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186 Cards in this Set
- Front
- Back
How do platinum compounds work?
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The N in each strand of DNA forms cross-links
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What is the most emetic chemotherapeutic agent?
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Cisplatin
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How does folate enter the cell?
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reduced folate carrier
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What happens to folate when it enters the cell?
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It it metabolized to have glutamates added to it
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How does MTX work?
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It enters the cell through RFC
Gets glutamated Blocks the Folic acid + DHFR reaction whcih normally --> THF --> AA + NTs |
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How does fluoruracil work?
What is specifically inhibited? |
It inhibits thymidylate synthase when 5-FU --> FdUMP
Specifically inhibits DNA synthesis- RNA synth not affected |
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How does Arabinoside work?
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It poisons topoisomerase (it's a pro-drug, must be comverted to Ara-CTP)
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How does GEM work?
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It's a pro-drug
It inhibits DNA synthesis/repair, by incorpating itself into DNA |
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How do 6MP and 6TG work?
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They inhibit purine synthesis
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What is a side effect of 6TG?
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Hepatic veno-occulsive disease
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How does hydroxyurea work?
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Inhibits riboNT --> deoxyNT
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How does L-asparaginase work?
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Doesn't enter tumor cells
Tumor cells can't make Asp (although it's not normally an essential AA in healthy tissue) As a result, protein synthesis is inhibited |
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How do the -rubicins work?
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Creates free radicals
Inhibits topo II promotes strand breaks Blocks DNA/RNA synthesis |
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What other drug is in the -rubicin family?
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Etoposide
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What is one of the major toxicities of the -rubicins?
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Cardiotoxicity
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How does Irinotecan/Topotecan work?
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Inhibits Topo I
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How do the vincas and taxanes work?
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They inhibit MTs
They affect metaphase |
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What is the major side effect of the vincas/taxanes?
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Neurotoxicity
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What does tamoxifen/toremifene do?
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treats breast CA
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What are the drugs that are SERMS?
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Tamoxifen
Toremifene Raloxifene Faslodex |
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What does SERMS stand for?
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Selective estrogen receptor modulators
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What do aromatase inhibitors do?
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Inhibits the conversion of androgens --> estrogens
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What are the antigonadotropins?
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Leuprolide
Goserelin |
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What do leuprolide and goserelin do?
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Inhibit LH and FSH release from pituitary
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What does leuprolide/goserelin treat?
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prostate CA
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What are the anti-androgen drugs?
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Flutamide
Bicalutamide |
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What do flutamide and bicalutamide treat?
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prostate CA
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What is trastuzumab? What does it treat?
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mAB for HER2 + breast CA
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What is the main toxicity with trastuzumab?
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cardiotoxicity
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What is elevated in many types of epithelial cancers?
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EGFR (Her1)
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What is cituximab? What does it treat?
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mAB to EGFR receptor
Colon CA |
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Side effect of cituximab?
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rash
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How does ERlotinib work?
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Inhibits EGFR kinase
Inhibits intracellular phosphorylation of TK associated with EGFR |
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What is another name for imatinib mesylate?
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Gleevac
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What is imatinib mesylate used to treat? Mechanism?
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CML
Inhibits abl kinase |
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What is dasatinib?
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Effective against mutant forms of abl, in case there is resistance to imatinib mesylate
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What is the major toxicity for imatinib mesylate?
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mostly edema... very low toxicity
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What is bevacizumab?
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mAB to VEGF
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What are the toxicities associated with bevacizumab?
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minimal: HTN, proteinuria
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What drugs are VEGFR inhibitors?
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Sunitinib
Soraenib |
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What do sunitinib/sorafenib inhibit?
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VEGFR
Raf kinase |
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HOw does bortezomib work?
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proteasome inhibitor
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What are the toxicities associated with L-asparaginase?
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Allergic reaction (it's bacterially derived) --> anaphylaxis
Toxic to lymphoblasts... Decreased synthesis of clotting factors adn clotting inhibitors --> thrombosis/hemorrhage Hyperglycemia d/t decreased insulin production Cerebral dysfxn Pancreatitis |
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Examples of adenosine analogs?
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Fludarabine
pentostatin cladribine |
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What does fludarabine treat?
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CLL
Hairy cell leukemia Non-Hodgkin's |
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How does pentostatin work?
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It inhibits adenosine deaminase (ADA) --> accumulation of deoxyadenosine and dATP, which exerts negative feedback on riboNT reductase --> imbalance in deoxynNT pools --> toxic to lymphocytes
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Side effects from pentostatin?
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Neurotoxicity
Somnolence Confusion Coma |
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What is not a common side effect for adenosine analogs?
