Pharm Flashcards
pharmacology
study of substances interacting w/ living systems thru chemical processes (binding, activating, inhibiting)
pharmacokinetics. involves: Absorption vs Distribution vs Metabolism vs Excretion/elim
what body does to drug –> determines drug conc in body. drug from administration site to circ vs drug REVERSIBLY goes from circ to tissue vs aka biotransformation; drug modified by enzymes in various cells; active to inactive, active to active/toxic, inactive to active, unexcretable to excretable vs drug/metabolites IRREVERSIBLY elim from body by removing intact drug or removing drug that underwent biotransformation
pharmacodynamics. involves Mechanism of action
what drug does to body. specific biochem interaction where drug produces pharmacological effect
chemotherapy vs pharmaceutics vs pharmacogenomics vs pharmacognosy vs pharmacotherapeutics vs pharmacy vs therapeutics vs toxicology
using drugs to prevent and tx dz vs making drugs vs relationship b/w pt’s genetics and their response to drugs vs study drugs isolated from natural sources like plants and microbes vs using drugs to tx dz vs science involving prep, store, dispense, and use drugs vs using drugs to prevent and tx dz vs study of poisons and organ toxicity
drug resources: small molec drugs vs biologics vs biosimilars
natural (plants, microbes, animals, minerals), semi synthetic (chemically modifying from natural src), synthetic (made in chem lab) vs genetically engineered in living org vs biological product similar to FDA approved product; made from living organisms
excipient
inactive by themselves, goes w/ active ingredient for flavor, bulking/binding, improve manufacture/bioavailability/stability
immediate release vs delayed release vs sustained/extended release vs targeted release vs oral disintegrating tablets (ODT)
conventional, release drug immediately vs release discrete portions some time after admin; enteric coated drugs protect envelope from stomach acid to move to GI tract –> good for acid labile drug vs control drug release for many hours –> slower absorption & longer duration vs release drug at/near intended physiologic site (can be IR or ER) vs disintegrates in saliva, no water needed
is SR/ER drug good for urgent situations?
nope
admin routes: enteral vs parenteral vs other
involves esophagus, stomach, sm/lg intest (PO, SL, PR) vs not involve GI tract (IV, IM, subq, IO) vs inhalation (most rapid), intranasal, intraventricular, topical, transdermal
legend vs nonlegend drugs
rx, more harmful side effects –> don’t self medicate vs OTC, less harmful side effects –> can self medicate
controlled and noncontrolled drugs criteria
based on med use, abuse potential, safety, dependence liability
Schedule I vs II vs III vs IV vs V controlled drugs
highest potential for abuse, no current accepted medical use –> only for research (ex: mj, LSD, heroin) vs high potential for abuse that could lead to physical/physiological dependence (ex: morphine, hydrocodone, amphetamines, cocaine) vs potential for abuse less than I and II that could lead to moderate/low physical dependence or high physiological dependence (ex: codeine, anabolic steroids) vs low potential abuse less than III (ex: alprazolam, diazepam, clonazepam, carisoprodol, tramadol) vs low potential for abuse (ex: combination products w/ limited amts of narcotics, pregablin)
indication vs off label use
med has been evaled for safety and efficacy by FDA –> approved vs rxing meds that has not been FDA approved
adverse drug event vs rxn/side effect
harm to pt from drug exposure d/t drug error; you don’t expect rxn from drug vs pt experiences rxn from drug exposure even if drug admin appropriately; you expect rxn from drug
relative vs absolute contraindication
only rx drug when benefit < risk vs AVOID b/c life threatening
black box warning
most severe warning from FDA about drug
category A vs B vs C vs D vs X
good to go for preg vs no evidence in risk of animal studies w/o controlled studies of preg OR or adverse effects in animal studies w/o controlled human studies vs only give if benefit > risk; evidence of risk on animals (teratogenic, embryocidal) w/o controlled human studies OR no reproduction studies avail for animals or humans vs evidence of fetal risk but benefit > risk vs evidence of fetal risk, risk > benefit –> don’t give
dz oriented evdience vs pt oriented evidence that matters
hard data; answer questions about etiology, pathophysiology, pharmacology; intermediatae or surrogate outcome vs soft data; answers questions that physicians and pts care about and outcome may change practice
how to rx CIII-V vs noncontrolled drugs vs CII drugs
expire 6mo after it’s written, 5 refills up to 6mo period vs no fed specific time limit, VA expires 12mo from date of issue vs no expiration date, no refills, “do NOT fill before [date]”, up to 90d supply
How is drug admin route determined?
