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142 Cards in this Set
- Front
- Back
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Ficks Law
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(C1-C2)* (Area * permeability Coeff)/(thickness)
-ability of molecule to passively diffuse across a compartment. Reflects driving force via osmotic potential, surface area, and thickness as well as ability to travel through a membrane -c1=out -c2=in |
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Henderson hassselbalch
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log (pr/unpr)=pKa-pH
-indicates how much of a form will be present |
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Drug Receptor Types
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1) transport proteins and Ion channels
2) Regulatory proteins( Nt, hormones, most drugs) 3)Enzymes (many antibiotics, aspirin) 4)Structural Proteins (anti inflammatory) 5)Lipids (alchohol, anasthetics) 6)nucleic acids (hormones, antibiotics) |
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Concentration effect curve, when response to DRUG is measured
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E= (Emax*C)/(C+EC50)
E=effects at C Emax=maximal drug effect produced EC50=C that produces 50% maximal effect |
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Concentration effect, when receptor drug binding is measured
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B=(Bmax*C)/(C+Kd)
C= free unbound drug KD=equilibrium dissociation constant |
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Kd
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measure for the affinity of the drug to receptor
Kd=k2/k1 -Free drug in which half maximal binding is observed or the drug in which half the receptors are filled |
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emax
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all receptors bound by agonist
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Efficacy Vs. Potency
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potency= ease of drug binding to receptor
Efficacy= amount of change produced after drug is bound |
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Spare Receptors
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allow low affinity agonist to produce full response at concentrations less than what is required to occupy all receptors
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Spare Receptors with regards to KD
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Kd>>>>>>>>EC50
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competitive antagonist
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block binding pocket of recpeotr
-shifts agonist dose response curve to the right |
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Irreversible Antagonist
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- ligand that binds to the receptor with an affinity that may be so high that the receptor will be no longer available to bind to any agonists
-ligand covalently linked -effects cannot be overcome by adding more agonist -decreases E max, or shifts curve down |
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Partial agonist
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- produce a lower response than full agonist when all receptors are bound, effect has nothing to do with affinity of the drug for the receptor
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physiologic anatagonist
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drug binds to a different receptor, producing oppositte effect to that produced by the drug it is antagonizing
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chemical antagonist
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- a drug that interacts directly witht he drug being antagonized to remove it or to prevent it from reaching target
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Transmembrane signaling
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-intracellular receptor
-transmembrane receptor cytoplasmic enzyme activity -transmembrane receptor that binds to and activates a cytoplasmic protein tyrosine kinase -Ion channels -G protein linked receptors |
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Intracellular receptors
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Gas, steroid receptors,...
-lag period -effects can last for days -effects not related to plasma levels |
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Ligand regulated TM enzymes
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-tyrosine kinase: insulin, EDG, PDGF
- Guanylyl cyclase: atrial natriuretic factor, vascular tone - serine kinase: transfroming growth beta factor |
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cytokine receptors
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Growth and cellular differentiation
- growth hormone -erythropoiten - inteferon |
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Ligand Gated Ion channels
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- peripheral and central nervous ion channels
:nicotinic ACH : gamma amino butyric acid :excitatory amino acid channels, such as glycine, aspartate, glutamate -mechanism : increase in ion flow |
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G protein coupled receptors
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-family of similar proteins
-when bound to agonist, they all transmit information to inside the cell via activation of G proteins - G protein activation produces change sin effector enzymes which produce second meessengers resulting in cellular response -1/2 of non-antibiotic drug action -main second messengers: cAMP, calcium, phosphoinostiteds, IP3, cGMP |
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Gs
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B adrenergic receptors
= increases adenylyl cyclases increasing cAMP increasing PKA |
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Gi 1-3
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alpha 2 adrenergic R, muscarinic R, many m ore
- decreases adenylyl cyclase, decreasing cAMP |
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Gq
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Muscarinic and alpha one adrenergic receptor
- increases PLC, increasing IP3 and DAG, increasing calcium, increasing PKC _ |
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Golf
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Odorant receptors
- increases adenylyl cylcase, increasing cAMP |
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Gt
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Photons
- CGMP phosphodiesterase, decreasing cGMP |
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Go
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NT in brain
- unclear |
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therapeutic index
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- LD50/ED50
-measure of drug safety margin |
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pharmacokinetic parameter
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-volume of distribution
-drug clearance |
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volume distribution
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-measure of apparent space in body available to contain the durg
-relates the drug amount in body to the concentration of drug in the blood or plasma depending on the fluid measured -Vd= (amount of drug in body/Cplasma) |
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drug clearance
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-the measure of the ability of the body to eliminate the drug
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characteristics of volume distribution
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-varies with physical drug properties
-changes with age -part of the calculation for drug half life -used to calculate loading doses |
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characteristics of clearance
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Clearance is a term to describe flow or volume per time (it says something about the particular drugs ability to be filtered, reabsorbed and secreted). Excretion is a term for amount per time. Excretion amount changes with plasma concentration (flow time amount). While clearance is normalized to plasma concentration so it remains constant. Cl = flow X amount/amount in plasma.
