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504 Cards in this Set
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- Back
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Eicosanoids
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Substance involved in inflammation and cellular signaling
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Innate/Adaptive Immune system is involved in the first response?
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Innate
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What type of granulocyte is responsible for bacterial defense?
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Neutrophils
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What type of granulocyte is responsible for defense against parasitic infection?
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Eosinophils
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What type of granulocyte is involved in immune reactions?
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Basophils and mast cells
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What types of cells are antigen presenting cells?
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Macrophages and dendritic cells
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What is the process from APC to Activation of adaptive immune system?
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Phagocytosis of bacterium or parasite by the APC, digestion produces antigens, antigens displayed with MHC proteins on cell surface. MHC recognized as non-self – activation of adaptive immune system
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What type of cell is responsible for recognizing and responding to MHC II?
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CD4+ T-cell (Bacteria)
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What type of cell is responsible for recognizing and responding to MHC I?
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CD8+ T-cell (viruses)
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Humoral immunity = B cell/T cell production?
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B cell
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Cellular immunity = B cell/T cell production?
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T cell
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What type of cell medicates the response of cytokine such as I-L or stimulates production of B cells?
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Helper T cell
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Give some examples of eicosanoids
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Prostaglandins, prostacyclins, thromboxanes, leukotrienes
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What is the common precursor to eicosanoids?
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Arachidonic acid
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What are the 2 pathways of arachidonic acid metabolism?
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Cyclooxygenase pathway and lipooxygenase pathway
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Which pathway metabolizes arachidonic acid to prostaglandins, prostacyclins, and thromboxanes?
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Cyclooxygenase pathway
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Which pathway metabolizes arachidonic acid to leukotrienes?
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Lipoxygenase pathway
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What substances are produced by the cyclooxygenase pathway?
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prostaglandins, prostacyclins, and thromboxanes
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What enzyme is involved in the cyclooxygenase pathway that can be inhibited with medications?
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COX enzyme
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What are some of the end results of activation of the cyclooxygenase pathway?
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Vasoconstriction , platelet activation (TxA2), vasodilation, hyperalgesia, fever, dieresis, immunomodulation (PGE2), smooth muscle contraction, bronchoconstriction, abortion (PGF2a), smooth muscle contraction inhibits platelet aggregation (PGD2), inhibition of platelet aggregation , vasodilation (prostacyclin)
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The lipooxygenase pathway leads to activation of what cells?
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Mast cells, basophils, eosinophils, or neutrophils
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What are the results of activation of the lipooxygenase pathway?
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Activation of mast cells, basophils, or eosinophils: Bronchoconstriction, vasoconstriction, decreased coronary blood flow, decreased cardiac contractility, plasma exudation. Activation of neutrophils: margination, migration, degranulation, superoxide anion generation, eicosanoid synthesis, plasma exudation.
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Explain the pathophysiology of somatic and visceral pain vs neuropathic pain.
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Somatic and visceral pain are results of direct stimulation of afferent nerves. Neuropathic pain is due to injury to peripheral nerves.
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Somatic pain description
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Dull, aching, well localized
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Visceral pain description
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Poorly localized
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Neuropathic pain description
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Sharp, burning, shooting
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Management of somatic pain?
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Conventional analgesics
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Management of visceral pain?
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Conventional analgesics
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Management of neuropathic pain?
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Antidepressants, anticonvulsants, non-drug therapy
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Non-opioid analgesic examples?
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Acetominophen, no-acetylated salicylates, acetylated salicylate, selective cox2 inhibitor, and traditional NSAIDS
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Name 3 non-acetylated salicylates
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Choline magnesium trisalicylate, diffunisal (Dolobid), magnesium salicylate
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Name an acetylated salicylate
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ASA
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Name a selective COX2 inhibitor on the market today
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Celebrex
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Some traditional NSAIDS
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Ibuprofen (Motrin), naprosyn, daypro, voltaren, lodine, indocin, toradon, Relafen, clinoril, tolectin, feldene, mobic, ansaid.
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What type of agents are first line agents for mild to moderate pain?
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Non-opioid analgesics (ASA, APAP, NSAIDS)
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T/F the analgesic celing may be higher with NSAIDS than ASA?
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TRUE
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What is the ceiling effect of ASA and APAP?
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650-1300mg
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Does tolerance develop to non-opioid analgesics?
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NO
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What is the drug that has similar efficacy and potency as ASA but no anti-inflammatory effect?
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APAP
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What is damagaged with overdose of APAP?
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Liver – can be serious or even fatal
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What non-opioid analgesic should be used with caution in pts on isoniazid or heavy ETOH users?
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APAP – liver toxicity
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What is the maximum safe dose of APAP for those over 12 years of age?
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4grams per day
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What is the new limit of APAP in combination drugs that is intended to help prevent accidental overdose?
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325mg per tablet or capsule
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The label on OTC APAP reads a maximum dose other than the maximum safe dose – what is this limit?
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3 grams per day unless directed by HCP
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What non-opioid analgesic binds irreversibly to inhibit COX?
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ASA
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How long does a single dose of ASA inhibit platelet function?
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The lifetime of platelets – 4-7days
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What non-opioid analgesic must be used with caution in asthma patients and why?
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ASA – can precipitate asthma attack by blocking COX pathway leukotriene pathway can increase stimulating asthma attack (if ASA sensitive)
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AE of ASA?
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GI bleeding and PUD, Reyes syndrome when used during viral syndromes in children & teens, overdose can cause metabolic acidosis and tinnitus,
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What is the dose given if ASA is prescribed for analgesic/antipyretic use?
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325-650mg
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What is the dose given if ASA is prescribed for anti-inflammatory use?
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1000 mg (3-5g/day)
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If ASA is used for anti-inflammatory use, what parameters must be followed?
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Increase dose gradually, follow serum salicylate levels
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Why is ASA rarely used as an anti-inflammatory?
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GI side effects – higher dosing for anti-inflammatory effect
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Why are non-acetylated salicylates preferred over ASA for pain?
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More favorable toxicity profile, do not interfere with platelet aggregation, rarely associated with GI bleeding, well tolerated by asthmatic pts.
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T/F Traditional NSAIDs are more effective at treating pain than full doses of ASA or APAP?
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TRUE
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T/F Traditional NSAIDS effectiveness at pain treatment is equal to or greater than usual doses of an opioid combined with APAP?
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TRUE
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MOA of NSAIDS
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Reversible COX inhibition, blocks conversion of arachidonic acid to PGs, decreases production and release of PGs. analgesic, anti-inflammatory, antipyretic activity
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Why are NSAIDS well absorbed in the stomach?
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Weak acids, unionized
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T/F NSAIDS are not highly protein bound and thus have a high Vd
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FALSE – highly protein bound
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What is the half life of NSAIDS?
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Varies - <6 to >12h
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How are NSAIDS excreted?
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Urine
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Why are NSAIDS not used to prevent cardiac issues like ASA?
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Effect on TxA2 is reversible – inhibition of platelet aggregation is reversible – with ASA it is irreversible.
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Can NSAIDS be used during pregnancy?
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Cat B drug in 1st and 2nd trimester, avoid in 3rd trimester – CAT D
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Why should NSAIDS not be used during the 3rd trimester of pregnancy?
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Premature closure of the ductus arteriosus
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How do NSAIDS cause GI adverse effects?
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Inhibition of PGs that maintain normal gastric and duodenal mucosa – increases acid production, decreases mucus production & gastric blood flow. Also local irritation can be caused by lipid solubility at low pH – enter gastric mucosal cells – lose lipid solubility, become trapped in cell.
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What are risk factors for AE with NSAIDS?
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High doses, prolonged use, previous GI ulcer or bleeding, excessive ETOH intake, elderly, corticosteroid use.
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Name some medications that can be used with NSAIDS for prevention of GI adverse effects
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Prostaglandin analog misoportic (Cytotec), Arthrotec, PPIs, H2 receptor agonists, or sucralfate (carafate).
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Other than medications, what can be done to help decrease the AE of NSAIDS?
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Take with food
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How does carafate help with GI adverse effects of NSAIDS?
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Used for dyspeptic symptoms only – coats stomach
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What drugs are at highest risk for GI adverse effects?
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ASA, tolmetin, pioxicam, indomethacin, ketorolac
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Do NSAIDS cause any renal AE? If so, how?
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YES! Decreased synthesis of renal vasodilator PGs leads to decreased renal blood flow, fluid and Na retention, can cause renal failure or HTN, interstitial nephritis (rare).
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What are the risk factors for renal AE with NSAIDS?