Drug properties (water/lipid solubility, ionization) and therapeutic objective (onset, duration, site of action)
Factors influencing drug absorption
pH of area (nonionized = penetrate cell membrane), AUI/BPI; blood flow to absorption site (drug to intestines > stomach b/c intest has more vasculature), total SA for absorption, drug exposure to absorption surface (drug to GI = not good if pt has diarrhea)
1st pass effect/metabolism
Drugs absorbed from gut to liver via hepatic vein before entering circ —> converted to inactive metabolites —> dec bioavailability
bioavailability. How to calculate it?
Rate and extent to which drug reaches circ. How much drug administered, how much drug absorbed (if 100mg of drug = admin, but 70mg of drug = absorbed —> bioavailability = 70%)
When are 2 pharmaceutical equivalents vs bioequivalents?
Have same active ingredient, identical in strength/conc/dose/admin route vs bioavailability of both = not significantly diff
Bioequivalent vs biosimilar based on size and origin
Smaller; chemically synthesized vs bigger; made from living organisms
Factors that affect drug distribution
Blood flow (more vascular = better), capillary permeability (blood brain barrier), binding of drugs to plasma and tissue proteins, size (ex: heparin = too big) and lipophilicity of drug (lipophilic drugs can move thru cell membrane better; hydrophilic drugs can’t —> pass thru slit jxns)
vol of distribution
vol of liquid in which drug needs to be dissolved to mimic same plasma conc; calc by V = D/Co (V = vol of distribution, D = amt of drug in body/total dose, Co = plasma conc at time zero)
one vs two vs multicompartment model of distribution
whole body = 1 compartment –> applicable to drugs that distribute to tissue simul or stay in plasma and elim immediately begins; reality: N/A for majority drugs vs whole body = 2 compartments –> central compartment = init vol of distribution, final compartment = vol of distribution after equil –> applicable to drugs that distribute to tissue slowly or equilibriate slowly b/w plasma and tissue; reality: applicable for majority drugs vs drugs that distribute into mult tissues at significantly diff rates (drugs taken up by vessel rich groups –> muscle –> adipose); so many diverse rates –> drug may never reach equil b/w plasma and tissue
where can metab/biotransformation occur?
liver –> 1st pass effect, has microsomal enzymes; GI tract, lungs, kidney, brain
ex of phase I vs phase II biotransformation rxns
hydrolytic rxns, reductive rxns, oxidative rxns (HRO) vs conjugation rxns, acetylation, glucuronide formation, sulfation, UGTs –> all make it highly soluble
other names and fxns of P-glycoprotein 1 (PGP1) (drug transport protein)
aka multidrug resistance protein 1 (MDR1) or ABC binding cassette sub family B member 1 (ABCB1). Transport drugs back into GI tract, back out of the brain (part of BBB), or into proximal tubule for excretion; uses 2 ATP to pump out 1 molec of drug; lipo>hydrophilic drug preference; protects pt (pumps foreign substances out)
drug transport protein affects?
ADME
renal elim
drug elim thru urine. 1) glomuerular filtration: plasma binding of drug, measure GFR –> 2) active and carrier mediated tubular secretion –> 3) passive tubular reabsorption of nonionized WA/B, ionized WA/B = trapped in nephrons and get elim thru urine, feces, biliary
biliary and fecal elim
drug elim thru liver. 1) active drug and metabolite secretion into bile –> 2) some drugs/metabolites cn be reabsorbed from intestine to body by making them less hydrophilic via gut microbes => enterohepatic recycling
1st vs 0 order/nonlinear kinetics of elim
most drugs use 1st order kinetics; clearance mechanisms = NOT saturable; rate only depends on plasma drug conc; looks like straight line on semilog plot (like MM enzyme plot); rate of admin > rate of elim b/c plasma conc = too low –> as drug = still admin, rate of elim inc and rate of admin = constant –> rate of admin = rate of elim vs for carrier mediated elim; enzymes saturated by unbound drug conc –> plasma drug conc > Km; rate = independent of drug conc
drug Clearance defs and eqn
body’s efficiency in elim drug from circ; vol of plasma from which drug = removed per unit time or rate of drug elim from body relative to plasma drug conc. CL = V/Css (CL = clearance, V = rate of elim, Css = steady state conc)
what is CLtotal vs extraction ratio?
