Sgu Pharm 2012 Exam 2

Front 1

Aluminum hydroxide

Back 1

Antacid

MOA:
-weak base that reacts with HCl to raise gastric pH.

AE:
-reacts with HCl to form aluminum chloride-->constipation.
-bioavailability of TC, digoxin, and antimuscarinic drugs may be reduced

Front 2

Magnesium hydroxide

Back 2

Antacid

MOA:
-weak base that reacts with HCl to raise gastric pH.

AE:
-digoxin and TC absorption may be reduced.
-diarrhea

Front 3

Calcium carbonate

Back 3

Antacid

MOA:
-weak base that reacts with HCl to raise gastric pH.

AE:
-nephrolithiasis and dense fecal matter formation.

Front 4

Cimetidine, Famotidine, Ranitidine, Nizatidine

Back 4

H2 antagonists

MOA:
-only partially inhibit gastric secretion by ACh or bethanechol.
-fully inhibit secretion by histamine.

Use:
-healing gastric, duodenal ulcers and preventing recurrence.

PK:
-Cimetidine: given orally, inhibits p450, short half-life
-Ranitidine: 5-10 times more potent than Cimetidine, longer acting
-Famotidine: 20 to 50 times more potent than ranitidine.
-Nizatidine: no first-pass metabolism, eliminated by kidney.

AE:
-headache, dizziness, diarrhea, muscular pain.
-CNS: confusion, hallucinations occur in elderly patients or after IV administration.
-Endocrine: Cimetidine has antiandrogenic effects - gynecomastia, galactorrhea, and reduced sperm count
-ketoconazole may not be absorbed properly when taking with these H2 antagonists b/c of pH changes.

Front 5

Omeprazole, Esomeprazole

Back 5

Proton pump inhibitors

MOA:
-bind to the H+/K+ ATPase, a proton pump, of the parietal cell.
-acid-resistant coat is removed in alkaline duodenum, and the prodrug, a weak base, is absorbed and transported to the parietal cell canaliculus.
-converted to active form that reacts with a cysteine residue to the H+/K+-ATPase

Use:
-healing peptic ulcers
-erosive esophagitis, duodenal ulcer, ZE syndrome, gastrinoma
-GERD (PPI in morning+H2 antagonist in evening improves symptoms)
-hemorrhagic uclers (b/c promote platelet aggregation)
-eradication of H. pylori

AE:
-Omeprazole inhibits the metabolism of warfarin, phenoytoin, diazepam, and cyclosporine.
-decrease bioavailability of B12, digoxin, ketoconazole (b/c acid is required for absorption)
-Calcium carbonate requires low pH, so instead use calcium citrate for source of calcium
-small increase in respiratory and GI infections.
-rarely pancreatitis, hepatoxicity, and interstitial nephritis

Front 6

Sucrasulfate

Back 6

Cytoprotective (Mucosal protective) agent

MOA:
-forms complex gel with epithelial cells, creating a barrier against HCl and prevents degradation of mucus by pepsin and acid.
-also stimulates PG and bicarbonate release

PK:
-requires low pH, so dont give with H2 antagonists.

Front 7

Bismuth subsalicylate

Back 7

Cytoprotective (Mucosal protective) agent

MOA:
-inhibit pepsin, increase secretion of mucus
-some antimicrobial properties
-interact with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer crater.

Note:
-Bismuth salts DO NOT neutralize stomach acid.

Front 8

Misoprostol (PGE1)

Back 8

Cytoprotective (Mucosal protective) agent

MOA:
-inhibits secretion of HCl and stimulates secretion of mucus and bicarbonate.

Use:
-prevention of gastric ulcers induced by NSAIDs
-less effective than H2 antagonists and PPIs for treatment of peptic ulcers.

AE:
-produces uterine contractions, hence is contraindicated in pregnancy.
-dose-related diarrhea and nausea.

Front 9

Pirenzepine

Back 9

Anticholinergic

MOA:
-suppress acid secretion via M3 receptor.

Use:
-peptic ulcer (in refractory cases)

AE:
-dryness of mouth
-blurred vision, urinary retention, arrhythmias, and constipation

Front 10

Dicyclomine

Back 10

Anticholinergic

MOA:
-inhibits acid secretion by binding to mAChR in parietal cells. Not as effective as H2 or PPI.

Use:
-irritable bowel syndrome (IBS)

AE:
-dryness of mouth
-blurred vision, urinary retention, arrhythmias, and constipation

Front 11

PPI, clarithromycin, amoxicillin, metradinazole, tetracycline, bismuth subsalicylate, ranitidine

Back 11

regimen for H. pylori eradication

-First line: PPI+clarithromycin+amoxicillin
-2nd line: PPI+clarithromycin+metrodinazole
-3rd line: add bismuth subsalicylate, tetracycline + Ranitidine/PPI

Front 12

Metoclopramide

Back 12

Prokinetic drug

MOA:
-D2 antagonist and mixed 5-HT3 antagonist / 5-HT4 agonist

Use:
-anti-emetic via D2 and 5-HT3
-gastroparesis (prokinetic activity via 5-HT4)
-GERD

AE:
-makes Parkinson's worse
-makes prolactinomas worse

Front 13

Cisapride

Back 13

Prokinetic drug

MOA:
-release ACh in myenteric plexus
-increases muscle tone in esophageal sphincter.