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Old age, CHF, HTN, renal insufficiency, ascites, volume depletion, diuretic therapy. Highest risk meds – ketorolac & indomethacin
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What are the “renal sparing” NSAIDS?
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Sulindac, nabumetone, celecoxib (lower risk of renal AE – not devoid)
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What DI are possible with NSAIDS?
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Displaces other highly protein bound meds (warfarin, phenytoin, sulfonylureas, sulfonamides, digoxin), reduces effect of diuretics, B-Blockers, ACEIs, via suppression of renal PGs, increases lithium levels, probenicid increases levels of most NSAIDS (avoid with ketorolac)
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What is the only NSAID available in the US as injectable for short term until approval of IV ibuprofen?
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Ketorolac
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What are the restrictions on the use of Ketorolac IV?
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Do not exceed 5 days use
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AE of Ketorolac?
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Serious GI bleeding, ulceration, perforation, and or/renal toxicity can occur (esp in the elderly)
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What is the only selective NSAID agent available today?
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Celecoxib (celebrex)
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Why were Vioxx and Bextra withdrawn from the market?
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Increased MI risk
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MOA of Selective NSAIDS?
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Selectively inhibit COX-2.
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Why would a selective COX-2 inhibitor be prescribed over a traditional NSAID if it is no more effective at reducing pain and inflammation?
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Decreased risk of GI effects.
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How do selective COX2inhibitors cause MI?
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Cox2 inhibition = COX1 unchecked effects which can lead to increased platelet aggregation and cause MI
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Why is celecoxib (celebrex) different from Vioxx and Bextra and thus still on the market today?
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Celecoxib may inhibit Cox 1 to some degree decreasing risk of MI
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Define substance dependence (addiction)
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Maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by 3 or more characteristics including tolerance, withdrawal, & giving up or reducing important social, occupational, or recreational activities because of substance abuse over a 12 month period.
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Does the term substance abuse refer to prescribed subatances?
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No abuse applies specifically to nonprescribed substances whether or not it is available as a prescription.
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Define drug misuse
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Improper use of pres cribbed substances when the user legally obtains the substance with a valid prescription for a valid diagnosis
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Define tolerance
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Decreased effect of a drug that develops with continued use. Larger doses are needed to produce the same response
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Define physical dependence
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Adverse physical signs and symptoms results from the withdrawal of a drug
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Define psychological dependence
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Drug affects the reward system of the brain and pleasurable sensations cause the user to want to continue taking it. Upon withholding the drug, dysphoria & drug craving occur. Can occur even with drugs that do not produce tolerance and physical dependence
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MOA of nicotine
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Nicotine directly activates nicotinic Ach receptor centrally, peripherally, and at the Nm junction. Centrally: produces strong dependence, craving for cigarettes is directly tied to decreases in plasma nicotine levels, high addiction potential
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Name some medications used for tobacco cessation other than nicotine replacements
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Bupropion (zyban, Wellbutrin) and Varenicline (Chantix)
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How does nicotine replacement work?
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Reduces nicotine withdrawal and craving
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How much nicotine is contained in nicotine replacement medications?
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1/3-1/2 the nicotine in most cigarettes
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Why are nicotine replacements less likely to cause dependence?
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Longer time for systemic absorption compared to cigarettes
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Why are nicotine replacement medications better than cigarettes if both contain nicotine?
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Eliminates toxins in cigarettes such as tar, carbon monoxide, and other chemicals
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Pregnancy and nicotine replacement?
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Nicotine replacement linked to low birth weight, but far less harmful than cigarettes – try other non-nicotine replacement strategies first
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Name some nicotine replacements
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Nicorette (gum), Commit (lozenges), Nicoderm CQ (patch), Nicotrol inhaler (oral) Nicotrol NS (Nasal inhaler)
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What are the special instructions regarding nicotine gum?
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Keep between cheek and gums (not chewed)
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AE of nicotine gum?
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Tingling on tongue, hiccups, jaw pain, nausea/heartburn if chewed
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Special instructions for nicotine lozenge?
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Do not swallow!
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AE of nicotine lozenges?
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HA, flatulence, hiccups, heartburn/nausea if swallowed
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AE of nicotine patch?
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Skin rash 2nd to sticky backing of the patch or nicotine itself – alleviate with topical antihistamine. Sleep disturbances – body not used to receiving nicotine at night (remove at night or may be withdrawal symptoms
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AE of nicotine inhalers?
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Cough, scratchy throat, GI upset. Avoid in pts with respiratory disease (asthma)
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What is the one year quit rate for smokers taking bupropion (Zyban)?
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23-33%
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What can be added to bupropion (Zyban) to increase a smoker’s chances of quitting?
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Nicotine replacement product, counseling and support
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AE of bupropion (Zyban)
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Difficulty sleeping (take in am), difficulty concentrating, tremor, GI upset
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MOA of Bupropion (zyban)?
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Unknown. Presumed that its noradrenergic and dopaminergic effects play a role
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MOA of Varenicline (Chantix)
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Agonist at a sub-type of the nicotinic Ach receptor prevents nicotine from binding to these receptors which are responsible for reinforcement and reward experienced from smoking
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DI of Varenicline (Chantix)?
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No known DI’s
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AE of Varenicline (Chantix)?
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Nausea, HA, insomnia, abnormal dreams
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Black Box warning for Bupropion (for smoking cessation) and Varenicline?
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Serious neuropsychiatric events. Depression, suicidal ideation, suicide attempts, completed suicides, changes in behavior – aggression, hostility, agitation. Weigh risk vs benefits!
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What receptors are affected by ETOH?
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GABA, NMDA glutamate, and cannabinoid receptors
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T/F ETOH withdrawal is not a life threatening situation
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FALSE – can be severe and in some cases, life-threatening
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What do GABA receptors mediate?
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Anxiolytic and sedative effects as well as motor coordination, tolerance, and dependence
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What are benzodiazepines used for?
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Sleep, anxiety, alcohol withdrawal, seizures, anesthesia.
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Benzodiazepines withdrawal symptoms?
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Anxiety, insomnia, irritability, nausea, blurred vision, confusion, delirium, seizures
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How can you avoid withdrawal symptoms with benzodiazepines?
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Better for temporary use – long term use = increased risk of withdrawal effects
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MOA of Disulfiram (Antabuse)?
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Inhibits aldehyde dehydrogenase, a critical enzyme in the alcohol metabolism pathway.aldehyde accumulates and causes facial flushing, HA, N/V, weakness, & orthostatic hypotension.
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MOA for Acamprosate (Campral)
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Unknown – maintenance of alcohol abstinence. Chronic alcohol exposure thought to alter the normal balance of neuronal excitation & inhibition, acamprosate may restore the balance by affecting glutamate & GABA neurotransmitters.
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Does Acamprosate (Campral) cause alcohol aversion?
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NO
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What medication used for alcohol abstinence lacks antidepressant, anxiolytic, anticonvulsant activity and does not cause alcohol aversion?
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Acamprosate (Campral)
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What drug has properties of each class – stimulant, sedative, tranquilizer, and hallucinogenic?
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Marijuana (delta-9-tetrahydrocannibinol [TCH])
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Does marijuana produce physical dependence?
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No
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Does marijuana produce psychological dependence?
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As with any drug, yes,it is possible.
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What is the name for synthetic THC available to prescribe to patients for appetite stimulation(approved in AIDS p[atients) and tx of emesis (approved for chemo n/v)?
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Dronabinol (Marinol)
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What are the short term effects of marijuana?
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Euphoria, distorted perceptions, memory impairment, and difficulty concentrating
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What potential therapeutic effects does marijuana possess?
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Pain relief, appetite stimulation, antiemetic
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What is the local anesthetic and a strong CNS stimulant that causes intense euphoria by acting on neurons in major centers in the brain responsible for reward?
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Cocaine
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MOA of cocaine?
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Blocks reuptake of dopamine into presynaptic terminals with a lesser effect on norepinephrine and serotonin reuptake
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What are the effects of cocaine?
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Psychostimulation, paranoia, delusions, involuntary movements, tachycardia, hypertension, peripheral vasoconstriction/vasospasm, and dilated pupils. Some users experience restlessness, irritability, and anxiety
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What are the routes of administration for cocaine use?
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IV, IM, intranasal, and respiratory inhalation.
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What is “free basing”
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A popular practice in the 1980”s because of its rapid onset of action (7-10 seconds), ease of repeat administration, and unwarranted belief by users that smoking cocaine was less harmful and less likely to produce addiction than injecting.
