Block 2 Drugs

Question 1

Aldosterone

Answer 1

Made in zona glomerulosa from desoxycorticosterone
Release by renin-angiotensin and potassium
Traditional mineralocorticoid

Question 2

Cortisol

Answer 2

Made in zona fasciculata and reticularis
Release by ACTH
Traditional glucocorticoid

Question 3

Glucocorticoid - Effects

Answer 3

Mediated by glucocorticoid receptor
Enhances liver gluconeogenesis
Stimulates amino acid mobilization (degrading skeletal muscle, skin, etc.)
Increases plasma glucose, liver glycogen, urinary nitrogen excretion
Reduces peripheral glucose utilization
Redistribution of body fat - moon face, buffalo hump
Fatty acid release

Question 4

Mineralocorticoid - Effects

Answer 4

Mediated by mineralocorticoid receptor in kidney
Increases sodium reabsorption
Increase potassium and hydrogen ion excretion
Responsible for CV effects

Question 5

Dexamethasone

Answer 5

Strong glucocorticoid, no mineralocorticoid activity

Question 6

Prednisolone

Answer 6

Primarily glucocorticoid, weak mineralocorticoid

Question 7

Fludrocortisone

Answer 7

Very potent mineralocorticoid (stronger) and glucocorticoid

Question 8

Primary use of glucocorticoid

Answer 8

Anti-inflammatory and immunosuppression

Question 9

Metyrapone

Answer 9

Synthesis inhibitor of steroids
Blocks 11-beta hydroxylation to stop synthesis at 11-desoxycortisol
Causes ACTH levels to increase
Diagnostic test

Question 10

Mifepristone

Answer 10

Competitive antagonist at progesterone and glucorticoid receptor
Termination of pregnancy
Treat Cushings Disease

Question 11

Drospirenone

Answer 11

Progesterone agonist - With estrogen to suppress ovulation or as HRT in post-menopausal women
Mineralocorticoid receptor antagonist - Diuretic, antagonizes salt retention of estrogen
Androgen receptor antagonist

Question 12

Azathioprine

Answer 12

Metabolized to 6-mercaptopurine
Delivery: Orally active
Mechanism: Purine anti-metabolite inhibiting de novo and salvage
Therapeutic Use: Inhibit rejection of transplanted organs and some autoimmune disease (ex. rheumatoid arthritis)
Side effects: Bone marrow suppression (main), GI and hepatic toxicity (secondary)

Question 13

Cyclophosphamide

Answer 13

Mechanism: Alkylating agent results in cross-linking DNA, esp toxic in B-cells
Delivery: Orally active
Therapeutic Use: Treatment of autoimmune in combination with other drugs. Not for graft rejection.
Side effects: Bone marrow depression is major side effect

Question 14

Methotrexate

Answer 14

Mechanism: Inhibitor of dihydrofolate reductase, purine synthesis
Therapeutic Use: Autoimmune disease
Side effects: Hepatic toxicity

Question 15

Mycophenolate Mofetil

Answer 15

Metabolized to active mycophenolic acid
Mechanism: Inhibits IMP dehydrogenase, de novo purine synthesis (GMP), targets lymphocytes
Therapeutic Use: Renal allograft rejection with cyclosporine and corticosteroids; Autoimmune diseases (rheumatoid arthritis and refractory psoriasis)
Side effects: Infection, leukopenia, anemia
Caution with: GI disease, reduced renal function, infections, pregnancy

Question 16

Cyclosporine

Answer 16

Mechanism: Inhibition of IL-2 synthesis by blocking NFAT transcription factor, decreases T-cell helper function, proliferation, cytotoxicity
Delivery: Orally active
Therapeutic use: Rejection of transplanted organs (more effective, fewer side effects); Some autoimmune diseases
Side effect: Nephrotoxicity (major, reversible), Hepatotoxcity

Question 17

Tacrolimus

Answer 17

Binds FK binding protein
Same mechanism as cyclosporine
50-100x extra potency
Less nephro/hepatotoxicity

Question 18

Sirolimus

Answer 18

Mechanism: Inhibits T-cell activation and proliferation downstream of IL-2, Binds FKBP-12 to block cell cycle progression
Therapeutic Use: Same as cyclosporine, coating of cardiac stents

Question 19

Zileuton

Answer 19

Inhibitor of 5-lipoxygenase
Pharmacokinetics: Oral administration; half-life of 2.5 hrs, CYP metabolized
Mechanism: Inhibits cys-LTs (bronchoconstriction; increases vascular permeability) and LTB4 (chemotaxis)
Therapeutic use: Prophylactic of mild asthma
Adverse effects: few, increase liver enzymes

Question 20

Zafirlukast

Answer 20

Cysteinyl leukotriene receptor antagonist
Mechanism: Inhibits cys-LTs
Pharmacokinetics: Oral administration; half-life of 10 hrs, CYP2C9/3A4 metabolism
Therapeutic Use: Prophylactic treatment of mild asthma
Adverse effects: Minimal

Question 21

Dinoprostone - Cervical use

Answer 21

PGE2 Analog
Mechanism: Activation of collagenase, relaxes cervical smooth muscle, EP4 receptor subtype
Therapeutic use: Cervical ripening in pregnancy
Delivery: Cervical gel