Use:
-GERD, diabetic gastroparesis, constipation

AE:
-long QT syndrome (predisposes to arrhythmias with erythromycin and ketoconazole)
-diarrhea

Front 14

Senna

Back 14

Laxative (stimulant)

MOA:
-causes evacuation of the bowels within 8 to 10 hours.
-water and electrolyte secretion into the bowel.

Use:
-used with docusate (makes stools softer and easier to pass) for opioid-induced constipation.

Front 15

Bisacodyl

Back 15

Laxative (stimulant)

MOA:
-directly acts on the nerve fibers in the mucosa of the colon, stimulating it.

AE:
-abdominal cramps
-potential for atonic colon

Front 16

Castor oil

Back 16

Laxative (Irritant)

MOA:
-broken down in SI to ricinoleic acid, irritating the gut, and increasing peristalsis.

AE:
-contraindicated in pregnancy (b/c it may stimulate uterine contractions)

Front 17

Methylcellulose, psyllium seeds, bran

Back 17

Bulk laxatives

MOA:
-form gels in LI, causing water retention and intestinal distention, thus increasing peristaltic activity.

AE:
-potential for intestinal obstruction (contraindicated in bed-bound patients)

Front 18

Magnesium citrate, Mg sulfate, Mg phosphate, and Mg hydroxide

Back 18

Saline and Osmotic laxatives

MOA:
-hold water in the intestine by osmosis and distend the bowel causing stimulation, followed by defecation.

Front 19

Lactulose

Back 19

Osmotic laxative

MOA:
-disaccharide that is degraded by colonic bacteria to form lactic, formic, and acetic acid, which increases osmotic effect.

Use:
-hepatic encephalopathy and hyperammonia (helps draw out ammonia)

Front 20

PEG (polyethylene glycol)

Back 20

Laxative

Use:
-colonic lavage for endoscopic and radiological procedures

Front 21

Docusate sodium, docusate calcium, and docusate potassium

Back 21

Stool softeners (emollient laxatives or surfactants)

MOA:
-surface active agents emulsified with stools make it softer and easier to pass.

Front 22

Mineral oils, glycerin suppositories

Back 22

Lubricant laxatives

MOA:
-lubricants aid in easy passage of stools

Front 23

Scopolamine

Back 23

Anticholinergic, antiemetic

Use:
-motion sickness

Front 24

Dimenhydrinate, Dimenhydramine, Meclizine, Cyclizine

Back 24

H1-receptor antagonists, antiemetics

Use:
-motion sickness among other things

Front 25

Prochlorperazine (Phenothiazine) and
Haloperidol, Droperidol (Butyrophenones)

Back 25

D2 antagonists

Use:
-low or moderately emetogenic chemo drugs (e.g. fluorouracil and doxorubicin)

AE:
-hypotension and restlessness
-extrapyramidal symptoms and sedation

Front 26

Odansetron, Granisetron

Back 26

5-HT3 blockers, antiemetics

MOA:
-block 5-HT3 receptors in the periphery (visceral vagal afferents) and in the brain (CTZ)

AE:
-long QT with dolasetron

Front 27

Lorazepam, Alprazolam

Back 27

Benzodiazepines

Use:
-antiemetic potency is low
-mostly used for sedative, anxiolytic, and amnesic properties.
-anticipatory vomiting

Front 28

Dexamethasone, Methylprednisone

Back 28

Corticosteroids

MOA:
-antiemetic mechanism is not known but maybe due to blockage of PGs.

Use:
-mild to moderate emetogenic chemotherapy.

AE:
-insomnia, hyperglycemia (diabetes)

Front 29

Marijuana derivatives including dronabinol and nabilone

Back 29

Cannabinoids

Use:
-mild to moderate emesis-chemotherapy indued
-not first line emetics

AE:
-dysphoria, hallucinations, sedation, vertigo, and disorientation

Front 30

Aprepitant

Back 30

NK1 antagonist

MOA:
-new antiemetic, blocks neurokinin-1/substance P in the brain.

PK:
-extensive metabolism by cyp 3A4
-can also induce the above enzyme and shorten half-life of warfarin.

AE:
-constipation and fatigue

Front 31

Apomorphine and Syrup ipecac

Back 31

Emetics

MOA:
-stimualte CTZ / gastric mucosal irritation

Use:
-accidental poisoning

Front 32

Diphenoxylate and Loperamide

Back 32

Antidiarrheals, antimotility agents

MOA:
-activate presynaptic opioid receptors in the enteric system to inhibit ACh release and decrease peristalsis.