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How long does the euphoria last from smoking cocaine?
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2-20 minutes
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What is the onset and duration of action of cocaine?
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Very fast onset of action and very short duration of action
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Describe the tolerance effect of cocaine
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Tolerance develops to the euphoric effects of cocaine, leaving the user chasing the initial high that is nearly impossible to achieve with subsequent exposures.
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Describe withdrawal symptoms of cocaine
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Brady, sleepiness, fatigue, depression, anhedonia (inability to experience pleasure).
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Does re-administration of cocaine alleviate all symptoms of withdrawal?
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NO
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What FDA approved medication is used for cocaine addiction?
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NONE. Antidepressants have been shown to decrease cravings but have not been shown to prevent cocaine use.
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What is MDMA?
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Ecstasy
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What drug is chemically related to amphetamine, causes serotonin release into the synaptic cleft, inhibits 5HT synthesis, and inhibits 5HT reuptake?
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MDMA
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What is the MOA and result of MOA of MDMA?
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Serotonin (5HT) release into synaptic cleft, inhibits 5HT synthesis, & inhibits 5HT reuptake. MOA results in increased 5HT in the synapse and depletion of 5HT stores.
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High doses of ______ can interfere with the ability to regulate boy temp, resulting in a sharp increase in body temp (hyperthermia), leading to liver, kidney, and cardiovascular failure.
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MDMA
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Effects of MDMA?
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Euphoria, increased energy, increased motor activity, alertness, tachy, HTN, perceptual changes including enhanced tactile sensations, and increased need for stimulation. Tremor, involuntary teeth clenching, muscle cramps, and blurred vision. Psych and physical damage can last weeks and includes confusion, anxiety, depression, and paranoia.
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Chronic use of MDMA can cause?
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Neurotoxicity and brain damage. Long-term, even permanent, problems with memory and learning can occur.
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What is the onset of action and duration of action of MDMA?
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Onset of action after oral ingestion occurs within 30-45min and lasts 4-6hours.
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What should be considered prior to starting a pt on celecoxib?
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Risk for cardiovascular events & risk for GI events. Weigh risk vs. benefit
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What should be taken with celecoxib?
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Food!
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Black Box warning for celecoxib?
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Cardiovascular risk – increased risk of serious CV thrombotic events, MI, stroke, which can be fatal. CI for tx of peri-operative pain in setting of CABG surgery increased risk of bleeding, ulceration, perforation of the stomach or intestines, which can be fatal.
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CI for celecoxib?
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Tx of perioperative pain in setting of CABG surgery
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Which of the following have significant anticholinergice effects and can cause cardiac conduction abnormalities via NS channel interference? Selegeline, paroxetine, amitryptiline, bupropion, sumatriptan
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Amitryptiline
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MOA of SNRIs?
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Blockage of 5HT and NE reuptake transporter (concentration-dependent)
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What are the effects of agonism of 5HT and 5HT1a?
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Improved mood (it is an autoreceptor -= decreased release of 5HT)
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What is the effect of agonism of 5HT2?
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Increased anxiety, jitteriness, sexual dysfunction, sleep disturbances (initially)
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What is the effect of agonism of 5HT3
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Nausea, diarrhea
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What is the building block of 5HT (serotonin)?
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Tryptophan
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What is the building block of NE?
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Tyrosine
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What are beneficial and adverse effects of agonism of NE at adrenergic receptors?
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Increased interest, energy, concentration, mood, increased heart rate, increased blod pressure, and increases anxiety.
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What happens with the chronic use of antidepressant medication?
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Initially, autoreceptors will increase activity and less 5HT will be produced. Autoreceptors become desensitized eventually. This is why it takes several weeks to work properly.
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What is MAO?
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Monoamine oxidase – degrades monoamines 5HT and NE
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MAOI’s inhibit degradation of monoamines which increases available ___ & ___
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5HT and NE
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What are MAO-B selective drugs used for?
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Parkinsons – inhibits dopamine
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What are the different types of MAOI’s (formulations)?
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Non-selective reversible, Non-selective irreversible, and selective reversible.
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TCA’s antagonize ____ reuptake transporters increasing levels of ____ in the synaptic cleft
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5Ht & NE NA+/5HT &NE
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Do TCA’s have an effect on dopamine reuptake?
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NO
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What are low-dose TCAs used to treat?
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Neuropathic pain
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SSRIs are selective for _____ transporters increasing synaptic neurotransmitter levels
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5HT
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Are SSRIs more or less selective at higher doses?
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Less
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SNRIs block ____ reuptake transporters
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5HT and NE
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AE of MAOIs?
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Tyramine toxicity via inhibition of GI and hepatic MAO-A (responsible for tyramine metabolism).
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Tyramine displaces catecholamines leading to ???
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Excess release of epi and norepi
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_____ delivery of MAOIs avoids the GI tract and decreases AE
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Transdermal patch
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What type of foods to patients on MAOIs need to avoid?
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Foods high in tyramine – wine, cheese, processed meats
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Bupropion (wellbutrin) inhibits ____ reuptake?
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Dopamine
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Which atypical antidepressant has the least sexual side effects?
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Bupropion
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Bupropion (Wellbutrin) should be avoided in individuals with what disorders?
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Seizure disorder and eating disorders
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Bupropion is used to treat depression and is marketed as (Zyban) for _____ as well.
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Smoking cessation
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MOA of Buspiorne (Buspar)
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Antagonizes 5HT1a
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Name the non-selective irreversible MAOIs
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Phenetzine (Nardil) and isocarboxazid
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Describe the pathophysiology of depression
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Decreased serotonin and or NE neurotransmission. (simplified explanation)
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TCAs MOA?
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Prevents reuptake of norip & serotonin into the neuron (non-selective)
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Explain the difference between TCAs secondary amines and tertiary amines
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Secondary amine – more effects on NE than 5HT (less/no H1, M1, a1 effects). Tertiary amines – more effects on 5HT than NE (unwanted H1, M1, a1 effects).
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Name the TCAs
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Imipramine, amitriptyline, deipramine, nortriptyline, clomipramine
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Which TCAs have secondary amines?
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Nortriptyline (Pamelor) and Desipramine (Norpramine)
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Which TCAs have tertiary amines?
|
Amitriptyline (Elavil) (metabolized to nortiptyline), imipramine (Tofranil) (metabolized to deiptramine), Doxepin (Sinequan) and Clomipramine (Anafranil)
|
|
|
What type of drug has interactions with TCAs SSRIs, pseudoephedrine, and dextromethorphan?
|
MAOIs
|
|
|
What type of MAOI delivery avoids first-pass and decreases tyramine sensitivity?
|
Transdermal patch
|
|
|
What type of antidepressant antagonizes 5HT and NE reuptake transporters increasing levels of both 5HT and NE in the synaptic cleft and has NO effect on dopamine?
|
TCAs
|
|
|
What are TCAs used to treat when prescribed at lower doses?
|
Neuropathic pain
|
|
|
What are the AE of TCAs?
|
First-degree AV block, bundle branch block
|
|
|
What type of medication antagonizes muscarinic cholinergic receptors causing anticholinergic effects, antagonizes histamine receptors causing sedation, weight gain, and confusion, and antagonizes adrenergic receptors causing orthostatic hypotension, reflex tachycardia, drowsiness, and dizziness?
|
TCAs
|
|
|
AE of SSRIs
|
Sexual dysfunction, serotonin syndrome-hyperthermia, muscle rigidity, myoclonus, rapid fluctuations in mental status and vital signs.
|
|
|
SSRIs _____ & ______ are substrates and inhibitors of CYP2D6
|
Fluoxetine and paroxetine
|
|
|
Why are SSRIs first line therapy for depression and anxiety?
|
Higher selectivity and less AE (although efficacy is similar to TCAs)
|
|
|
Venlafaxine (Effexor) metabolism:
|
metabolized to active metabolite (desvenlafaxine(pristiq)) by CYP2D6
|
|
|
Duloxetine (Cymbalta) metabolism:
|
Metabolized by CYP2D6 and 1A2
|
|
|
AE of Duloxetine (Cymbalta)
|
Increased transaminases, slight chance of increased BP
|
|
|
Why shouldn’t pts with HTN and depression be taking Effexor?
|
AE: increased BP
|
|
|
What antidepressant has the least sexual side effects?
|
Bupropion (Wellbutrin)
|
|
|
Contraindications of Bupropion (Wellbutrin)?
|
Seizure disorder and eating disorders – precipitates seizures
|
|
|
Pharmacokinetics of Bupropion (Wellbutrin)?