Question 22

Dinoprostone - Uterine use

Answer 22

PGE2 Analog
Mechanism: Uterine contractions via EP1/3
Therapeutic use: Termination of early pregnancy/abortion
Delivery: Vaginal suppository
Adverse effects: GI-related (nausea, vomiting, diarrhea), fever, uterine-rupture (contraindicated in women with history of C-section, uterine surgery)

Question 23

Carboprost - Pregnancy use

Answer 23

PGF2 Analog
Mechanism: Uterine contractility stimulated at FP receptors
Therapeutic use: Termination of pregnancy during the second trimester (wks 13-20)
Delivery: Intramuscular injection

Question 24

Carboprost - Postpartum

Answer 24

PGF2 Analog
Mechanism: Myometrial contractions via FP receptors
Therapeutic: Postpartum hemorrhage that is not responding to traditional methods
Preparation: Intramuscular injection
Adverse effects: GI-related (nausea, vomiting, diarrhea), fever, uterine-rupture (contraindicated in women with history of C-section, uterine surgery), rare bronchoconstriction

Question 25

Misoprostol

Answer 25

PGE1 Analog Mechanism: Suppression of gastric acid secretion by stim. EP3 receptors on parietal cells, Decrease in cAMP. increase mucin and bicarb secretion, mucosal blood flow Therapeutic: "Replacement therapy" for prevention of ulcers caused by long-term NSAID usage Preparation: Oral administration Adverse effect: Diarrhea-common, contraindicated in pregnancy

Question 26

Alprostadil - Penile

Answer 26

PGE1 Mechanism: Increase in cAMP to relax muscle of corpus cavernosum Therapeutic use: Impotence/ED Preparation: Intracavernous or intra-urethral Adverse effect: Pain at site of injection, priapism (prolonged erection)

Question 27

Alprostadil - Neonate

Answer 27

PGE1 Mechanism: cAMP-mediated relaxation of ductus arteriosus smooth muscle Therapeutic: Maintenance of patent ductus arteriosus Mechanism of action: cAMP-mediated relaxation of ductus arteriosus smooth muscle Adverse effect: Apnea in about 10% of neonates; <2 kg

Question 28

Epoprostenol

Answer 28

PGI2 Mechanism: cAMP-mediated dilation of pulmonary artery vascular smooth muscle Therapeutic effect: Primary pulmonary HTN (rare)

Question 29

Bimatoprost - Non-cosmetic

Answer 29

PGF2 Mechanism: Increases outflow of aqueous humor Therapeutic use: Glaucoma Preparation: Opthalmic solution Adverse effects: eye redness, itching, increased brown pigment, eyelid skin; increase length and number of eyelashes

Question 30

Bimatoprost - Cosmetic

Answer 30

PGF2 Mechanism: Increase the percent and duration of hairs in the growth phase Therapeutic use: Eyelash hypotrichosis Preparation: Opthalmic solution Adverse effects: Excess. unwanted hair growth, brown iris pigmentation, eye redness, itching

Question 31

Acetylsalicylic Acid (Aspirin)

Answer 31

Irreversible inhibitor of both COX (Aspirin specific) via acetylation of serine group Pharmacokinetics: Plasma half-life is dose-dependent (with OD has zero-order kinetics), absorbed from stomach and small intestine, highly bound to plasma proteins and crosses BBB/placental barriers, renally eliminated Delivery: Oral tablet, buffered (anti-stomach acid) vs enteric (passes stomach unaltered) coating Pharmacological Effects: NSAID Uric acid excretion: low doses decrease/high dose increase CNS: high dose/toxic effects of stimulation followed by depression, tinnitus, high-tone deafness, confusion, dizziness, delirium, psychosis, coma, nausea and vomiting Respiration Adverse reactions (Most NSAID related): GI, Platelet (irreversibility of aspirin requires new platelets to overcome), Hypersensitivity (less with non-acetylated salicylates), Kidney, Uterus/Fetus, Reye's syndrome (Specific) Therapeutic Use: Low dose - CVD; Intermediate Dose - Fever, Pain; High Dose - Inflammatory Disease; Cancer?

Question 32

General NSAIDs

Answer 32

Pharmacological effects: Anti-inflammatory, Analgesia, Anti-pyretic Adverse reactions: GI - Ulceration and irritation due to loss of cytoprotective PGs Platelets - Increase bleeding time by inhibiting platelet Hypersensitivity - Respiratory, not IgE, more common with asthmatics/nasal polyps Kidney - Decrease renal blood flow, promote salt and water retention especially on elderly who are more dependent on vasodilatory PGs Uterus/Fetus - Prolonged gestation, labor, increased postpartum hemorrhage, intrauterine closure of PDA, avoid in 3rd trimester

Question 33

Ibuprofen

Answer 33

Proprionic NSAID Mechanism: Reversible COX1/2 inhibitor Pharmacokinetics: Shorter half-life than naproxen Pharmacological effects: NSAID Adverse effects/toxicity: NSAID (less GI than Aspirin) Therapeutic: Inflammatory diseases, rheumatoid disorders, mild-to-moderate pain, fever, dysmenorrhea, osteoarthritis, injection to induce patent ductus arteriosus in premature infants

