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Pharm- Pharmacokinetics- Quiz 1

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nodujayi's version from 2017-10-04 13:17

Pre-quiz

Question Answer
what is pharmacokinetics?"what happens tothe drug in the animal's body" offical def. = study of charateristics of the time course and extent of drug exposure in individuals and populations
The 5 big words relating to pharmacokinetics?absorption, distribution, metabolism, excretion, (transport)
what are two big things pharmoacokinetcs dictate?dose regiments, routes of administration (how much and where)
the 9 big routes of admin.?enteral (oral or rectal), local, subcutaneous, topical (skin), intramuscular, inhalation, intra-abdominal, intra-osseus, intra-arterial
what does oral bioavailability depend on? (7)pKa of drug, pH at site of absorption, surface area, feeding, disease, drug transporters, first pass effect.
what type of bioavailability is oral admin? rectal?oral is systemic or local, rectal is systemic
examples of local admin?intra-articular, intramammary, intra-uterine, regional perfusion (temp. cut off veins and admin for a high conc. locally. 30min max), subconjunctival, epidural
advantages of local admin?drugs stay locally! higher concentrations achieved so less drug is needed. prevention of systemic concentrations
disadvantages of local admin?possible systemic concentrations
what is subcutaneous absorbency like? how is it influenced?absorbance is like IM but more variable. influenced by autonomic control over blood flow
advantages of subqt admin?potential for slow and prolonged absorption (such as testosterone pellets giving linear absorption rate for 2mo.), can be used for drugs which can't be administered orally, and large amounts can be given (owner compliance)
what is the one thing a drug must be in order for it to be given topically?LIPID SOLUABLE!
topical admin-- where should it be? what does it avoid? speed? penetration is dependent on what?should be in areas of high blood flow, avoids first pass, slow and variable, penetration is dependent on lipid/water partition coefficients
what is IM injection dependent on?the site of injection! muscle used more frequently means more perfusion means better uptake (in example graph, m. serratus(best)->biceps->pecs->glutes->subcutaneous)
what is critical about inhalation admin? benefits?small particle size. Lg. surface area, rapid absorption and onset of action
what animals is intra-abdominal admin used on? benefits? type of effect?usually small animals. Lg surface area, rapid uptake, systemic effects.
where does a drug reach to be considered bioavailable?the central compartment (blood/heart)
three major influences on drug absorption?drug factors, patient factors, site of injection
What is an ABC?ATP Binding Casette transporter. Outwards transport of endogenous and exogenous compounds (transports drug out before it is absorbed)
family of ABC transporters prevent what?"prevention of the absorption of certain types of toxins, xenobiotics, or drugs" (first pass effect and enterohepatic circulation is partly regulated by xporters in the liver and GI tract
what do all drugs need to cross? which makes what drugs inherently easier to process?the lipid bilayers of membranes-- which means hydrophobic drugs are easier to absorb
Define bioavailabilitythe proportion of the administered dose that reaches the central compartment (blood).
least bioavailable administration is?orally
what is the role of food intake with drugs?feeding has influence on absorption!
Drug distribution is dictated by what 5 things?(1) membrane permeability (2) plasma protein binding (acidic drugs bind to albumin, basic bind to alpha-1-acid glycoprotein), (3) blood flow, (4) depot storage (fat storage), (5) apparent volume of distribution
what plasma protein do acidic drugs bind to?albumin (A-A)
what plasma protein do basic drugs bind to?alpha-1-acid glycoprotein (A1AG)
what should be noted about plasma protein binding as a distribution method?proteins are big! gets you close but not into cell
depot storage means?fat storage
the three groups of drugs based on distribution?1) confined to plasma 2) limited distribution 3) extensive distribution
examples/types of drugs confined to plasma?dextrans, mannitol, highly protein bound drugs (Dexter, a confined man, eats a lot of protein)
types of drugs with limited distribution?large non-lipid soluable drugs, polar drugs
type of drugs with extensive distribution?lipid soluble drugs
what compartment of the body is difficult for drugs to get in and out of?the deep compartments
what is Vd? what does a high or low Vd mean?apparent volume of distribution. high Vd= wider distribution=high bioavailability. low Vd = stays in blood= low bioavailbility
*what is the formula for calculated volume? what do the parts of the formula mean?Calculated volume is: Cl = Vd*Kel . Cl= clearance, Vd= apparent volume of distribution, Kel= elimination constant
Vd (volume of distribution) clinical significance for what two main things?(1) effective concentrations (does the drug reach the problem area? intracellular spaces? accumulation in the tissues?) (2) vulnerable structures (CNA, eye, embryo, testis, milk) and side effects!
