Exam 1 Flashcards

Question

What are the three main physiochemical properties of drugs?

Answer 1

1. **Molecular size** - determined by the number and type of atoms, and the stereochemistry (how the atoms are arranged) 2. **Solubility** - determined by overall polarity of the drug, measured using the parition coefficient 3. **Charge** - determined by the acidic, basic or neutral characteristics of the drug

Answer 2

* PC is measured experimentally using water and 1-octanol * PC > 1 = hydrophobic * PC < 1 = hydrophilic * PC = [Drug]_fat / [Drug]_water

Answer 3

* Ionized (charged) drugs tend to be hydrophilic and stay in the plasma * Unionized (uncharged) drugs tend to be hydrophobic and diffuse into plasma * Both acids or bases can diffuse into plasma, if they are unionized (ex: a weak acid is unionized in a very low pH) * Ionized/unionized character largely depends on pH of the solution

Answer 4

* HA <--> H⁺ + A^- * Equilibrium with weak acids involve an equilibrium constant (K_eq) and are pH dependent * [A-] / [HA] = ionized / unionized

Answer 5

1. Filtration through pores - all forms 2. Passive diffusion (simple and carrier facilitated) - unionized, nonprotonated, uncharged 3. Active transport - charged, ionized, protonated 4. Minor endocytosis - not used often

Answer 6

1. Enteral - absorbed in GI tract * Oral, sublingual, rectal 2. Parenteral - absorbed somewhere other than GI tract * Subcutaneous, intramuscular, intravenous (IV), intraarterial, inhalation, intrathecal 3. Topical - drug placed on surface of tissue * Patches, intravaginal, dermatological/ophthalmic applications

Answer 7

1. Physiochemical properties of the drug 2. Biological membranes encountered 3. Protein binding and storage 4. Blood perfusion 5. Disease states

Answer 8

* Basic drugs enter tissues by passive diffusion, then become protonated (ionized) * Ionic form of basic drug can't diffuse out and "ion trapping" occurs * Happens to basic drugs in acidic environments (stomach, prostate gland, etc.)

Answer 9

* Protein binding occurs in plasma and tissues * Free drug - unbound drug, able to move freely * Drugs bound to proteins (like albumin) cannot move and diffuse as easily * Another substance (such as another drug) may compete and bind to the protein, thus increasing the free drug concentration

Answer 10

* **Initial distribution**: depends primarily on blood flow to a body region * **Redistribution**: can terminate actions of drugs (particularly hydrophobic drugs), depends on factors other than blood flow

Answer 11

* **Biotransformation**: drug metabolism, a change in chemical structure caused by a living system * Primarily occurs in the liver * Product is a **metabolite** - more polar, more water soluble, excreted faster * **Results**: activates an inactive drug, inactives an active drug, active drug to active metabolite, safe metabolite or drug to toxic one

Answer 12

* Phase I - oxidation, reduction, hydrolysis * Phase II - conjugation or synthesis

Answer 13

* **Fat** - lipid soluble drugs, environmental chemicals, anesthetics * **Bone** - tetracyclines (and other calcium replacement), metals (lead) * **Kidneys** - aminoglycosides, cephalosporins

Answer 14

* Located in smooth ER * Catalyzes biotransformations * To be metabolized by microenzymes, substrates must be hydrophobic * Acetaminophen, ethanol --> metabolized by CYP 2E1 * Different types: MFO, CYP * Activity is inducible: * Tobacco smoke induces CYP 1A2 * Ethanol --> CYP 2E1 * Antiepileptic drugs --> CYP 3A4 * Grapefruit juice --> inhibits CYP 1A2 + 3A4

Answer 15

* Side chain/alkyl hydroxylation * Aromatic ring hydroxylation * N-/O-/S- demethylation * Oxidative deamination * Sulfoxide formation * N-oxidation or hydroxylation * Dehalogenation * Glucuronide formation * Reduction of nitro and azo groups

Answer 16

* Located in the cytosol, mitochondria, blood (esterases) * Activity is generally not inducible

Answer 17

* Alcohol/aldehyde dehydrogenase * MAO * Esterases * Amidases * Conjugations of sulfate, acetylation, glycine, methylation, glutathione

