trough conc if measure for therapeutic effect can compare to the known therapeutic range

Answer 65

When there is serious toxicity when pharmacokinetics are strongly affected by patient factors drugs that cause enzyme induction, drugs with low TI, if drug appears not to be working

Answer 66

All drugs approved for use inf ood animals have mandated withdrawal times - expressed in days, based on half-lived. Drug movement slower in meat/fat than in blood so withdrawal times tend to be quite long Gvmt imposes fines and penalties on producers if there are drug residues discovered VT role to educate producers regarding purpose of withdrawal times and to ensure they are aware of the withdrawal time on any particular drug they are using

Answer 67

can occur when two or more drugs are administered at the same time can alter pharmacokinetics (one drug is made more effective and/or one drug is made less effective) or if both drugs have similar effects, can inc toxicity

Answer 68

one drug may alter the absorption of another such as antacids alter pH of stomach GI protectants block intestinal absorbency GI motility drugs inc or dec rate of GI passage drugs that cause vasoconstriction dec absorption of SQ and ID administered drugs two solutions with diff pH when mixed together will alter overall pH; solutions precipiate when mixed togehter

Answer 69

Diuretics will dec volume of distribution so drug is present in both tissue and blood compartment at higher conc plasma-protein binding drugs compete with one another (if two drugs bind to plasma proteins, the drug with less affinity for binding to albumin will be present in plasma in "active" form at higher than expected conc)

Answer 70

drug that are hepatotoxic will dec drug metabolism - drugs with adverse hepatic effects will affect albumin, globulins, biotransformation enzymes (ex. steroids, methotrexate, phenobarbital) Competition for biotransformation enzymes - if equal binding; both drugs will have dec metabolism If Drug A binds with greater affinity, it will be metabolized first while drug b accumulates

Answer 71

cytochromee P45- liver - drugs such as phenobarbital can inc the # of cytochrome P450 enzymes; this inc rate of metabolism of the phenobarbital and other drugs Cytochrome P450 inhibition - direct inhibition by grapefruit and ketoconazole

Answer 72

Certain drugs act directly on kidneys and inc/dec renal elimination - diuretics will inc renal elimination Some drugs can cause renal damage and dec function - aminoglycoside class of antibiotics are very nephrotoxic

Answer 73

if 2 drugs have same physiological effect and are taken together, overall physiological effect amplified. Additive; 4 and 4 = 8 or synergist; 4 and 4 = 16 Pertains to desired effects and adverse effects like opioids + NSAIDs to prod an inc in analgesia Steroids, NSAIDs both dec GI mucus prod and GI healing; cause GI ulcers if taken together Acepromazine, isoflurane and dexmedetomidine all contribute to hypotension

Answer 74

drugs that shouldn't be used together some (but not all) are listed under drug label under drug incompatibility to contraindications

Unit 2 - Pharmacokinetics Flashcards

(99 cards)