Question 34

Naproxen

Answer 34

Proprionic NSAID Mechanism: Reversible COX1/2 inhibitor Pharmacokinetics: Longer half-life than ibuprofen Pharmacological effects: NSAID Adverse effects/toxicity: NSAID (less GI than Aspirin) Therapeutic: Management of ankylosing spondylitis, osteoarthritis, rheumatoid disorders, acute gout, mild-to-moderate pain, tendonitis, bursitis, dysmenorrhea, fever

Question 35

Indomethacin

Answer 35

Acetic Acid NSAID Mechanism: Reversibly COX1/2 inhibitor Pharmacokinetics: Plasma half-life 3 hrs, 90% bound to plasma proteins Pharmacological effects: NSAID Adverse effects/toxicity: Frequent, GI toxicity, CNS - severe frontal headache Therapeutic: Acute gouty arthritis, acute bursitits/tendonitis, moderate-to-severe osteoarthritis, rheumatoid arthritis, ankylosing spondylitis; IV for closure of patent ductus arteriosus Unlabeled use: Pre-term labor

Question 36

Kertolac

Answer 36

Acetic Acid NSAID Mechanism: Reversibly COX1/2 inhibitor Pharmacokinetics: Absorbed orally and intramuscularly, highly plasma protein bound Pharmacologic effects: Analgesic and anti-pyretic, less anti-inflammatory activity Therapeutic applications: Oral, injection for short term management of moderate-to-severe acute pain requiring analgesia at the opioid level

Question 37

Nabumetone

Answer 37

Acetic Acid NSAID Mechanism: Active metabolite is a reversible of COX1/2 (predominantly 2) Pharmacokinetics: Converted to active metabolite, 6-methoxy-2-naphthylacetic acid, long half-life Pharmacologic effects: Anti-inflammatory, analgesic Adverse effects/toxicity: Well tolerated, less GI effects, mainly only COX2 effects Therapeutic applications: Osteoarthritis, rheumatoid arthritis

Question 38

Piroxicam

Answer 38

Oxicam NSAID Mechanism: Reversible of COX1/2 Pharmacokinetics: Plasma half-life 50 hours, 99% bound to plasma proteins Pharmacologic effects: NSAID Adverse effects/toxicity: GI toxicity Therapeutic: Symptomatic treatment of acute and chronic rheumatoid arthritis and osteoarthritis, advantageous of long half-life

Question 39

Sulfasalazine

Answer 39

Salicylate NSAID, Mesalamine (5-ASA) is active component Mechanism: No clear COX inhibition, possibly inhibition of IL-1, TNFa, lipoxygenase pathway, NF-kB Pharmacokinetics: Oral which reaches distal GI due to azo linkage Pharmacological effects: Local effect in GI to inhibit the inflammatory response Adverse effects/contraindications: Sulfa moiety related. Headache, nausea, fatigue, hypersensitivity, reversibly decreases the number and motility of sperm, inhibits folate absorption Therapeutic uses: Mild or moderately active ulcerative colitis, Rheumatoid arthritis and ankylosing spondylitis

Question 40

Celecoxib

Answer 40

Selective COX-2 Inhibitor Mechanism: Binds to side pocket in COX-2 obstructing active site Pharmacokinetics: Oral administration (peak conc. 3 hrs), highly bound to plasma proteins, metabolized by CYP2C9 to inactivate Pharmacologic effects: NSAID Adverse: NSAID, GI irritation, Adverse CV thrombotic events (MI, stroke), Anemia - rare cases Contraindications: Sulfonamide toxicity, prior NSAID hypersensitivity, pre-existing CV risk, post-coronary artery bypass graft surgery, caution in patients that have a def. of CYP2C9 Therapeutic applications: Signs/symptoms of rheumatoid arthritis, osteoarthritis, primary dysmenorrhea, acute pain management, polyp reduction in familial adenomatous polyposis

Question 41

Acetaminophen

Answer 41

Mechanism: Not well understood, no affinity for COX1/2 activity site, prevents COX from reaching peroxidase form, more selective for COX in brain? COX-3? Pharmacokinetics: Oral administration, effectively absorbed from GI tract, plasma half-life is 2 hours, little binding to plasma proteins, metabolism by phase I enzymes important for toxicity Pharmacologic effects: Analgesic, antipyretic, NOT anti-inflammatory Adverse: Primarily due to excessive use, no GI effects, Hepatotoxicity: Due to large doses, symptoms include vomiting, nausea, abdominal pain, treatment is with N-acetylcysteine, mechanism: glutathione substitute, risk with EtOH Therapeutic applications: Mild-to-moderate pain and fever

Question 42

Cromolyn Sodium

Answer 42

Inhaled Anti-Inflammatory Agent Mechanism: Stabilizes mast cell membranes and prevents release of histamine Delivery: Inhalation Adverse Effects: Few Therapeutic Uses: Preventative management of asthma, allergic rhinitis, conjunctivitis, food allergies