|
Hepatically metabolized by CYP2B6
|
|
|
What atypical antidepressant antagonizes 5Ht/3 and a2 adrenergic receptors (mechanism of antidepressant activity unknown) and is a substrate of CYP3A4?
|
Mirtazapine (Remeron)
|
|
|
AE of Mirtazapine (Remeron)?
|
Increased appetite, sedation
|
|
|
Which atypical antidepressant inhibits the 5HT transporter?
|
Nefazodone (Serzone)
|
|
|
AE of Nefazodone (Serzone) atypical antidepressant?
|
Hepatotoxicity and fulminant liver failure (2nd or 3rd line drug!) substrate AND inhibitor of CYP3A4
|
|
|
What is the AE of Trazadone?
|
Priapism
|
|
|
How is trazodone metabolized?
|
CYP3A4
|
|
|
What atypical antidepressant is used as a sleep agent at lower doses and has the AE of priapism?
|
Trazodone
|
|
|
Name some mood stabilizers for bipolar disorder
|
Carbamazepine & valproic acid
|
|
|
Name a serotonin receptor agonist
|
Buspirone (Buspar) – agonizes 5HT1A receptor
|
|
|
Name the non—benzodiazepine anxiolytic, non-sedating, non-addictive
|
Buspirone (Buspar)
|
|
|
AE of Buspirone (Buspar)
|
Dizziness, nausea
|
|
|
What drug works by interfering with formation of cAMP and IP@ as well as numerous and complex effect on neurotransmitter systems and controls mania & depression?
|
Lithium
|
|
|
How long is the half life of lithium?
|
12-27h
|
|
|
AE of lithium?
|
Nausea, thirst, polyuria, hypothyroidism, tremor, weakness, mental confusion, teratogenesis
|
|
|
PK and drug interactions of lithium?
|
Lithium is secreted and reabsorbed in the renal tubules; diuretics, probenacid, renal insufficiency can increase lithium levels
|
|
|
Second-line agents for anxiety/depression?
|
Amphetamine, methamphetamine, methylphenidate (Ritalin, cencerta, etc…)modafinil (Provigil), armodafinil (Nuvigil)
|
|
|
MOA of triptans?
|
5HT1B/1D agonists in vasculature. Potent vasoconstriction of intracranial blood vessels. Inhibits vasoactive peptides. Interruption of pain signal transmission^
|
|
|
Examples of triptans?
|
Sumatriptan (Imitrex), rizatriptan (Maxalt), almotriptan (Axert), frovatriptan (Frova), eletriptan (Relpax), zolmitriptan (Zomig), naratriptan (Amerge)^
|
|
|
Which triptan has the slowest onset of action?
|
Naratriptan^
|
|
|
Which triptan has the lowest recurrence rate?
|
Naratriptan^
|
|
|
Which triptan has the fastest onset of action ?
|
Rizatriptan^
|
|
|
What DI do you need to be aware of with rizatriptan?
|
Dose adjust with propanolol – inhibits metabolism^
|
|
|
CI of triptans?
|
Ischemic heart disease, uncontrolled HTN, ischemic stroke, pregnancy. Many CI with MAOIs since metabolized by MAO (exceptions eletriptan, frovatriptan, naratriptan)^
|
|
|
What DI do you need to be aware of with eletriptan?
|
Metabolized by CYP3A4 – do not administer within 72 hrs of potent CYP3A4 inhibitors^
|
|
|
What is the risk of combining triptans with SSRIs and SNRIs?
|
Serotonin syndrome^
|
|
|
MOA of Ergots?
|
5HT1B/1D agonists^
|
|
|
When is ergotamine useful?
|
In pts with prolonged duration of attacks (>48hrs)^
|
|
|
Why is ergotomine seldom used?
|
Poor bioavailability with oral and rectal forms (2-5%), poor tolerability – worsening of N/V, dose associated vascular occlusion and rebound HA^
|
|
|
Avoid ergotamine in what pts?
|
CAD, PVD, HRN, hepatic or renal disease^
|
|
|
Why is DHE45 preferred over ergotamine?
|
Fewer side effects, no physical dependence, no rebound HA. IV, IM SubQ, intranasal administration^
|
|
|
CI of DHE45?
|
HTN, ischemic heart disease, in combination with MAOIs, elderly^
|
|
|
First-line agents for acute migraines?
|
NSAIDs, ASA(1000mg), APAP(1000mg), combo products^
|
|
|
Monotherapy agents used for migraine other than triptans, NSAIDs, ASA, or APAP?
|
Antiemetics (metoclopramide, chlorpromazine, prochlorperazine), benzodiazepines, opioids, barbiturates (NOT for chronic use)^
|
|
|
Medications for prevention of migraines and tension HA?
|
Beta blockers, Ca Ch blockers, TCAs, Anticonvulsants (phenytoin, carbamazepine, valproate, gabapentin, topiramate), and ergot derivatives^
|
|
|
The ______ contains high concentrations of emetogenic receptors
|
Mid-brain^
|
|
|
Midbrain emetogenic receptors fall in what four classifications?
|
Dopamine (D2) receptors, Muscarinic – cholinergic receptors, Histamine receptors, and 5HT-3 receptors^
|
|
|
What 3 agents have the highest binding affinity for dopamine receptors (antagonize dopamine)?
|
Benzamides, butyrophenones, phenothiazines ^
|
|
|
The 5HT3 antagonists that exert potent antiemetic effects are highly bound to serotonin type 3 receptors both _____ and ______
|
Centrally and peripherally^
|
|
|
How do antihistamines act as antiemetics?
|
Act directly on the vomiting center and vestibular pathways^
|
|
|
How do anticholinergics act as antiemetics?
|
Block cholinergic muscarinic receptors^
|
|
|
How do corticosteroids (e.g. dexamethasone) act as antiemetics?
|
Often used to prevent chemotherapy-induced N/V due to possibly membrane stabilizing and anti-inflammatory role^
|
|
|
Name the 5HT3 antagonists used for anti-emetic properties
|
Ondansetron (Zofran), dolasetron (Anzemet), granisetron (Kytril)^
|
|
|
Name the anticholinergics used as antiemetics
|
Scopolamine, meclizine^
|
|
|
Name the corticosteroids used as antiemetics
|
Bethamethasone, dexamethasone^
|
|
|
Name the butyrophenones use as antiemetics
|
Droperidol, haloperidol (Haldol)^
|
|
|
Name the Benzamide used as antiemetics
|
Metoclopramide (Reglan)^
|
|
|
Name the phenothiazines used as antiemetics
|
Chlorpromazine, prochlorperazine (Compazine), promethazine (Phenergan)^
|
|
|
Name the antihistamines used as antiemetics
|
Cuclizine, hydroxyzine (Atarax), diphenhydramine (Benadryl)^
|
|
|
Why would a 5HT3 antagonist be used as an antiemetic? Why not?
|
Less side effects due to only affecting serotonin receptors – no anticholinergic effects. $$$Expensive!!^
|
|
|
Define seizure
|
Abnormal function of ion channels and neural networks. Rapid synchronous, uncontrolled spread of electrical activity^
|
|
|
Name the sodium-channel inhibitors
|
Phenytoin (Dilantin), fosphenytoin (Cerebyx), carbamezapine (Tegretol), Oxcarbazepine (trileptal), Lamotrigine (Lamictal)^
|
|
|
MOA of sodium channel inhibitors used for seizure?
|
Slows rate of channel recovery from inactivated state to closed state. Only affects channels that open and close at high frequency^
|
|
|
PK of Sodium channel inhibitors Dilantin and Cerebyx?
|
90-95% albumin bound, dose-dependent T1/2 7-42h, hepatically metabolized by and inducer of CYP3A4, 1A2, 2C9/19. Zero order kinetics^
|
|
|
Define zero order kinetics
|
Ability of receptor to be saturated – can build up excess^
|
|
|
Define first order kinetics
|
If you increase the dose, you can also increase the excretion of the product, no build-up^
|
|
|
AE of Sodium Channel blockers Dilantin and Cerebyx?
|
CNS depression, N/V/C, hirsuitism, gingival hyperplasia, acne, SJS, alteration of vit D metabolism (osteoporosis)^
|
|
|
Differences between sodium channel blockers dilantin and Tegretol?
|
Dilantin 90-95% protein bound/Tegretol 75-90%. Tegretol is an autoinducer – induces it’s own metabolism eventually affecting dosing. Dilantin 0 order kinetics/Tegretol 1st order kinetics^
|
|
|
AE of tegretol?