Use:
-diarrhea
-atropine is added to discourage abuse

AE:
-drowsiness, abdominal cramps, and dizziness
-contraindicated in toxic megacolon and colitis.
-diphenoxylate has analgesic properties at higher doses and can lead to opioid dependence.
-loperamide has no analgesic properties or any potential for addiction.

Front 33

Octreotide and bismuth subsalicylate (pepto bismol)

Back 33

Antidiarrheal

MOA:
-coats intestinal epithelium and decreases GI irritation.

Front 34

Drugs for IBD (UC and Crohns)

Back 34

-Steroids (predisone, prednisolone)
-MTX, 6-MP
-Sulfasalazine: sulfonamide derivative, has anti-inflammatory effect. It is a prodrug converted to Sulfapyridine + 5-ASA in GI.
-Mesalamine (5-ASA): inhibits PGs and LTs, various preps of 5-ASA include Pentasa, Asacol, and Olsalazine.
-Natalizumab: mab against cellular adhesion molecule, alpha-4 integrin.
-Infliximab: mab against TNF-alpha, inhibiting inflammation.

Front 35

Drugs for IBS (bowel disorders characterized by abdominal pain, discomfort, bloating and alteration of bowel habits)

Back 35

-Loperamide, Diphenoxylate, codeine (opioid analogs, antidiarrheals)
-Hyocyamine or dicyclomine (anticholinergic antispasmodics)
-Alosetron (5-HT3 antagonist)

Front 36

alpha-amylase, lipase, proteases (trypsin, chymotrypsin)

Back 36

Pancreatic enzymes

-alpha-amylase: starch digestion, secreted in active form.
-lipase: fat digestion
-trypsin, chymotrypsin: protein digestion, secreted as proenzymes

Use:
-pancreatic insufficiency (chronic pancreatitis)
-malabsorption syndrome (steatorrhea)
-cystic fibrosis

Front 37

Aspirin

Back 37

NSAID (Non-selective COX inhibitor)

MOA:
-irreversibly acetylates COX.
-deacetylated to salicylate, which is a weak reversible competitive inhibitor of COX.
-salicylates uncouple oxidative phosphorylation-->elevated CO2-->hyperventilation and respiratory alkalosis. At toxic levels, central respiratory paralysis and respiratory acidosis occurs.
-inhibit TXA2 production from platelets, but not PGI2 from endothelial cells.

Uses:
-anti-inflammatory, antipyretic, and analgesic (headache, joint and muscle pain, and dysmenorrhea, rheumatoid arthritis)
-reduce risk of MI, strokes, TIAs
-reduce risk of colon cancer

PK:
-analgesic and antipyretic doses: 325-650 mg every 4-6 hrs
-anti-inflammatory: initial: 2.4-3.6 g/day; maintenance: 3.6-5.4 g/day
-low does for cardioprotective effects: <100 mg daily
-1 g or more-->zero order kinetics. First order is not observed until concentration drops to 300 mg.

AE:
-GI: epigastric distress
-increase bleeding (avoid in hypoprothrombinemia, vit. K deficiency, hemophilia, and hepatic damage)
-hypersensitivity: vasomotor rhinitis, angioedema, urticaria, bronchial asthma, flushing, hypotension, shock, bronchoconstriction. (d/t diversion to lipoxygenase pathway)
-Reye's syndrome (when given during viral illness to children)
-Uricosuric effects (competes with uric acid for secretion at low doses, and competes for uric acid reabsorption at high doses, hence blocks effects of probenecid and other uricosuric agents)
-Hepatic effects: jaundice, elevated liver enzymes
-pregnancy: category C during trimesters 1 and 2, category D during trimester 3
-Salicylism: chronic salicylate intoxication that includes headache, dizziness, tinnitus, difficulty hearing, drowsiness, thirst, hyperventilation, nausea, vomiting, lassitude, diarrhea
-Severe intoxication: after acute salicylate overdose (initially respiratory alkalosis and metabolic acidosis, but with prolonged exposure causes respiratory acidosis due to respiratory failure)

Front 38

Celecoxib, Etoricoxib, Meloxicam

Back 38

COX-2 inhibitors

MOA:
-selectively block site of COX-2
-fewer GI effects, but no cardioprotective effects b/c COX-1 is unaffected

Use:
-anti-inflammatory when adverse GI effects is not desired.

AE:
-renal toxicities
-cardiovascular thrombotic events
-Etoricoxib is not approved in US, while Celecoxib is the only one that is.

Front 39

Acetaminophen

Back 39

NSAID (technically not)

MOA:
-weak COX-1 and COX-2 inhibitor, but no significant antiinflammatory effects.

