Block 2

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ssbhat
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173876
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Block 2
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2012-10-16 11:31:57
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Pharmacology
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Inflammation, GI, Antihypertensives, & More
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  1. Histamine
    Source: mast cells, basophils

    Response: vasodilation, increased vascular permeability, pain

    Mechanism: activation of GPCRs

    Pharm: Antihistamines (H1 antagonists)
  2. Bradykinin
    Source: endothelial cells

    Response: vasodilation, increased microvessel permeability, pain

    Mechanism: activation of GPCRs

    Pharm: BK receptor antagonists being tested
  3. Complement System
    Source: synthesized by liver, circulate in blood

    Response: chemotaxis, promote release of mediators from neutrophil, increase vascular permeability, excessive activation may contribute to tissue injury

    Mechanism: complement protein complexes cause osmotic lysis, activation of GPCRs

    Pharm: treat rare blood disorders and prevent organ rejection
  4. C-Reactive Protein
    Source: Produced in liver in response to cytokines, also adipocytes

    Response: Acute-phase reactant, activates complement cascade, mediates phagocytosis, marker of inflammation

    Mechanism: bind to phospholipids in bacteria and damaged cells, maybe specific receptors in macrophages

    Pharm: elevated CRP may be associated with increased risk of diabetes, hypertension, and CV disease.  Drugs like statins may be effective in patients with elevated CRP.
  5. Cyotkines
    Source: all inflammatory cells

    • Response:
    •     TNF-alpha: Acute phase reaction, fever sepsis
    •     IL-1: acute phase reaction, fibroblast and lymphocyte proliferation, fever

    Mechanism: Bind to specific receptor proteins to induce gene expression of number of proteins via activation of NFkB and AP-1 - increase cycloxygenase (fever) and lipoxygenase, increase adhesion molecule expression, induce colleganse

    Pharm: Etanercept, infliximab
  6. Adenosine
    Source: All cells

    Response: increased extraceullarly during injury, anti-inflammatory, inhibit cytokine action

    Mechanism: activation of GPCRs

    Pharm: Adenosine A2 agonists, methotrexate for rheumatoid arthritis
  7. Cell Adhesion Molecules
    Source: endothelial cells, platelets, leukocytes

    Response: Leukocyte adhesion to endothelium is a pivotal event in host defense and tissue repair.  Endothelial adhesion molecules contribute to recruitment of activated platelets.

    Mechanism: "contact molecules" calcium dependent

    Pharm: Anti-platelet drugs, treatment of MS and Crohn's disease
  8. Prostaglandins
    Source: All cells

    Response: vasodilation/vasoconstriction, pain, fever, platelet aggregation, activation of GPCRs

    Pharm: NSAIDs

    increased concentrations in cancer - induce cellular proliferation
  9. Leukotrienes
    Source: macrophages, neutrophils

    Response: increase vascular permeability, bronchoconstriction

    Mechanism: Activation of GPCRs

    Pharm: 5 lipoxygenase inhibitors (Zileuton) and cys-leukotriene receptor antagonists (Zafirlukast)

    Synthesized by 5-lipoxygenase

    BRONCHOSTRICTOR RESPONSE TO LEUKOTRIENES PREDOMINATES IN BRONCHIAL/TRACHEAL SM
  10. Glucocorticoid
    Source: Adrenal cortex

    Response: inhibition of cytokines, inhibition of phospholipase A2, inhibition of COX2, inhibition of cell adhesion molecules

    Mechanism: activation of nuclear receptors

    Pharm: steroids
  11. Cyclooxygenase
    two isoforms exist

    mediate production of prostaglandins, thromboxane, and prostacyclin

    increased by cytokines to induce fever

    inhibited by glucocorticoids
  12. Etanercept
    Cytokine inhibitor

    Used to treat rheumatoid arthritis

    mechanism: fusion protein that binds TNF

    IV or SC

    • T1/2 = 3 days
    • onset of action = 1-2 weeks

    Adverse effects: infections
  13. Infliximab
    cytokine inhibitor

    Use to treat rheumatoid arthritis, Crohn's disease, ulcerative colitis disease

    mechanism of action: chimeric IgG monoclonal antibody that binds TNF - results in cell lysis

    IV infusion

    Adverse effects: infection, delayed hypersensitivity, lupus like symptoms, fever, non-Hodgkin lymphoma
  14. Zileuton
    5-lipoxygenase inhibitor

    INHIBITS SYNTHESIS OF LEUKOTRIENES

    Pharmacokinetics: oral administration, half-life of 2.5 hrs, metabolized by CÁP enzymes - inhibits bronchoconstriction

    Adverse effects: few, increased liver enzymes

    Therapeutic Use: prophylactic treatment of mild asthma - particularly effective in aspirin induced asthma
  15. Zafirlukast
    Competitive antagonist of cys-leukotriene receptor

    Pharmacokinetics: oral administration; half-life of 10 hrs, metabolized by CYP2C9/3A4

    Mechanism: inhibits cys-LTs

    Adverse Effects: minimal

    • Use: prophylactic treatment of mild asthma
    • particulary effective in aspirin induced asthma
  16. Aspirin
    Non-steroidal anti-inflammatory durg that inhibits the action of cyclooxygenase.  Most widely used medication in the world.
  17. NSAIDs
    Nonsteroidal anti-inflammatory drug

    Inhibitors prostaglandins

    • Anti-inflammatory: in large doses
    • Analgesia: low intensity pain alleviation
    • Antipyretic: reduces fever by inhibiting PG production

    All (except aspirin) are REVERSIBLE inhibitors of COX 1 and COX 2 (except celecoxib only blocks COX 2)

    • Toxicity & Contraindications
    • 1) GI: gastric irritation leading to ulcers, COX-1 inhibition prevents production of protective PGs

    2) Blood: increased bleading time d/t lack of TX production

    3) Hypersensitivity: bronchoconstriction, edema, d/t leukotrienes b/c of shunting of AA pathway from COX to lipoxygenase

    4) Renal: decreased RBF and GFR; salt and water retention

    5) NSAID use in pregnancy = decreased uterine contractions, may prolong labor
  18. Steroid
    Glucocorticoid

    Most potent and effective agents for controlling chronic inflammatory diseases

    First-line treatment for asthma

    Mechanism: binds to cytoplasmic receptors

    Activated receptor-steroid complex: localizes to nucleus/binds DNA (glucocorticoid response elements) - transcription of certain target genes (induction or repression)

    Small minority of patients are resistant

    Limitations to use are side effects
  19. Arachidonic Acid
    The most abundant precursor of eicosanoids.

    Low concentrations in cells, found esterified to membrane phospholipids.

    Release is calcium-dependent

    Phospholipase A2 hydrolyzes the sn-2 ester bond.

    In brain, coupled to ethanolamine to form anadamide which binds cannabinoid receptors and displays biochemical and behavioral effects similiar to THC.
  20. Eicosanoids
    Describes the families of prostaglandins, leukotrienes, and other related compounds.

    Derived from 20-carbon essential fatty acids that contain 3, 4, or 5 double bonds.
  21. Cysteinyl Leukotriene
    Present on mast cells and eosinophils

    Mediate inflammation, asthma

    Zafirlukast is the receptor antagonist
  22. PGE2
    hyperalgesia

    initiation and progression of labor by inducing uterine contractility and mediating ripening of cervix

    vasodilator - systemic blood pressure decrease

    tone of ductus arteriosus 

    relaxes bronchail/tracheal smooth muscle

    increases RBF b/c of vasodilation, promotes diuresis

    inhibits gastric acid secretion, increases gastric mucosal blood blow, stimulates release of viscous mucus, stimulates bicarb secretion, contracts GI smooth muscle
  23. PGI2
    hyperalgesia

    inhibits platelet aggregation via IP receptor coupled to cAMP,  synthesized by endothelial cells NOT platelets

    quiescent state of uterine activity during eary pregnancy, relaxation of uterine tone via increased cAMP

    CV/Vascular SM vasodilator, profound hypotension after IV administration

    relaxation of bronchial/tracheal smooth muscle

    increase RBF b/c of vasodilation in kidney, promotes diuresis & naturesis

    inhibits gastric acid secretion, increases gastric mucosal blood flow
  24. TXA2
    made from arachidonic acid by COX-1 in response to activation of platelet membrane PLA2

    promotes platelet aggregation by stimulating TP receptor that couples to increase in intracellular calcium

    pathway activated in acute coronary artery syndromes

    potent vasoconstrictor in CV/Vascular SM

    Constricts bronchial/tracheal muscle
  25. PGF2alpha
    mediates uterine contractility during labor

    primary dysmenorrhea: concentrations increase in menstrual fluid and cause vasoconstriction, uterine contraction, pain - COX1 and COX2 involvement

    CV/Vascular SM: vasoconstriction

    Bronchial/tracheal smooth muscle: constrict
  26. LTB4
    chemoattractant for neutrophils in inflammatory and immune response
  27. LTC4
    constricts bronchial/tracheal smooth muscle

    increases vascular permeability in inflammatory and immune responses
  28. LTD4
    constricts bronchial/tracheal smooth muscle

    increases vascular permeability in inflammatory and immune responses
  29. Thromboxane
    Vasoconstrictor and a potent hypertensive agent

    Facilitates platelet aggregation.
  30. Dinoprostone
    synthetic analog of PGE2

    • Use: Cervical ripening in pregnancy
    • Prep: Cervical gel
    • Mechanism: promotes cervical ripening - activation of collagenase, relaxes cervical smooth muscle EP4 receptor subtype

    • Use: terminate an early pregnancy/abortion
    • Prep: vaginal suppository
    • Mechanism: uterine contractions via EP1/3 receptors

    • Adverse effects: GI-related, fever, uterine rupture
    • Contraindicated: women w/ C-section or uterine surgery
  31. Misoprostol
    PGE1