Answer 18

* Enzyme activity inducers (drugs, smoking, etc.) * Enzyme inhibitors * Age * Liver function * Nutritional state * Genetics (polymorphisms) * Gender

Answer 19

Path: 1. Absorption 2. Portal vein/general circulation, hepatic artery 3. Sinusoid in liver 4. Hepatocyte * Back to blood 5. Bile canaliculus 6. Bile ductule 7. Gallbladder * MW = 0-220 --> urine 8. MW = 300+ --> bile 9. Small intestine * Enerocyte to liver (again) - **enterohepatic cycle** * General circulation * Excretion

Answer 20

1. Filtration of drugs through pores in glomerular capillary membrane 2. Active transport of anionic and cationic forms of drugs in the proximal portion of the nephron 3. Non ionic back diffusion of uncharged drugs occurs in the distal portion of the nephron

Answer 21

* A change in [blood] = change in the effect of the drug * Usually, an increase in the dose = increase [plasma] = increase effects

Answer 22

* 1 body = 1 compartment * Drug rapidly equilibrates between plasma and tissues * Change in [plasma] reflects a proportional change in [tissue] * On a semi-log plot, a one-compartment model is a straight line.

Answer 23

* 1 body = 2 compartments (central and peripheral) * Drug takes longer to equilibrate * Elimination happens from central compartment * 2 phases: initial distribution phase and elimination phase * On a semi-log plot, the two compartment model is one line with 2 straight segments

Answer 24

* Rate of decrease in [drug] is directly proportional to the amount of drug in the body * A constant fraction of drug is eliminated. The constant fraction is dose independent. * 10% of drug is eliminated per hour * Starts at: 100 mg * 1st hour: 90 mg * 2nd hour: 89 mg * 3rd hour: 80.1 mg * Most drugs follow first order kinetics * On a linear plot, first order kinetics are curved. (Semi-log plot, first order is linear) * **C = (dose / V_d)e^-kt** * ke --> elimination rate constant * C --> concentration

Answer 25

* Enzymes are saturated. * A constant amount of a drug is eliminated, independent of the dose * Example: 10 mg eliminated per hour * Starts at: 100 mg * 1 hour: 90 mg * 2 hours: 80 mg * 3 hours: 70 mg * On a linear plot, zero order kinetics is a straight line

Answer 26

* Fraction of unchanged drug that reaches systemic circulation following administration * IV drugs have F = 1, all other drugs are less than (or equal to) 1. * To determine F: * Administer drug via IV and measure [plasma] over time * Administer same dose by different route and measure [plasma] over time * The area under the curve (AUC) is an index of the extent of the drug that enters the bloodstream and body * **F = (AUC_oral)/(AUC_IV)**

Answer 27

* The time for total plasma drug concentration to decrease by 50%, expressed in hours or minutes * After 1st half life - 50% remains * 2nd half life - 25% remains * Depends on both CL and V_d * **Four half lives rule**: A drug is considered essentially eliminated after 4 half lives (6% remains in body) * **t_1/2 = (ln 2)/(ke) = (0.693)/(ke)** * Fraction of drug remaining = 1/2ⁿ, n = # half lives

Answer 28

* The apparent volume that a drug is distributed within the body once an equilibrium is established between the tissue and plasma, expresses in L or L/kg body weight * V_d can be greater than total body weight * Warfarin V_d = 9 L (99% protein bound) * Thiopental V_d = 140 L * Morphine V_d = 245 L * **V_d = (Dose_IV) / (C₀)**

Answer 29

* The volume of blood from which a drug is totally removed in a given time, expressed as L/hr or mL/min * Due to metabolism and excretion * If V_d remains constant and t_1/2 increases, then CL will decrease * **CL = (ke)(V_d)** * ke = (ln 2) / (t_1/2

Answer 30

* Following a single dose administration, the [plasma] is proportional to the dose administered * **A = (C)(V_d)** * A = dose administered, C = concentration

Answer 31

* The average [plasma] when a balance is achieved between drug intake and elimination * To achieve CSS, a drug must be given at regular intervals * It takes 4 half lives to attain CSS * **CSS = (MD) / (CL)** * MD = maintenance dose