Use:
-antipyretic and analgesic without antiplatelet or antiinflammatory effects.
-mild to moderate pain: headaches, myalgia, postpartum pain
-drug of choice for pain relief in osteoarthritis
-better than aspirin in treatment of patients with history of peptic ulcers, hemophilia, gout, or bronchospasm
-drug of choice for treating children with fever and flulike symptoms.
-drug of choice for short-term treatment of fever and minor pain during pregnancy.

AE:
-hepatotoxicity at high doses
-antidote is acetylcysteine

Front 40

Diclofenac, Ibuprofen, Indomethacin, Ketorolac, Naproxen, Piroxicam, Tolmetin, and Aspirin

Back 40

NSAIDs (Non-selective COX inhibitors)

MOA:
-Analgesic: inhibiting PGE2 (which sensitizes nerve endings to bradykinin, histamine, and other chemical mediators), inhibits pain
-Antipyretic: inhibiting PGE2 (increase set point of hypothalamus), inhibiting fever

Use:
-Indomethacin is commonly used in treatment of gout. All NSAIDs except aspirin, salicylates, and Tolmetin can be used for gout.
-colon cancer and FAP
-inflammatory conditions like osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, dysmenorrhea
-Niacin tolerability (NSAIDs inhibit the side effect of flushing mediated by PGD2)
-Indomethacin is the drug of choice for closing PDA.

AE:
-GI effects: inhibits PGI2 and PGE2, which inhibit acid secretion and promote secretion of cytoprotective mucus. This leads to damage of the lining of the stomach.
-can also cause ulcers directly via local irritation.
-Risks of GI effects: Piroxicam>Tolmetin>Indomethacin>Naproxen>Diclofenac>Aspirin>Ibuprofen>Celecoxib
-decrease in RBF (d/t inhibition of PGs). Leads to sodium and water retention-->peripheral edema, weight gain, increased BP, and rarely CHF
-acute interstitial nephritis (d/t type I hypersensitivity to NSAIDs)
-Analgesic Nephropathy: prolonged exposure to analgesics leads to renal papillary necrosis, a chronic interstitial nephritis.

Front 41

Methotrexate (MTX)

Back 41

Anticancer (Antimetabolite), DMARD (Disease Modifying Anti-Rheumatic Drug)

MOA:
-competitive inhibition of AICAR transformylase. This enzyme is needed for the final steps for IMP synthesis.
-inhibition of AICAR transformylase leads to accumulation of adenosine -Adenosine-->potent anti-inflammatory mediator -->acts on A2b receptors-->suppresses NF-kB activation induced by TNF and other cytokines.
-MTX is also a folic acid analog and inhibits DHF reductase, decreasing dTMP synthesis.

Use:
-drug of choice for rheumatoid arthritis
-psoriasis, abortion, ectopic pregnancy
-cancers: leukemias (ALL), lymphomas (Burkitts), choriocarcinoma, sarcomas (osteosarcoma).

AE:
-nausea and mucosal ulcers (mucositis)
-hepatotoxicity (macrovesicular fatty change)
-rare "hypersensitivity" lung reaction and pseudolymphomatous reaction.
-contraindicated in pregnancy
-myelosuppression
-nephrotoxicity (d/t crystal deposition in kidney tubules, give adequate hydration to prevent this)
-pulmonary toxicity especially if given to children.

Antidote:
-leucovorin (folinic acid) that will reverse myelosuppression

Front 42

Cyclophosphamide

Back 42

DMARD, Alkylating agent (Nitrogen mustard)

MOA:
-cross-links DNA and prevents cell replication, suppressing T-cell and B-cell function.
-covalently X-link (interstrand) DNA at guanine N-7. Require bioactivation by liver.
-metabolite is acrolein that is cytotoxic

Use:
-rheumatoid arthritis when given orally, not IV
-SLE and other rheumatic diseases
-vasculitides (Wegner's)
-NHL, breast, and ovarian cancer

AE:
-bone marrow suppression
-hemorrhagic cystitis (d/t irritation of bladder by acrolein)
-rarely, bladder carcinoma
-Alopecia, SIADH
-dose-limiting infertility in men and women (gonadal failure)
-Acrolein, one of the drug's metabolites, can cause urinary toxicity.
-Antidote is mesna (thiol group of mesna binds to acrolein)

Front 43

Azathioprine

Back 43

DMARD, Antimetabolite

MOA:
-antimetabolite precursor to 6-MP, which inhibits de novo purine synthesis. This leads to T-cell and B-cell suppression.

Use:
-kidney transplantation
-autoimmune disorders (glomerulonephritis and hemolytic anemia)

AE:
-bone marrow suppression
-Allopurinol increases toxicity (b/c it inhibits xanthine oxidase, which metabolizes 6-MP)
-GI disturbances

Front 44

Leflunomide

Back 44

DMARD

MOA:
-metabolite inhibits dihydroorotate reductase, leading to decreased OMP and UMP.
-leads to translocation of p53 to nucleus, and cell arrest at G1, inhibiting T-cell proliferation and production of autoantibodies by B-cells.
-other types of cells are not affected b/c pyrimidines synthesis via salvage pathway still works, whereas lymphocytes require a greater amount of pyrimidines.