    Use: replacement therapy for prevention of ulcers caused by long-term administration with NSAIDs

    Prep: oral administration/requires 4x/day dosing

    Mechanism: suppresses gastric acid secretion by stimulating EP3 receptors on parietal cells; causes a decrease in cAMP, increase mucin and bicarbonate secretion, increase mucosal blood flow

    Adverse Effect: diarrhea/cramping; contraindicated in pregnancy, and IBS
  32. Alprostadil
    PGE1

    • Use: Impotence and erectile dysfunction
    • Prep: intravernous injection
    • Mechanism: increase cAMP which relaxes smooth muscle of corpus cavernosum
    • Adverse effect: pripism - prolonged erection

    • Use: maintenance of patent ductus arteriosus
    • Prep: IV
    • Mechanism: cAMP-mediated relaxation of ductus arteriosus SM
    • Adverse effect: apnea in 10% neonates
  33. Epoprostenol
    PGI2


    Effect: primary pulmonary hypertension, rare idopathic disease mainly observed in young adults; increased incidence in females leads to right heart failure, frequently fatal

    Prep: continuous intravenous infusion

    Mechanism: cAMP-mediated dilation of pulmonary artery vascular smooth muscle

    Adverse effects: nausea, vomiting, headache, flushing
  34. Bimatoprost
    PGF2alpha


    • Use: glaucoma
    • Prep: ophthalmic solution
    • Mechanism: increase outflow of aqueous humor
    • Adverse effects: eye redness, itching, may cause permanent changes in eye colors, eyelid skin' may increase length and number of eyelashes

    • Use: eyelash hypotrichosis
    • Prep: ophthalmic solution
    • Mechanism: increase the percent and duration of hairs in the growth phase
    • Effects: excess, unwanted hair growth, brown iris pigmentation, eye redness, itching
  35. Cromolyn sodium
    inhibits release of histamine

    inhaled anti-inflammatory agent

    Mechanism: stabilizes most mast cell membranes and prevents release of histamine - prevents transmembrane influx of calcium into mast cells required for degranulation - may bind to a plasma membrane calcium channel to inhibit activity

    Few side effects

    Uses: preventive management of asthma, allergic rhinitis, conjunctivitis, food allergies

    MUST BE USED IMMEDIATELY BEFORE EXPOSURE TO STIMMULANT OF ASTHMA ATTACK
  36. Omalizumab
    monoclonal antibody

    Mechanism: decrease amount of antigen specific IgE that normally binds to and sensitizes mast cells

    Subcutaneous administration

    Major adverse effects: life-threatening anaphlaxis and bleeding

    Uses: allergic asthma
  37. Diphenhydramine
    First generation Hblocker

    Allergies (profound sedation)

    Motion sickness (d/t anticholinergic effects)

    Nonprescription sleeping tablets

    Early stage Parkinson's disease
  38. Dimenhydrinate
    First generation H1 blocker

    Vestibular disturbances

    Motion sickness (d/t anticholinergic effects)

    Acts at inner ear vestibular afferents and brain stem

    Side Fx: drowsiness
  39. Chloropheniramine
    First generation Hblocker

    Less prone to drowsiness for allergy treatment
  40. Promethazine
    First generation H1 blocker

    • motion sickness (d/t anticholinergic effects)
    • Chemotherapy-induced nausea/vomiting
  41. Fexofenadine
    2nd generation H1 blocker

    Treats allergies

    No CNS effects - no sedation
  42. Loratadine
    2nd generation H1 blocker

    Treats allergies

    No CNS effects - no sedation

    No associated cardiact toxicity
  43. Desloratadine
    2nd generation Hblocker

    Treats allergies

    No CNS effects - no sedation
  44. Cetirizine
    2nd generation H1 blocker

    Treats allergies

    Higher incidence of sedation compared to other 2nd generation drugs
  45. Cimetidine
    • Hblocker - reversible competitive inhibition
    • -inhibits CYP - prolongs half life of other drugs
    • -decreases basal/nocturnal acid secretion
    • -use approrpriate dose reduction for patients w/ impaired renal fxn
    • -duration of action = 4-5 hrs
    • longer term use at high doses: decreases testosterone binding and inhibits a CYP enzyme that hydroxylates estradiol --> men: gynecomastia, reduced sperm count, impotence

    Least potent

    Used to treat Zollinger-Ellison Syndrome (non beta cell tumor of the pancreas with overproduction of gastric)
  46. Ranitidine
    H2 blocker

    • -decreases basal/nocturnal acid secretion
    • combined w/ bismuth sulfate

    Inhibits CYP but with only 10% affinity of cimetidine

    Minimal side effects

    Medium potency
  47. Famotidine
    Hblocker

    Minimal side effects

    Most potent
  48. Acetylsalicylic Acid; Aspirin
    Irreversible inhibitor of COX via acetylation of serine residue

    • Pharmacokinetics: 
    • -rapid absorption
    • -buffered vs enteric-coated
    • -hihgly bound to plasma proteins
    • -crosses BBB & placenta
    • -hydrolyzed to salicylic acid (still active), then to variouus less polar metabolites
    • -T1/2 is dose dependent (0 order kinetics)
    • -kidney excretion

    • Non-COX related effects
    • 1) increased uric acid levels at low dose
    • 2) decreased uric acid levels at high dose
    • 3) delirium, psychoses b/c croses BBB, nausea, vomiting

    4)respiration: increased RR, respiratory alkalosis, renal compensation via increased HCO3 excretion

    • Adverse Reactions specific to Aspirin:
    • Salicylism: slight respiratory stimluation, nausea, vomiting, tinnitus, deafness, dehydration

    Reye's syndrome: illness related to viral epidemics, result in liver failure and death - affects kids often following a viral illness - perhaps d/t mitochondrial damage
  49. Ibuprofen
    T1/2 = 2 hrs

    highly bound to plasma

    anti-inflammatory, analgesic, anti-pyretic

    Tx: rheumatoid arthritis, dysmenorrhea, pain, fever, osteoarthritis

    Injection: closure of patent ductus arteriosus in premies when usual tx is not effective
  50. Naproxen
    T1/2= 14 hrs

    highly bound to plasma

    anto-inflammatory, analgesic, anti-pyretic

    management of ankylosing spondylitis, osteoarthritis, rheumatoid disorders, acute gout, tendonitis, bursitis, dysmenorrhea, fever
  51. Indomethacin
    T1/2 = 3 hrs

    Tx: acute gouty arthritis, acute bursitis/tendonitis, moderate-to-severe osteoarthritis, ankylosing spondylitis

    IV: alternative to surgery for closure of PDA

    Off-label: pre-tern labor
  52. Ketorolac
    • Absorbed orally and intramuscularly
    • Highly plasma bound

    Use: oral, injection: short term (<5 days) management of moderate-to-severe acute pain requiring analgesia at the opiod level (post-operative pain for ptx who can't tolerate narcotics)
  53. Nabumetone
    COX2>COX1 inhibition

    • converted to active metabolite
    • long half life

    well tolerated side effects

    Tx: osteoarthritis, rheumatoid arthritis
  54. Piroxicam
    T1/2 = 50 hrs

    may offer advantage in tx of osteoarthritis b/c of long half life
  55. Sulfasalazine
    • Not clear if inhibits COX
    • Inhibition of production of IL-1 & TNFalpha, inhibition of lipoxygenase pathway, scavenging of free radicals and oxidants, inhibition of NF-kB

    Prodrug cleaved by colon bacteria (active forms: mesalamine + sulfapyridine)

    Tx: ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis

    Side Fx: decreased folate absorption, sperm motility; headache, nausea, vomiting, fever, malaise
  56. Celecoxib
    Inhibition of COX2 - specific binding site not present in COX1

    Oral administration, bound to plasma proteins

    Metabolized via CYP450 2C9 to inactive metabolites

    Tx: rheumatoid arthritis, primary dysmenorrhea, acute pain, decrease polyps in FAP

    Side FX: increase GI ulceration, bleeding, increased risk of thrombosis

    Contraindications: patients w/ sulfonamide toxicity, prior NSAID hypersensitivity, pre-existing CV factors or disease, deficient CYP 2C9
  57. Acetaminophen
    mechanism not understood, no affinity for COX 1 or 2

    • oral administration
    • absorbed in GI tract
    • T1/2=2 hrs
    • little binding to plasma proteins

    metabolized by CYP2E1, CYP1A2, and CYP3A4

    NOT anti-inflammatory

    • Adverse effects: related to excessive use
    • hepatic toxicity
    • treatment = N-acetylcystein
    • alochol may increase risk of liver damage
  58. Colchicine
    Used to treat gout

    Antimimotic effect: decreases crystal-induced secretion of chemotactic factors and superoxide anions by activated neutrophils

    • oral administration
    • metabolized by CYP 3A4

    • adverse effects: GI, dairrhea
    • latent period before onset of toxic symptoms great limits use of drugs

    hepatic/renal disease should receive reduced doses 

    treatment of familiar mediterranea fever
  59. Allopurinol
    competitively inhibits xanthine oxidase (which produces uric acid)

    concenctration of uric acid in plasma decreases and excretion increases

    plasma concentrations of hypoxanthine and zanthine increase but are efficiently excreted without tissue deposition

    lowers [uric acid] in plasma below the limit of its solubility

    adverse effects: incidence of acute attacks of gouty arthritis may increase as a consequence of mobilization of tissue stores or uric acid (give w/ colchicine or NSAIDs)

    hypersensitivity reactions

    drug interactions: increase half life of probenecid, increased risk of hypersensitivity if taken with ACE inhibitors

    Use: prevention of attack of gouty arthritis and nephropathy, treatment of secondary hyperuricemia
  60. Probenecid
    mechanism: inhibition of organic acid transport in renal tubule

    competes with uric acid for the exchange so that reabsorption of uric acid decreases

    oral administration

    adverse effects: well tolerated, GI irritation

    use: chronic gout, not in patients with kidney stones or with overproduction or uric acid because at higher doses there is increased tendency to produce uric acid stones, may need to combine with colchicine

    If given with penicillin, results in increased plasma [penicillin]
  61. Anakinra
    Use: rheumatoid arthritis 

    Mechanism: antagonist of interleukin-1

    SC injection

    Adverse effects: infections, should not be used in combination with tumor necrosis factor antagonists
  62. Phenylalkylamines
    Class of CCB that acts preferentially on cardiac cells

    Verapamil

    Use-dependent - binding site deep within channel, rapidly firing of action potentials in the myocardium and the SA and AV node promote binding of CCBs - effective block in myocardium and cardiac conducting cells
  63. Benzothiazepine
    Class of CCB that acts preferentially on cardiac cells

    Diltiazem

    Use-dependent - binding site deep within channel, rapidly firing of action potentials in the myocardium and the SA and AV node promote binding of CCBs - effective block in myocardium and cardiac conducting cells
  64. 1,4-Dihydropyridines
    Class of CCB that bind preferentially to vascular smooth muscle to induce vasodilation

    Binding site is on ouside surface of channel protein and bind to depolarized state of the channel.