total drug clearance from body from all organs vs fraction of drug cleared by organ
Css. how to reach it?
drug lvls = constant in plasma and target tissue. takes 4-5 half lives to reach Css; when drug = 1st order kinetics, rate of admin > rate of elim b/c plasma conc = too low –> as drug = still admin, rate of elim inc and rate of admin = constant –> rate of admin = rate of elim
what does Css depend on?
drug dose administered, bioavail, drug clearance or half life
2 types of half life: 1/2 life of elim vs 1/2 life of accumulation
time required to reduce drug amt by 1/2 after dosing stops vs time required to inc drug amt by 1/2 during constant infusion
standard dose vs therapeutic range vs drug selectivity
based on trials of healthy volunteers with average ADE –> not suitable for q pt –> individualizes efficacy and toxicity/adverse effects vs Drug conc when pharmacologic response shows desired effects & no adverse effects/toxicity vs ability of drug to show desired effects & minimize adverse effects/toxicity
loading vs maintenance dose
single dose of drug to reach desired plasma conc as fast as possible, followed by MD; base on therapeutic range; usually for IV but if not –> consider bioavailability vs amt of drug given over time to maintain desired plasma conc; based on therapeutic range; rate of drug going in = going out
cont IV infusion vs intermittent dosing for Css
plasma conc inc till it reaches equil –> rate of drug going in = out vs when conc v time curves = superimposable
dosing interval
The frequency of intermittent drug administration, based on the drug’s half-life
vancomycin
glycoside abx; IV active against gram pos, orally active against C diff b/c not absorbed in GI tract; time dependent bacterial killing –> need min conc for therapeutic effects
what is a drug interaction?
when 1+ drugs react w/ e/o, food/drinks, or medical conditions that change PK, PD, metab, or drug properties; can be harmful or helpful
types of drug interaction: drug-drug vs drug-food vs drug-dz aka drug-medical condition interaction vs therapeutic duplication vs pharmaceutical interaction
2+ drugs interact w/ e/o, involves CYP450 vs food/drink changes how drug behaves; alc inc sedatives, Ca2+ chelates doxycycline vs pseudoephedrine inc bp vs 2 meds for same indication vs incompatible chem rxn –> precipitate
what’s special about CYP2C19?
main metabolic pathway susceptible to genetic polymorphisms influenced by race
how do statins lower chol? what are their adverse effects?
inhibit HMG CoA reductase. myalgia/muscle pain, myopathy, weakness, elevated CK, rhabdomyolysis
herbal supplements. example?
not FDA approved, no studies or tests required –> minimal PK/PD studies to support use; USP certification = voluntary. St John’s wort
which enzyme mainly converts prodrug to active drug?
CYP450
polypharmacy
anyone taking 1+ drug and with 1+ comorbidity
who’s at risk for drug interactions?
age, severity of dz, long term dz
characteristics of drugs that more likely to interact
narrow therapeutic window, metab to active metabolite, lower bioavail, metabolized by on CYP450 or by 1 pathway, red flag drugs
digoxin
effluxed into the intestine & not absorbed; lvls dec when PGP inc (lvls inc when PGP dec) b/c not absorbed; non therapeutic index drug –> requires monitoring
theophylline
asthma and COPD tx; narrow therapeutic index –> requires monitoring
synergism vs additive vs antagonism
sum of responses for greater effect vs sum of individual responses vs opposite effects, reduction of total effects
some drugs don’t fit drug-receptor model. what do they do?
physical actions –> osmotic diuretics (inc urine osmolarity; urea, mannitol) or osmotic cathartics (inc intestinal osmolarity; MgSO4). chemical actions –> antacids, chelating agents
what proteins can be drug targets?
structural proteins, circulating proteins, molecular transporters
specificity of receptor’s binding site = based on?
3D structure, shape, charge, chemistry of environ (hydrophobic/philicity, pKa)
transduction in receptor-ligand binding
drug binds to receptor –> alters cellular components linked w/ receptor –> produces response
receptor-ligand binding = d/t which IM forces?
attractive forces: reversible or irreversible/covalent; repulsive forces –> conformational change
drug selectivity = determined by?