Answer 32

* Drugs are often given for intervals of 7-10+ days. * During this time, [drug] has peaks and troughs * Peaks - highest concentration * Troughs - lowest concentration, right before next dose * The longer the dosing interval, the greater the variation between the peak and trough values * ** MD = (dose * F) / (dosing interval) = CSS * CL** * If drugs are given via IV, substitute MD for infusion rate. * ** CSS = (Infusion rate) / (CL)**

Answer 33

* A single large dose, administered via IV, given to achieve CSS in a short period of time * Loading dose is followed by an MD to maintain CSS * **Loading dose = (CSS * V_d) / F

Answer 34

* **Dose**: the amount of drug administered * **Response**: a change in biological activity * **Dose response relationship**: relationship between amount of drug administered and observed changes in biological function

Answer 35

1. **Occupation theory**: magnitude of a response is proportional to the number of receptors occupied by a drug 2. **Rate theory**: magnitude of a response is proportional to the rate of formation of the drug-receptor (D-R) complex

Answer 36

* **Dissociation constant (K_D)**: the tendency of a substance to reversibly dissociate in a solution * K_D = (k₂) / (k₁) * k's are association rate constants * **Affinity**: the ability of a drug to bind to a receptor

Answer 37

* **Intrinsic activity**: ability of a drug to produce a biological effect * **Efficacy**: maximal effect produced by a drug * **Potency**: determined by the dose needed to produce a particular effect of a given intensity

Answer 38

* **Specificity**: ability of a drug to act through a single mechanism of action * **Selectivity**: ability of a drug to induce one effect in preference to another effect

Answer 39

* An increase in efficacy is up the y-axis * An increase in potency is to the left on the x-axis * Partial agonists will not reach the same efficacy (same height on the y-axis) as full agonists * The most potent drug will be furthest to the left.

Answer 40

1. Competitive * Maximum efficacy remains the same * Curve shifts to the right (lower potency) 2. Non competitive * Maximum efficacy decreases (shift down)

Answer 41

* **Agonist**: a drug with affinity and intrinsic activity * **Antagonist**: a drug with affinity, but no intrinsic activity. Decreases either the potency or the efficacy of an agonist

Answer 42

* **Graded**: a drug's concentration vs magnitude of effect in a single individual * The y-axis can go above 100%, because it shows the increase in desired effect of a single individual * **Quantal**: a drug's concentration vs the percent of people in a population who experience a certain level of effect (e.g., can sleep) * The y-axis cannot go above 100% because you can't have more than 100% of the population experiencing something

Answer 43

* **ED₅₀ (median effective dose)**: dose required to produce a therapeutic effect in 50% of test subjects * **LD₅₀ (median lethal dose)**: dose required to produce death in 50% of test subjects

Answer 44

* **Therapeutic index or ratio (TR or TI)**: the difference in an effective dose and a toxic dose * TI = (LD₅₀) / (ED₅₀) * **Certain safety factor (CSF)** = (LD₁) / (ED₉₉) * If CSF > 1, then no overlap between the therapeutic and toxic curves * If CSF < 1, then the therapeutic and toxic curves overalp

Answer 45

* **Tolerance**: decrease in efficacy with repeated drug administration (e.g., narcotics) * **Tachyphylaxis**: acute tolerance to rapid, repeated drug administration (e.g., nitroprusside) * **Resistance**: a decrease or complete lack of responsiveness to drugs that normally inhibit growth or cause cell death (e.g., chemotherapeutics)

Answer 46

* **Additive effect**: the total effect equals the sum of the effects of drug A + drug B * Cancer chemotherapeutic agents * **Synergy**: the total effect > effects of drug A + drug B * Penicillin + Amino glycoside * **Potentiation**: drug A has little to no intrinsic activity, but increases the effects of drug B. * Cocaine + NE * Moves dose response curve to the left

Answer 47

* **Pharmacokinetics**: what the biological system does to the drug (absorption, distribution, etc.) * **Pharmacodynamics**: what the drug does to the biological system (mechanism of action, effects, etc.)