Question 43

Omalizumab

Answer 43

Monoclonal Ab Mechanism: Decreases amount of Ag specific IgE that binds to mast cells Delivery: Subcut. Adverse Effects: Major ones include life-threatening anaphylaxis and also bleeding related effects Therapeutic uses: Allergic asthma

Question 44

Diphenhydramine

Answer 44

First generation ethanolamine H1 Blocker Delivery: Nasal/ophthalmic Adverse reactions: Strong sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain Therapeutic use: Allergies, motion sickness, nonprescription sleeping tablets, early stage Parkinson's

Question 45

Dimenhydrinate

Answer 45

First generation ethanolamine H1 Blocker Delivery: Nasal/ophthalmic Adverse reactions: Strong sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain Therapeutic use: Motion sickness, vestibular disturbances

Question 46

Chlorpheniramine

Answer 46

First generation alkylamine H1 Blocker Delivery: Nasal/ophthalmic Adverse reactions: Sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain Therapeutic use: Allergies

Question 47

Promethazine

Answer 47

First generation phenothiazine H1 Blocker Delivery: Nasal/ophthalmic Adverse reactions: Strong sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain Therapeutic use: Motion sickness, chemotherapy-induced nausea/vomiting

Question 48

Fexofenadine

Answer 48

Second generation piperdine H1 Blocker Delivery: Nasal/ophthalmic Metabolism: Metabolized from terfenadine Adverse reactions: Loss of appetite, nausea, vomiting, GI distress, rarely weight gain Therapeutic use: Allergies

Question 49

Loratadine

Answer 49

Second generation piperdine H1 Blocker Delivery: Nasal/ophthalmic Metabolism: Metabolized to desloratadine by 3A4, 2D6 Adverse reactions: Loss of appetite, nausea, vomiting, GI distress, rarely weight gain Therapeutic use: Allergies

Question 50

Desloratadine

Answer 50

Second generation piperdine H1 Blocker Delivery: Nasal/ophthalmic Metabolism: Metabolized from loratadine Therapeutic use: Allergies

Question 51

Cetirizine

Answer 51

Second generation piperazine H1 blocker Delivery: Nasal/ophthalmic Metabolism: Active metabolite of hydroxyzine Adverse reactions: Loss of appetite, nausea, vomiting, GI distress, rarely weight gain Therapeutic use: Allergies

Question 52

Cimetidine

Answer 52

H2 Blocker (Least potent) Pharmacology: Competitive inhibitors of histamine at H2 receptors, inhibit gastric acid secretion from parietal cells, reduce volume of gastric acid and H+ concentration Pharmacokinetics: Rapidly absorbed following oral administration, small amounts undergo liver metabolism, parent drug & metabolites: excreted by kidneys Adverse reactions (H2 blocker general): Minor diarrhea, headache, drowsiness, CNS effects with IV use or in elderly Adverse reactions (Cimetidine specific): Inhibits P450 enzymes, decreases testosterone binding and inhibits a CYP enzyme that hydroxylates estradiol, gynecomastia, reduced sperm count, impotence in men Therapeutic use: Major - GERD, Minor - healing of gastric and duodenal ulcers

Question 53

Ranitidine

Answer 53

H2 Blocker (Moderately potent) Pharmacology: Competitive inhibitors of histamine at H2 receptors, inhibit gastric acid secretion from parietal cells, reduce volume of gastric acid and H+ concentration Pharmacokinetics: Rapidly absorbed following oral administration, small amounts undergo liver metabolism, parent drug & metabolites: excreted by kidneys Adverse reactions (H2 blocker general): Minor diarrhea, headache, drowsiness, CNS effects with IV use or in elderly Adverse reactions (Ranitidine specific): Inhibits P450 enzymes minorly Therapeutic use: Major - GERD, Minor - healing of gastric and duodenal ulcers

Question 54

Famotidine

Answer 54

H2 Blocker (Most potent) Pharmacology: Competitive inhibitors of histamine at H2 receptors, inhibit gastric acid secretion from parietal cells, reduce volume of gastric acid and H+ concentration Pharmacokinetics: Rapidly absorbed following oral administration, small amounts undergo liver metabolism, parent drug & metabolites: excreted by kidneys Adverse reactions (H2 blocker general): Minor diarrhea, headache, drowsiness, CNS effects with IV use or in elderly Therapeutic use: Major - GERD, Minor - healing of gastric and duodenal ulcers

Question 55

Lysergic Acid Diethylamide (LSD)

Answer 55

Potent hallucinogen | Full or partial agonist at 5-HT2 receptors

Question 56

Buspirone

Answer 56

Partial agonist at 5-HT1A receptors | Antianxiety agent

Question 57

Sumatriptan

Answer 57

Agonist at 5-HT1D receptor Used in the treatment of migraine headaches, stop existing headache Side effects include nausea and vomiting, angina, dizziness, flushing

Question 58

Fluoxetine

Answer 58

Serotonin specific reuptake inhibitors (SSRI) Increase amount of serotonin at synapse Treatment of affective disorders, OCD, panic attacks

Question 59

Pheneizine

Answer 59

Monoamine oxidase inhibitor (MAOI) | Treatment of depression and narcolepsy. Side effects include food include food induced hypertensive crisis