|
CNS depression, hyponatremia, cholestatic jaundice, rash, leucopenia, aplastic anemia^
|
|
|
Which sodium channel inhibitor is hepatically metabolized to active metabolite?
|
Tegretol^
|
|
|
What is the sodium channel inhibitor that is a derivative of carbamazepine with less drug interactions and AE?
|
Oxcarbazepine (Trileptal)^
|
|
|
Is Lamictal as highly protein bound as Dilantin?
|
No! 55% (Dilantin 90-95%)^
|
|
|
AE of lamictal?
|
CNS depression, N/V, benign rash, serious rash associated with rapid titration^
|
|
|
Which seizure medication has a serious rash associated with rapid titration?
|
Lamictal^
|
|
|
Name the calcium channel inhibitors used for seizure
|
Ethosuximide, Valproic acid (Depakote, Depakene), Gabapentin (Neurontin)^
|
|
|
Is Ethosuximide highly protein bound?
|
No substantial protein binding^
|
|
|
Does ethosuximide have a long or short half-life?
|
Long^
|
|
|
AE of ethosuximide?
|
GI upset, anorexia, sleep terrors, aggressiveness, psychosis, mania, leucopenia, eosinophilia^
|
|
|
Other than calcium channel inhibition, what effects does Valproic acid have?
|
Also slows rate of Na+ channel recovery after inactivation and increases GABA activity^
|
|
|
Is Valproic acid highly protein bound?
|
Yes – 80-90%^
|
|
|
AE of Valproic acid?
|
CNS depression, tremor, GI upset, LFT elevation, thrombocytopenia, alopecia^
|
|
|
TDM of Valproic acid (Depekote Depakene)?
|
50-120mcg/mL^
|
|
|
TDM of Carbamezapine (Tegretol)?
|
6-12mcg/mL^
|
|
|
TDM of Phenytoin (Dilantin)?
|
10-20mcg/mL^
|
|
|
Does gabapentin have a long or short half life?
|
Short^
|
|
|
AE of gabapentin?
|
CNS depression, weight gain^
|
|
|
Why is gabapentin not often used for seizure?
|
Not very effective^
|
|
|
Is gabapentin hepatically or renally eliminated or both?
|
100% renally eliminated^
|
|
|
MOA of Gabapentin?
|
Enhances GABA-mediated inhibitors; structural analogue of GABA^
|
|
|
Other than gabapentin, what medications are used to enhance GABA-mediated inhibition?
|
Benzodiazepines, barbiturates^
|
|
|
Name a glutamate receptor inhibitor
|
Felbamate (Felbatol)^
|
|
|
MOA of Felbamate (Felbatol)?
|
Inhibits glutamate receptors, also enhances GABA transmission and limits Na+ firing^
|
|
|
Black Box warning for Felbamate (Felbatol)?
|
Acute hepatic failure and aplastic anemia (limits use)^
|
|
|
Excretion of Felbamate (Felbatol)?
|
Renally eliminated 50% as inactive metabolite and 50% unchanged^
|
|
|
Metabolism of Felbamate (Felbatol)/ DI indications?
|
Inducer of CYP3A4, inhibitor of CYP2C19^
|
|
|
MOA of Tiagabine (Gabitril)?
|
Inhibits GABA reuptake^
|
|
|
Is Tiagabine (Gabitril) protein bound?
|
YES 96%^
|
|
|
AE of Tiagabine (Gabitril)?
|
Mild CNS depression^
|
|
|
AE of Topiramate (Topamax)?
|
Mod-to-severe CNS depression, nausea, weight loss, kidney stones, angle-closure glaucoma^
|
|
|
Is Topiramate (Topamax) protein bound?
|
Minimal protein binding^
|
|
|
MOA of Topiramate (Topamax) and use?
|
Blocks Na+ channels, enhances GABA neurotransmission, increases GABA concentrations, inhibits glutamate receptors. Seizures^
|
|
|
MOA of Levetiracetam (Keppra)?
|
Unknown!^
|
|
|
Is levetiracetam (Keppra) hepatically or renally eliminated or both?
|
Renally eliminated^
|
|
|
AE of Levetiracetam (Keppra)
|
Mild CNS depression, irritability^
|
|
|
MOA of Zonisamide (Zonegran) and Use?
|
Blocks Na+ and T-type Ca2+ channels. Seizures^
|
|
|
Is Zonisamide (Zonegran) hepatically or renally eliminated or both?
|
60% hepatically metabolized^
|
|
|
AE of Zonasamide (Zonegran)?
|
Mild-to mod CNS depression, sulfonamide agent, kidney stones^
|
|
|
What drug is used for absence seizures?
|
Ethosuxamide^
|
|
|
What drugs are used for generalized or partial onset seizures?
|
Felbamate, lamotrigine, levetiracetam, rufinamide, topiramate, valproate, zonisamide^
|
|
|
What drugs are used for simple partial, complex partial, and secondarily generalized seizures?
|
Carbamezapine, gabapentin,lacosamide,oxcarbazepine, Phenobarbital, phenytoin, pregabalin, primidone, iagabine, vigabatrin^
|
|
|
Stimulation of D1 receptors is excitatory/inhibitory?
|
Excitatory^
|
|
|
Stimulation of D2 receptors is excitatory/inhibitory?
|
Inhibitory^
|
|
|
At onset of first symptoms of parkinson’s disease, ____% of neurons have already been destroyed?
|
70^
|
|
|
At autopsy of Parkinson’s patients ____% of neurons are destroyed?
|
95^
|
|
|
What are the symptoms of Parkinson’s disease?
|
Bradykinesia, rigidity, impaired postural balance, tremor^
|
|
|
Do parkinson’s drugs cure parkinson’s disease?
|
No, only treat symptoms. There is no change in underlying symptoms^
|
|
|
What is the most effective treatment for parkinson’s symptoms? Why?
|
Levodopa – readily transported across BBB via protein transport (unlike dopamine)^
|
|
|
L-DOPA is converted to dopamine in the _____ and ____
|
CNS and GI tract^
|
|
|
__-__% of levodopa reaches CNS unchanged when administered alone
|
1-3%^
|
|
|
Continued use of levodopa always results in ____ and ______ requiring higher doses or fluctuations between “off” and “on” periods
|
Tolerance and desensitization^
|
|
|
AE of levodopa?
|
Dyskinesia – uncontrollable rhythmic movements of head and trunk^
|
|
|
Name the dopamine receptor agonists
|
Bromocriptine (Parlodel (ergot derivative)), Pramipexole (Mirapex), Ropinirole (Requip).^
|
|
|
AE of dopamine receptor agonists?
|
Sedation, vivid dreams, hallucinations^
|
|
|
Do dopamine receptor agonists have a shorter or longer half life than levodopa?
|
Longer (less blood level fluctuations)^
|
|
|
How do Parlodel, Mirapex, and Requip work for parkinson’s disease?
|
Directly target postsynaptic dopamine receptors – agonist^
|
|
|
Name 2 MAO-B inhibitors used for parkinsons as adjucant medication with levodopa
|
Selegiline (Eldepryl) and rasagiline (Azilect)^
|
|
|
What is the potentially toxic metabolite of selegiline (Eldepryl) that causes sleeplessness and confusion?
|
Amphetamine^
|
|
|
Name the COMT inhibitors used for parkinsons as adjuvant medication with levodopa
|
Tolcapone (Tasmar), entacapone (Comtan)^
|
|
|
AE of tolcapone (Tasmar)
|
Can cause hepatotoxicity^
|
|
|
Does entacapone work peripherally or in the CNS?
|
Peripherally^
|
|
|
Name 3 non-dopaminergic agents used for Parkinson’s disease
|
Amantadine (Symmetrel), Trihexyphenidyl (Artane), and benztropine (Cogentin)^
|
|
|
What is Amantadine used for?
|
Treatment of levodopa induced dyskinesias – blocks excitatory NMDA receptors^
|
|
|
What is trihexyohendyl (Artane), and benztropine (Cognetin ) used for?
|
Reduction of parkinson’s related tremor. Muscarinic receptor agonist with anticholinergic effects^
|
|
|
Positive symptoms of psychosis-schizophrenia?
|
Delusions, hallucinations, disorganized speech, catatonic behavior^
|
|
|
Negative symptoms of psychosis-schizophrenia?