Answer 48

* Inverse agonists are agents that stabilize a receptor in its inactive conformation * Losartan - AngII receptor blocker * Famotidine - H2 receptor blocker

Answer 49

* Receptors are classified based on the effects and potencies of select agonists/antagonists, and on molecular biology * Cholinergic receptors * Nicotinic & Muscarinic (M_1-4) * Adrenergic receptors * Alpha (A₁, A₂) & Beta (B_1-3)

Answer 50

1. Membrane receptors associated with enzymes 2. Intracellular receptors 3. Receptors on membrane ion channels 4. Receptors linked to effectors via G-proteins

Answer 51

* Protein kinases (e.g., tyrosine kinases) * Insulin, growth hormones * Protein kinase-associated receptors * Cytokines, interferon gamma receptors * Guanylyl cyclase * Membrane bound (ANP, BNP), soluble (nitric oxide)

Answer 52

* Includes receptors for several neurotransmitters * Nicotinic ACh, GABA_A, Glutamate, Aspartate, Glycine * Alters ion movement across cell membrane * Alters membrane electrochemical potential

Answer 53

* Ligand must be hydrophobic and able to passively diffuse through cell membranes * Once bound to the receptor, usually DNA transcription is altered to increase or decrease the rate of protein synthesis * Examples: steroids, retinoids, thyroid hormones

Answer 54

* GCPRs are the largest superfamily of receptors * GCPRs have 7 helical domains that span the membrane * On the outside, they bind the ligand * On the inside, they bind a G-protein, with alpha, beta, and gamma subunits * The alpha unit contains a GTP binding site. * To trigger a G-protein signal transduction: 1. A ligand binds to the extracellular portion of the GCPR. 2. The intracellular G-protein undergoes a conformational change. 3. The alpha subunit swaps its bound GDP for a GTP. 4. The G-protein dissociates into a beta-gamma subunit and an alpha subunit. 5. The alpha subunit triggers a cascade to carry and amplify the "message"

Answer 55

* G_q * M₁, M₃, A₁, serotonin * Activates Phospholipase C * Increases IP₃ and DAG * Increases Ca²⁺ and protein kinase activity * G_s * B-adrenergic, D₁, histamine * Stimulates adenylyl cyclase * Increases cAMP * Increases Ca²⁺ influx and enzyme activity * G_i * A₂, M₂, opioids * Inhibits adenylyl cyclase * Decreases cAMP * Decreases Ca²⁺ influx and enzyme activity * Increases K⁺ efflux

Answer 56

* Made by adenylyl cyclase * 1 active AC = multiple cAMP produced * Regulates activity of PKAs * PKAs can phosphorylate targets such as insulin, glucocorticoid receptor, etc. * Inactivated by PDE (phosphodiesterase)

Answer 57

* Made by different forms of guanylyl cyclase (GC) * Nitric oxide stimulates soluble GC * Natriuetic peprides + guanylins stimulate particulate GC (membrane spanning) * Regulates activity of PKGs * Important effects: smooth muscle relaxation, platelet inhibition

Answer 58

* Both cAMP and cGMP can activate ligand gated channels for Ca²⁺ * PLC (phospholipase C) cleaves PIP2 into DAG and IP₃ * DAG --> activates PKC * IP₃ --> releases Ca²⁺ from the ER * Changes in [Ca²⁺] and activation of PKC regular many cellular functions

Answer 59

Long term administration of agonist --> continuous stimulation --> tachyphylaxis and tolerance

Answer 60

Long term administration of an antagonist --> chronic reduction of receptor stimulation --> super response

Answer 61

* Antacids: CaCO₃, Al(OH)₃, Mg(OH)₂ * Osmotic diuretics: Mannitol (laxative) * Cholesterol binding resins: WelChol * Antibiotics (have target receptors in bacteria but not in humans)

Answer 62

* Medical care based on specific biological characteristics of the disease process in individuals * First case- breast cancer * Treatment (Herceptin) interfered with the overexpression of HER2 gene that was causing the cell proliferation and cancer * Other treatments just targeted all the cells as a whole, rather than the specific element of a cell causing the cancer

Answer 63

The study of the structure, content and evolution of genomes

Answer 64

1. **Length polymorphisms** - insertions/deletions (indels), microsatellites 2. **Sequence variation** - SNPs

Answer 65

* **Loci (locus)**: a single position on a chromosome (may be that of an allele, gene, segment, etc.) * **Alleles**: alternate "forms" of DNA at a specific locus * "Forms": sequence variations, length polymorphisms, protein expressions, etc.

