GMS 6551 Final Exam 2025

Drugs usually target - -non-human protein Natural products include - -plants, algae, bacteria, fungi Chemical banks include - -synthetic compounds that number in thousands or millions Rational drug design - -utilizes side effects from another drug to treat another disease by modifying a natural ligand Computer aided drug design (molecular docking) - -take crystal structure of target protein, look at it in 3d program. Computer program calculates chemical attraction. Structure activity relationships - -use organic chemistry to add functional groups, test new compounds, take best and add more functional grounds, then begin clinical trials Drug - -any substance that interacts and modulates a living system Agonist - -drug that activates biological response Antagonist - -drug that inhibits biological response Nomenclature - -chemical name given based on chemical structure Non-generic name - -name given based on chemical or pharmacologic class Proprietary name - -name given at marketable point Fda-approved beta blockers - -end in -lol Drugs classified based on chemical properties - -benzodiazepines, sulfonamides Drugs classified based on mechanism of action - -ace inhibitors, calcium channel blockers, carbonic anhydrase inhibitors Drugs classified based on disease or condition used to treat - -analgesics, antidepressants, antihypertensives Drugs classified based on abuse potential - -class i, ii, iii, iv Flumencinol - -treatment of hyperbilirubinemia in newborn infants unresponsive to phototherapy GMS 6551 GMS 6551 Antithrombin iii - -treatment of patients with hereditary antithrombin iii deficiency in connection with surgical or obstetrical procedures or when they suffer from thromboembolism Gancyclovir - -treat cmv in immunocompromised patients EGF - -wound healing Zidovudine/AZT - -treat aids Succimer - -treat lead poisoning Somatrem, somatropin - -treating growth hormone deficiency Acetylcysteine - -treat acetaminophen overdose Glatiramer acetate - -treat multiple sclerosis Class i controlled substances - -high abuse potential (heroin, lsd, marijuana) cannot be prescribed Class ii controlled substances - -high abuse potential, no refills (morphine, amphetamine, high dose codeine) Class iii controlled substances - -moderate abuse potential (ketamine, low dose codeine) 5 max refills within 6 months Class iv controlled substances - -low abuse potential (benzodiazepines) 5 refills max within 6 months Class v controlled substances - -lowest abuse potential (dephenoxylate) T0 - -basic science research, pre-clinical & animal studies. Defining mechanisms, targets, or lead molecules T1 - -translation to humans, phase 1 clinical trials T2 - -translation to patients, phase 2 & 3 clinical trials T3 - -translation to practice, phase 4 clinical trials T4 - -translation to community Unmet health need - -condition whose treatment or diagnosis is not addressed adequately by available therapy GMS 6551 GMS 6551 Pre-discovery - -3-6 years Clinical trials - -6-7 years FDA review - -0.5-2 years Small molecule weight limit - -900 da Device - -intended to affect structure or function of body without chemical action and is not dependent on being metabolized Class i device - -bandages, gloves Class ii device - -acupuncture needles, powered wheelchair, infusion pump, surgical drapes Class iii device - -pacemaker, defibrillator Top selling biologic drug - -humira 16.1 billion Sensitivity - -probability that an individual with the disease tests positive Specificity - -probability that an individual without the disease tests negative Ectopic xenograft - -ectopic implantation of cell/tissue Orthotropic models - -implantation of cell line into organ of origin Germ-line and conditional transgenic - -spontaneous or autochthonous development Primary human tumor graft - -direct implantation of freshly excised tumor Carcinogen/tumor promoter - -development in response to carcinogen/tumor promoting agent Phase i trial primary endpoints - -establish maximum tolerated dose & define dose/schedule for phase ii Phase i secondary endpoint - -route of drug administration, half life, bioavailability, engagement of target, therapeutic efficacy Fast tracking - -FDA relaxes stringent guidelines to prioritize first in class therapeutics and life-threatening diseases without an effective standard of care Alternative to MTD - -target engagement, plasma drug levels, surrogate markers GMS 6551 GMS 6551 GMS 6551 Combination therapeutic/biomarker - -allows assessment of the degree to which the therapeutic is producing the desired biochemical effect Prevention trial - -vaccines Screening trial - -identify approaches to detect diseases/conditions Treatment trial - -test effectiveness of new treatments for diseases/conditions Behavioral trial - -identify/evaluate/compare new approaches to promote behavioral changes to improve health Quality of life trial - -improve comfort in patients with diseases/conditions Phase 0 clinical trial - -exploratory studies with limited human exposure with no therapeutic or diagnostic goals Phase 1 clinical trial - -small group of healthy volunteers to assess safety; find out drug's most frequent and serious adverse effects are and how its metabolized and excreted Phase 2 clinical trial - -gather preliminary data on effectiveness and further evaluate safety, define target population Phase 3 clinical trial - -300 patients to thousands; study different populations and different dosages and use the drug in combo with other drugs Phase 4 clinical trial - -studies after FDA has approved a drug for marketing Heterogeneity contributes to a decrease in: - -accuracy, reliability, generalization of findings of study Informed consent - -voluntary agreement to participate in research Parallel trial design - -two groups of treatments are given so that one group only receives one and the other group only receives the other Factorial trial design - -groups of participants receive one of several combinations of interventions