AE:
-diarrhea
-reversible alopecia, rash, myelosuppression
-contraindicated in pregnancy

Front 45

Cyclosporine

Back 45

DMARD, Immunosuppressant

MOA:
-binds to cyclophilins, forming a complex that inhibits calcineurin, a phosphatase, necessary to activate a T-cell specific transcription factor.
-the transcription factor, NFAT (nuclear factor of activated T lymphocytes), is required for induction of cytokines.
-thus blocking NFAT, blocks IL-2 production

Use:
-organ rejection after transplantation
-selected autoimmune disorders

AE:
-nephrotoxicity (preventable with mannitol diuresis)
-tremor, hypertension, hyperglycemia, hyperlipidemia, osteoporosis, hirsutism, gum hyperplasia
-gout

Front 46

Hydroxychloroquine

Back 46

DMARD, Antimalarial

MOA:
-unclear

Use:
-moderately effective for RA
-malaria (duh)

AE:
-hemolysis in G6PD patients
-retinal damage (discontinued when this appears)
-use during pregnancy is relatively safe

Front 47

Sulfasalazine

Back 47

DMARD

MOA:
-consists of sulfapyridine (antibacterial) and 5-aminosalicyclic acid (anti-inflammatory).
-activated by colonic bacteria
-5-ASA is not very important in terms of antiinflammatory in RA

Use:
-ulcerative colitis, crohn's disease

AE:
-nausea, anorexia, and rash
-hepatitis, leukopenia, and agranulocytosis are rare
-lupus-like syndrome
-hemolysis in G6PD patients
-probably (lol) safe in pregnancy
-reversible oligospermia

Front 48

Gold sodium thiosulfate, Auranofin

Back 48

DMARDs, Gold compounds

MOA:
-gold salts are taken up by macrophages and suppress phagocytosis and lysosomal enzyme activity.
-this stops bone and articular destruction.

PK:
-gold sodium thiosulfate (IM)
-Auranofin (orally)

AE:
-stomatitis, rash, proteinuria
-less commonly, leukopenia and thrombocytopenia
-not recommended during pregnancy

Front 49

Adalimumab, Infliximab, Etanercept

Back 49

DMARD, anti-TNF-alpha drugs

MOA:
-Adalimumab: IgG1 anti-TNF mab. Prevents TNF-alpha interaction with p55 and p75 receptors.
-Infliximab: chimeric mab against TNF-alpha.
-Etanercept: p75 receptor moeities linked to the Fc portion of human IgG1. Also inhibits lymphotoxin-alpha.

Use:
-Infliximab: crohn's disease, RA, ankylosing spondylitis, psoriasis

AE:
-infliximab: b/c it is chimeric, body can produce HACA, so use MTX to prevent this. Sometimes, ANA and anti-dsDNA are seen.
-TB, infections, cytopenias

Front 50

Anakinra

Back 50

DMARD, IL-1 receptor antagonist

MOA:
-non glycosylated version of human IL-1RA (receptor antagonist)

Use:
-anti-inflammatory

Front 51

Glucocorticoids as DMARD

Back 51

MOA:
-inhibit phospholipase A2.
-also selectively inhibit COX-2

Use:
-RA

AE:
-osteoporosis, weight gain, fluid retention, cataracts, poor wound healing, gastric ulcers, GI bleeding, hyperglycemia, hypertension, adrenal suppression

Front 52

Drugs used for acute gout

Back 52

Indomethacin and other NSAIDs, Colchicine, Glucocorticoids

Glucocorticoids - used for acute polyarticular gout. Also can be injected directly into the site of inflammation when NSAIDs and colchicine are ineffective.

Front 53

Drugs used for chronic gout

Back 53

Allopurinol, Probenecid, Sulfinpyrazone, Rasburicase

Front 54

Colchicine

Back 54

Anti-gout, anti-microtubule

MOA:
-binds to tubulin, preventing formation of microtubules.
-also blocks cell division by disrupting mitotic spindle.
-also inhibits release and synthesis of LTs.

Use:
-relieves pain in acute gout

AE:
-nausea, vomiting, abdominal pain, diarrhea
-chronic administration leads to myopathy, neutropenia, aplastic anemia, and alopecia
-contraindicated in pregnancy, hepatic, renal, and cardiovascular disease.