Answer 66

* **Homozygous**: 2 identical alleles at a given locus * **Heterozygous**: 2 different alleles at a given locus

Answer 67

* **Genotype**: genetic constitution of an organism * **Phenotype**: observable physical properties

Answer 68

* **Dominant**: heterozygote phenotype = homozygote phenotype * **Recessive**: heterozygote phenotype is not the same as the homozygote phenotype * **Wildtype**: most common phenotype

Answer 69

* The presence of 2+ alleles at a given locus for a population * More alleles = more polymorphism = more chance an individual is heterozygous for that locus

Answer 70

* CYPs are the most common drug metabolizing enzyme in humans * CYPs are responsible for: * synthesis of cholesterol, steroids, prostacyclins, thromboxane A₂, and other important lipids

Answer 71

* **Allelic heterogeneity**: two or more different alleles (genetic variants on the same gene) that result in the same phenotype * **Locus heterogeneity**: two or more different genes result in the same phenotype

Answer 72

* \*1S\ --> deletion of AT, loss of function * \*6\ --> insertion of A, frameshift * \*20\ --> insertion of A, frameshift

Answer 73

7th chromosome, q = long arm, region 22.1

Answer 74

* - means upstream of the gene * 392 is the number of base pairs * Most have A nucleotide base, but some have G

Answer 75

CYP3A4 \*1A\

Answer 76

* A variation in phenotype caused by environmental conditions (not genetics) * Example: Statins inhibit CYP 2D6 --> affects codeine/morphine pathway --> codeine has less of an effect

Answer 77

* **No CYP2D6** (gene deletion) --> poor metabolizers --> codeine does not become morphine --> little to no pain relief * **Lots of CYP2D6** (gene duplication) --> extensive metabolizers --> codeine quickly turns to morphine --> toxic levels of morphine

Answer 78

* Extensive metabolizer * Prodrug --> super effect (toxic levels, turns active too quickly) * Active agent --> No effect (no response to the drug, it's eliminated too fast) * Poor metabolizer * Prodrug --> No effect (isn't turned into an active form) * Active agent --> Super effect (toxic levels, not eliminated efficiently)

Answer 79

1. Drug metabolizing enzymes (CYP) 2. Drug transporters 3. Drug targets

Answer 80

* CYP2C9: S-Warfarin (active) --> hydroxywarfarin (inactive) * Reduced function of CYP2C9 = Warfarin not eliminated = high exposure to active drug (toxic levels) = greater risk of bleeding

Answer 81

* TPMT (thiopurine-S-methyltransferase): phase II enzyme that catalyzes S-methyltransferase of thiopurine drugs (inactives them) * Reduced function of TPMT = drug reaches toxic levels

Answer 82

* Tamoxifen is a selective estrogen receptor modulator. It is the less active form of the drug * CYP2D6: Tamoxifen ---> Endoxifen (more active form) * Reduced function of CYP2D6 = less response from drug

Answer 83

* SLCO1B1 transports Simvastin to liver cells for metabolism * Reduced function of SLCO1B1 = takes longer to eliminate Simvastin, increases effects, greater risk of myopathy * Pt outcomes are more complicated to predict due to: * Multiple different transporters for a drug * Rarely do transporters or enzymes have a total loss of function (usually only partial loss)

Answer 84

* S-Warfarin (active) inhibits VKORC1 * VKORC1 plays a key role in the Vitamin K pathway (which partialy controls clotting) * If VKORC1 is resistant to Warfarin --> decreased Warfarin effect

Answer 85

* CYP3A5: * \*3\ - transition substitution * \*6\ - transition substitution * \*7\ - insertion/deletion * ABCB1: * 1236 - silent * 2677 * 3435 - silent

Answer 86

* Tacrolimus (immunosuppressant): rapidly absorbed and extensively bound to erythrocytes in the blood stream * Highly metabolized in the liver and small intestines by **CYP3A5** * Genetic variation in CYP 3A5 --> causes variability in Tacrolimus clearance

Answer 87

* **Silent site substitutions** do not cause phenotype variation on their own * However, they are often part of a haplotype block and are closely linked with other mutations * **Haplotype block** - a set of DNA variations (polymorphisms) that tend to be inherited together

Answer 88

* Members of a family of oxygenated products of polyunsaturated long-chain fatty acids * Leukotrienes (LTs) * Prostaglandins (PGs) * Thromboxanes (TXs)