what is the total plasma concentration formula? which fraction is active?C = Cfree + Cbound. Only free fraction is active.
describe albumin in terms of a plasma protein which can bind drugsLarge capacity. 50% of plasma proteins and mult. binding sites. most weak acids, neutral substances, even some weak bases.
describe alpha-I-glycoprotein in terms of a plasma protein which can bind drugsone specific binding site. levels increase during inflammation (acute phase proteins: APPs)..bind MOST weak bases.
example of how plasma protein decrease affects active concentration?if drug binds to PP 99%, then the PP conc decreases, then only 95% is bound so instead of 1% being active, 5% is. This means there was a 500% increase of active component, which can be bad.
how does low volume of distribution affect depot storage?low volume of distribution wont get into fat storage.
how is drug distribution affected by inflammation?1) increased membrane permeability (more drug gets into tissue) (2) increased blood flow (increased leakage)
how is drug distribution affected by local anaesthetics?(1) basic drugs (pKa 7.6 - 8.9) diff of pH and pKa increase, therefore drug gets ionized, gets a charge, and cant pass membrane. (2) bind to Na-channel inside axon (Less distribution)
examples of the blood-brain-barrier failing during drug distribution?the BBB protects against absorption of toxins, drugs, etc..have transporters which as soon as something passes the membrane, the protein picks them up and puts them back out. (1) less well protected during inflammation-- tight junctions lose their integrity. (2) certain dogs breeds are sensitive to ivermectin because the PgP (permeability glycoprotein- an 'out' exporter) is not as effective so ivermectin gets into the brain
why is drug elimination a difficult process?most drugs are lipophilic and most exits from the body are watery
10 elimination routesliver (bile), kidney (urine), GI tract (feces), lung (exhalation), saliva (ruminants), skin (lipophilic drugs), milk (public health consideration), eggs (public health consideration), sweat glands, tears
2 ways of how drugs are eliminated?changed or unchanged.
drug metabolism (in terms of elim.) can be in what 5 places?liver, kidney, GI tract, lungs, skin
what is first pass effect? when does it ONLY happen?**only after ORAL admin. it's a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall. it affects oral bioavailability of drugs.
3 ways first pass can occur?(1) metabolism of drugs into inactive compounds by the liver (2) metabolism of drugs into inactive compounds in gut wall. (3) immediate outward transport of drugs by transporter proteins (ABC transporters) so they stay in the GI and are excreted.
what is enterohepatic circulation? how is it different from first pass?**occurs with ALL ROUTES of administration. drug *already entered* systemic circulation, then it goes to the liver to be metabolized, then flora in intestine can reverse liver metabolism and be taken up again.
how can liver disease affect bioavailability?can be more bioavail, because first pass and enterohepatic circ. decrease.
how does metabolism work? (what does it do, what does it leave?)metabolism eliminates the substrate, but leaves the product (metabolite) in the circulation (more polar = excreteable)
what is a metabolite?product of metabolism, what is left over after substrate is eliminated.
what are 3 types of metabolites left after metabolism?1) inactive metabolites (2) active metabolites (bensodiazepines), (3) toxic metabolites
example of an active metabolite?benzodiazepines (Ben is a super active guy- his metabolism must be crazy!)
what is a prodrug?a prodrug is an inactive drug that can be metabolized into an active drug.
two examples of prodrugs and their metabolites?1) inactive netobimine -> active albendazole sulphoxine (use prodrug bc poor oral bioavailibity) (2) olaslazine -> 5-amino salacylic acid (A pro? Neato! Hola!)