    Preferentially block L-type Ca channels in ARTERIES and have little effect on veins - reduce cardiac afterload NOT preload

    • Nifedipine
    • Amlodipine

    Often used in combo with beta blockers to prevent reflex tachycardia

    Contraindicated in patients with tachyarrhythmias

    Higher protein binding percentages than phenylalkylamines and benzothiazepines

    Side Fx: hypotension, headache, flushing, and peripheral edema
  65. Diltiazem
    Prototype of benzothiazepine family

    often used in angina- used for typical stable angina - decreases oxygen demand

    • reduces cardiac workload because decreases SA firing rate
    • orally to chronically tx HTN

    potential dilator of coronary arteries allowing increased blood flow to myocardium

    also used in supraventricular arrhythmias

    Not much 1st pass metabolism

    Best tolerated: less potent cardiac effects than verapamil, less dramatic peripheral vasodilation than nifedipine

    reflex tachycardia but not as much as w/ other vasodilators

    SE: flushing, headaches, negative inotropic effects, edema, constipation
  66. Verapamil
    Prototype of phenylalkylamine family

    Used in supraventricular arrhthmias because reduce the firing rate of SA node and reduce conduction through AV node.  Helpful in reducing ventricular response rates if atria is firing too fast.

    tx of stable angina - decreases oxygen demand

    Extensive first pass metabolism

    Side Fx: constipation(worse than other 2 Ca blockers). worsen CHF, AV block, flushing, headaches, negative inotropic effects, edema
  67. Nifedipine
    Prototype of 1,4-dihydropyridine family

    • Used in hypertension because potent vasodilator
    • vasospastic angina d/t vascular effects
    • may aggravate angina symptoms in patients with typical stable angina if they are not used in combo w/ beta blocker

    Not much first pass metabolism

    SE: flushing, headaches, negative inotropic effects, decreased AV conduction, edema(more than other 2 Ca blockers), constipation
  68. Amlodipine
    slow onset, slow affect as compared to others in 1,4-dihydropyridine family

    longer half life than others - so less reflex tachycardia, but harder to adjust dose
  69. Aldosterone
    Synthesized in the zona glomerulosa

    Actions: carbohydrate and protein metabolism, lipid metabolism, mineral and electrolyte metabolism, responsible for hypertension by increasing sodium reabsorption and increasing K and H+ excretion.  causes sleepiness, lability of mood.

    Immune System: reduces access of cells to target tissueAnti-inflammatory activity

    Uses: adrenal insufficiency, rheumatoid arthritis, osteoarthritis, allergic diseases, inflammatory diseases, cerebral edema
  70. Cortisol
    Synthesized in the zona fasciculata and reticularis

    Actions:

    carbohydrate and protein metabolism, lipid metabolism, mineral and electrolyte metabolism, responsible for hypertension by increasing sodium reabsorption and increasing K and H+ excretion.  causes sleepiness, lability of mood.

    • Immune System: reduces access of cells to target tissue
    • Anti-inflammatory activity

    Uses: adrenal insufficiency, rheumatoid arthritis, osteoarthritis, allergic diseases, inflammatory diseases, cerebral edema
  71. Example Steroid Drugs
    Dexamethasone

    Prednisolone

    Fludrocortisone

    Aldosterone

    Cortisol

    Contraindication: existing infection (TB)

    Toxicity: rapid withdrawl may cause adrenal insufficiency

    Prolonged therapy: suppression of pituitary

    Cushing's Syndrome
  72. Metyrapone
    Glucocorticoid synthesis inhibitor

    Blocks 11-beta hydroxylation so synthesis is stopped at 11 desoxycortisol --> plasma ACTH levels increase

    Used as diagnostic test
  73. Mifepristone
    competitive antagonist at progesterone and glucocorticoid receptor

    termination of pregnancy

    treat cushing disease
  74. Spironolactone
    competitive antagonist at mineralocorticoid receptor

    diuretics

    treat hypertension

    cardiac hypertrophy and heart failure
  75. Drospirenone
    • Progesterone receptor agonist:
    • Use with estrogen to suppress ovluation and as hormone replacement therapy in post-menopausal women

    • Mineralocorticoid receptor antagonist:
    • diuretic
    • antagonizes the salt retaining effects of estrogen

    Androgen receptor antagonist
  76. Prednisolone
    Corticosteroid

    Reduces access of cells to target tissue - redistribution of cells out fo vascular space.

    Prevent neutrophil adherence to endothelium

    Inhibit action of chemotactic factors

    • Interference with macrophage antigen processing
    • Blocks actions of lymphokines
    • Inhibits binding to Fc receptors

    Used in combo w/ other drugs in autoimmune diseases and to prevent graft rejection


    Toxicity: supression of adrenal-pit axis.  Acute adrenal insufficiency on abrupt withdrawl, Cushing's Syndrome

    Contraindicated in presence of existing infection
  77. Azathioprine
    Cytotoxic agent

    Kill rapidly proliferating cells

    • Metabolized to 6-mercaptopurine
    • Orally active
    • Purine anti-metabolite that inhibits purine biosynthesis/DNA synthesis.
    • INHIBITS DE NOVO AND SALVAGE PATHWAYS

    Use: inhibits rejection of transplanted organs and rheumatoid arthritis

    Side Fx: bone marrow depression, GI and hepatic toxicity
  78. Cyclophosphamide
    Alkylating agent that results in cross-linking of DNA to kill replicating and non-replicating cells

    Toxic effect more prnounced on B-cells so more effective in suppressing humoral immunity

    Orally active

    Used in the tx of autoimmune diseases in combo w/ other drugs.  Not effective in preventing graft rejection

    Side Fx: bone marrow depression
  79. Methotrexate
    Inhibitor of dihydrofolate reductase - inhibits folate dependent steps in purine synthesis- inhibits DNA synthesis

    Used to treat autoimmune diseases

    Side Fx: Hepatic toxicity
  80. Mycophenolate Mofetil
    2nd generation immunosupressant

    Metabolized to active mycophenolic acid

    • Mechanism: Lymphocyte selective immunosuppressant
    • Inhibits IMP dehydrogenase (necessary for de novo purine synthesis) - no effect on salvage pathway

    lymphocytes cannot make GMP via salvage pathway, thus selectively toxic for lymphocytes

    orally active

    used with cyclosporine and corticosteroids to prevent renal allograft rejection.

    Used to treat autoimmune diseases - rheumatoid arthritis and refractor psoriasis

    Used with caution in patients w/ active GI disease, reduced renal function, and infections

    Side Fx: infection, leukopenia, anemia

    No used in pregnacy
  81. Cyclosporine
    Immunosuppressant

    Lipophilic peptide antibiotic

    Binds receptor and inhibits Ca-dependent phosphatase - Calcineurin.  Blocks action of transcription factor necessary for IL-2 production.  Blocks T-cell helper function.  

    Orally active.

    Used to prevent rejection of transplanted organs.  Used in autoimmune diseases.

    Nephrotoxicity is a major side effect.  Hepatoxicity may occur.
  82. Tacrolimus
    Immunosuppresant

    Binds FK binding protein, a cyclophilin-related protein.  Inactivates calcineurin. Same mechanism of action as cyclosporine.

    50-100 times more potent than cyclosporine.

    Less nephro- and hepatotoxicity.
  83. Sirolimus
    Immunosuppressant

    Inhibits T-cell activation and proliferation downstream of IL-2.

    Binds FKBP-12.  Does not affect calcineurin activity.  Binds and inhibits mTOR, kinase involved in cell cycle progression.  Blocks G1 --> S1 transition.

    Side Fx: infection

    • Used to prevent rejection of transplanted organs and autoimmune diseases.
    • Coating of cardiac stents.
  84. Omeprazole
    R & S isomers

    Inhibits H+/K+ ATPase

    Prodrugs activated by protonation 

    Action longer than half life

    Inhibits acid secretion

    Drug for Zollinger-Ellison syndrome, ulcers, GERD

    Side Fx: can reduce hepatic metabolism of other drugs. rebound hypergastrinemia
  85. Esomeprazole
    S isomer

    Inhibits H+/K+ ATPase

    Prodrugs activated by protonation

    Action longer than half life

    Inhibits acid secretion

    Drug for Zollinger-Ellison syndrome, ulcers, GERD

    Side Fx: can reduce hepatic metabolism of other drugs. rebound hypergastrinemia
  86. Lansoprazole
    Inhibits H+/K+ ATPase

    Prodrugs activated by protonation

    Action longer than half lifeInhibits acid secretion

    Drug for Zollinger-Ellison syndrome, ulcers, GERD

    Side Fx: can reduce hepatic metabolism of other drugs. rebound hypergastrinemia
  87. Aluminum hydroxide
    Neutralizes HCL

    (slow reaction)

    Side Fx: constipation

    Rapid onset of action, immediate relief, short duration of action

    Often combined w/ sucralfate to protect gastric lining
  88. Calcium Carbonate
    Neutralizes HCl

    rapid onset of action, immediate relief, short duration of action

    (fast reaction)

    Side Fx: constipation
  89. Magnesium hydroxide
    HCl neutralization

    (Moderate reaction)

    Rapid onset, immediate relief, short duration of action

    Side Fx: diarrhea - used at treatment for diarrhea - saline laxative, causes osmotic water retention to increase bulk and intestinal peristalsis - contraindicated with electrolyte imbalance, renal, or cardiac disease
  90. Sucralfate
    octasulfate of sucrose + aluminum hydroxide

    with acid it forms a polymer gel to protect the gastric lining from acid and pepsin digestion.