Answer 89

* Most abundant and most important precursor of eicosanoids * Synthesized in liver from linoleic acid * 20 carbons with 4 unsaturated (double) bonds

Answer 90

1. Membrane phospholipids are converted to arachidonic acid by phospholipase A2 2. Arachidonic acid is converted to LTs by lipoxygenase, in a linear pathway 3. Arachidonic acid is converted to PGs and TXs by PGH synthase (COX-1 and COX-2) in a cyclic pathway

Answer 91

1. Arachidonic acid is converted to 5-HPETE by 5-lipoxygenase 2. 5-HPETE ---> LTA4 3. LTA4 ---> LTC4 by glutathione * Can also be converted to LTB4 by hydrolase 4. LTC4 ---> LTD4, LTE4

Answer 92

* 5-HETE (5-HPETE), LTB4 * Chemotactic agents * LTB4 can produce hyperalgesia * Human colonic epithelial cells synthesize LTB4. Patients with IBD have substantial amounts of LTB4. * LTC4, LTD4, LTE4 * Chemoattractant for eosinophils * Potent bronchoconstrictors * Increase vascular permeability * Components of slow reacting substances of anaphylaxis

Answer 93

* Zileuton: 5-Lipoxygenase inhibitor * Zafirlukast, Montelukast: Competitive LTD4 receptor antagonist

Answer 94

* Competitive, reversible LTD4 receptor antagonist * Inhibits the LT mediated effects on bronchoconstriction and vascular permeability * **Used for**: * Prophylactic treatment for asthma * Allergic rhinitis * Aspirin sensitivity induced asthma (Montelukast only)

Answer 95

* 5-10% of people with asthma respond to very small doses of aspirin and NSAIDs * Results in bronchoconstriction and symptoms of systemic release of histamine, such as flushing and abdominal cramps * NSAIDs block the COX pathway, forcing arachidonic acids to shift to the lipoxygenase pathway and form LTs * Montelukast can be used in these patients

Answer 96

* **Adverse effects**: * Headache, pharyngitis * Increased liver enzymes - rare * **Drug Interactions**: * Inhibits CYP 3A4 and 2C9 * Creates numerous drug interactions

Answer 97

* 4-5% patients have elevated hepatic transaminase * Zileuton increases the response of: Theophylline, Warfarin, Propanolol * Contraindicated in liver disease

Answer 98

* **COX-1** * Constitutive form * House keeping functions, always present, widely distributed * **COX-2** * Inducible form * Elevated by inflammation and cytokinds * Immediate early response gene product in inflammatory/immune cells * **COX-3** * New isoform

Answer 99

* Acts localy, short half life * Activates G proteins (increase cAMP, decrease Ca²⁺) OR phosphatidylinositol metabolism (increase Ca²⁺) * Major effects are on four types of smooth muscle - vascule, gastrointestinal, airway, reproductive

Answer 100

* Vascular * Powerful vasodilator * Platelet * Inhibits platelet aggregation by all recognized agonists * Airway * Powerful bronchdilator * Used clinically to treat pulmonary and portopulmonary hypertension * GI * Inhibits gastric acid secretion * Increases mucus secretion * Renal * Increases GFR and renal blood flow * Increases water and sodium excretion * Reproductive * Relaxes uterine muscles * Pain * Induces pain * **Receptors** * IP (Gs - increases cAMP)

Answer 101

* Vascular * Vasodilator * Platelet * At low concentrations - enhances platelet aggregation * At high concentrations - inhibits aggregation * Airway * Powerful bronchdilator * GI * Inhibits gastric acid secretion * Increases stomach mucus secretion * Renal * Increases GFR and renal blood flow * Increases water and sodium excretion * Reproductive * Contracts uterine muscles * Pain + fever * Induces pain * Induces fever * **Receptors** * EP1-EP4 (Gs, Gq)

Answer 102

* Vascular * Potent vasoconstrictor * Platelet * Major product of platelet COX-1 * Stimulates platelet aggregation * Airway * Bronchoconstrictor * Renal * Intra-renal vasoconstriction * Decline in renal function * Reproductive * Contracts uterine muscles * **Receptors** * TP (Gq-PLC)