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N/V although it does occur
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What enzyme does hydroxyurea inhibit?
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RiboNT reductase
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Which is the only rubicin drug that can be given orally?
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Idarubicin
All the others require IV |
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What happens during phase I trials?
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Way to determine doses
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What happens during phase II trials?
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Treat pts with the doses det previously in order to determine the efficacy of the drug
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What happens during phase III?
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New drug is compared to standard therapies for particular cancers
Randomized trials are performed |
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What are the -parin drugs?
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LMWH
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What is the MOA of -parins?
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Doesn't inhibit thrombin
Enhances activity of ATIII (breaks down IX, X, XI, XII) |
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What is fondaparinux?
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LMWH that doesn't cause HIT
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MOA of hirudin?
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inactivates fibrin bound to thrombin found in clots
Causes no thrombocytopenia |
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How is hirudin administered? monitered?
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IV
PTT |
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MOA of bivalirudin?
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Inhibits platelet aggregation
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What is bivalirudin used to treat?
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Cariac angioplasty
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MOA of argatroban?
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Blocks and binds thrombin
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How is argatroban metabolized?
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Metabolized in liver, excreted in bile
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MOA of melagotran?
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Binds and blocks thrombin
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Advantage of melagotran over argatroban?
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No p450 interations with other drugs
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MOA of streptokinase?
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Activates plasminogen specifially found on clots
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MOA of anistreplase?
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Activates plasminogen everywhere (breaks down good and bad clots)
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MOA of alteplase, reteplase, tenecteplase?
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Activates plasminogen bound to clots; doesn't cause allergy and good for ppl who are allergic to streptokinase
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Where does urokinase come from?
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Synthesized in kidney
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MOA of urokinase?
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Converts plasminogen to plasmin
Breaks down good and bad clots |
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MOA of clopidogrel?
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Inhibits binding of ADP to platelet receptors (thsi inhibits platelet aggregation)
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MOA of ticlopidine?
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Inhibits binding of ADP to platelet receptors (thsi inhibits platelet aggregation)
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Adverse effects of clipidogrel and ticlopidine?
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Rash
Diarrhea Abdominal pain Intracranial hemorrhage (Clopidogrel has less adverse effects) |
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MOA of abciximab?
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mab against GPIIb/IIIa
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Adverse effect of abciximab?
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Acute coronary syndrome
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MOA of eptifimab?
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mab against GPIIb/IIIa
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MOA of tirofban?
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mab against GPIIb/IIIa
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MOA of dipyradimol?
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vasodilator that inhibits adenosine and cGMP phosphodiesterase activity
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What is dipyradimol used with?
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Aspirin to prevent TIA
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MOA of cilostazil?
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Phosphodiesterase inhibitor that promotes vasodilation and inhibits platelet aggregation
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MOA of aminocaproic acid (EACA)?
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Synthetic inhibitor of fibrinolysis
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What is Tranexamic acid?
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Analog of EACA
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What is tranexamic acid used to treat?
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Hemophilia
Prevents post-surgical bleeding Stops hemorrage secondary to radiation and drug induced cystitis (possibly from cyclophosphamide?! :)) |
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Where are the alpha-1 receptors found?
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Vascular smooth muscle of skin and splanchnic
GI, bladder sphincters Iris |
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Where are the alpha-2 receptors found?
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Presynaptic nerve terminals
Platelets Fat Cells GI walls |
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Where are the beta-1 receptors found?
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AV/SA node
LV |
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Where are the beta-2 receptors found?
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Vascular smooth muscle of skeletal muscle
Bronchial smooth muscle GI, bladder walls |
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Describe the parasympathetic nerve signal conduction?
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long presynaptic --> nicotinic receptor --> short postsynaptic nerve --> muscarinic receptor
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Describe sympathetic nerve signal conduction?
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short presynaptic --> nicotinic r --> long postsynaptic --> alpha/beta r
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Describe somatic nerve conduction?
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1 long nerve, uses ACh on nicotinic receptors
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Receptor speciificity for Epi?
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all are =
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Receptor specificity for NorE? Uses?
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A1=A2, B1>B2
BP control |
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Receptor specificity for Dobutamine? Uses?
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B1>B2 >>> A
Inotropes, CHF |
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Receptor specificity for Isoproterenol?
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B1=B2 >>>> A
Heart block |
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Receptor specificity for DA?
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D1=D2 >>> B1 >>>> A
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Uses for low doses of DA?
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At low doses, vasodilation of renal, mesenteric, and coronary beds
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Receptor specificity for phenylephrine?