    It also binds bile and stimulates prostaglandin production.

    Side Fx: constipation, may interfere with absorption of drugs
  91. Scopolamine
    Anti-emetic

    Anticholinergic agent

    Tx: motion sickness

    Mechanism: blocks neural pathway in inner ear and vomiting center

    Used prophylactically, injected/transdermal patch

    Side Fx: muscarinic blockage stuff like xerostomia
  92. Ondansetron
    Tx: chemotherapy, radiation or post operative nausea

    Serotonin 5-HT3 receptor antagonist

    Acts centrally at the CTZ and/or at vagal afferent nerves in upper GI tract

    Side Fx: headache, fatigue, constipation, diarrhea
  93. Granisetron
    Tx: chemotherapy, radiation or post operative nausea

    Serotonin 5-HT3 receptor antagonist

    Acts centrally at the CTZ and/or at vagal afferent nerves in upper GI tract

    Side Fx: headache, fatigue, constipation, diarrhea
  94. Prochlorperazine
    Anti-emetic "general use"

    Dopamine2 receptor antagonist

    Some anticholinergic, antihistamine activity

    side effects, concerns
  95. Dronabinol
    tetrahydrocannabinol - natural product may mimic endogenous cannabinoid-compound

    used for chemotherapy-induced emesis refractory to other treatments

    SE esp. elder: dysphoria, vetigo, dizziness, lack of concentration, depersonalization
  96. Dexamethesone
    glucocorticoid

    anti-emetic effect when given in conjunction with other emetics

    chemotherapy, cancer

    mechanism of action - decreased inflammation and PGs
  97. Aprepitant
    substance P receptor antagonist

    inhibits P/NK, receptor

    Used in combo w/ other antiemetics for acute and delayed nausea and vomiting associated with chemotherapy, poster operative nausea

    SE: fatigue, nausea, constipation, hiccups
  98. Metoclopramide
    prokinetic agent that promotes gastric emptying and GI motility by enhancing coordination

    dopamine2 antagonist, may interact w/ serotonin receptor

    has central antiemetic effects at CTZ (5-HT receptors) and promotes gastric emptying by enhancing acetylcholine release in myenteric plexus

    used for mild to moderate cases of nausea and vomiting (diabetic induced gastroparesis and GERD) - best with GI dysmotility disorders

    little effect on large bowel

    SE: rare, dystonia, Parkinson-like symptoms
  99. Erythromyocin
    Pokinetic agent that promotes gastric emptying and GI motility by enhancing coordination

    activates motilin receptors in gastric antrum and duodenum

    • non-antibiotic mediated event
    • stimulates duodenal motility and gastric empting

    (off-label) used to treat diabetic gastroparesis
  100. Loperamide
    anti-diarrheal therapy

    opioid derivate

    OTC, best agent, poorly penetrates CNS
  101. Diphenoxylate
    • anti-diarrheal therapy
    • opioid derivate
    • OTC
    • has some CNS side effects
    • active metabolite is difenoxin
    • abuse potential - preparations include subtherapeutic atropine to limit abuse
  102. Bismuth subsalicylate
    • traveler's diarrhea - pepto bismol
    • displacement of intestinal bacteria from mucous into lumen where lysis occurs
    • also used to treat H. pylori
    • some relief of gastric and intestinal cramping/discomfort
    • causes black stools and tongue d/t bismuth sulfate formation
  103. Octreotide
    treatment for carcinoid syndrome - enterochromaffin cell tumor that makes excess serotonin, vasoactive intestinal peptide, bradykinin, and gastrin (secretory diarrhea)

    somatostatin analong, physiology antagonizes hormone secretion

    useful for dumping syndrome after surgery

    many side effects
  104. Lactulose
    osmotic laxative

    non-absorbed disaccharide, hydrolyzed in the intestine to organic acids, which osmotically pull water into the intestine

    SE: gas and abdominal distention

    useful in portal-system encephalopathy, acidifies ileum and colon causing NH3 to get trapped in lumen
  105. Polyethylene Glycol (PEG)
    long chain PEGs are poorly absorbed.

    Widely used for surgical/radiological prep to cleanse the colon.  Osmotic retention of water.
  106. Docusate Salts
    anionic surfactant- lowers sufrace tension of the stool to enhance mixing.

    softens stool and enhances intestinal secretion.

    marginal efficacy
  107. Bisacodyl
    • stimulant laxative
    • irritant
    • prodrug
    • acts primarily on colon
    • 6 hour latent period with oral administration
  108. Lubiprostone
    Laxative

    • Chloride channel activator - increasing secretions in intestine
    • used for idiopathic constipation and for women w/ IBS

    contraindications: undiagnosed abdominal pain and constipation b/c of intestinal obstruction
  109. Prednisone
    Immunosuppresive therapy used for IBD

    • Corticosteroid
    • Used for acute attacks, moderate to severe
  110. Budesonide
    Immunosuppressive therapy for IBD

    enteric release steroid used to treat mild-moderate acute Crohn's
  111. Olsalazine
    5-aminosalicylate for moderative ulcerative colitis

    NOT related to cox inhibition

    prodrug converted to mesalamine
  112. Mesalamine
    • 5 aminosalicylate
    • used for mild to moderate ulcerative colitis

    NOT related to cox inhibition

    less side effects than sulfasalazine
  113. Captopril
    ACE inhibitor

    Inhibits formtion of Ang. II and degradation of BK

    Block actions of Ang. I and potentiates actions of BK

    • Orally active
    • Competitive enzyme inhibitors
    • Use in treatment of hypertension and congestive cardiac failure (lowers BP w/out changing HR)
    • Therapeutic effect enhanced by diuretic

    SE: agranulocytosis, rash, proteinuria, angiodema, coughing

    Contraindicated in pregnancy

    • Should be used w/ caution in volume-depleted patients or patients on diuretics - hypotension possible
    • Lowers aldosterone release so hyperkalemia may occur
  114. Enalapril
    • ACE inhibitor
    • Inhibits formtion of Ang. II and degradation of BK
    • Block actions of Ang. I and potentiates actions of BK
    • Orally active
    • Competitive enzyme inhibitors
    • Use in treatment of hypertension and congestive cardiac failure (lowers BP w/out changing HR)
    • Therapeutic effect enhanced by diuretic
    • SE: angiodema, coughing
    • Contraindicated in pregnancy

    • Should be used w/ caution in volume-depleted patients or patients on diuretics - hypotension possible
    • Lowers aldosterone release so hyperkalemia may occur
  115. Lisinopril
    • ACE inhibitor
    • Inhibits formtion of Ang. II and degradation of BK
    • Block actions of Ang. I and potentiates actions of BK
    • Orally active
    • Competitive enzyme inhibitors
    • Use in treatment of hypertension and congestive cardiac failure (lowers BP w/out changing HR)
    • Therapeutic effect enhanced by diuretic
    • SE: angiodema, coughing
    • Contraindicated in pregnancy

    • Should be used w/ caution in volume-depleted patients or patients on diuretics - hypotension possible
    • Lowers aldosterone release so hyperkalemia may occur
  116. Losartan
    • angiotensin receptor antagonist - block AT1 receptors
    • competitive inhibitor of Ang. II 
    • orally active
    • Used to treat HTN w/out change in HR, effective related to PRA
    • Slow onset of action
    • Activity enhanced by diuretic
    • Reduces BP w/out increasing HR - should be used w/ caution in patients with volume depletion or on diuretics - hypotension possible
    • Contraindicated in pregnancy
    • Renal function may decrease in patients with CHF or renal artery stenosis

    SE: dizziness, cough, angioedema, upper respiratory infections
  117. Aliskiren
    • Renin inhibitor
    • Potent active site, non-peptide inhibitor
    • Orally active
    • Long acting - T1/2=24h
    • Use to treat HTN w/out changing HR - effect comparable to angiotensin receptor antagonist
    • Effect enhanced by diuretic, ACE, or AT1 antagonist
    • Decreases plasma ang. II and aldosterone 
    • Antihypertensive effect related to pretreatment PRA
    • Side effects comparable to placebo
  118. Propranolol
    Beta blocker (non-selective)

    • used for chronic tx of stable angina (may worsen vasospastic angina)
    • decreases oxygen demand for myocardium


    • reduces renin release
    • decreased HR to reduce CO
    • inhibition of norepi release from central/peripheral neurons

    more effective in lowering blood pressure in young vs. old patients

    effect enhanced by diuretic

    SE: cardiac depression, increase airway resistance, mask symptoms of hypoglycemia, sedation, impotence, nightmares

    use w/ cautions in patients w/ asthma, CHF, peripheral vascular disease.  useful in patients w/ angina pectoris.

    w/drawl syndrome - supersensitivity to beta stimulation may cause angina, arrhythmias, or infarction
  119. Metoprolol
    • Beta1 blocker
    • reduces renin release

    used for chronic tx of stable angina (not useful for variant vaspospastic angina and may worsen condition if used alone) - decreases oxygen demand of myocardium - decrease HR, contractility, and afterload