a measure of the volume of blood (or plasma) from which the drug is (totally) eliminated during a given period of time, per body weight CL = K(Vd) -CL= rate of elimination/C |
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First order kinetics
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-non saturable
-clearance rate doesn't vary with drug concentration. Rate of elimination is directly proportional to drug concentration -most drugs are first order -a constant fraction of the drug is eliminated per unit time -non saturable: blood flow can be limiting factor -half life is constant -inverse parabola -more drug equals more elimination -CL= rate of elimination/ C |
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zero order kinetics
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-also known as michealis menten
-At high concentrations, elimination becomes independent of concentration -drugs; ethanol, phenytoin, and aspirin -constant amount of drug is eliminated per unit time -no fixed half life = Vmax* C/(km+C) |
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Two major sites of elimination and clearance
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-kidney and liver
kidney- excreted through urin CL=GFR when there is no reabsorption or secretion and no plasma protein binding protein bound drug is not cleared albumin alpha 1-acid glycoprotein -CL= free fraction* GFR Liver- biotransformation and excreted into bile blood flow rate is 1.5 L /min usually not limiting but can be important for some drugs with high clearance values changes with disease state |
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Bioavailability (F)
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-fraction of unchanged drug reaching the systemic circulation following administration by any route
-depends on amount absorbed and fraction metabolized before reaching systemic circulation |
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Oral absorption and bioavailability
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- oral absorption may be incomplete if the drug is:
-too hydrophillic -to lipophillic -bacterial metabolized -pumped out (p-glycoprotein inhibited by grapefruit juic) |
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First pass elimination
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-first pass elimination via the liver can be calculated using the extraction ratio
ER=CLliver/Q Q is the hepatic blood flow, normally 90 L/h, 70 kg person) -drugs with high first pass affect: nitroglycerine, lidocaine, verapamil, isoniazid, morphine, proponolol, TCA-s |
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Systemic Bioavailability (F)
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F= f*(1-ER)
ER=extraction ratio in liver, which is .67 f=extent of absorption of drug |
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Bioequivelance
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preparations of drug have the same bioavilability... trade vs. generic
-same AUC |
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drugs effects vs . time
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-immediate
-delayed effects -cumulative -active metabolite -reversible vs. irreversible inhibition |
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Half life
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-time required to reduce druge amount in the the body by half
-main use is it indicates time required to reach 50% of steady state levels half life= .7*VD/ DL |
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STEADY state
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the amount given matches the amount cleared, in equals out
- dependent on drug concentration and dosing rate. goal is to adjust dosing to keep drug concentration above minimum effective dose and below toxic dose -time to steady state is dependent on drug half life only |
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steady state versus half life
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50% of steady state equal one half life
75% percent of steady state equals two half lifes 87.5 % steady state equals 3 half lives 93.75% steady state equals four half lives |
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time course of drug effect
IMMEDIATE |
drug effect usually reflects plasma concentration but not always
- if drug is low compared to the EC50 the half life reflects drug effect duration - if drug is high compared to the EC50, the half life does not always reflect duration of drug effect |
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course of drug delayed effect
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-time required to distribute from plasma to site of action