Answer 103

* Vascular * Vasoconstrictor * Airway * Contacts airway smooth muscle * Reproductive * Contacts uterine muscles * Eye * Decreases intraocular pressure * **Receptors** * FP (Gq-PLC)

Answer 104

* Adjunct to NSAID therapy - to reduce ulcer formation * Inhibits gastric acid secretion * Contraindicated in pregnancy - may cause contractions

Answer 105

* Ophthalmic preparation * Used for open angle glaucoma to lower intraocular pressure

Answer 106

* Temporarily maintains patent ductus arteriosus in newborns until surgery can be don * Improves blood oxygenation

Answer 107

* Ductus arteriosus (DA) in fetus carries blood from pulmonary artery to aorta (since lungs are collapsed before birth) * PGE2/1 and PGI2 keep the DA open in the fetus * After birth, PGE2/1 and PGI2 decrease, and the DA closes * If the DA does not close, Indomethacin can be used * If the DA must be kept open for surgery, Alprostadil is used

Answer 108

* Antipyretics - inhibit PG synthesis in hypothalamus to lower temperature * Analgesics - reduction of mild to moderate pain associated with inflammation * Good anti inflammatory properties - inhibits PG synthesis in localized areas

Answer 109

* Increased risk of GI ulcers and pain * Increased risk of bleeding * Inhibits PG mediated effects in the kidney, causing sodium and water retention * Aspirin - hypersensitivity

Answer 110

* ACE inhibitors * Glucocorticoids * Warfarin

Answer 111

* Irreversible inhibitor of COX 1 and COX 2 * Acetylates the enzymes (Ser 530 in COX-1 and Ser 516 in COX-2) * Irreversibly inhibits platelet COX-1

Answer 112

* **Ibuprofen, Naproxen** - Proponic acid derivatives * **Ketorolac** - Heteroarylacetic acid derivative * **Diclofenac** - Phenylacetic acid derivative * **Indomethacin** - indole derivative * **Celecoxib** - selective COX-2 inhibitor

Answer 113

1. Competive, reversible active site inhibitors of COX-1 and COX-2 2. * Both: analgesic, antipyretic, anti inflammatory, treats symptoms of rheumatoid and osteoarthritis * Ibuprofen: fever, dysmenorrhea, acute migraines * Naproxen: acute gout, ankylosing spondylitis (spine joint pain)

Answer 114

1. Seasonal allergy, recovery from cataract surgery, analgesic 2. GI bleeding, ALT/AST level change, elevated creatinine 3. Do not use : with history of peptic ulcer or GI bleeding, with other NSAIDs, in renal disease, during labor/delivery or lactation. Stop using before surgeries

Answer 115

1. Rheumatoid, osteoarthritis, ankylosing spondylitis, primary dysmenorrhea, for postoperative pain and inflammation following cataract surgery 2. GI pain, nausea, cramps, diarrhea, modest elevation of ALT in plasma 3. Diclofenac + Misoprostol = Arthrotec - used in patients with a risk of gastric or duodenal ulcers

Answer 116

1. * Oral: acute gouty arthritis, rheumatoid and osteoarthritis, tendinitis, ankylosing spondylitis * IV: Closes DA in newborns 2. GI pain, severe frontal headache, displacement of bilirubin from albumin, decreased urine output 3. Hyperbilirubinemia, renal failure

Answer 117

1. Selective COX-2 inhibitor (less effect on COX-1) 2. Rheumatoid and osteoarthritis, primary dysmenorrhea, ankylosng spondylitis 3. Metabolized by CYP 2C9 (interacts with drugs that inhibit CYP 2C9), inhibits CYP 2D6 4. GI pain (high dose), nausea 5. Lower incidence of GI pain compared to other NSAIDs

Answer 118

* All have basically same mechanism, but different sensitivities to COX inhibition * If sensitive to aspirin, do not use NSAIDs * Most common side effect is GI bleeding and ulceration * Do not use in last trimester of pregnacy (premature closure of DA, increased uterine bleeding during delivery, inhibits uterine motility) * Do not combine NSAIDs * Switch between dose and type of NSAID used

Answer 119

* PGI₂ and PGE₂: increase GFR and renal blood flow * PGE₂: inhibits Cl- reabsorption (NSAIDs lower PGs)