    • decreased HR to reduce CO
    • inhibition of norepi release from central/peripheral neurons
    • more effective in lowering blood pressure in young vs. old patients
    • effect enhanced by diuretic

    SE: cardiac depression, increase airway resistance, mask symptoms of hypoglycemia, sedation, impotence, nightmares

    use w/ cautions in patients w/ asthma, CHF, peripheral vascular disease.  useful in patients w/ angina pectoris.

    w/drawl syndrome - supersensitivity to beta stimulation may cause angina, arrhythmias, or infarction
  120. Spironolactone
    • Competitive aldosterone antagonist at mineralocorticoid receptor
    • Diuretics
    • Orally active
    • Reduce cardiac hypertrophy; heart failure
  121. Eplerenone
    • Competitive aldosterone antagonist at mineralocorticoid receptor
    • Diuretics
    • Orally active
    • Reduce cardiac hypertrophy; heart failure
  122. Fenoldopam
    • DA1 agonist - high concentrations blocks alpha-receptors.  activates adenyl cyclate and increases cAMP
    • vasodilator
    • increases RBF w/out reducing GFR
    • decreases FF
    • weak diuretic due to compensatory sodium reabsorption in more distal segments
    • limited pharm uses
    • lowers systolic and diastolic blood pressure in severe hypertension - equivalent to sodium nitroprusside - dilate renal and mesenteric vascular beds
    • increases intra-ocular pressure, flushing, headache, tachycardia, may precipitate angina

    contrainidcated in glaucoma, angina, and heart failure
  123. Dopamine
    • DA1 agonist
    • vasodilator
    • increases RBF w/out reducing GFR
    • decreases FF
    • weak diuretic due to compensatory sodium reabsorption in more distal segments
    • limited pharm uses
  124. Atriopeptins
    • DA1 agonist
    • vasodilator increases RBF w/out reducing GFR
    • decreases FF
    • weak diuretic due to compensatory sodium reabsorption in more distal segments
    • limited pharm uses
  125. Mannitol
    • osmotic diuretic
    • freely filterable at glomerulus
    • limited reabsorption by tubule
    • not metabolized by kidney
    • pharmacologically inert

    mchanism of action: non-reabsorbed solute limits the reabsorptin of water from the tubule, Na is reabsorbed w/out water, reduced Na concentration diminishes, NET SODIUM REABSORPTION FALLS, enhanced K excretion occurs in distal tubule due to increased Na available for exchangee, urine flow increases as does Na, K, and Cl excretion.

    Uses: IV, prophylaxis of acute renal failure, edematous conditions in which a volume load is not detrimental, glaucoma

    SE: related to volume overload and expansion of intravascular fluid volume, rare hypersensitivity
  126. Acetazolamide
    • Carbonic anhydrase inhibitor
    • Secreted into proximal tubule by organic transporter (OAT)
    • Blockade of CA decreases carbonate reabsorption and thereby sodium reabsorption in proximal tubule causing urine pH to decrease
    • K+ secretion in distal tubule increases
    • Urine volume increases as does the excretion of Na+, K+, and bicarb, urinary excretion of Cl- falls

    Uses: glaucoma (reduces aqueous humor formation), alkaline urine to decrease drug toxicity, treat symptoms of acute altitude sickness

    SE: metabolic acidosis occurs which reduces renal response to the drug
  127. Furosemide
    lool/high ceiling diuretic

    • mechanism:
    • Na/K/2Cl symport inhibitors
    • secreted into proximal tubule by organic acid transporter
    • act on cortical and medullary segments of ascending limb of loop of Henle to inhibit active Cl reabsorption, reducing reabsorption of both Na and Cl by inhibiting the symporter.

    • potent diuretics
    • increases RBF and often GFR
    • increases urine volume and excretion of Na, Cl, and K

    • Uses:
    • rapid onset, shurt duration
    • management of edema d/t cardiac, hepatic or renal disease
    • acute pulmonary edema
    • hypertension

    • SE:
    • hypokalemia
    • hyperuricemia
    • hyperglycemia
    • ototoxicity - deafness w/ high doses
    • volume depletion
  128. Bumetanide
    • lool/high ceiling diuretic
    • mechanism:
    • Na/K/2Cl symport inhibitorssecreted into proximal tubule by organic acid transporteract on cortical and medullary segments of ascending limb of loop of Henle to inhibit active Cl reabsorption, reducing reabsorption of both Na and Cl by inhibiting the symporter.

    • potent diuretics
    • increases RBF and often GFR
    • increases urine volume and excretion of Na, Cl, and K

    • Uses: rapid onset, shurt duration
    • management of edema d/t cardiac, hepatic or renal disease
    • acute pulmonary edema
    • hypertension

    • SE:
    • hypokalemia
    • hyperuricemia
    • ototoxicity - deafness w/ high doses
    • volume depletion
  129. Ethacrynic acid
    lool/high ceiling diuretic

    • mechanism:
    • Na/K/2Cl symport inhibitors
    • secreted into proximal tubule by organic acid transporter
    • act on cortical and medullary segments of ascending limb of loop of Henle to inhibit active Cl reabsorption, reducing reabsorption of both Na and Cl by inhibiting the symporter.

    • potent diuretics
    • increases RBF and often GFR
    • increases urine volume and excretion of Na, Cl, and K

    • Uses: rapid onset, shurt duration
    • management of edema d/t cardiac, hepatic or renal disease
    • acute pulmonary edema
    • hypertension

    • SE:
    • hypokalemia
    • hyperuricemia
    • ototoxicity - deafness w/ high dosesvolume depletion
  130. Chlorothiazide
    Thiazide diuretic

    • Mechanism:
    • Na/Cl symport inhibitor
    • Secreted into proximal tubule by OAT
    • Act on CORTICAL diluting segment of ascending limb of loop of Henle to inhibit NaCl reabsorption

    • Intermediate activity (8-10%)
    • Reduces GFR
    • K secretion increases d/t increased Na delivery to distal tubule
    • Impairs kidney's ability to produce dilute urine
    • Enhance urate reabsorption in proximal tubule
    • Decrease renal excretion of calcium
    • Urine volume increases and Na, Cl, and K excretion - excretes a hypertonic urine

    • Uses:
    • diuresis is rapid with long duration
    • managemnt of edema d/t congestive cardiac failure
    • hypertension
    • management of hypercalciuria in patients with renal calculi composed of calcium salts

    • SE: 
    • hypokalemia
    • hyperuricemia
    • hyperglycemia - d/t increased insulin secretion
    • should not be used when GFR < 25 ml/min
  131. Hydrochlorothiazide
    Thiazide diuretic

    • Mechanism:
    • Na/Cl symport inhibitor
    • Secreted into proximal tubule by OAT
    • Act on CORTICAL diluting segment of ascending limb of loop of Henle to inhibit NaCl reabsorption

    • Intermediate activity (8-10%)
    • Reduces GFR
    • K secretion increases d/t increased Na delivery to distal tubule
    • Impairs kidney's ability to produce dilute urine
    • Enhance urate reabsorption in proximal tubule
    • Decrease renal excretion of calcium
    • Urine volume increases and Na, Cl, and K excretion - excretes a hypertonic urine

    Uses:diuresis is rapid with long duration

    • managemnt of edema d/t congestive cardiac failure
    • hypertension
    • management of hypercalciuria in patients with renal calculi composed of calcium salts

    • SE: hypokalemia
    • hyperuricemia
    • hyperglycemia - d/t increased insulin secretion
    • should not be used when GFR < 25 ml/min
  132. Metolazone
    Thiazide Diuretic

    • Mechanism:
    • Na/Cl symport inhibitor
    • Secreted into proximal tubule by OAT
    • Act on CORTICAL diluting segment of ascending limb of loop of Henle to inhibit NaCl reabsorption

    • Intermediate activity (8-10%)
    • Reduces GFR
    • K secretion increases d/t increased Na delivery to distal tubule
    • Impairs kidney's ability to produce dilute urine
    • Enhanced urate reabsorption to proximal tubule
    • Decrease renal excretion of Ca
    • Urine volume increases and Na, Cl, and K excretion - excretes a hypertonic urine

    • Ues:
    • diuresis is rapid with long duration
    • management of edema d/t congestive cardiac failure
    • hypertension
    • management of hypercalciuria in patients with renal calculi composed of calcium salts

    • SE: 
    • hypkalemia
    • hyperuricemia
    • hyperglycemia - d/t increased insulin secretion
    • should not be used when GFR <25 ml/min
  133. Spironolactone
    Potassium sparing diuretic

    • Mechanism:
    • acts on distal tubule as a competitive antagonist of aldosterone
    • requires endogemous aldosterone activity
    • urine volume increases.  urinary excretion of Na increases while K excretion decreases

    weak diuretic (2-3% of filtered Na load is excreted)

    • Use:
    • hypertension
    • refractory edema
    • Primary aldosteronism
    • Used with thiazide or loop diuretic to enhance diuretic effect and reduce K loss
    • long duration of action T1/2=24 hrs

    • SE: 
    • hyperkalemia: should not be used with K supplements and used with care in patients w/ severe renal sufficiency
    • gynecomastia - weak progesterone agonist
  134. Eplerenone
    Potassium sparing diuretic

    • Mechanism:
    • acts on distal tubule as competitive antagonist of aldosterone
    • requires endogenous aldosterone activity
    • urine volume increases, urinary excretion of Na increases while K excretion decreases

    weak diuretic (2-3% of filtered Na load is excreted)

    • Use:
    • hypertension
    • refractory edema
    • Primary aldosteronism
    • Used with thiazide or loop diuretic to enhance diuretic effect and reduce K loss
    • long duration of action (T1/2 =24 hrs)



    • SE: 
    • hyperkalemia: should not be used w/ K supplements

    tiny bit of gynecomastia
  135. Triamterene
    Potassium-sparking diuretic - Sodium channel inhibitor