-mechanisms of action requires a cascade of events that may have a rate limiting step -vitamine K epoxidase>warfarin> clotting factor synthesis(long half lives)>degradation of existing clotting factors> clot formation |
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course of drug cummulative effects
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-some drugs produce effects when given for several doses over long periods of time
-cancer chemo -aminoglycoside antibiotic renal toxicity |
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time course active metabolites
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parent drug is metabolized into a product which does the same thing=duration of drug effects include both molecules
-benzodiazepines |
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time course irreversible inhibition
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-drug duration is much longer than half life
-aspririn can have antiplatelet affects upt to 8 days |
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Rational dosage regimen
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-target concentration
-maintenance dose -loading dose -strategy -evaluating drug concentration measurements -dosing rate steady state= rate of elimination of steady state= CL*TC dosing rate oral= dosing rate/ Foral intermittent dosing= dosing rate*dosing interval rational dosing regimen means that rate in is equal to the rate out |
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maintenance dose
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after you get the dosing rate,
then you can find maintenance dose (dosing rate/F)*dosing interval |
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`Loading Dose
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-promptly raises concentration to steady state
-amount in the body immediately following the loading dose, influenced by Vd loading dose= Vd*TC Calculation of the loading dose assumes prompt distribution in total Vd This is not true in many cases (multi-compartment distribution), therefore To avoid toxic blood concentrations inject loading dose in installments give all IV injections slowly (in minutes, NOT seconds!) |
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therapeutic drug monitoring
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Vd- decreases with age, obesity, and accumulation of fluids
half life- changes with age and Vd absorption- patients health bowel conditions gut metabolism clearance- kidney function and liver metabolism - if measured drug concentration is different from targeted desired value by more than 20%, make sure that steady state has been reached, and reacalculate dose -congestive heart failure and hypoxia can cause hepatic clearance to be reduced |
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Adjusting Dose
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- in obese indivduals, Vd for non lipophilic drugs is calculated based on ideal body weight
- if ascites or edema is present, Vd should be increased -if renal function is compromised, the dose of drugs cleared by the kidney should be adjusted corrected dose=average dose*(patients creatinine clearance/ normal creatinine clearance) |
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summarize target concentration strategy
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-choose target TC
-predict Vd and CL based on typical values, adjust for weight and renal function -give loading dose or maintenance dose calculated from TC, Vd, and CL -measure response -revise Vd and CL based on measured drug concentration -repeat steps until response is optimized |
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biotransformation
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lipophilic molecules must be charged to be excreted
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Phase I
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-add or expose functional group on parent molecule(OH,NO2, SH)
-located on smooth ER -mixed function oxidases monooxygenases, or microsomal oxidases -Cytochrome P450 family , CYP, drug interactions, inhibited, induction (gene expression) |
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Phase II
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-biosynthetic reactions
-covalent linkage with various molecules -glucuronic acid, sulfate , glutathione, amino acids, acetate -mostly cytosolic localization -may precede phase one reactions with some drugs |
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Places biotransformation occurs
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- Major is the liver: first past metabolism for some oral drugs
-Minor are the kidneys, GI tract, Lungs, Skin the GI tract first past effect: clonazepam, chorpromazine, lidocaine gastric acids: penicllin digestive enzymes; insulin microgorganisms |
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Cytochrome P450