Question 60

Cyproheptadine

Answer 60

5-HT2 receptor antagonist, also H1 antagonist Used in treatment of skin allergies (pruritus and urticaria) Treatment of carcinoid

Question 61

Ondansetron

Answer 61

5-HT3 receptor antagonists Very effective in treatment of chemotherapy-induced nausea and vomiting Acts both at GI and brain receptors IV and oral forms

Question 62

Alosetron

Answer 62

Selective 5-HT3 antagonists Treat with diarrhea-predominant IBS who don't respond to normal treatment Produce severe GI adverse effects Restricted prescribing program

Question 63

Nitroglycerin

Answer 63

Nitrate Mechanism: Relaxation of arterial and venous smooth muscle Therapeutic use: Heart failure Toxicity: Hypotension

Question 64

Nitroprusside

Answer 64

Nitrate Mechanism: Relaxation of arterial and venous circulations Therapeutic use: Heart failure; Hypertensive (HTN crisis) Toxicity: Hypotension

Question 65

Hydralazine

Answer 65

Direct Vasodilators Mechanism: Arterial circulation Therapeutic use: Heart failure Toxicitiy: Hypotension

Question 66

Minoxidil

Answer 66

Direct vasodilator: ATP-sensitive K+ Channel Opener Mechanism: Arterial circulation Therapeutic use: Heart failure and hypertension

Question 67

Diazoxide

Answer 67

Potassium channel dilator Mechanism: Cell membrane actions Therapeutic: Hypertension

Question 68

Phosphodiesterase 3 Inhibitors

Answer 68

Bolded drugs: Milrinone, Inamrinone, Cilostazol Intracellular Signaling Heart Failure

Question 69

Phosphodiesterase 5 Inhibitors

Answer 69

Bolded drugs: Sildenafil, Tadalafil Intracellular signaling Erectile dysfunction

Question 70

Prazosin

Answer 70

Alpha-adrenergic blocker | Arterial and venous circulation

Question 71

B2 Agonist

Answer 71

Bronchodilators Bolded drugs: Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol Mechanism: Intracellular Signaling - Cyclic AMP/PKA Adverse reactions: Cardiotoxicity

Question 72

Anti-cholinergic

Answer 72

Bronchodilators Bolded drugs: Ipratropium, tiotropium Mechanism: Muscarinic receptors Adverse effects: Mucous secretion

Question 73

Methylxanthine

Answer 73

Bronchodilators Bolded drugs: Theophylline, aminophylline Mechanism: Phosphodiesterase inhibition Adverse effects: Adenosine receptor antagonism

Question 74

Aliskiren

Answer 74

Mechanism: Renin inhibitor, potent active site, non-peptide inhibitor Delivery: Orally active, long acting (24 h) Therapeutic use: Treating HTN (Lowers BP with no change in HR) Adverse reactions: Fatigue, headache, GI symptoms (comparable to placebo)

Question 75

Losartan

Answer 75

AT1 receptor blocker Mechanism: Prevents Angiotensin II action Delivery: Orally active Therapeutic use: Reduces BP w/o increasing HR, Improves heart failure Adverse reactions: Contraindicted in pregnancy, dizziness, cough, angioedema Other Notes: No hyperkalemic effects, concentration increases in patients with reduced liver function, does not alter lipid profile

Question 76

Captopril

Answer 76

Mechanism: Angiotensin I Converting Enzyme (ACE) to block AT2 formation and bradykinin degradation Therapeutic use: Reduce BP without increasing HR, Improves heart failure Adverse reactions: Rash, proteinuria and neutropenia, cough angioedema

Question 77

Enalapril

Answer 77

Mechanism: Angiotensin I Converting Enzyme (ACE) to block AT2 formation and bradykinin degradation Therapeutic use: Reduce BP without increasing HR, Improves heart failure Delivery: Pro-drug conversion to enalaprilate Adverse reactions: Cough angioedema

Question 78

Lisinopril

Answer 78

Mechanism: Angiotensin I Converting Enzyme (ACE) to block AT2 formation and bradykinin degradation Therapeutic use: Reduce BP without increasing HR, Improves heart failure Delivery: Pro-drug conversion to lisinoprilate Adverse reactions: Cough angioedema

Question 79

Spironolactone

Answer 79

Potassium Sparing Diuretic Mechanism: Competitive aldosterone antagonists at mineralocorticoid receptor Therapeutic use: Diuretics, reduce mortality from heart failure, decreases cardiac hypertrophy, fibrosis, sodium retention, treat HTN or edema with thiazide or loop diuretic Delivery: Orally active Adverse Reaction: Hyperkalemia, gynecomastia

Question 80

Eplerenone

Answer 80

Potassium Sparing Diuretic Mechanism: Competitive aldosterone antagonists at mineralocorticoid receptor Therapeutic use: Diuretics, reduce mortality from heart failure, decreases cardiac hypertrophy, fibrosis, sodium retention, treat HTN or edema with thiazide or loop diuretic Delivery: Orally active Adverse Reaction: Hyperkalemia