    • Mechanism:
    • inhibit entry of Na into principal cell - Na/K exchance does not occur
    • Effects independent of aldosterone
    • Urine volume increases, urinary excretion of Na increases while K excretion falls
    • At high doses, reduces GFR

    Weak diuretic --> 2-3% of filtered Na load excreted

    • Uses:
    • used with thiazide or loop diuretic to enhance diuretic effect and reduce K loss
    • treatment of edema or hypertension

    • SE: 
    • hyperkalemia - should not be used with K supplements
    • mild azotemia
  136. Amiloride
    K sparing diuretic  - Na channel inhibitor

    • Mechanism:
    • inhibit entry of Na into principal cell.  Na/K exchance does not occur.  Blocks Na/H exchance at higher concenctration.

    effects are independent of aldosterone

    urine volume increases, urinary excretion of Na increases while K excretion falls.

    weak as diuretic (2-3% of filtered Na load is excreted)

    • Uses:
    • thiazide or loop diuretic to enhance diuretic effect and reduce K loss
    • treatment of edema or hypertension



    • SE:
    • hyperkalemia - don't give w/ K supplements
    • mild azotemia
  137. Hydralazine
    vasodilator that relaxes vascular smooth muscles to cause vasodilation

    acts mainly at peripheral arterioles

    little effect on veins

    reduces peripheral resistance

    • orally active vasodilator
    • used in chronic tx of HTN in bombo w/ other drugs
    • acts mainly on arterioles with little effect on veins
    • acetylation is major route of inactivation

    SE: headache, palpitations, tachycardia, dizziness, edema, and lupus-like syndrome
  138. Minoxidil
    • orally active vasodilator
    • used in chronic tx of refractory HTN
    • dilates mainly arterioles
    • opens ATP-sensitive potassium channels in vascular SM
    • long lasting

    SE: tachycardia, edema, hair growth
  139. Diazoxide
    • Parenteral vasodilator
    • Used to treat hypertensive emergencies -BP rarely falls below normal
    • Dilates mainly aterioles by opening ATP-sensitive potassium channels in vascular smooth muscle
    • Highly bound to plasma proteins - must be given by IV bolus

    SE: reflex tachycardia, hyperglycemia, edema
  140. Sodium Nitroprusside
    Parenteral vasodilator given by IV infusion - must monitor blood pressure - can cause hypotension

    Tx: hypertensive emergencies

    Dilates arteries AND veins - CO decreases, venous pooling occurs

    Metabolized to nitric oxide - acts by increasing cyclic GMP in vascular smooth muscle

    short T1/2

    SE: headache, methemoglobinemia, palpitations

    Metabolized to cyanide and thiocynate - can accumulate with prolonged therapy and excreted slowly
  141. Phenoxybenzamine
    sympatholytic drugs

    irreversible atagonist of alpha 1 and alpha 2 receptors - long duration of action

    orally active inhibitor used in hypertension that is refractory to conventional therapy and in pheochromocytoma  

    SE: many - postural hypotension, nasal stifness, inhibition of ejaculation
  142. Phentolamine
    competitive REVERSIBLE alpha antagonists

    short acting

    orally active used in hypertension that is refractory to conventional therapy in pheochromocytoma - used parenterally to treat sympathetic excess

    SE: postural hypotension, gastrointestinal stimulation, inhibition of ejaculation
  143. prazosin
    competitive, reversible alpha1 antagonist

    treat chronic hypertension

    first dose effect - extreme hypotension w/ initial dose

    reflex tachycardia - less than alpha1/2 antagonists

    no inhibition of sexual function

    SE: headache, drowsiness
  144. labetalol
    competitive inhibitor of alpha1 and beta1/2 receptors.

    orally active to treat chronic essential hypertension

    may be used IV for HTN emergencies

    reduces CO and peripheral resistance

    SE: mild orthostatic hypotension, headaches
  145. carvedilol
    competitive inhibitor of alpha1 and beta1/2 receptors

    orally active to treat chronic essential HTN

    may be used IV for HTN emergencies

    reduces CO and peripheral resistance

    SE: mild orthostatic hypotension, headaches
  146. Guanethidine
    neuronal blocking sympatholytic drug

    inhibits norepi release and depletes neuronal amine stores

    orally active to treat severe HTN

    polar compound - does not enter CNS

    long acting

    must enter neuron by amine pump to be effective; effect inhibited by tricyclic antidepressants

    SE: numerous, limit use - orthostatic hypotension, interferes w/ sexual fxn, diarrhea, muscle weakness, edema
  147. Guanadrel
    neuronal blocking sympatholytic drug

    inhibits norepi release and depletes neuronal amine stores

    orally active to treat severe HTN

    long acting

    must enter neuron by amine pump to be effective; effect inhibited by tricyclic antidepressants

    SE: numerous, limit use - orthostatic hypotension, interferes w/ sexual fxn, diarrhea, muscle weakness, edema
  148. Reserpine
    depletes neuronal amine stores

    orally active compound used to treat essential HTN in combo w/ other drugs.  rarely used.

    enters CNS, long acting, slow onset

    SE: sedation, diarrhea, orthostatic hypotension, increased gastric acid secretion
  149. trimethaphan
    ganglionic blocking drug - blocks action of ACTH at autonomic ganglia - blockage of sympathetic ganglia produces hypotension

    blockage of parasympathetic ganglia produces: dry mouth, constipation, urinary retention, inhibition of sexual function, blurred vision

    rarely used b/c of erratic absorption

    used to produce controlled hypotension during surgery for dissecting aneurysm
  150. alpha-methyl dopa
    centrally acting agent - reduces BP by reducing sympathetic tone on blood veessels

    must be metabolized in CNS

    • alpha2 adrenergic agonist - reduces sympathetic outflow
    • alpha-methyl group prevents metabolism by MAO and prolongs action

    decrease peripheral resistance, heart rate, and CO

    SE: sedation, flu-like syndrome, positive Coomb's test, edema, rebound hypertension w/ sudden discontinuation
  151. Clonidine
    alpha2 agonist that directly stimulates central alpha adrenergic receptors to reduce sympathetic outflow

    • causes prolonged blood pressure lowering
    • decreases HR and CO
    • long acting
    • rebound hypertension occurs w/ withdrawl
    • SE: sedation, dry mouth, edema
  152. Guanabenz
    alpha2-adrenergic agonist which directly stimulates central alpha2 adrenergic receptors to reduce sympathetic outflow

    reduces peripheral resistance and produces a sustained reduction in blood pressure

    HR decreases slightly

    • hypertension occurs w/ sudden withdrawl
    • SE: sedation, dry mouth, headache
  153. Atenolol
    • Beta blocker
    • reduces renin release
    • decreased HR to reduce CO
    • inhibition of norepi release from central/peripheral neurons
    • more effective in lowering blood pressure in young vs. old patients
    • effect enhanced by diuretic

    SE: cardiac depression, increase airway resistance, mask symptoms of hypoglycemia, sedation, impotence, nightmare

    suse w/ cautions in patients w/ asthma, CHF, peripheral vascular disease.  

    useful in patients w/ angina pectoris.

    w/drawl syndrome - supersensitivity to beta stimulation may cause angina, arrhythmias, or infarction
  154. Digoxin
    Only cardiac glycoside available in US

    • In patients w/ heart failure:
    • Direct Effects:
    • 1) Positive inotropic effect of failing heart d/t direct effect to increase contractile state of myocardium and increasing CO

    2) Increases vagal tone (slows heart rate)

    • Secondary effects d/t reduced neuroendocrine activation:
    • Decreased herat rate
    • Arterial and venous dilation
    • Decreased venous pressure
    • Normalized arterial baroreceptors

    • Molecular site of action:
    • Inhibition of Na/K ATPase in cardiomyocytes, indirectly results in increased intracellular concentration of Ca.  K+ competes for binding of digoxin to the Na/K ATPase.

    • Electrophysiological Actions:
    • Increased vagal nerve activity (decreased HR, conduction velocity in AV node, increased refractory period in AV node, heart block can sometimes develop)

    ECG: increased PR interval

    Kinetics: T1/2 = 36-48 hrs, orally absorbed, excreted unchanged in kidney

    Adverse effects/toxicity: Low therapeutic index. GI most common (anorexia, nausea, vom., diarrhea), visual disturbances, neurological (hallucination/disorientation), muscular(weakness, fatigue), cardiac (arrhthmia).  Toxicity enhanced with hypokalemia.
  155. Nitroglycerin
    dilate venous vasculature better than arterial

    decreases preload via NO production

    rapidly dissolvable tablet or aerosol spray both for sublingual administration

    fast onset (few mins) and short duration (15-30 mins)

    • acute episodes of angina and chronic tx of typical stable angina
    • can also be used in acute heart failure
    • available for IV administration
    • used in tx of left ventricular dysfunction due to acute infarction

    side effects: hypotension, orthostatic hypotension, tachycardia, throbbing headaches

    tolerance develops for a few hrs, but rapidly reverses

    don't give in combo w/ PDE inhibitor = hypotension

    inactivated by high capacity organic nitrate reductase in liver
  156. isosorbide dinitrate
    oral nitrovasodilator (much greater effect on venous blood vessels)

    used in combination with hydralazine

    • prolong life and is particularly effective in AAs
    • used for acute episodes of angina and chronix tx of typical stable angina

    also used for chornic therapy - long duration of action compared to nitroglycerine

    extensive first pass metabolism

    more expensive than nitroglycerin

    no significant advantage over nitroglycerin

    side effects: hypotension, orthostatic hypotension, tachycardia, throbbing headaches

    tolerance develops for a few hrs, but rapidly reverses
  157. isosorbide mononitrate
    does not undergo 1st pass metabolism