specificity for receptors (cisplatin interacting w/ DNA, omezaprole interacting w/ proton pumps) and for receptor-effector coupling (Ca2+ channel blockers work for pacemaker cells > ventricular muscle cells)
agonist (full vs partial vs inverse). antagonist (competitive vs noncompetitive)
activates receptor and keeps it in active form (causes maximal activation vs partial activation; shift dose-response curve down; can act as partial antagonist if full agonist = present => mixed agonist-antagonists vs reduces receptor activity). prevents receptor from activation but preserves activity (reversibly blocks active site; can be overcome by high substrate conc; inc Kd, dec potency, no effect on efficacy vs ir/reversibly binds allosteric site or irreversibly/covalently binds active site; inc Kd, no effect on potency, dec efficacy)
type I drug receptors = ion channels. describe the 3 subtypes
ligand gated (ligand binds to specific site on receptor –> alters pore size –> ions pass thru; ex: asp/glu = excitatory aa receptors, GABA/glycine = inhibitory aa receptors). voltage gated (change in transmembrane potential –> depolarization –> opens channel for ions to pass thru; ex: Na+, K+, Ca2+ channels). secondary msgr (modulated by G protein coupled receptor)
type II drug receptors = G protein coupled receptors
7 transmembrane regions: extracellular domain binds to ligand, intracellular domain binds and activates G protein; G protein has 3 subunits: alpha, beta/gamma
Gs vs Gi vs Gq vs G12/13
activates Ca2+ channels, activates adenylyl cyclase –> inc cAMP vs activates K+ channels, deactivates adenylyl cyclase –> dec cAMP vs activates PLC –> inc IP3 –> inc Ca2+ vs activates Rho for PLT aggregation
type III drug receptors = transmembrane enzymatic receptors
single membrane spanning unit + intracellular domain has cyto MOA –> membrane bound and cytosolic; receptors may dimerize upon activation; ex: kinase, phosphatase, guanylyl cyclase
can AC and GC be metab by PDE? can they be activated by G protein?
yes. yes
type IV drug receptors = intracellular
target intracellular enzymes (vit K), transcpxn factors (steroids/cortisol, glucocorticoids/prednisone), structural proteins (abx targeting 50/30S ribosomes), nuclear receptors (glu)
drug-receptor occupancy theory
When sufficient amount of receptors = bound by a drug –> cumulative effect of receptor occupancy = more apparent as a cell response
Response in many cells –> bigger response observed in organ or organism/patient
how to find dissociation constant Kd b/w ligand/receptor interaction. how to find binding affinity/% bound?
[L][R]/[LR]. binding affinity = LR/Ro (LR = bound receptor, Ro = total amt of receptor); higher binding affinity –> low L
graded dose-response vs quantal dose-response relationship
dose-response curve for individual –> response = graded, depends on dose vs dose-response curve for pop –> response = present or absent
2 parameters for graded dose response relationship: potency (EC50) vs efficacy (ECmax)
drug conc where drug causes 50% of maximal response vs maximal response produced by drug
3 parameters for quantal-dose relationship: median effect dose (EC50) vs median toxic dose (TD50) vs median lethal dose (LD50)
drug conc where drug causes 50% of maximal response vs drug conc where 50% of pop have toxic effects; indicators of toxicity vs tested on animals; indicators of toxicity
what does it mean for drug to have high TI value?
wide therapeutic index –> desired effects curve and toxic effects curve don’t overlap –> excess drug = okay to give for therapeutic effects
nonreceptor antagonists: chemical vs physiologic
binds to agonist and neutralizes it before it can work vs produces effect that’s opposite to agonist effect
spare receptors
extra receptors to induce response when not enough main receptors = occupied; occupancy = NOT related to strength of response (ie. you don’t need to fill all main receptors to induce response, just enough to pass threshold)
clinical ex of spare receptors: insulin receptors vs heart
1% receptor occupancy required for max response –> 99% = spare –> large fxnal reserve vs 90-95% receptor occupancy required for max response –> 5-10% = spare –> little fxnal reserve
how do spare receptors act in presence of low vs high conc of noncompetitive antagonists?
still get max response vs can’t get max response
how do agonists shift curve low vs high conc of noncompetitive antagonists?
shifts curve down like competitive antagonist vs shifts curve down and to right
how do allosteric activators shift curve?