Question 81

Verapamil

Answer 81

Phenylalkylamine Therapeutic use: Supraventricular arrhythmias Mechanism: Inhibition of conduction of L-type Ca channels, heart rate moderation, cardiac vasodilation, use-dependent binding Delivery: Oral but extensive first-pass effects Adverse reactions: Constipation, exacerbate CHF, 2nd or 3rd degree AV block

Question 82

Diltiazem

Answer 82

Benzothiazepine Therapeutic use: Angina pectoris, Supraventricular arrhythmias Mechanism: Inhibition of conduction of L-type Ca channels, heart rate moderation, cardiac vasodilation, use-dependent binding Delivery: Oral, not much first-pass effect Adverse reactions: 2nd or 3rd degree AV block (less than verapamil), best tolerated of original calcium channel blockers

Question 83

Nifedipine

Answer 83

1,4-Dihydropyridines Therapeutic use: HTN, Angina pectoris Mechanism: Inhibition of conduction of L-type Ca channels, peripheral vasodilation, voltage-dependent binding Delivery: Oral, not much first-pass effect, high protein binding Adverse reactions: Hypotension, headache, flushing, peripheral edema

Question 84

Amlodipine

Answer 84

1,4-Dihydropyridines Therapeutic use: HTN, Angina pectoris Mechanism: Inhibition of conduction of L-type Ca channels, peripheral vasodilation, voltage-dependent binding Delivery: Oral, not much first-pass effect, high protein binding Adverse reactions: Hypotension, headache, flushing, peripheral edema, better tolerated than nifedipine

Question 85

Fenoldopam

Answer 85

``` Vasodilator Diuretic (DA1 Agonist) Mechanism: Increase RBF without reducing GFR, reduces net reabsorption Pharmacological Use: Increase RBF in shock ```

Question 86

Dopamine

Answer 86

``` Vasodilator Diuretic (DA1 Agonist) Mechanism: Increase RBF without reducing GFR, reduces net reabsorption Pharmacological Use: Increase RBF in shock ```