    T1/2= 5 hours

    used to treat acute and chronic angina
  158. Nitroprusside
    direct NO donor that dilates both arteries and veins by increasing cGMP levels in vascular SM
  159. dopamine
    can be used in acute heart failure

    beta adrenergic agonist

    dose-dependent sympathomimetic

    limited utility because vasoconstriction can lead to afterload and worsening of performance

    sometimes use at low dose to increase RBF to help maintain GFR
  160. dobutamine
    overall affect of racemic mixture = beta agonist

    agent of choice in management of severe dysfunction (doesn't increase systemic vascular resistance the way dopamine can)

    increases stroke volume and increases inotropy

    little effect on heart rate

    tolerance develops in 4 days
  161. inamrinone
    used for acute heart failure

    phosphodiesterase inhibitor

    decreases cAMP degradation resulting in elevated cAMP in cardiac and smooth muscle

    positive inotropif effect

    balanced arterial and venous dilator (decrease preload and afterload)

    combined effects produce a substantial increase in CO

    available IV for short-term circulatory support

    major adverse reactions: arrhythmias
  162. nesiritide
    recombinant form of the B-type natriuretic peptide normally produced by ventricles in response to stretch

    counter regulates the effects of renin-angiotensin-aldosterone system

    vasodilation

    increases sodium excretion

    net effect = decrease blood volume, BP, afterload; increases CO


    used for acute decompensated heart failure mainly for reducing dyspnea
  163. ranolazine
    blocks specific sodium current during ischemia, results in decrease in calcium overload during ischemia

    sustained release prep

    used in combo w/ other agents

    no hemodynamic effects

    only use in effort angina patients unresponsive to standard therapy
  164. Quinidine
    Antiarrhythmic drug

    Inhibitors of depolarization

    Class I antiarrhythmic agents - Na channel blockers

    Moderate phase 0 depression and slowed conductino (2+) - prolong repolarization

    • Increase AP threshold
    • Decrease Vmax
    • Increase ERP


    Indirect effects: blocks K+ channels --> early after depolarizations, vagolytic effect (unwanted)

    Inhibits P450 system (metabolism of narcotics is reduced)

    Proarrhthmic - not necessarily related to the arrhythmia being treated

    Metabolized in liver; tolerated in patients with renal failure

    Use: Atrial flutter or fibrillation, prevent ventricular tachycardia and fibrillation

    Side FX: diarrhea, cramps, vagolytic (digitalize first)
  165. Disopyramide
    Class I antiarrhythmic drug - Na channel blocker

    Moderate phase 0 depression and slowed conduction (2+); prolong repolarization
  166. Lidocaine
    Class IB antiarrhthmic drug - Na channel blocker

    Minimal phase 0 depression and slow conduction (0-1+); shorten repolarization

    • Increase AP threshold
    • Block Na channels (decrease Vmax) at high HR and in depolarized cells (can target diseased ischemic cells)
    • Decreases AP during and ERP

    • Side Fx: Dizziness, seizures
    • Use: ventricular tachycardia
    • Digitalis- induced arrhythmias
    • Safe for patients long QT syndrome
  167. Flecainide
    Class Ic antiarrythmic

    Marked phase 0 depression and slow conduction (4+); little effect on repolarization

    • Increase AP threshold
    • Decrease Vmax (conduction velocity)

    Side Fx: pro-arrhythmic (CAST trial) (more so than treating the arrhythmia)

    Use: approved for use in life-threatening situations when supraventricular and ventricular arrhythmias are resistant to toher drugs
  168. Amiodarone
    Class III Potassium channel blocker

    prolongs repolarization (AP duration increases)

    Main common effect is increased ERP.

    • Potent K channel blocker
    • Modest Na channel blocker
    • Modest Ca channel blocker
    • Modest alpha/beta adrenergic receptor blocker

    Uses: effective against ventricular tachyarrhythmias and fibrillation.  Also used in the prevention of recurrent paroyxsmal atrial fibrillation or flutter.

    Side Fx: triggered arrhythmias, altered thyroid function, pulmonary fibrosis(irreversible)
  169. Sotalol
    Class III Potassium channel blocker

    prolongs repolarization

    also has secondary beta receptor blocking actions

    Side Fx: triggered arrhythmias
  170. HMG CoA Reductase Inhibitor
    structurally similiar to HMG CoA substrate

    Reversible inhibitor for active site in INITIAL RATE LIMITING STEP IN CHOLESTEROL BIOSYNTHESIS
  171. Lovastatin
    • HMG CoA Reductase inhibitor
    • isolated from mold

    USE: first line therapy for those w/ increased risk of MI d/t hypercholesterolinemia

    Mechanism: reduced cholesterol increases LDL receptor gene

    • Administered as inactive lactone
    • T1/2 = 1-4 hrs

    Extensive first pass metabolism - CYP3A4

    • Drugs that increase statin serum concentrations:
    • Antifungal
    • Macrolide antibiotics
    • Grapefruit juice

    SE: GI symptoms, myopathy, rhabdomyolysis, hepatoxicity

    Greater risk factors when taken with gemfibrozil

    Contraindications: hypersensitivity, active liver disease, WOMEN WHO ARE PREGNANT OR LACTATING
  172. Simvastatin
    • HMG CoA Reductase inhibitor
    • Administered as inactive lactone
    • T1/2 = 12 hrs

    Use: 1st line therapy for those w/ increased risk of MI d/t hypercholesterolinemia

    CYP3A4

    SE:L GI symptoms, hepatoxicity, myopathy, rhabdomyolysis

    • W/ niacin = increased risk for myopathy in chinese
    • Greater risk factors when taken w/ gemibrozil
  173. Fibric Acids/Fibrates
    • triglyceride lowering agents
    • effects mediated by PPARs
    • increase lipolysis and plasma clearance of TG rich lioproteins

    Tx: patients w/ high TGs

    example: gemfibrozil
  174. PPAR Activators
    • Peroxisome proliferator activated receptors
    • Regulate gene expression to increase lipolysis and plasma clearance of TG rich lipoproteins
  175. Gemfibrozil
    fibric acid/PPAR activator used to lower TGs

    • use: metabolic syndrome, hypertriglyceridemia, avoid in patients w/ elevated LDL w/out elevated TGs
    • inhibits uptake of active hydroxy acid forms of statins by transporter

    first-pass hepatic uptake of these statins by transporter after their oral administration

    activated PPAR-alpha 

    • decrease VLDL production
    • increase VLDL clearance
    • decrease LDL particles
    • increase HDL production

    combination therapy: w/ statins increased myopathy and increased creatine kinase--> renal failure
  176. Cholestyramine
    • Bile acid binding resin
    • Anion exchange resins that exchange Cl for bile salts in small intestine, increasing bile excretion in feces
    • Less bile = increased cholesterol breakdown d/t feedback inhibitor
    • Lower plasma LDL-cholester --> more LDL receptors



    SE: constipation/bloating sension, gritty consistency, interferes w/ absorption of other drugs, modest increase in TG/with time returns to baseline
  177. Nicotinic Acid/Niacin
    • Use:
    • hypertriglyceridemias and elevated LDL-cholesterol (particularly in patients w/ low HDL and high LDL)
    • severe hypercholesterolemias that do not respond to resin therapy
    • only lipid-lowering drug that reduces Lp(a) levels

    • Mechanism: not related to vitamin effects
    • adipose tissue: decreases TG synthesis
    • liver: decreases synthesis rate of VLDL-TG
    • inhibits uptake of HDL-apoA1 - less removal from plasma

    SE: intense cutaneous flush and pruitus, GI, abnormal liver function tests, uricemia, increase fasting glucose levels

    Contraindicated: patients w/ peptic ulcer, gout, hepatic dysfunction, diabetes

    Combined w/ statin = myopathy (especially in Chinese)
  178. Ezetimibe
    cholesterol absorption inhibitor

    • uses: primary hypercholesterolemia  for patients resistant to statin therapy
    • - combined with statins - simvastatin + ezetimibe - further decrease in LDL-cholesterol

    • mechanism:
    • protein transporter called NPC1L1
    • reduced cholesterol flux from intestine to liver

    • oral administration
    • metabolized to active 

    SE: well tolderated
  179. Heparin
    Unfractionated, high MW

    • Uses: 
    • deep vein thrombosis
    • pulmonar embolism
    • unstable angina/acute MI
    • surgery requiring cardiopulmonary bypass
    • during/after coronary angioplasty or stent placement
    • low dose used prophylactically to prevent DVT and thromboembolism

    Mechanism: Catalyzes antithrombin III which inhibits coagulation proteases - catalyzes inhibition of thrombin and Xa (DOES NOT AFFECT SYNTHESIS OF CLOTTING FACTORS OR LYSE EXISTING CLOT)

    • Not absorbed orally - IV infusion or subQ
    • Cleared/degraded by reticuloendothelial system and liver
    • Does not cross placenta - yay pregnancy!
    • monitor aPTT (clotting time 1.5 to 2.5 times the normal mean aPTT is therapeutic)

    SE: bleeding/hemorrhage, thrombocytopenia (decreased platelet count)

    Contraindications: active bleeding, severe uncontrolled HTN, recent surgery of eye, brain, spinal cord
  180. Low molecular weight heparins
    fragments of standard-molecular weight heparin

    Enoxaparin/Dalteparin

    Inhibitor of Factor X, accelerates activity of ATIII poorly catalyze inhibition of thrombin

    • longer half life than standard heparin
    • decreased risk of hemorrhage
    • theoretically less risk of thrombocytopenia
    • administered subQ

    Use: acute DVT, prophlaxis of DVT, hip replacement surgery, during and following hospitalization, acute unstable angina and MI

    more predictable anti-coagulant response than unfractionated heparin
  181. Enoxaparin
    low molecular weight heparin

    administered sub q

    Use: acute DVT, prophlaxis of DVT, hip replacement surgery, during and following hospitalization, acute unstable angina and MI

    longer T1/2 than heparin

    more selectively for activated factor X than thrombin
  182. Dalteparin
    Low molecular weight heparin