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- old genes 3.5 billion years old
-functional requirements: NADPH-cytochrome reductase(flavoprotein) NADPH is electron donor Flavin adenine dinucleotide flavin mononucleotide cytochrom hemoprotein: must bind heme and iron for activity, molecular oxygen. |
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phase I CYP dependent oxidative reactions
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-Dealkylation
-hydroxylation -oxidation -deamination |
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Phase I reactions
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-azo, nitro, carbonyl reductions
-hydrolyses (esters, amides) |
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CYP enzymes with different specificity to drugs
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- CYP3A4/5: enzyme that acts on fifty percent of drugs
-CYP2D6: 25% of drugs - |
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Phase I enzymes, and drugs ability to regulate the number and activity of CYP...INDUCTION
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-occurs when a drug binds to DNA binding protein and induces transcription of a CYP resulting in more CYP molecules that are able to modify drugs at a faster rate. Inhibition of activity of existing CYP enzymes also occurs
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Phase I enzymes and INHIBITION
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- drugs can h ave a significant influence of the metabolism of other drugs -a very common source for drug drug interactions
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Human liver P450 Family
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1A2,2C9,2D6,2E1,3A4
3A4- fifty percent of drugs general inducers and general inhibtors -grapefruit juice inhibits CYPsA metabolism -eznyme inductionvia ciggs, industrial chemmicals, pesticides |
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Genral Inducers
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Barn takes Phen phen and Refuses Greasy Carbs
barbituates phenytoin Rifampin Griseofulvin Carbamazepine more enzymes means a faster metabolism, and lower drug effect rifampins 4 R's: RNA polymerase inhibitor, Revs up microsomal P 450's, Red orange body fluids, Rapid resistance |
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Enzyme Induction
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Tolerance: loss of drug effect after use. Necessitates the need to use more drug to achieve desired result
Pharmacokinetic tolerance: induction of enzymes by drugs increases its metabolism and can produce tolerance pharmacodynamic tolerance: altered receptor responses. occurs as well |
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Enzyme Inhibition
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-Reversible inhibiton of Cyps: cimetidine, ketoconazole, macrolides
Permanent inhibition: suicide inhibitors drugs that when metabolized by enzyme from reactive intermediates that form covalent bonds with enzyme, inactivating it -hormones: spironolactone, grapefruit furanocoumarins, clopidogrel, ritonavir, glitzone antidiabetic drugs drug drug interaction: less enzymes=increased toxicity |
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Examples of Inducers
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-barbituates user require more warfarin(anticoagulent)
-St. johns wort users have reduced oral contraceptive levels -epileptics on phenytoin require more cortisol |
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Examples of Inhibitors
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-ketoconazole, erythromycin, grapefruit juice produced cardiac arrhythmias in patiens on antihistamine terfenadine or seratonin antagonist cispride
-cimetidine potentiates the action of anticoagulants and sedatives -cimetdine and ketoconazole inhibits steroid synthesis causing gynecomastia in men |
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Phase II Reactions Conjugations-
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- energy requiring transferases conjugate polar molecules unto drugs... increases excretion and often inactivates drugs
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Types of Phase II reactions
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-glucuronidaton
-acetylation -sulfation -glutathione conjugation (GHS) -endogenous substrate originate in diet.. therefore nutrition plays a critical role in the regulation of drug conjugation |
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acetominophen and acetylcysteine
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Although in many cases acute acetaminophen poisoning is a straightforward problem, the vignette illustrates a common situation for which there are no clear answers.