|
Flat affect, alogia (lack of speech), avolition^
|
|
|
Off-target effects of atypical antipsychotics (muscarinic and alpha antagonism)
|
Anticholinergic effects, orthostatic hypotension, failure to ejaculate, sedation^
|
|
|
Typical antipsychotics antagonize ____ receptors in all ____ dopaminergic pathways
|
D2/CNS^
|
|
|
Insufficient dopamine at the nirgrostriatal pathway causes___ ___ symptoms
|
EPS motor symptoms^
|
|
|
Excess dopamine at the mesolimbic pathway contributes to ____ symptoms
|
Positive^
|
|
|
Insufficient dopamine at the mesocortical pathway contributes to _____ symptoms as well as ADHD
|
Negative^
|
|
|
Insufficient dopamine at the tuberinfundibular pathway increases _____ levels causing what symptoms?
|
Prolactin; sexual dysfunction, gynecomastia, milk secretions, menstrual cycle disturbances^
|
|
|
Insufficiency of NE in the _____ ______ results in ADHD
|
Frontal cortex^
|
|
|
Antagonism of _____ receptors in the mesolimbic pathway decreases ____ symptoms
|
Dopamine/positive^
|
|
|
AE On-target effects of D2 antagonism
|
EPS, tarditive dyskinesia (may be irreversible) Neuroleptic malignant syndrome, increased prolactin secretion^
|
|
|
Symptoms of increased prolactin secretion due to typical antipsychotic use?
|
Pituitary gland; women – amenorrhea, galactorrhea, false-positive pregnancy tests; men – gynecomastia, decreased libido^
|
|
|
What is neuroleptic malignant syndrome?
|
hypothalamus (rare but life-threatening; catatonia, stupor, fever),^
|
|
|
Describe EPS
|
Parkinsonian symptoms^
|
|
|
Describe tarditive dyskinesia
|
After chronic use of typical antipsychotics; repetitive, involuntary movements of facial muscles, arms, and trunk ^
|
|
|
What are the off-target effects (Muscarinic and alpha antagonism) of typical antipsychotics?
|
Anticholinergic effects, orthostaticc hypotension, failure to ejaculate, sedation^
|
|
|
How does potency affect on/off target effects of typical antipsychotics?
|
Higher potency – D2 related AE vs off-target effects. Lower potency – more off-target effects than D2 related^
|
|
|
Atypical/typical antipsychotics are more effective at treating negative symptoms?
|
Atypical antipsychotics^
|
|
|
____ is more effective than Haldol at treating positive symptoms
|
Risperidone^
|
|
|
MOA of atypical antipsychotics?
|
5HT2 and D2 antagonism. D2 antagonism (not involved in movement – mainly psychosis), relatively fast dissociation from D2 receptors = less EPS^
|
|
|
Which traditional antipsychotics have a low potency?
|
Chlorpromazine (Thorazine), THioridazine (mellanil), Mesoridazine (Serentil)^
|
|
|
Which traditional antipsychotics have high potency
|
Haloperidol (Haldol), Fluphenzine (Prolixin) and thiohixene^
|
|
|
What are the side effects of blocking a1, H1, and M1?
|
Anticholinergic effects^
|
|
|
What are the side effects from blocking D2 (higher potency traditional antipsychotics especially)?
|
Increased negative symptoms and cause EPS^
|
|
|
40% D2 saturation will cause ______, 60% will improve _____ symptoms, and 80% will cause _____
|
Akathisia/positive symptoms/dystonias^
|
|
|
Describe how to treat acute EPS symptoms
|
Dystonia (muscle stiffness) – anticholinergics restore balance; benzos relax muscles. Akathisia (restlessness) – beta blockers (propanolol-lipophilic, CNS penetration; benzos (undesirable to use chronically), pseudoparkinsonism (rigidity, bradykinesia, tremor) – anticholinergics; amantadine (releases dopamine)^
|
|
|
Chronic EPS symptoms?
|
Pseudoparkinsonism, tarditive dyskinesia^
|
|
|
Describe NMS
|
Neuroleptic malignant syndrome – fever (hyperthermia), muscle rigidity, increased CPK, myoglobin (renal failure-hydration), delirium
|
|
|
What is the last-line atypical antipsychotic; reserved for treatment-resistant pts?
|
Clozapine^
|
|
|
What is the atypical antipsychotic that has a risk of life-threatening agranulocytosis (1-2% in the 1st 6 mos) and requires strict monitoring of CBC?
|
Clozapine^
|
|
|
What important lab work should be done weekly X 6 mos, biweekly x next 6 mos, then q4wks when prescribing Clozapine?
|
CBC – to check for life-threatening agranulocytosis^
|
|
|
AE of Clozapine?
|
Orthostatic hypotension, weight gain, hyperglycemia, sedation, constipation and agranulocytosis^
|
|
|
How is clozapine metabolized?
|
CYP2D6, 3A4, 1A2 (smoking increases metabolism!)^
|
|
|
What is the primary active metabolite of risperidone?
|
Paliperidone (Invega)^
|
|
|
Important instructions for paliperidone (Invega) osmotic delivery capsule?
|
Do not crush or chew!^
|
|
|
Can paliperidone (Invega) be taken in pts with liver disease?
|
Yes, unique – 50% renal excretion; does not require intact hepatic function ^
|
|
|
DI’s of paliperidone (Invega)?
|
No identified drug interactions^
|
|
|
AE of iloperidone (Fanapt)?
|
Orthostatic hypotension, QT prolongation^
|
|
|
Metabolism of Iloperidone (Fanapt)?
|
Metabolized by CYP2D6^
|
|
|
MOA of abilify?
|
Partial agonist at D2 – elicits reduced response compared to natural neurotransmitter. Partial agonist at 5HT1a, antagonist at 5HT2a, H1, a1. ^
|
|
|
Is abilify used in combination with other antipsychotics? Why/why not?
|
No used in comvination with other antipsychotics – partial agonism leads to unpredictable levels of receptor activity^
|
|
|
Metbolism of Olanzapine (Zyprexa)?
|
CYP1A2 (smoking increases metabolism particularly in pts who are stable on a dose while in a non-smoking hospital and ten resume smoking when discharged)^
|
|
|
What is 1 reason Quetiapine (Seroquel) may be chosen over Zyprexa as an antipsychotic?
|
Wide dosing range (making drug interactions less clinically significant)^
|
|
|
Other than antipsychotic uses what can Quetiapine (Seroquel) be prescribed for?
|
Useful for sedation at lower doses^
|
|
|
What are some antipsychotics that come in ODT formulation?
|
Aripiprazole, olanzapine, risperdone^
|
|
|
Which antipsychotics can be given IM?
|
Aripiprazole, olanzapine, seprasidone^
|
|
|
What are the long acting antipsychotics?
|
Risperdone (every 2 weeks; continue oral for at least 3 weeks), Paliperidone (every 4 weeks)^
|
|
|
T/F eventually every therapy used for dementia/alzheimers disease will fail due to neurodegeneration
|
True^
|
|
|
Pathophysiology of alzheimers
|
Depleted levels of acetylcholine, persistent activation of NMDA receptors by glutamate ^
|
|
|
Name the acetylcholinesterase inhibitors used for alzheimers
|
Tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne)^
|
|
|
MOA of acetylcholinesterase inhibitors
|
Centrally acting, reversible inhibition of Ach esterase which increases the amount of Ach available to post-synaptic neurons^
|
|
|
AE of acetylcholinesterase inhibitors in general
|
GI intolerance – N/V/D, fatigue, insomnia, loss of appetite, weight loss^
|
|
|
AE of Tacrine (Cognex)
|
Elevated LFTs (not used much)^
|
|
|
Which acetylcholinesterase inhibitor has the fewest AEs and is the only drug approved for all stages of Alzheimer’s disease; available as oral tablet or ODT?
|
Donepezil (Aricept)^
|
|
|
AE of rivastigmine (Exelon)?
|
HA, dizziness ^
|
|
|
Which acetylcholinesterase inhibitor can be given as a skin patch?
|
Rivastigmine (Exelon)^
|
|
|
AE of Galantamine?
|
High incidence of N/V^
|
|
|
DIs of acetylcholinesterase inhibitors?
|
Synergistic effects with cholinergic agonists, antagonistic effects with anticholinergics, CYP2D6, CYP3A4 inducers decrease levels of donepezil (Aricept)^
|
|
|
MOA of Memantine (Namenda) use for Alzheimer’s disease?
|
NMDA receptor antagonist – helps regulate glutamate, which may be produced in excess in Alzheimer’s pts.^
|
|
|
AE of Memantine (Namenda)
|
GI intolerance, hypertension, dizziness, HA^
|
|
|
Metabolism of Memantine (Namenda)
|
50/50 hepatic metabolism and unchanged renal excretion^
|
|
|
Name all of the NMDA receptor antagonists
|
Namenda is the only drug in its class; can be used in combination with acetylcholinesterase inhibitors^
|
|
|
What stage of Alzheimers is Memantine (Namenda) used for?