Question 87

Atriopepins

Answer 87

``` Vasodilator Diuretic (Atrial Natriuretic Peptides) Mechanism: Increase RBF without reducing GFR, reduces net reabsorption Pharmacological Use: Limited ```

Question 88

Mannitol

Answer 88

Osmotic Diuretic Mechanism: Non-reabsorbed solute to prevent water reabsorption Delivery: IV, limited to inpatients Therapeutic use: Prophylaxis of acute renal failure, edematous conditions in which a volume load is not detrimental, glaucoma Adverse Reactions: Related to volume overload and expansion of IV fluid volume, rare hypersensitivity

Question 89

Acetazolamide

Answer 89

Inhibitor of Carbonic Anhydrase (Diuretic) Mechanism: Decreases bicarbonate reabsorption and therefore sodium reabsorption Therapeutic Use: Glaucoma (reduction of aqueous humor formation), alkalinize urine to decrease drug toxicity, treat symptoms of acute altitude sickness Adverse reactions: Metabolic acidosis to reduce renal response to drug, generally safe

Question 90

Furosemide

Answer 90

Loop or high ceiling diuretics Mechanism: Inhibit active chloride reabsorption, ruining Na/K/2Cl symporter, extremely potent Therapeutic uses: Rapid diuresis (15 mins) and short in duration (2-3 hrs), management of edema due to cardiac, hepatic or renal disease, acute pulmonary edema, hypertension Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia, ototoxicity, volume depletion

Question 91

Bumetanide

Answer 91

Loop or high ceiling diuretics Mechanism: Inhibit active chloride reabsorption, ruining Na/K/2Cl symporter, extremely potent Therapeutic uses: Rapid diuresis (15 mins) and short in duration (2-3 hrs), management of edema due to cardiac, hepatic or renal disease, acute pulmonary edema, hypertension Adverse reactions: Hypokalemia, hyperuricemia, ototoxicity (least), volume depletion

Question 92

Ethacrynic acid

Answer 92

Loop or high ceiling diuretics Mechanism: Inhibit active chloride reabsorption, ruining Na/K/2Cl symporter, extremely potent Therapeutic uses: Rapid diuresis (15 mins) and short in duration (2-3 hrs), management of edema due to cardiac, hepatic or renal disease, acute pulmonary edema, hypertension Adverse reactions: Hypokalemia, hyperuricemia, ototoxicity (most), volume depletion

Question 93

Chlorothiazide

Answer 93

Thiazide and related diuretics Mechanism of Action: Na/Cl symport inhibitor Therapeutic uses: Rapid diuresis (1 hr) and long in duration, edema management due to congestive cardiac failure, hypertension, hypercalciuria in patients with renal calculi from calcium salts Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia (decreased insulin secretion) Contraindication: GFR < 25 ml/min

Question 94

Hydrochlorothiazide

Answer 94

Thiazide and related diuretics Mechanism of Action: Na/Cl symport inhibitor Therapeutic uses: Rapid diuresis (1 hr) and long in duration, edema management due to congestive cardiac failure, hypertension, hypercalciuria in patients with renal calculi from calcium salts Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia (decreased insulin secretion) Contraindication: GFR < 25 ml/min

Question 95

Metolazone

Answer 95

Thiazide and related diuretics Mechanism of Action: Na/Cl symport inhibitor Therapeutic uses: Rapid diuresis (1 hr) and long in duration, edema management due to congestive cardiac failure, hypertension, hypercalciuria in patients with renal calculi from calcium salts Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia (decreased insulin secretion) Contraindication: GFR < 25 ml/min

Question 96

Triamterene

Answer 96

Potassium-Sparing Diuretics Mechanism of Action: Sodium channel inhibitor, aldosterone independent Therapeutic use: Edema, HTN, paired with thiazide or loop diuretic Adverse Reactions: Hyperkalemia, azotemia

Question 97

Amiloride

Answer 97

Potassium-Sparing Diuretics Mechanism of Action: Sodium channel inhibitor, can also block Na-H exchange, aldosterone independent Adverse Reactions: Hyperkalemia, azotemia

Question 98

Heparin

Answer 98

Anti-coagulant Mechanism: Catalyzes antithrombin's suicide activity against coagulation factors (Xa, IXa, Thrombin) by providing a binding scaffold Therapeutic Use: DVT, Pulmonary Embolism, Management of unstable angina or acute MI, low dose prophylaxis against DVT, hemodialysis, anticoagulant during pregnancy Delivery: IV or Sub-q, Half-life is dose dependent, Cleared by reticuloendothelial system and liver Adverse reactions: Bleeding, thrombocytopenia Contraindications: Active bleeding, recent surgery, severe uncontrolled HTN

Question 99

Low molecular weight heparins (LMWH)

Answer 99

Bolded ones to know: Enoxaparin, Dalteparin Anti-coagulant, Same as heparin except when noted Mechanism: More targeting for Xa, too short for thrombin Therapeutic use: Same as heparin but specifically used for hip surgery also Delivery: Cannot be absorbed through GI mucosa, absorbed more uniformly than heparin via Sub-q, longer half-life than heparin, cleared via kidney Adverse effects: Less severe than heparin

Question 100

Lepirudin

Answer 100

Anti-coagulant Mechanism: Binds tightly to catalytic site and exosite I of thrombin Therapeutic use: Alternative to heparin for coronary angioplasty or cardiopulmonary bypass Delivery: Administered IV, excreted by kidneys, Half-life is 1.3 hrs Adverse reactions: Bleeding, cautiously in renal failure patients due to risk of accumulation in kidney Contraindications: Active bleeding, recent surgery, sever uncontrolled HTN, Renal Disease

Question 101

Bivalirudin

Answer 101

Anti-coagulant Mechanism: Binds tightly to catalytic site of thrombin until thrombin cleaves the linkage Therapeutic use: Alternative to heparin for coronary angioplasty or cardiopulmonary bypass Delivery: Administered IV, excreted by kidneys; Half-life of 25 minutes Adverse reactions: Bleeding, cautiously in renal failure patients due to risk of accumulation in kidney Contraindications: Active bleeding, recent surgery, sever uncontrolled HTN, Renal Disease

Question 102

Fondaparinux

Answer 102

Anti-coagulant Mechanism: Synthetic pentasaccharide that causes an antithrombin-mediated selective inhibition of Xa Therapeutic use: FDA approved - prophylaxis of DVT for hip, knee, or abdominal surgeries; treatment of PE and DVT Off-label - Prophylaxis of DVT in patients with history of heparin-induced thrombocytopenia, acute thrombosis in patients with a past history of HIT; acute symptomatic superficial vein thrombosis of legs Delivery: Sub-q injection, excreted in urine, half-life of 17 hours Adverse reactions: Hemorrhage anywhere Contraindications: Active bleeding, recent surgery, severe uncontrolled HTN, renal impairment