Answer 120

* PGE₂: inhibits effects of ADH * PGI₂ and PGE₂: stimulates renin release (NSAIDs lower PGs. This causes water retention and K+ retention)

Answer 121

1. Weak COX-1 and COX-2 inhibitor, acts on peroxide site of enzyme, exact mechanism unknown, possibly modifies COX-3 2. Alcohol 3. Hepatic toxicity - #1 cause of drug induced liver failure in US 4. Antipyretic, analgesic, weak anti inflammatory agent

Answer 122

* Immune modulators believed to restore normal immune environment within the joint synovium * Used for active rheumatoid arthritis when not responding to NSAID treatment * Prevents joint damage and preserves structure/function of joints

Answer 123

* Medulla * Inner section produces Epi and NE * Cortex * Zona glomerulosa - Aldosterone * Zona fasciculata & Zona reticularis - Cortisol, androgens

Answer 124

* Cholesterol is building block * Biosynthesis occurs in zona fasciculata and zona reticularis

Answer 125

* Upregulates Na+K+ATPase, which regulates Na+ handling by the kidney * Promotes hypertension

Answer 126

* Cortisol levels are regulated by circadian rhythm (high in morning, low in afternoon/night) * Hypothalamus produces CRH, which stimulates ACTH * ACTH promotes cortisol production in adrenal gland * Regulated by feedback loops

Answer 127

* Nervous System * Bad for Psychiatric disorders * Cardiovascular System * Bad for CV disease * Immune System * Good for organ transplants * MSK System * Good for rheumatoid arthritis * Bad for osteoporosis * Visual System * Good for Uveitis, Keratitis * Bad for Glaucoma * Respiratory System * Good for asthma and COPD * Glucose & liver metabolism * Bad for obesity and hyperglycemia * Reproductive System * Good for preterm birth * Bad for Gonadal virilization * Integumentary System * Good for Psoriasis and Eczema

Answer 128

Excess - Cushing's Syndrome Low - Addison's Disease

Answer 129

* Increases lipcortin levels by inhibiting phospholipase A2 activity * Reduces NF-kappa B levels, which leads to reduced levels of: * Proteolytic enzymes * Vasoactive enzymes * Chemotractant cytokines * COX-2 * NOS

Answer 130

1. Absorption * Many orall active * Water soluble esters given via IV to give rapid high concentrations * More prolonged effect when given IM * Absorption from local sites is possible 2. Transport * 90% cortisol in plasma is protein bound by CBG and albumin 3. Metabolism * Hepatic conjugation with glucoronides/sulfates * First pass effect varies * Renal excretion

Answer 131

* Use short term * Use highly localized * Reduce withdrawal effect by tapering off dose after prolonged therapy

Answer 132

* Long term use suppresses HPA axis * Decreased ACTH induced coritsol secretion * Leads to secondary adrenocortical insufficiency

Answer 133

* Rheumatic disorders * Rheumatoid arthritis * Respiratory diseases, like asthma and COPD * Allergies * Respiratory distress syndrome * Inflammatory dermatoses * COVID-19 (low dose dexamethasone recommended for patients on ventilator)

Answer 134

* Pregnancy, breast feeding - potential for growth and development inhibition * Can mask viral and fungal infections * Congestive heart failure or hypertension * Can induce osteoporosis, long bone fractures, femoral/humoral necrosis * Can exacerbate psychiatric disorders

Answer 135

* Can induce CYP 3A4 and reduce levels of other drugs (estrogens, antivirals, etc.) * Hepatic microsomal enzyme induces will promote metabolism * Estrogens increase CBPs, which increases the half-life but reduces the free concentration of corticosteroids

Answer 136

Antagonist for muscarinic acetylcholine receptor

Answer 137

Antagonist for beta adrenergic receptor

Answer 138

Agonist for muscarinic

Answer 139

Agonist for beta adrenergic receptor

Answer 140

Partial agonist for serotonin receptor

Answer 141

Inverse agonist for AngII receptor (blocker)

Answer 142

Inverse agonist for H2 receptor (blocker)

Answer 143

Protein kinases (receptors as enzymes), specifically inhibiting tyrosine kinases

Answer 144

Ligand-gated ion channels

Exam 1 Flashcards

(173 cards)