Published protocols have focused on patients with acetaminophen poisoning who present with a toxic acetaminophen concentration and without liver injury. These patients will do well as long as they receive timely acetylcysteine therapy. Patients who present with liver failure have a less favorable prognosis, but it is clear that acetylcysteine treatment improves their chance of surviving. The best treatment for the patient who cannot be risk-stratified with the use of the Rumack–Matthew nomogram, or who has hepatic injury without hepatic failure, is less well defined. On the basis of the established benefit of acetylcysteine therapy in other specific settings, I favor treatment of the patient described in the vignette. I would choose oral therapy and administer the loading dose of 140 mg per kilogram in the emergency department. Since the patient does not appear to have intended to harm himself and is clinically well, I would discharge him from the emergency department with additional doses of 70 mg per kilogram to be taken every 4 hours. I would recommend that he be seen in the outpatient clinic 12 hours after discharge in order to obtain a repeat measurement of alanine aminotransferase activity; if it is clearly decreasing, his therapy can be terminated before he completes a course of 17 doses. |
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Patient Variability
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-range from 2 fold to 30 fold variation in drug disposition and effects
-genetic factors -diet and environment -age and sex -drug drug interactions -diseases |
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Age and sex affects with drugs
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drugs metabolized at reduced rate during prepubertal perios
-very young and elderly metabolize less -males may metabolize faster |
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Diseases in drug metabolism
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-liver diseases, cardiac disease creates limited flow to liver, renal failue
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pharmacogenomics
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-mutations in genes involved in drug metabolism and transport(pharmacokinetic) and drug action (pharmacodynamic) can produce individual variability in drug response and toxicity
-now we have a gaussian distribution for target dose and drug type -future: tailored drug dose an type based on individual gentoyping -pharmacodynamic difference in target receptors or enzymes: drug effects altered or increased toxicity |
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some drugs that affect others differently due to pharmacodynamics
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-wrfarins target; vitamin K epoxide reductase enzyme=excess bleeding
- beta 2 adrevergic recpetor altered aa leads to faster desensitization -Altered bradykinin receptor leads to cough and angiodema with ACE inhibitors |
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Polymorphisms in drug transport and metabolism
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- p glycoprotein
-neurotransmitter transport - amino acid transport |
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CYPD26
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a decrease in it leads to autosomal recessive trait... increases drug effects or toxicity
-an increase in it leads to auto recessive trait, and leads to reduced drug effects -decrease leads to mephenytoin; poor metabolizers, profound sedation, high in japanese |
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Polymorphism in Phase II reactions
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-decrease in n-acetylations
-drugs are isoniazid and hyralazine -slow metabolizers: lupus like syndrome with hydralazine peripheral neuropathy with isoniazid auto recessive trait: 50% americans, 60-70% northern europeans |
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Phase one drug development
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non blind small study in healthy volunteers comparing animals to humans testing safe dose, pharmacokinetics
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Phase two drug development
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single blind small study in patients with target disease. efficcy in patients
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phase three drug development
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double blind large multi center study in patients with target disease. efficacy in patients without placebo effect
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Phase four drug development
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post marketing and surveillance
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1A2 P450 liver family
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12% of drugs
-acetominophen and theophylline -induces aromatics, hydrocarbons, vegetables, omeprazole -inhbits fluvoxamine |
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2C9 P450 liver family
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4% of drugs
-phenytoin, warfarin -general inducers |
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2D6 P450 liver family
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28% of drugs , many CV and CNS drugs
-induces st. johns wart, rifampin -inhibits paroxetine, quinidine |
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2E1 liver family P450
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-acetominophen, gas, anasthetics
-induces ethanol , isoniazid -inhibits disulfram |
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3A4 liver P450 family
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-50% of drugs,
-general inducers -inhibitors: grapefruit juice |
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human liver p450 family
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Diet effects CYPs: Charcoal broiled foods and cruciferous (mustard greens and cress type) vegetables induce CYP1A enzymes
grapefruit juice is known to inhibit CYP3A metabolism Enzyme induction via cigarettes, industrial chemicals, pesticides, etc. |
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synthesis of Arachodonic acid metabolites
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-cell membrane damage, usually increased intracellular calcium, endotoxin exposure, ect. results in A acid production