up and to left
osteoporosis
inc bone resorption, fx risk; dec bone formation, bone mass; microarchitectural disruption
sunshine vs vit D vs low Ca2+ vs PTH vs calcitonin
inc endogenous vit D3/cholecalciferol in skin –> inc vit D/calcitriol –> inc bone turnover vs prohormone vit D –> calcidiol –> calcitriol (active) –> inc bone turnover by inc osteoblasts and clasts; D2 = ergocalciferol, D3 = cholecalciferol vs inc PTH and calcitriol to inc bone resorption vs low exogenous PTH –> inc bone turnover, high exogenous PTH –> bone resorption vs inhibit clasts –> dec bone resorption
estrogen vs GH
dec clasts –> indirectly inc bone formation vs inc blast activity –> inc bone formation
primary vs secondary risk factors of osteoporosis
inc age, previous fxs, fhx, cauc/asian, low body wt, menopause vs steroids/heparin/excess thyroid hormones, alc/caffeine/tobacco, inactivity, diet
universal recs for osteoporosis
adeq intake of Ca2+ (calcium carbonate/citrate, milk/yogurt/cheese), adeq intake of vit D (D2/3, sun, fortified milk), wt bearing exer, fall prevention, stop smoking/alc
which 3 bones DEXA measures?
femoral neck, total hip, lumbar spine
paget’s dz of bone
localized dz d/t uncontrolled osteoclastic bone resorption –> bone formation = unorganized –> bone pain, deformity, fx, arthritis
sxs of Paget’s
mostly asx; bone pain, deformity, fx, arthritis, hypercalcemia, osteosarcoma
how to tx Paget’s?
adeq intake of Ca2+ and vit D, bisphosphonates (zoledronic acid = tx of choice), NSAIDs, calcitonin
chemical mediators of inflamm
histamine, complement proteins, eicosanoids (metabolites from arachidonic acid), cytokines (IL1, TNF alpha), ROS/RNS
How does arachidonic acid become eicosanoids?
TNF alpha stimulates PLA2 –> PLA2 releases AA from phospholipid membrane –> prostaglandins sensitize nociceptors –> promote blood flow to injured tissues –> inc leuks, edema, inflamm
COX/prostaglandin H synthase has 2 enzymatic activities: cyclooxygenase vs peroxidase
catalyzes O2-dep cyclization of AA to PGG2 vs catalyzes reduction of PGG2 to PGH2
COX1 vs COX2 vs COX3
protection and maintenance: vasc homeostasis, maintenance of GI and renal blood flow and fxn, PLT fxn vs inflamm, fever, pain, mitogenesis vs potential binding site of acetominophen
5 manifestations of inflamm
heat, swelling, redness, pain, loss of fxn
examples of COX inhibitors
NSAIDS: ASA (salicylate), ibuprofen (like Motrin/Advil; propionic acid derivative), indomethacin (acetic acid derivative). COX2 inhibitors: celecoxib. acetaminophen = NOT a trad NSAID b/c not fully antiinflamm and structurally diff
antipyretics and analgesics tx?
rheumatic fever, rheumatoid arthritis, and inflammatory joint conditions
trad NSAIDs can tx?
tx pain and fever
relieve inflammation for arthritic d/o and injuries
slow progression of Alzheimer’s
dec risk of colon ca
ASA adverse effects
epigastric distress, ulcer, hemorrhage, resp depression, Reyes, hypersensitivity
Reyes syndrome
occurs when ASA given to children w/ viral infxn –> fatal fulminating hepatitis w/ cerebral edema
how does ASA affect PLTs?
TxA2 –> inc plt aggregation
PGI2 –> dec plt aggregation
ASA –> dec COX1 in plts –> dec TxA1 in plts –> dec plt aggregation –> anti-thrombogenesis –> prophylaxis of MI and stroke
how does ASA affect kidneys?
PGE/I2 maintain renal blood flow. ASA –> dec COX –> dec PGE/I2 –> dec renal blood flow –> renal dysfxn –> water/salt retention
acetaminophen key points
not a NSAID; can inhibit COX3 –> tx mild pain and fever; OD = liver injury (responsible for 46% of liver failure in USA) –> N-acetylcysteine as antidote –> cys –> glutathione –> detox toxic metabolites of acetominophen
propionic acid derivatives key points
ibuprofen = potent NSAID; reversibly inhibits COX. naproxen = single enantiomer and more potent than ASA. ketoprofen inhibits both COX and lipoxygenase. flurbiprofen for ophthalmic. oxaprozin has long 1/2 life, mildly uricosuric –> tx gout
acetic acid derivative key points
indomethacin and diclofenac = potent; indomethacin for patent ductus arteriosus; diclofenac for arthritis and opththalmic, has serum aminotransferases. sulindac dec colon ca. etodolac = COX2 selective
oxicam derivative key points
piroxicam has long 1/2 life, tx arthritis. meloxicam = COX2 selective