Question 103

Protamine Sulfate

Answer 103

Heparin antagonist Mechanism: Binding of heparin to inactivate, high affinity for negatively charged molecules, minor anti-coagulant if used alone Therapeutic use: Used to reverse heparin following cardiopulmonary bypass Adverse reactions: Anaphylactic reactions with bradycardia, cutaneous vasodilation, hypotension; severe pulmonary HTN

Question 104

Warfarin

Answer 104

Anti-coagulant Mechanism: Vitamin K antagonist by blocking Vitamin K reductase (VKORC1), leaving Vitamin K in the oxidized state, prevents PTM of factors II, VII, IX, X Therapeutic use: Long-term treatment of venous thromboembolic disease, prophylaxis against thromboembolism in atrial fib, prosthetic heart valve, and dilated cardiomyopathy Delivery: Oral - rapid and completely absorbed after administration, 99%+ bound to albumin, inactivated by CYP2C9, delayed for several hours to days because it does not affect circulating factors Adverse reactions: Variable dosing window due to variations of CYP2C9, tetrogenic in pregnancy, skin necrosis (rare), blue-tinged discoloration of plantar surfaces Contraindications: Prolonged activity in liver/kidney disease, Vit K def

Question 105

Dabigatran

Answer 105

Anti-coagulant Mechanism: Prodrug dabigatran etexilate is converted to dabigatran: specific, reversible, direct thrombin inhibitor (including fibrin-bound thrombrin) Therapeutic use: Post-op thromboprophylaxis for hip and knee replacements; stroke and systemic embolism prevention in patients with nonvalvular A-fib Delivery: Orally available prodrug, half-life is 14 to 17 hrs, renal excretion. Dabigatran etexilate is a substrate for the Pgp transporter in gut and kidneys; Pgp inducers decrease plasma dabigatran Adverse reactions: No worse than warfarin for bleeding, but risk with patients with renal bleeding. No antidote for overdose.

Question 106

Rivaroxaban

Answer 106

Anti-coagulant Mechanism: Selective direct-acting factor Xa inhibitor. Therapeutic use: Post-op thromboprophylaxis for hip and knee replacements; stroke and systemic embolism prevention in patients with nonvalvular A-fib Delivery: Oral bioavailability > 80%, 1/3 excretion by kidney unchanged, 2/3 metabolized by liver and split between renal and fecal excretion, Pgp efflux transporter substrate Adverse reactions: Related to bleeding, but less than other anticoagulants, no hepatotoxicity

Question 107

Endogenous Tissue-type Plasminogen Activator

Answer 107

Endogenous Thrombolytic Mechanism: Binds to fibrin to activate fibrin-bound plasminogen to plasmin. Low t-PA at early stage clot formation, because of plasminogen activator inhibitors (PAI-1/2) Relatively non-specific plasminogen activation

Question 108

Alteplase

Answer 108

Thrombolytic Agent Mechanism: Fibrin-bound plasminogen specific activator Therapeutic use: Management of ST-elevation MIs for coronary thrombi, acute ischemic strokes, acute pulmonary emoblism Delivery: Continuous IV administration, half-life of 1 to 4 minutes, liver elimination Contraindications: Active bleeding, recent surgery within 10 days (major surgery, organ biopsy, trauma, CPR), GI bleeding within 3 months, cerebralvascular problems, hemorrhagic disorder, known hypersensitivity, severe uncontrolled HTN, pregnancy or postpartum

Question 109

Aminocapronic Acid

Answer 109

Procoagulant Drugs Mechanism: Lysine analog that binds to plasminogen and plasmin, prevents plasmin activation Therapeutic use: Reverse states associated with an excessive breakdown of fibrin, effective in decreasing hemorrhage with surgical procedures

Question 110

Dipyridamole

Answer 110

Anti-platelet Mechanism: Phosphodiesterase inhibition, block adenosine uptake, increase cAMP, inhibits platelet aggregation Therapeutic Use: Prevention of thromboemboli with warfarin in patients with prosthetic heart valves Delivery: Oral Adverse Reactions: Headache, GI upset, Dizziness

Question 111

Clopidogrel

Answer 111

Anti-platelet Mechanism: Irreversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation Therapeutic use: Unstable angina or NSTEMI with aspirin, STEMI, recent MI, stroke, established peripheral arterial disease Delivery: Prodrug activated mainly by CYP2C19 Adverse effects: Bleeding, less neutropenia, drug interactions with PPIs: competes for CYP2C19 activation

Question 112

Prasugrel

Answer 112

Anti-platelet Mechanism: Irreversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation Therapeutic use: Reduce rate of thrombotic CV events (stent thrombosis) for percutaneous coronary intervention (PCI) management of UA, NSTEMI, STEMI Delivery: Prodrug, undergoes esterase-mediated hydrolysis and then activation by CYP oxidation, higher potency, faster honest, and more consistent level of platelet inhibition than clopidogrel Adverse effects: Bleeding, less neutropenia

Question 113

Ticlopidine

Answer 113

Anti-platelet Mechanism: Irreversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation Therapeutic use: Not often used, largely replaced by clopidogrel, prasugrel, and ticagrelor Delivery: Prodrug activated mainly by CYP2C19 Adverse effects: Bleeding, high neutropenia

Question 114

Ticagrelor

Answer 114

Anti-platelet Mechanism: Reversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation Therapeutic use: Conjunction with aspirin for secondary prevention of thrombotic events in patients with UA, NSTEMI, or STEMI managed medically with PCI or coronary artery bypass graft Delivery: Not prodrug Adverse effects: Bleeding, less neutropenia

Question 115

Abciximab

Answer 115

Anti-platelet Mechanism: Fab fragment binding to platelet GP IIb/IIIa receptors to prevent fibrinogen binding and cross-linking of platelets Therapeutic use: Percutaneous cornary interventions (i.e. coronary angioplasty and stent placement) in combination with aspirin and heparin/LMWH; Adjunct to thrombolysis with alteplase Delivery: IV, biphasic plasma half-life of 10 minutes and 30 minutes, functional half-life due to slow clearance is 7 days Adverse effects: Bleeding, thrombocytopenia, hypotension, bradycardia

Question 116

Eptifibatide

Answer 116

Anti-platelet Mechanism: Preventing cross-linking of fibrinogen via competitive, reversible inhibition of GP IIb/IIIa receptors. Highly specific KGD sequence Therapeutic use: Unstable angina and MI often in combination with LMWH Delivery: IV with maximum effect by 15 minutes, lasts up to 4-8 hours after discontinuation, renal clearance Adverse effects: Bleeding, thrombocytopenia, hypotension, bradycardia Contraindications: Renal disease