-AA from diet, omega three and six -PIPa2: cytosolic, most common, secreted which is inducible, calcium dependent, -inhibited by corticosteroids |
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products of PGH2: note that PGH2 is synthesized via PGH synthase, COX I and COX II
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-PGF2a
-TXA2 -PGI2 -PGD< PGE< PGE |
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COX I
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GI mucosal integrity
platelet aggregation renal function |
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COX II
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inflammation
-mitogenisis and growth femal repro reg bone formation renal function reduces platelet aggre |
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leukotriene biosynthesis
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-lipoxygenagse and dehydrase activities are exerted by a single enzyme, 5-lipoxygenase
-not inhibited by NSAIDS -LTA4, LTB4, LTC4, LTD4,LTE4 |
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5-lox
leukotriene synthesis |
-central mediator of inflammation
-active in stimulated inflammatory cells, PMN, basophils, mast cells, eosinophils, macrophages -sig in asthma and sshock -target for drug action |
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effects of leukotrienes
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-affects cardiovascular, airways, blood cells
-SM chemoattractant -reduce contractility and coronary blood flow: cardio Airways: LTC4 and LTD4 are bronchoconstrictors, induce plasma exudation, mucus secretion -primary components of sRS-A -blood cells: chemoattractants for PMN, eosinophils, promote eosinophil adherence and degrantulation -phagocyte attraction, t cell moduation |
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prostaglandins organ effects
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-smooth muscle relaxation
-PGI2,PGD2,PGE1 all activate cAMP -cAMP inhibits myosin -LC kinase -overall increase of cAMP, and relaxing effects on smooth muscle, inhibition of platelet aggregation |
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Thromboxane organ effects
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-TXA2, PGF2a, PGE2, receptors activate IP3
-IP3 activates myosin LC kinase, releasing intracellular calcium -causes smooth muscle contraction -constricting effects on smooth muscle stimulation of platelet aggregation |
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PGI2
TXA2 PGF2a P-D,E,E |
PGI2: inhibits agregation, prostacyclin
TXA2: platelet aggregation PGF2a: smooth muscle contraction Prosts: smooth muscle relaxation |
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PGE2 and PGE1
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pregnancy termination
dinoprostone: promotes uteruin contraction and cervical softening |
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dinoprostone gel-eicoasonoid
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misoprostol: facilitate labor
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dysmenorrheea-eicosanoid
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endometrial synthesis of PGE2 and PGF2a
-prevented by NSAIDS |
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aloprostadil-eicosanoid
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male impotence
alo is PGE1 |
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COX II inhibition
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prevent prostacylin from being made in inflammatory cells which may overbalance TXA2 production leading to thrombosis
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misoprostol, enprostil
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-cytoprotection: E prostaglandins protects against gastric ulcers
-need COX II specific inhibitors |
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Latanoprost
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-glaucoma: eye drops increases AH outflow via vasoconstriction
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ZIleuton
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5 lox inhibitor
used for asthma |
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glucocorticoid physiologic function
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cortisol and corticosterone
-help regulate car,protein and fat metabolism -increase in hepatic output by stimulating catabolism of peripheral fat and protein to provide substrate for hepatic gluconeogensis -protects glucose dependent brain and heart by increasing blood glucose levels -resist stressful stimuli -dampens immune response, modulates -diminishes response to catecholamines |
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Glucocorticoid anti inflammatory effects
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-decreases immune cells
-decreases arachodonic cascades reduces: neutrophils, monocytes, lymphocytes, basophils, cytokine production, antibody production, migration, PIPa2, COX II induction inhibited all above inhibited |
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antiinflammatory proteins and glucocoritoid
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annexin 1
MapK phosphatase |
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glucocoritcoids effects on arachidonic cascade
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-inhibits activation of PIPa2 and inductions of COX II -
-note: COX I goes to TXA2 |
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long acting glucocorticoids
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betamethasone
dexamethasone |
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NSAIDS
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nonspecific reversible inhibiton of COX I and COX II
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COXibs
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SELECTIVE reversible inhibtion of COX II
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aspirin
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nonspecific irreversible inhibtion of COX I and COX II enzymes
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clinical indications for NSAIDS
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inflammation
nalgesia antipyretic platelet aggregation -eicosanoids amplify bociceptive signals |
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analgesic effects of NSAIDS and aspirin
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-most effective on mild or moderate pain