3 phases of drug metabolism? (list)PHASE I: functionalism. PHASEII: conjugation (PHASE IIb-biotransformation of phase II conjugates), PHASE III: interaction with transport proteins (FCBI-- Fuck cunt bitch itch)
Phase I (functionalism) of drug metabolism. what are the two main purposes it serves?makes drugs more water soluable, creates substrates for phase II.
reaction for phase I (functionalisation) of drug metabolism? 2 examples?oxidation-reduction-hydrolytic reactions. ex) cytochrome p450 family of enzymes: monooxygenases (metabolizes 75% of all compounds). (ex) mixed function oxidases: N-oxidation, S-oxidation reactions (MFOs) (Phase one of passing this test-- take 450 oxys)
what causes 70% of all side effects?result of variations in biotransformaition capabilities (ex: species diff, gender diff)
what will enzyme inhibition cause? (part of biotransformation) what drugs can cause this?increased toxicity, increased side effects. ex: erythromycin, ketoconazole
what will enzyme induction cause? (part of biotransforamtion) what drugs can cause this?decreased effectivity/tolerance (they speed up metabolism) ex) barbituates, dioxin, phenytoin (barb wants to induce the pregnancy)
what is phytotherapeutics? how can you do this?pts is modulation of endogenous (hormones) and exogenous substances. you can put inhibitors and inducers in animal's foodstuffs. (use of extracts of natural origin as medicines or health-promoting agents)
what is phase II? what is meant by this word?conjugation. conjugation with GLUCURONIC ACID (or glutathione, sulphate, methyl,acetyl, methionine, etc) to make more water soluble so more easily excreted via kidney or liver (bile/urine) (2 cups of sugar water please)
biotransformation clinical relevance. 4 major factors that will influence it?1) species diffs? (little glucuronidation in cats, little acetylation in dogs, little sulphation in pigs, no flutathion conjugation in g.pigs) 2) age differences influence biotransformation. 3) substrate competition for biotransformation enzymes (comedication) 4) disease processes will influence the effectiveness of the biotransformation process (species, age, competition, dz)
what cant cats do in terms of metabolism?only a little glucuronidation (think of cats doing a shitty job of CG animation)
what cant dogs do (metabolism)only a little acetylation
what cant pigs do (metabolism)only a little sulphation (pigs, sulpur farts)
what cant guinea pigs do (metabolism?)no flutathion conjugation
three parts of renal clearance? active or passive?1) glomerular filtration (PASSIVE diffusion- free fraction) 2) tubular secretion (ACTIVE transport. competition=probenicide) (from blood to tubule) (penicillins, frusemide, procaine, trimethoprim). 3) tubular reabsorption (active or passive)
what happens with the excretion of weak acids if low urinary pH? high pH?low pH= excretion of weak acids decreases b/c similar, so not ionized, so can be reabsorbed (ex: glucose has no charge so rebasorbed). high urinary pH means it's easier to excrete weak acids because they are ionized and wont leave tubule
what happens with the excretion of weak bases if urinary pH is low? high?low pH = high excretion of weak base. high pH= low excretion of weak base.
what is the average pH of carnivore urine? what do carnivores have trouble eliminating then? herbivores?carnivores have acidic urine, so they have delayed elim of low pKa drugs. herbivores are the opposite.
//explain// henderson-hasselbalch equationdegree of ionization depends on pH of environment and pKa of drug. If the difference is big, the drug is ionized and cant pass membranes. if the difference is small, the drug is non-ionized and wont pass through membranes.
what is the equation for henderson-hasselbalch equation?pH-pKa= log ([base]/[acid]) ratio of non-ionized to ionized drug (ppk- BA!)
what is the equation for body clearance? the definition?Cltotal = Clhepatic + Clrenal + Clx. It is the plasma volume that is completely cleared per minute. can be dependent on intrinsic clearance (biotransformation capacity), organ blood flow, and organ function.
how is dose affected in renal failure? hepatic failure?renal failure = 75% of normal dose. Hepatic is 50% of normal dose.
what is the equation for F= ?F= [AUCpo/AUCiv] F means bioavailability, AUC means area under curve, po means per os (oral admin), and iv means intravenously.
what is F= [AUCpo/AUCiv] about? how do we use it?it is for determining bioavailability, if IV's AUC (say, "2") is bigger than PO's AUC (say, "1"), then it's (1/2) according to the formula (po is over iv) so F = (1/2) so F is less than one (1 would be 100%)
Short 1 or two words for what eachdrug metabolism phase is actually doing?(1) more water soluable- kidney. (2) more water soluable- kidney and liver (2b) use enzymes on phase 2 shit (3) attach to things to help get it out
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