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A1>A2 >>> B
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Receptor specificity for clonidine?
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A2>A1 >>> B
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Receptor specificity for Albuterol?
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B2 > B1 >>>> A
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Receptor specificity for Ritodrine?
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B2 > B1 >>>> A
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What are the effects of clonidine?
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Inhibits sympathetic output
bradycardia, hypotension, sedation |
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What effect does albuterol/ritodrine have on teh uterus?
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It relaxes it, prevents premature labor
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What are examples of direct non-catecholamines?
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Clonidine
Phenylephrine Ritodrine Albuterol |
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What are direct catecholamine examples?
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DA
NorE Epi Isoproterenol Dobutamine |
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What are examples of indirect non-catecholamines?
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Cocaine
Amphetamine Tyramine |
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What class of drugs is ephedrine in?
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Mixed non-catecholamien (direct and indirect)
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Receptor specificity for phenoxybenzamine? Used to treat?
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A1 + A2 antagonist
Pheo |
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Receptor specificity for Phentolamine? Used to treat?
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A1 + A2 antagonist
Pheo Hypertensive crisis |
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What are the alpha-1 blockers?
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Prazosin
Terazosin Tamsulosin |
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What are the alpha 1 blockers used to treat?
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HTN
BPH |
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Why is tamsulosin a good drug?
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A1a specific...
Promotes urine flow in BPH w/o BP effects |
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What are the pharmacokinetic properties of carbechol?
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Resistant to hydrolysis
Long duration of action |
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What does carbechol treat?
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Glaucoma
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What are the pharmacokinetic properties of bethanechol?
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Resistant to hydrolysis
Long duration of action |
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What does bethanechol treat?
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Relief of urinary retention post-op
GI paralysis Increase tone of LES |
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What are the pharmacokinetic properties of pilocarpine?
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Tertiary amine
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What does pilocarpine treat?
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sialogogue
glaucoma miosis q |
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What is structure of neostigmine? What does it degrade to?
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Tertiary amine
Alcohol + carbamoyated enzyme |
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What does neostigmine treat?
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AChE inhibitor
MG, ileus, NM blockade |
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Neostigmine is poorly absorbed through...?
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Skin, eyes, lungs
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What class of drug is physostigmine? Structure?
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AChE inhibitor
Tertiary amine |
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What does physostigmine treat?
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MG
Glaucoma |
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What are the adverse effects from physostigmine?
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Weakness
Abdominal cramps Diarrhea |
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What is structure of echothiophate? Drug Class?
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Organophosphate
AChE inhibitor |
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What does echothiophate treat?
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Glaucoma
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What is parathion?
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Organophosphate
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What effects are seen from parathion and malthion?
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DUMBBELSS
Diarrhea Urination Miosis Bradycardia Bronchoconstriction Excitation of skel muscle Lacrimation Salivation Sweating |
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How are the effects of parathion and malthion overcome?
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Atropine (for the muscarinic effects)
Praloxime (for the nicotinic effects) |
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What class of drug is ambenonium?
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AChE inhibitor
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What does ambenonium treat?
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MG
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What drug class is demarcarium?
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AChE inhibitor
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What does demarcarium treat?
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Glaucoma
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What are the different types of drugs that can treat glaucoma?
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Beta blockers
Muscarinic mimetics Physostigmine Echothiophate Demarcarium Pilocarpine |
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What type of drug is pyridostigmine?
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AChE inhibitor
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What does pyridostigmine treat?
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MG
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What are the drugs that treat MG?
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Neostigmine
Physostigmine Ambenonium Pyridostigmine |
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What type of drug is atropine?
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Anti-muscarinic
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What effects does atropine have?
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Midriasis
Decreased GI activity Decreased bladder activity Bradycardia (at low doses) Tachycardia (at high doses) |
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What is atropine used to treat?
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Antispasmotic for GI and bladder
Antidote for cholinergic agonists (insecticides) |
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What are the common side effects from atropine?
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Dry mouth
Flushing Mydriasis Delirium Tachycardia "Dry as a bone, blind as a bat, red as a beet, mad as a hatter" |
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What type of drug is scopolamine?
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Anti-muscarinic
Long-acting Treats motion sickness **If given topically --> mydriasis and cycloplegia** Blocks short-term memory |
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What type fo drug is propantheline?
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Quarternary amine
Anti-muscarinic |
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What does propatheline treat?
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Peptic disease
Hypermotility |
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What does glycopyrrolate treat?
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Peptic disease
Hypermotility Traveler's diarrhea |
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What type of drug is tolterodine?
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Tertiary amine
Anti-muscarinic with M3 selectivity |
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What does tolterodine treat?