    • administered subq
    • longer half-life than heparin

    Use: acute DVT, prophlaxis of DVT, hip replacement surgery, during and following hospitalization, acute unstable angina and MI
  183. Lepirudin
    Direct thrombin inhibitor

    IV administration

    Inactivates thrombin by blocking the substrate binding site in a 1:1 complex

    Derived from the leech

    Use: alternative to heparin in patients who have heparin induced thrombocytopenia

    SE: hemorrhage
  184. Protamine Sulfate
    Heparin antagonist

    Low MW, + charged

    SE : weak anticoagulant properties in high doses, analphylactic reaction, severe pulmonary hypertension

    USE: used for heparin overdose with acute bleeding that can't be controlled by stopping heparin - reverse heparin following cardiopulmonary bypass
  185. Warfarin
    • Fat soluble, structural analog of Vit. K 
    • Highly bound to plasma proteins

    Use: long-term venous thromboembolic disease, prophylaxis against thromboembolism in atrial filbrillation, prosthetic heart valves, dilated cardiomyopathy)

    Oral administration

    • Mechanism:
    • 3 types of warfarin - racemic (administered), S (more active), and R
    • Vitamin K antagonist
    • **inhibits vitamin K epoxide reductase, not allowing Vit. K to be recycled and used to form clotting factors

    therapeutic effect not seen for several hrs to days - delayed because active clotting factors are not degraded by warfarin

    • Measure therapeutic effect via prothrombin time(PT btwn 15-26 secs) or INR (btwn 2-3)
    • Inactivated by liver microsomes - CYP2C9

    SE: hemorrhage, purple toe syndrome, skin necrosis/gangre

    Contraindications: pregnancy, liver or kidney disease, CYP2C9 polymorphism, genetic variations in VKOR, Vit. K deficiency

    Reversal: transfusion with fresh frozen plasma, vit. k would have a time delay before you would see effectiveness

    • Drug interactions are common
    • Interactions w/ food (increase INR: cranberries, alcohol, Vit. E) (decrease INR: green vegetables, green tea, soy beans, vit. k supplements)
  186. Dabigatran
    Orally active reversible direct thrombin inhibitor

    • Use: 
    • long-term tx of venous thromboembolic disease
    • prophylaxis against thromboembolism in a fib., prosthetic heart valves, & dilated cardiomyopathy

    • Mechanism:
    • Prodrug 
    • reversible direct inhibitor of clot-bound and free thrombin - inhibit thrombin's activation of platelets

    No monitoring (unlike warfarin) - little efect on PT or INR

    • More predictable than warfarin 
    • Rapid onset of action (don't have to wait to block synthesis of new clotting factors, directly inhibits active clotting factor)

    Not substrate of CYP450

    SE: increased risk of bleeding (less than warfarin), GI upset (more than warfarin)

    Drug Interactions: substrate for P-gp efflux transporter - other drugs can increase elimination of drug, and also drugs that inhibit transporter to increase plasma concentration
  187. Rivaroxaban
    orally active reversible Xa inhibitor - inhibits free and thrombus-associated factor Xa

    Use: reducing risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation & prophylaxis of DVT in patients undergoing knee or hip replacement surgery

    No monitoring required

    SE: bleeding, interactions with CYP3A4 and Pglycoprotein inhibitors
  188. Tissue Plasminogen Activator (t-PA)
    endogenous activator that converts plasminogen to plasmin, synthesized by vascular endothelial cells and released at local sites of thrombosis

    early stage of clot formation: little released b/c of plasminogen activator inhibitors (PAI-1 and PAI-2)

    later: production increases to allow breakdown of clot and recanalization of injured vessel

    Uses: acute MI, pulmonary embolism/DVT, stroke (w/in first 3 hrs)

    contraindications: active bleedingrecent surgery (w/in 10 days)GI bleedingrecent CVA, intracranial surgery/mass/aneurysmknown hemorrhagic disorderknown hypersensitivitysevere, uncontrolled hypertensionrecent streptokinase therapypregnancy/postpartum period
  189. Alteplase
    • Exogenous plasmin activator
    • Also called t-PA

    Uses: acute MI, pulmonary embolism/DVT, stroke (w/in first 3 hrs)

    • poor enzyme in absence of fibrin
    • activates fibrin-bound plasminogen 100x more rapidly than free plasminogen

    • rapid hepatic clearance (T1/2=1-4 mins)
    • IV

    • contraindications: 
    • active bleeding
    • recent surgery (w/in 10 days)
    • GI bleeding
    • recent CVA, intracranial surgery/mass/aneurysm
    • known hemorrhagic disorder
    • known hypersensitivity
    • severe, uncontrolled hypertension
    • recent streptokinase therapy
    • pregnancy/postpartum period
  190. Aminocaproic Acid
    Potent inhibitor of fibrinolysis

    binds to lysine binding sides on plasminogen and plasmin thus blocking the binding of plasmin to fibrin

    reverse states associated with excessive breakdown of fibrin

    effect in decreasing hemorrhage with surgical procedures

    useful for tx urinary tract bleeding (concentration in urine 100x > plasma)
  191. Abciximab
    glycoprotein IIb/IIIa receptor blocker

    • Use: 
    • prevention of cardiac ischemic complications during coronary intervention
    • unstable angina not responding to conventional therapy
    • intended to be used with aspirin and heparin

    • mechanism:
    • binds intact platelet GPIIb/IIIa receptor to inhibit platelet aggregation by preventing binding of fibrinogen, VW factor, adhesive molecules

    steric hinderance

    • SE:
    • bleeding
    • thrombocytopenia
  192. Dipyridamole
    vasodilator and inhibitor of platelet aggregation

    use: primary orphylaxis of thromboemboli in patients w/ prosthetic heart valves (in combo w/ warfarin), in combo w/ aspirin for secondary prevention of MI or TIA

    • inhibition of phosphodiesterase - increases cAMP,
    • inhibits adenosine uptake

    oral administration

    SE: headache, GI upset, dizziness
  193. Ticlopidine
    • Use:
    • secondary prevention of cerebrovascular disease
    • myocardial infarction
    • unstable angina
    • coronary artery stenting
    • peripheral vascular disease
    • patietns w/ transient ischemic attacks; completed strokes

    • Mechanim:
    • act through P2Y1/P2Y12 receptors to inhibit ADP-induced platelet aggregation, decreasing levels of cAMP

    prlongs bleeding time, inhibits platelet aggregation, delays clot retraction

    • SE:
    • serious blood dyscrasias
    • neutropenia
  194. Clopidogrel
    • Use:
    • Myocardial infarction prophylaxis
    • Stroke prophylaxis
    • unstable angina
    • coronary artery stenting

    Mechanism: act through P2y1/P2Y12 receptors to inhibit ADP-induced platelet aggregation, decreasing levels of cAMP

    prlongs bleeding time, inhibits platelet aggregation, delays clot retraction

    METABOLIZED BY CYP2C19

    SE: CYP2C19 polymorphism, 

    Drug Interaction: patients take it w/ aspirin and have GI irritation - prescribe PPI (omeprazole) metabolized by CYP2C19 so has less therapeutic effect
  195. Salmeterol
    • b2 adrenoceptor agonist - bronchodilator
    • long acting b/c of lipophilic tail binds to exoreceptor in vicity of adrenoreceptor - gets anchored into cell membrane

    • relaxes airway smooth muscle
    • stimulates mucociliary transport
    • activate G protein --> cAMP
    • receptors undergo desensitization - decreased effectiveness

    toxicity: overrealiance, arrhythmias, don't use for HTN
  196. albuterol
    short acting b2 adrenoceptor agonist - bronchodilator

    • elaxes airway smooth muscle
    • stimulates mucociliary transport
    • activate G protein --> cAMP
    • receptors undergo desensitization - decreased effectiveness
    • toxicity: overrealiance, arrhythmias, don't use for HTN
  197. theophylline
    importance as therapeutic agent is waning b/c effectiveness of B2 and anti-inflammatories

    relaxes airway smooth muscle

    • phosphodiesterase inhibition
    • adenosine antagonist

    narrow therapeutic window d/t stimulant effects on CNS and CV system (convulsions)
  198. ipratropium bromide
    anticholinergic - bronchodilator

    • quaternary ammonium derivative of atropine
    • allows high dose to airway
    • poorly absorbed, limiting access to CNS

    • relaxes airway smooth muscle
    • decreases mucus secretion
    • may not be as effective b/c no sympathetic effects
  199. tiotropium
    long acting anticholinergic bronchodilator

    • relaxes airway smooth muscle
    • decreases mucus secretion
    • may not be as effective b/c no sympathetic effects
  200. beclomethasone
    glucocorticosteroid

    most effective and most often prescribed anti-inflammatory drug for treatment of chronic inflammation underlying asthma

    often used as first drug in newly diagnosed asthma

    chronic use: reduces airway smooth muscle hyperreactivity that is caused by inflammation

    used to treat inflammatory components of asthma by inhibiting leukotriene production of inflammatory mediators including PGs, leukotrienes, cytokines

    permissive effect on response to beta agonists

    mechanism: binding to glucocorticodsteroid receptors in cytosol, translocation of receptor-drug complex to nucleus where it binds to transcription factors leading to: increased transcription of lipocortin-1, inhibitor of phospholipase A2, decreased transcription for other inflammatory mediators, increased transcription of B2 receptor protein

    kinetics: not effective in acute attcks, used chronically

    SE: oropharyngeal candidiasis, hoarseness
  201. azithromycin
    antibiotic treatment for chronic pulmonary obstructive disease and cystic fibrosis

    treats acute exacerbations, acute bronchitis, and prophylaxis to prevent bronchitis
  202. recombinant human deoxyribonuclease (rhDNAase, dornase alpha)
    for cystic fibrosis

    reduces sputum viscosity by cleaving extracellular DNA that has been released from infiltrating neutrophils that accumulate in sputum

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