Cross-over trial - -each participant randomized to a sequence of treatments that will be administered during treatment periods Non-inferiority trial - -compares a novel treatment to an active treatment with a view of demonstrating that it is not clinically worse with regards to a specified endpoint GMS 6551 GMS 6551 New drug application - -provide enough info to permit fda review to reach key decisions (safe & effective, appropriate labeling, manufacturing methods & controls used) Enzyme drug targets - -cancer drugs, cholesterol lowering drugs, anti-hypertensive drugs, pain/inflammation Receptor drug targets - -cns disorders, cardiac Channel-linked receptors (ionotropic) - -milliseconds: nicotinic ach receptor G-protein coupled receptors (metabotropic) - -seconds: muscarinic ach receptor Kinase-linked receptors - -minutes: insulin, egf Receptors linked to gene transcription (nuclear receptors) - -hours: estrogen receptor Ligand gated channel receptors - -ach, gaba, serotonin, glutamate Cytokine receptors - -jak-stat signaling, growth hormone, leptin Intracellular receptors (steroid) - -ligand binding domain, dna binding domain Interactive/sequential signaling - -receptor activates downstream effect Amplification - -agonist binds to receptor, multiple ligands can bind & high level of response can be achieved Receptor occupancy theory - -in order for a drug to have an effect, it must occupy the receptor. Effect is proportional to number of receptors occupied Efficacy - -maximum response produced by a drug Potency - -concentration or dose of drug that produces 50% of the maximal response The more bonds, the higher the ______ for receptors - -affinity Competitive antagonist - -decreased affinity of agonist for receptor. Always changes potency but not efficacy Non-competitive antagonist - -binds to complete different site. Potency does not change, but efficacy does Inverse agonist inhibition - -blocks constitutive activity of receptor and blocks receptor, preventing response Desensitization - -fewer receptors on cell surface due to constant activation of receptors GMS 6551 Supersensitivity - -enhanced response due to agonist activation Graded concentration response - -exact response predicted in a controlled system at specified drug concentration Quantal dose response - -all or none response, group of individuals Therapeutic index - -td50/ed50 ; higher number = fewer toxic effects Enteral administration - -oral, sublingual, rectal Parenteral administration - -intravenous, intramuscular, topical, transdermal, inhalation Bioavailability - -absorbability of a drug usually measured in % Oral administration - -first pass metabolism, can never reach 100% bioavailability Single compartment model - -drug distributes evenly throughout body Unequal distribution - -metabolized before pure equilibrium Phase 1 metabolism - -activation of molecule to be conjugated with more polar group Cytochrome p-450 proteins - -have high expression in the liver and oxidize drugs Metabolism of steroids and lipids normally occurs during - -phase 1 metabolism Phase 2 metabolism - -biotransformation into more polar form to be excreted in urine, feces, or bile Phase 1 enzymes - -cyps, epoxide hydrolase, dpyd Phase 2 enzymes - -ugts, sults, gsts, nats, tpmt Oxidation - -acetanilid - acetaminophen Epoxidation - -naphthalene O-dealkylation - -phenacetin - acetaminophen ; codeine - morphine Reduction - -chloramphenicol Dehalogenation - -halothane Hydrolysis - -esters and amides ; benzocaine GMS 6551 GMS 6551 GMS 6551 Acetylation - -amine and hydroxyl groups ; sulfanilamide Glucuronidation - -hydroxyl and carboxyl groups readily conjugated ; salicyclic acid, morphine - morphine-6 glucuronide Sulfation - -acetaminophen Glutathionation - -important for removal of toxic metabolites ; naphthalene epoxide Glomerular filtration - -most drugs passively filtered into nephron ; 125 ml/min Active tubular secretion - -secretion of drug through ion transporters ; clearance 600 ml/min Passive reabsorption - -drugs passively reabsorbed in urine formation Ion trapping - -can speed up removal of drugs (ex. Bicarbonates in aspirin overdose) Biliary excretion - -active transport systems for basic and acidic compounds Entero-hepatic recycling - -can trap a drug and prolong its presence in the body; gut bacteria unconjugates metabolites which get transported back to the liver Breastmilk excretion - -unionized drug passively diffuses through mammary epithelium; anti-cancer drugs, lithium Steady state - -rate of drug infusion = rate of drug elimination First order elimination - -non-saturating, plateaus Zero order elimination - -linear relationship, high substrate concentrations Elimination rate - -elimination constant x drug concentration Half life - -0.693/elimination constant (first order processes only) Volume of distribution - -measures drug distribution between plasma and rest of body (dose/plasma concentration) Loading dose - -volume of distribution x desired plasma concentration Clearance - -describes relationship between drug concentration and rate of drug elimination from body Rate of elimination - -clearance x drug concentration GMS 6551 GMS 6551 Maintenance dose - -clearance x drug concentration x time interval Condition of state of being - -physiological set point P-450 inductors - -charcoal broiled food, broccoli/sprouts P-450 inhibitors - -grapefruit juice, tropical fruits Non-cyp enzymes - -alcohol, aldehyde dehydrogenase (ethanol metabolism) Diseased induced alteration in pk - -impaired renal or hepatic function, circulatory insufficiency, altered drug binding Disease induced alteration in pd - -hyperthyroidism Environmental factor that can affect tetracycline - -sunlight Genetics that can affect codeine conversion to morphine - -poor vs ultra-rapid metabolizers Genetics that can affect isoniazid metabolism - -slow vs fast acetylators Genetics that can affect warfarin metabolism - -reduced p450 metabolism, increase/decrease in target sensitivity to drug