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Urinary incontinence
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What type of drug is ipratropium?
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Quarternary amine
Anti-muscarinic |
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What does ipratropium treat?
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Asthma and COPD
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MOA of ipratropium?
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Relaxes bronchial smooth muscle, minimal systemic absorption b/c it's quarternary amine
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What is the structure of tubocurarine?
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Quarternary amine
NM blocking agent |
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What are the adverse effects of tubocurarine?
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Bronchoconstriction through release of histamine
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Where is the M1 receptor found?
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CNS neurons
Sympathetic postganglionic neurons Sometimes presynaptic |
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Where is M2 receptors found?
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Myocardium
Smooth msucle Some presynaptic sites |
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Where is M3 found?
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Exocrine glands
Smoooth muscle BV |
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Which muscarinic receptors utilize IP3/DAG?
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M1 and M3
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How does IP3/DAG work?
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Increases intracellular Ca
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Which muscarinic recpetors ultilize K channels?
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M2
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How does M2 send it's signal
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It opens K channels which inhibits adenylate cyclase
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How does ACh released from parasympathetic nerves interact wiht M receptors on nerve terminals?
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It inhibits the release of their neurotransmission
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What controlls the pupillary dilator muscle?
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alpha receptors
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What controls pupillary constrictor muscles?
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muscarinic receptors
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What controls ciliary musce?
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Muscarinic receptors
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What controls ciliary epithelium?
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Beta receptors
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What secretes aqueous humor?
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epithelium of ciliary body
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How do muscarinic cholinomimetics work in the eye?
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They mediate teh contraction of the ciliary muscle and the circular pupillary constrictor muscle --> miosis
Miosis puts tension on trabcular meshwork, facilitating outflow, reducing intraocular pressure |
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How long does atropine last?
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7-10 days
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How long does tropicamide last?
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.25 days (6 hrs)
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When is the ONLY time antimuscarinics should be used for mydriasis?
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If cycloplegia (weakening of ciliary muscles) results in loss of ability to accommodate
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What class of drug is sildenafil?
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Organic nitrate
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How does sildenafil work?
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Blocks PDE5, a phosphodiesterase that converts cGMP --> GMP
Increases cGMP, enhancing erections by increasing myosin light chain that is not bound by phosphate (--> smooth muscle relaxation) |
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How does verdemafil work?
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Same way that sildenafil works:
inhibit the conversion of cGMP --> GMP, this increases cGMP, which enhances erection by increasing the amount of mysosin unbound to phosphate --> relaxation |
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What type of drug is veramapil?
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Ca channel blocker, binds to open L channel, preventing further Ca influx
|
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How does veramapil work?
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Moderate vasodilation
Moderate direct cardiac suppression Moderate reflex cardiac activation Results: vasodilation with moderate cardiac suppression CO and HR are only modestly decreased |
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How does Nifedipine work?
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Binds to closed L-channel
Decreases frequency that it will be open Strong vasodilation Direct cardiac suppression Reflex cardiac activation Results: Vasodilation with modest cardiac stimulation systemic vasodilation of resistance |
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What are the advantages of nifedepine over veramapil?
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no aggravation of diabetes, peripheral vascular disease, bronchospasm, blood profiles of lipids, glucose or K
No tolerance develops! |
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What are the effects of nitroglycerine
|
No overall increase in coronary blood flow, but redistributes the blood to endocardium (preferential dilation of larger vessels)
Venodilation Reflex cardiac stimulation of rate and contractility |
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What drug is diltiazem similar to?
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Verapamil
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d
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d
|
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What effect does NO have on cells?
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It activates guanylate cyclase whihc increases cGMP which ultimately leads to dephosphorylation of myosin light chain --> muscle relaxation
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What happens to nitrates in the liver?
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They are inactivated by nitrate reductase
They are not deactivated in other tissues B/c of this though, it is possible to gain tolerance |
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Which preparation of isosorbide dinitrate is short acting? long acting?
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Sublingual
Oral |
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Which preparation fo nitroglycerine is short acing? long acting?
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Sublingual
Oral, sustained action |
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Important thigns about diltiazem?
|
Similar to verapamil, but less suppressive heart effects
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What do calcium blockers do in angina?
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Increase coronary blood flow
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Which is a stronger vasodilator: nifedifine or verapamil?
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NIfedipine
|
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Which provides more cardiac stimulation: nifedipine or verapamil?
|
Verapamil
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Why do the oral preps of nitro and isosorbide dinitrate have such long action times?
|
Orally they have low bioavailability (<20%), but once absorbed, the nitrate compounds have very short half lives.
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