-reduction of inflammation -inhibiton of pain stimuli in neurons |
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Antipyretic effects of aspirin and NSAIDS
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decrease in temp
increase heat dissipation caused by vasodilation -no evidence fever is good, excpet for neurosyphillis and chronic brucellosis |
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aspirin and NSAIDS
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-inhibit platelet aggregation
-neonatal patent ductus arteriosos -cancer chemo prevention Niacin tolerability |
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Aspirin, NSAIDS, Coxibs
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-aspirin: non specific irreversible inhibition of COX I and II enzymes
-NSAIDS just like aspirin, but reversible -Coxib: only one that is selective, reversible, of COX II |
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Adverse effects/toxicity of aspirin
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-lowest toxicity at 50mg/dl is a direct effect on medulla
-at 80 is acidosis -at 160 and above is depression of respiratory centers |
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salicylism
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-tinnitus, vertigo, decrease hearing, headache, dimness of vision, mental confusion, drowsyy, sweaty, vommiting, diahhrea
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inhibition of COX I synthesized prostglandin results in loss of:
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-gastric cytoprotection
-vascular homeostasis -platelet aggregation -CNS effects, |
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Adverse effects of aspirin and NSAIDS
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-pregnancy lactation, can effect labor, and postpartum hemorrhage
-increases hypersensitivity reactions, asthma, nasal polyops -cause mild hepatitis in liver -kidneys: prost made by COX I and II promote renal dilation and medullary blood flow... so can cause renal ischemia -decrease in glomular filtration rate -acute renal failure -interstitial nephritis - |
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GI effects with NSAIDS
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gastric upset in ten to twenty percetn
produced by undissolved tablets, decrease in cytoprotective prostglandins |
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how to reduce GI effects of NSAIDS
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-16500 deaths per year
-causes ulceration and bleeding - -reduce with concominant use of proton pump inhbitiors -reduce with misoprostol or selective COX II inhibitors -do not use in patients with peptic ulcer disease |
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COX II selective inhibitors
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-celecoxib: celebrex
-rofecoxib: viox -use selective COX II inhibitors when old, history of ulcers or bleeding, smoker and alchoholic, concominant glucocorticoid and anticoagulant use -associated with risk of increased cardiovascular disease -COX I has bulkier side groups |
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drug interactions, NSAIDS
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-low dose aspirin combined with NSAID: reversible prevents irreversible from binding
-ACE inhbitiors: block vasodilators -gluccocorticoids: gastric irritation both cause -warfarin:inreased bleeding |
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aceaminophin
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weak COX I and II inhbitors in peripheral tissues
-no antiplatelet or anti inflammatory properties -oral with toxic metabolites at high doses -increases hepatic enzymes |
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pathogenesis of rheumatoid arthritis
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-immunological disease
-thickened synovium due to hyperplastic hypertrophic synovicotyes and is infiltrated with immune cells -NSAIDS, STEROIDS, DMARDS, all help with disease, but only DMARDS stop progression when treated early |
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NSAIDS and Rheumatoid arthritis
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-should be used in combo iwth DMARDS
-GI bleeding can be dangerous -COX Ii specific can decrease side effects -proton pump inhibitors can help |
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Glucocorticoid drugs and rheumatoid arthritis
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-slows appearrance of new bone erosion
-adverse effects with prolonged use -never exceed 10 mg daily |
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DMARDS
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-immunosruppressive drugs
-inhibit function and division of immune cells -start soon after diagnosis -slow acting, take several months -efficacy of methotrexat, sulfasalazine, IM gold, and penicillamine is similar -antimalarials are less effective -suppress t and b cell function, purine antagonist, agents that prevent cellular replication, antimetabolites -methotrexate is best one to use, inhbits fast growing cells -leuflunomide: stops T and B cell production |
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types of biologic DMARDS
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-humanized, binds TNFa
-fully human, adalimumab -humanized, CD20 B lymphocytes are bound |
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drugs that inhbit TNF a function
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-abatecept
-eanercept -rituximab -adalimumab -infliximab |
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DMARDS: interleukan 1 receptor antagonist
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-Anakinra
-blocks type I IL receptors -short half life -may be more effective than MTX -investigated for use with gout -sepsis adverse effect |
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GOUT
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-famililal metabolic disease
-associated wit hyperuricemia -arthritis due to deposits in joints and cartiladge -high serum uric acid levels: end product of purine metabolism |
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gout therapies
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-inhibit production of prostaglandins or migration of immune cells for acute attacks
-for chronic focus on decrease of uric acid |