Front 55

Allopurinol

Back 55

Anti-gout, purine analog

MOA:
-inhibits xanthine oxidase (converts hypoxanthine to xanthine and xanthine to uric acid)

Use:
-facilitates dissolution of tophi

AE:
-during first 4-6 months, acute attacks of gouty arthritis may precipitate b/c of mobilization of tissue stores of uric acid. Hence, give colchicine and NSAIDs during first 4-6 months.
-hypersensitivity reactions, rashes, Steven-Johnson syndrome
-raises toxicity of 6-MP and AZT

Front 56

Probenecid

Back 56

Uricosuric agent

MOA:
-increases renal excretion and decreases endogenous formation of uric acid. Thereby, lowering plasma urate, dissolving urate crystals, and reversing the crystal deposition in synovial joints.

AE:
-contraindicated in patients with nephrolithiasis or with overproduction of uric acid.
-ineffective in patients with renal insufficiency
-mild GI irritation

Front 57

Sulfinpyrazone

Back 57

Uricosuric agent

MOA:
-same as probenecid

AE:
-GI irritation is MORE frequent than probenecid
-hypersensitivity reactions like rashes with fever occur LESS frequently than probenecid.
-depression of hematopoiesis
-inhibits warfarin metabolism

Front 58

Rasburicase

Back 58

Anti-gout

MOA:
-recombinant version of uricase, an enzyme that oxidizes uric acid to allantoin, a soluble compound easily excreted.

Use:
-in cancer chemotherapy, to prevent tumor lysis syndrome

Front 59

Morphine

Back 59

Opioid agonist

MOA:
-agonist at mu, weak agonist at delta and kappa

PK:
-conjugated to M3G (has neuroexcitatory effects) and M6G (4-6 times more analgesic potency)

Use:
-standard against which new analgesics are measured

Front 60

Hydromorphone and Oxymorphone

Back 60

Opioid agonists

Use:
-strong agonists in treating severe pain

Front 61

Heroin

Back 61

Opioid agonist

PK:
-metabolized to 6-MAM
-more liposoluble than morphine, so can cross BBB

Front 62

Meperidine

Back 62

Opioid agonist

MOA:
-mu receptor agonist

AE:
-has significant antimuscarinic effects, hence is contraindicated in tachycardia
-large doses produce tremors, muscle twitches, dilated pupils, hyperactive reflexes, convulsions
-dysphoria, myoclonus, and seizures
-serotonin syndrome (delirium, hyperthermia, headache, hypo/hypertension, rigidity, convulsions, coma, and death)

Front 63

Fentanyl (subgroup sufentanil, alfentanil, and remifentanil)

Back 63

Opioid agonist

MOA:
-mu agonist

PK:
-fentanyl is 100x more potent than morphine
-sulfentanil is 1000x times more potent than morphine
-alfentanil is seldom used

Front 64

Methadone

Back 64

Opioid agonist

MOA:
-mu receptor agonist, NMDA receptor antagonist, serotonin and NE reuptake inhibitor

AE:
-withdrawal symptoms are longer, but milder than morphine
-dose-related QT prolongation, torsades de pointes

Front 65

Levorphanol

Back 65

Opioid agonist

-similar to methadone, but longer half-life

Use:
-detoxification

Front 66

Codeine, Oxycodone, Hydrocodone

Back 66

Opioid (mild to moderate agonists)

PK:
-codeine is converted to morphine by cyp2D6

Front 67

Propoxyphene

Back 67

Opioid agonist

MOA:
-binds to mu receptors

AE:
-increased risk of seizures and cardiac conduction abnormalities
-has already been withdrawn from the market

Front 68

Tramadol

Back 68

Opioid (weak agonist)

MOA:
-weak mu agonist, NE and serotonin reuptake inhibitor

Use:
-neuropathic pain

AE:
-increased risk of seizures
-can't be used with other serotonergic drugs, or can result in serotonin syndrome

Front 69

Pentazocine, Butorphanol, Nalbuphine, Buprenorphine

Back 69

Opioid (mixed agonist-antagonist)

MOA:
-Pentazocine: kappa agonist and mu partial agonist/antagonist.
-Butorphanol: kappa agonist and a mu partial agonist/antagonist
-Nalbuphine: kappa agonist and a mu agonist
-Buprenorphine: partial mu agonist and a kappa antagonist

Use:
-mild to moderate pain
-buprenorphine is FDA-approved for management of opioid addiction
-not used in patients with severe pain d/t ceiling effect
-psychotomimetic effects

Front 70

Naloxone and Naltrexone

Back 70

Opioid Antagonists

MOA:
-high affinity for mu receptors, lower affinity for delta and kappa

Use:
-Naloxone: treatment of opioid overdose
-Naltrexone: maintenance drug for addicts. It has also been FDA-approved for chronic alcoholics (decreases alcoholic craving)

Front 71

Dextrometorphan and Codeine

Back 71

Opioids (antitussives)

MOA:
-acts on receptors different from other opioids (nobody knows which ones)

Use:
-suppression of cough

AE:
-dont use with MAOIs
-dextrometorphan has better AE profile than codeine and is equally as effective as an antitussive

Front 72

Opioids for mild-moderate pain

Back 72

Codeine, hydrocodone, oxycodone, meperidine, propoxyphene, tramadol

Front 73

Opioids for moderate-severe pain

Back 73

Morphine, Hydromorphone, Oxymorphone, Levorphanol, Fentanyl, Sufentanil, Methadone

Front 74

Patient-controlled anesthesia (PCA)

Back 74

gold standard for management of acute postoperative pain

Front 75

Amitriptyline and Imipramine

Back 75

TCAs

MOA:
-analgesic effects come from their inhibition of NE and 5-HT reuptake.