|
Moderat-to-severe disease^
|
|
|
Are opioid analgesics metabolized by CYP450?
|
NO^
|
|
|
Effects of mu1 stimulation?
|
Supraspinal analgesia, bradycardia, sedation^
|
|
|
Effects of mu2 stimulation?
|
Respiratory depression, euphoria, physical dependence^
|
|
|
Effects of delta stimulation?
|
Spinal analgesia, respiratory depression^
|
|
|
Effects of kappa stimulation?
|
Spinal analgesia, respiratory depression, sedation, dysphoria (psychotic effects)^
|
|
|
Effects of sigma stimulation?
|
Dyshphoria (psychotic effects), delirium, hallucinations^
|
|
|
Name the full agonist opioid medications
|
Morphine, oxycodone (oxycontin), hydromorphone (Dilaudid), methadone (Dolophine), merpidine (Demerol), Fentanyl (sublimaze), oxymorphone (Opana), hydrocodone (Hycodan), Codeine, and propoxyphene (Darvon)^
|
|
|
Name the partial agonists, mixed agonist-antagonist opioid drugs
|
Pentazoncine (Talwin), Butophanol (Stadol), Nalbuphine (Nubain), and Buprenorphine (Buprenex)^
|
|
|
Why is morphine not as effective orally?
|
1st pass metabolism^
|
|
|
What are the 2 main metabolites (active) of morphine?
|
Morphine 6-glucoronide and morphine 3-glucoronide^
|
|
|
What are the AE of morphine due to build-up of metabolites?
|
Nausea, myoclonus, hallucinations, pruritis due to histamine release^
|
|
|
What is combined with codeine as an expectorant when used as a cough suppressant?
|
Guaifenesin^
|
|
|
Is codeine a prodrug?
|
YES^
|
|
|
Metabolism of codeine
|
10%metabolized by CYP2D6 to active form - morphine^
|
|
|
What is important to remember when prescribing codeine to a pt who states it provides no relief?
|
10% Caucasians, 30% Asians lack 2D6 – no analgesic effect!^
|
|
|
Does the antitussive effect of codeine require the conversion to morphine?
|
No antitussive effect without conversion^
|
|
|
Is codeine better for cough or pain relief?
|
Cough (lower dose)^
|
|
|
Can hydrocodone be used as an antitussive?
|
Yes^
|
|
|
What opioid medications are safest for pts with renal dysfunction? Why?
|
Oxycodone, hydromorphone, methadone – no active metabolites^
|
|
|
What is the semi-synthetic opioid?
|
Hydromorphone (dilaudid)^
|
|
|
Which synthetic opioid medication is used for treatment of opioid addiction?
|
Methadone ^
|
|
|
How is methadone dosed when used for treatment of opioid addiction (maintenance)?
|
Once daily (long half life)^
|
|
|
Which opioid is used post-op for shakes/chills caused by volatile anesthetic agents, epidural and spinal analgesia?
|
Meperidine^
|
|
|
What is the main metabolite of meperidine?
|
Normeperidine^
|
|
|
T1/2 of meperidine?
|
Long – 15-20h^
|
|
|
What are the AE of meperidine metabolite accumulation?
|
CNS excitation/anxiety, and convulsions ^
|
|
|
Use caution when prescribing Meperidine to the ____ and those with ____ _____
|
Elderly/ renal dysfunction^
|
|
|
Popoxypphene is metabolized to_____
|
Norpropoxyphene^
|
|
|
T1/2 of propoxyphene?
|
Long – 30-36h^
|
|
|
AE of propoxyphene?
|
Stupor, coma, convulsions, cardiac toxicity^
|
|
|
Which opioid was removed from the market in Nov 2010 due to serious cardiac toxicity?
|
Propoxyphene^
|
|
|
Which opioid is 80-100xs more potent than morphine?
|
Fentanyl^
|
|
|
Fentanyl is used transdermally for chronic pain only after what?
|
Titration with short-acting opioid to assess affects^
|
|
|
Tansmucosal Fentanyl for breakthrough pain is ____-___% bioavailable
|
35-50%^
|
|
|
Which opioid analgesic is a partial agonist, similar to pentazocine, burophanol, and nalbuphine, has a ceiling effect and can precipitate withdrawal symptoms if already on a full agonist?
|
Buprenorphine^
|
|
|
Buprenorphine is more/less likely to cause dependence than a full agonist?
|
Less likely^
|
|
|
Which opioid analgesic is used sublinguially for treatment of opioid dependence? Names
|
Buprenorphine (alone – subutrex) (combined with naloxone – suboxone)^
|
|
|
Name the non-therapeutic opioid drugs of abuse
|
Heroin, 3-methylfentanyl (China White)^
|
|
|
What is the non-therapeutic opioid drug that is 3X more potent than morphine due to greater lipid solubility?
|
Heroin^
|
|
|
What is tne non-therapeutic opioid drug that is 1000x more potent than morphine and matebolites can accumulate during chronic use?
|
3-methylfentanyl (China white)^
|
|
|
What are the most common AEs of opioids?
|
Sedation, dizziness, nausea, vomiting, itching, sweating and constipation^
|
|
|
Most serious AE of opioids?
|
Respiratory depression^
|
|
|
With opioids, tolerance to sedative and emetic effects develop slowly but not constipation. T/F?
|
False – tolerance to sedative and emetic effects develop rapidly but not constipation^
|
|
|
What should be given with opioid prescriptions?
|
Stimulant laxatibe with or without a stool softener – start early!^
|
|
|
Which pts are at risk for the most serious AE of opioids?
|
Those with Chronic COPD, decreased rep reserve – both susceptible to respiratory depression^
|
|
|
T/F there is no minimum or maximum dose with opioids except limitation by the dose of APAP or ASA
|
True^
|
|
|
What type of opioid should be used for chronic pain?
|
Sustained release formulation^
|
|
|
What type of opioid should be used for breakthrough pain?
|
Immediate release^
|
|
|
What is the non-opioid analgesic medication that has a metabolite with 200x greater affinity for mu receptor, 6x more potent than the parent compound?
|
Tramadol^
|
|
|
MOA of tramadol?
|
Blocks reuptake of NE and 5HT^
|
|
|
Tramadol is indicated for what type of pain?
|
Moderate to severe^
|
|
|
Is tramadol’s analgesia reversible with naloxone?
|
Only partially^
|
|
|
AE /DI of tramadol?
|
Seizures possible in pts taking MAOIs, antipsychotics^
|
|
|
Define tolerance
|
Reduction in adverse effects^
|
|
|
What is the pure competitive opioid antagonist that is the drug of choice for reversal of opioid overdose associated with resp depression, sedation, coma, hypotension, opioid-induced psychotomimetic effects?
|
Naloxone (Narcan)^^
|
|
|
_____ precipitates withdrawal in opioid dependent subjects
|
Naloxone (Narcan)^
|
|
|
T1/2 of Naloxone?
|
30-90min^
|
|
|
What is the pure competitive opioid antagonist with a longer half life that is used for maintenance of opioid-free state in detoxified formerly opioid-dependent pts?
|
Naltrexone (Revia)^
|
|
|
T/F Naltrexone (Revia) is used for tx of alcoholism?
|
True^
|
|
|
How long do pts need to be off opioid medications prior to starting Naltrexone (Revia)?
|
7-10 days^^
|
|
|
MOA of Naltrexone (Revia)
|
Blocks effects of opioids if taken while on this drug^
|
|
|
What pure opioid antagonist with a T1/2 of 10h, is used for post-operative reversal of opioids and treatment of opioid overdose?
|
Nalmephene (Revex)^
|
|
|
Which opioid maintenance drug is dispensed only in a special clinic daily?
|
Methadone^
|
|
|
What opioid maintenance drug can be dispensed only at the dr’s office?
|
Buprenorphine^
|
|
|
What opioid maintenance drug can be taken by the patient at home?
|
Nuprenorphin/naloxone SL (Suboxone)^
|
|
|
Is opioid withdrawal life threatening?
|
No^
|
|
|
What types of pain are TCAs used to treat?
|
Diabetic neuropathy, postherpetic neuralgia, polyneuropathy, and nerve injury or infiltration with cancer (may also improve underlying depression and insomnia)^
|
|
|
What type of pain is Venlafaxine (Effexor) used to treat?
|
Neuropathic pain, HA, fibromyalgia, postmastectomy pain^
|
|
|
What type of pain is Duloxetine (Cymbalta) used to treat?
|
Neuropathic pain^
|
|
|
What type of pain is the anticonvulsant Carbamazepine (Tegretol) used to treat?
|
Trigeminal neuralgia^
|
|
|
What type of pain is the anticonvulsant Pregabalin (Lyrica) used to treat?
|
Fibromyalgia, diabetic neuropathy, postherpetic neuralgia, HIV neuropathy^
|
|
|
What type of pain is hydroxyzine used to treat (at low doses)?
|
Analgesic for cancer and post-op pain^
|
|
|
What type of pain are corticosteroids used to treat?
|
Inflammatory diseases, tumor infiltration of nerves^
|
|
|
How does capsaicin cream (Zostrix) work?
|
It is made from chili peppers – masks pain with heat^
|
|
|
Why is APAP not effective pharmacologic therapy for RA?
|
RA has inflammatory component – APAP is not anti-inflammatory^
|
|
|
Why is ASA rarely used pharmacologic therapy for RA?
|
AE – must be at anti-inflammatory doses which have higher AE^
|
|
|
What are the main pharmacologic therapy agents used for symptomatic therapy in RA?
|
NSAIDs and corticosteroids^
|
|
|
What is the main pharmacologic therapy agent used to prevent or slow the progression of RA?
|
DMARDs (most pts should be on a DMARD as the tx underlying disease process)^
|
|
|
Should corticosteroids be used long-term for treatment of symptoms of RA?
|
No –avoid long term use^
|
|
|
What are the indications for use of corticosteroids in RA?
|
Life threatening complications such as vasculitis, bridge time to onset of action of DMARDS, pulse therapy for acute flare-ups, intra-articular therapy for very acute inflammation (not on a recurrent basis)^
|
|
|
Long term AEs of Corticosteroids
|
Hyperglucemis, cataracts, glaucoma, aseptic necrosis of weigh bearing joints, osteoporosis, cushing’s syndrome, adrenal suppression, Na+ & H2O retention, CNS side effects with high doses^
|
|
|
With corticosteroids you should use the lowest/highest dose possible for treatment of RA symptoms
|
Lowest^
|
|
|
A pt must be tapered off of corticosteroids after using them for more than _____ ____
|
2 weeks^
|
|
|
Which corticosteroids have the greatest risk of mineralocorticoid activity?
|
Cortisone and hydrocortisone^
|
|
|
What happens when corticosteroids produce mineralocorticoid activity?
|
Promotes Na+/H2O retention^
|
|
|
What type of corticosteroids should be used in pts with CHF/HTN? Why?
|
Those with low mineralocorticoid activity due to Na+ and H2O retention. Methylprednisolone, triamcinolone, dexamethasone, betamethasone for example^
|
|
|
What type of medications should be started ASAP after diagnosis with RA as a standard of care?
|
DMARDS (Disease Modifying Anti-Rheumatic Drugs)
|
|
|
Why are DMARDs used in RA?
|
Prevents or slows progression of joint destruction or deformities (Disease Modifying Anti-Rheumatic Drugs)^
|
|
|
Name some conventional DMARDS
|
Hydroxychloroquine (Plaquenil, Quineprox), Methotrexate (MTX), Azathioprine (Imuran, AZA), gold, penicillamine, sulfasalazine (Aulfidine), Leflunomide (Arava), Minocycline, Cyclophosphamide^
|
|
|
Name some biologic DMARDS
|
Etanercept (Enbrel),Infliximab (Remicade), Adalimumab (Humira), Certolizumab pegol (cimzia), Golimumab (Simponi), Tocilizumab (Actemra), Rituximab (Rituxan), Abatacept (Orencia), Anakinra (Kineret)^
|
|
|
How long can it take before a response to DMARDS is seen?
|
Can take 3-6 mos for response. ^
|
|
|
What should be taken with DMARDS for 1st 3-6 mos of therapy and why?
|
NSAID or corticosteroid to maintain anti-inflammatory therapy for this period prior to response to DMARDs, if response incomplete NSAIDs should continue^
|
|
|
What should be monitored in pts taking DMARDS?
|
Monitor range of motion, activities of daily living^
|
|
|
Why are Gold and Penicillamine no longer the standard of care DMARDS?
|
High incidence of toxicity requiring discontinuation. Myelosupporession, proteinuria, stomatitis, rash, altered taste perception (penicillamine), visual changes (gold)^
|
|
|
What DMARD is an immunosuppressant also prescribed for use in Chrohn’s disease and is a prodrug for mercaptopurine?
|
Azathioprine^
|
|
|
Toxicities of Azathioprine?
|
Myelosuppression, hepatotoxicity, rash, infection. Reserved for aggressive disease or serious complications such as vasculitis^
|
|
|
What DMARD is primarily used for mild RA, may take 6 mos before any effect is seen, and is also an anti-malarial drug?
|
Hydroxychloroquine^
|
|
|
Toxicities of hydroxychloroquine?
|
Well tolerated (some GI upset), retinopathy (rare but ophthalmology exams recommended q6-12 mos)^
|
|
|
What is the DMARD used for mild to mod RA and is also used for Chrohn’s disease and ulcerative colitis?
|
Sulfasalazine ^
|
|
|
MOA of sulfasalazine (DMARD)?
|
Cleaved by intestinal bacteria to sulfapyridine (active metabolite and 5-aminosalicylic acid (5-ASA). Can bind iron and decrease absorption^
|
|
|
AE of sulfasalazine?
|
Gi upset, rash, bodily fluids can turn yellow-orange. If pt taking antibiotic, intestinal flora may be destroyed, reducing conversion to its active form.^
|
|
|
What DMARD is an inhibitor ofpyrimidine synthesis = altered lymphocyte activation and decreased inflammatory response?
|
Leflunomide^
|
|
|
Toxicities of Leflunomide?
|
Hepatotoxicity, reversible alopecia, GI distress. Teratogenic (category X). May discontinue in men who want to father a child. ^
|
|
|
In cases of lefunomide toxicity or in pts who wish to have a child, _____ can quickly lower drug levels which could otherwise take months.
|
Cholestyramine^
|
|
|
What DMARD is a folate antagonist = purine biosynthesis inhibition, cytokine production inhibition, adenosine production stimulation = anti-inflammatory effect?
|
Methotrexate^
|
|
|
How long does it take for pts taking methotrexate to have symptomatic relief?
|
Within 1 month for many patients^
|
|
|
What is the cheapest DMARD available and is well tolerated?
|
Methotrexate^
|
|
|
What should be given with Methotrexate?
|
Folic acid replacement^
|
|
|
Toxicities of methotrexate?
|
GI upset, megaloblastic anemia, hepatotoxicity.^
|
|
|
What are biologic DMARDS and what are their advantages/disadvantages over traditional DMARDS?
|
Genetically developed proteins with various effects on the pathogenesis of RA. Advantage – no routine lab monitoring. Disadvantages – risk of infections and malignancy, very expensive, injection site reactions are common. TB test required prior to use.^
|
|
|
What are the DMARDS that are TNFalpha Blockers?
|
Etanercept, infliximab, adalimumab, certolizumab, pegoli, golimumab.^
|
|
|
Why are TNFalpha blocker (DMARDs) used?
|
They downregulate or antagonize TNFalpha, akey cytokine contributing to RA^
|
|
|
Black Box warnings of TNFalpha blockers
|
Serious risk of infections (invasive fungal infections, active TB and reactivation of latent TB, bacterial infections, viral infections, opportunistic infections. Lymphoma and other malignancies in children and adolescents. ^
|
|
|
MOA of Rituximab?
|
Depletes B-cells which have been shown to be responsible for inflammation in RA used when pts fail traditional DMARDS and anti-TNF agents^
|
|
|
Black box warnings for rituximab?
|
Fatal infusion reactions, severe mucocutaneous reactions, Progressive encephalopathy caused by JC virus^
|
|
|
Which biologic DMARD inhibits T-cell activation?
|
Abatacept – used when pts fail traditional DMARDS and TNF agents^
|
|
|
What biologic DMARD antagonizes IL-1 receptors (a pro-inflammatory cytokine)?
|
Anakinra^
|
|
|
Can anakinra be used with other DAMARDS?
|
Yes, with conventional DMARDS but not with TNF agents (potential increased risk of infection) ^
|
|
|
What biologic DMARD inhibits IL-6?
|
Tocilizumab^
|
|
|
Black box warning for Tocilizumab?
|
Serious risk of infections^
|