Use:
-relive neuropathic pain including diabetic neuropathy, postherpetic neuralgia, polyneuropathy, and nerve injury or infiltration from cancer.
-fibromyalgia pain

Front 76

Venlafaxine and duloxetine

Back 76

TCAs (SNRIs)

MOA:
-inhibit reuptake of 5-HT and NE

Use:
-neuropathic pain

Front 77

Carbamazepine, Gabapentin, Pregabalin, Valproate, topiramate

Back 77

Anticonvulsants

Carbamazepine:
-drug of choice for treatment of pain d/t trigeminal neuralgia

Gabapentin:
-effective in postherpetic neuralgia and diabetic neuropathy

Pregabalin:
-approved for neuropathic pain associated with postherpetic neuralgia, diabetic neuropathy, and fibromyalgia

Valproate and topiramate:
-migraine prophylaxis

Front 78

Corticosteroids, Hydroxyzine, Clonidine, Lidocaine, Capsaicin, Caffeine in pain management

Back 78

Corticosteroids:
-dexamethasone is drug of choice for acute nerve compression, increased ICP, bone pain, visceral pain, anorexia, nausea, and depressed mood.

Hydroxyzine:
-postoperative and cancer pain while reducing incidence of nausea and vomiting.

Clonidine:
-improves pain and hyperalgesia in sympathetically maintained pain.

Lidocaine:
-patch is FDA-approved for postherpetic neuralgia.

Capsaicin:
-cream is used for neuropathic and osteoarthritic pain.

Caffeine:
-may enhance the analgesic effect of acetaminophen and NSAIDs.

Front 79

treatment of opioid-induced urticaria and pruritus

Back 79

hydroxyzine, diphenhydramine

Front 80

treatment of opioid-induced constipation

Back 80

magnesium hydroxide or lactulose

Front 81

treatment of opioid-induced nausea/vomiting

Back 81

hydroxizine, metoclopramide, or prochlorperazine

Front 82

treatment of opioid-induced sedation

Back 82

amphetamines, methylphenidate, or modafinil

Front 83

treatment of opioid-induced respiratory depression

Back 83

naloxone

Front 84

treatment of breakthrough pain

Back 84

-use an immediate-release preparation. (oral immediate acting fentanyl, morphine, hydromorphone)
-do not use extended-release for rescue dosing.

Front 85

mild pain (1-3/10)

Back 85

-nonopioid analgesic.
-drugs for initial therapy: acetaminophen, ibuprofen

Front 86

moderate pain (4-6/10)

Back 86

-add opioid for moderate pain
-drugs for initial therapy: acetaminophen+codeine, acetaminophen+oxycodone, tramodol

Front 87

severe pain (7-10/10)

Back 87

-high potency opioid
-drugs for initial therapy: morphine, hydromorphone

Front 88

functional pain

Back 88

-pain sensitivity d/t an abnormal processing or function of the CNS or PNS.
-examples include fibromyalgia and IBS

Front 89

neuropathic pain

Back 89

-d/t damage or dysfunction of the PNS or CNS, rather than stimulation of pain receptors.
-burning, tingling, numbness, stabbing, shooting, electric-like feelings

Front 90

inflammatory pain

Back 90

-d/t inflammation which is overriding the pain defense system unlike in nociceptive pain.
-inflammation occurs to stop movement or contact of the affected part until healing is complete, thus reducing further damage.

Front 91

nociceptive pain

Back 91

-in response to noxious stimuli at nociceptors
-somatic (arising from skin, joints, bone, muscle, or connective tissue)
-visceral (from internal organs)

Front 92

Penicillin

Back 92

cell wall synthesis inhibitor

MOA:
-bind penicillin-binding proteins
-block transpeptidase cross-linking of peptidoglycan.
-activate autolytic enzymes.

Use:
-Penicllin G (IV): drug of choice for syphilis, in strep infections (especially to prevent rheumatic fever) and for susceptible pneumococci.
-Penicillin V (oral): mild-moderate orpharyngeal infections and similar spectrum to Penicillin G.
-in general, used for gram-positive cocci (except beta-lactamase-producing staph, penicillin-resistant pneumococci, enterococci, and MRSA); gram-positive rods (Listeria); gram-negative cocci (Neisseria); most anaerobes (except bacteroides)

Toxicity:
-hypersensitivity reactions, hemolytic anemia

Front 93

methicillin, nafcillin, oxacillin

Back 93

Antistaphylococcal penicillins

MOA:
-same as penicillin (inhibit cell wall synthesis)
-penicillin-resistant because of bulkier R group

Use:
-S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).

PK:
-oral absorption of nafcillin

Toxicity:
-Hypersensitivity reactions
-methicillin: interstitial nephritis
-nafcillin: neutropenia
-oxacillin: hepatitis

Front 94

amoxicillin, ampicillin

Back 94

Aminopenicillins/Extended-spectrum penicillins

MOA:
-same as penicillin. Wider spectrum; penicillinase sensitive.
-combine with clavulanic acid to protect against beta-lactamase.

PK:
-amoxicillin has greater oral at bioavailability than ampicillin.

Use:
-HELPSS (H. influenzae, E. coli, Listeria, Proteus mirabilis, Salmonella, Shigella, enterococci)
-UTIs, acute otitis media, pharyngitis, pneumonia, skin infections, URIs.

Toxicity:
-maculopapular rash, pseudomembranous colitis, diarrhea, hypersensitivity reactions

Front 95

ticarcillin, carbenicillin, piperacillin

Back 95

Antispeudomonal Penicillins

MOA:
-same as penicillin. Extended spectrum.

Use:
-Pseudomonas, proteus, and enterobacter species.
-Piperacillin has superior activity against P. aeruginosa.
-Carbenicillin is better for UTIs.

Toxicity:
-Hypersensitivity reactions
-ticarcillin: bleeding diathesis

Front 96

Penicillin G procaine, Penicillin G benzathine

Back 96

Repository Penicillins

MOA:
-prolong the duration of penicillin G by slow release.
-Penicillin G benzathine produces the longest duration of all the repository penicillins.

Use:
-syphilis and rheumatic fever prophylaxis.

Front 97

clavulanic acid, sulbactam, tazobactam

Back 97

beta-lactamase inhibitors

Use:
-added to penicillin antibiotics to protect antibiotic from destruction by beta-lactamase (penicillinase).

Front 98

recommended treatment for infective endocarditis

Back 98

Penicillin in combination with an aminoglycoside (most commonly gentamicin)

Front 99

cefazolin, cephalexin

Back 99

1st generation Cephalosporins

Use:
-Gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae (PEcK).
-cefazolin: surgical prophylaxis

PK:
-cefazolin (parenteral)
-cephalexin (oral)

Front 100

cefaclor, cefoxitin, cefotetan, cefamandole, cefuroxime

Back 100

2nd generation Cephalosporins

Use:
-gram-positive cocci, H. influenza, Enterobacter aerogenes, Neisseria, Proteus mirabilis, E. coli, Klebsiella, Serrata marcescens (HEN PEcKs)
-cefamandole, cefaclor: sinus, ear, respiratory infections caused by H. influenzae or M. catarrhalis
-cefoteta, cefoxitin: Bacteroides fragilis, prophylaxis and therapy of infections in the abdominal and pelvic cavities.

Front 101

cefoperazone, cefotaxime, ceftazidime, ceftriaxone, cefixime

Back 101

3rd generation cephalosporins

MOA:
-cefotetan, cefoperazone, and cefomandole (2nd gen) contain NMTT (inhibits Vit. K and causes a disulfiram-like reaction)
Use:
-ceftriaxone: gonorrhea (pencillin-resistant) and meningitis (ampicillin-resistant H. influenzae in children), Lyme disease, prophylaxis of meningitis
-cefoperazone and ceftazidime: P. aeruginosa

Front 102

cefepime

Back 102

4th generation cephalosporin

Use:
-gram-positive activity of first-generation agents with the wider spectrum of Gram-negative spectrum of third-generation.
-increased activity against Pseudomonas

Front 103

imipenem, meropenem

Back 103

Carbapenems

MOA:
-synthetic beta-lactam antiobiotics.

Use:
-gram-positive cocci, gram-negative rods, and anaerobes.
-drugs of choice for enterobacter and extended spectrum beta-lactamase producing gram-negatives.

PK:
--imipenem is given with cilastatin (inhibitor of renal hydropeptidase I)
-meropenem has a reduced risk of seizures and is stable to renal dihydropeptidase I.

Toxicity:
-GI distress, skin rash, and seizures at high plasma levels.

Front 104

aztreonam

Back 104

Monobactam

MOA:
-contain a monocyclic beta-lactam ring-->resistant to beta-lactamases.
-inhibits cell wall synthesis (binds to PBP3).
-no cross-allergencity with penicillins.

Use:
-gram-negative rods only
-for penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.

Toxicity:
-skin rashes, elevation of serum aminotransferases.
-thrombophlebitis and pain at the injection site.

Front 105

vancomycin

Back 105

Antibiotic

MOA:
-inhibits cell wall formation by binding to D-ala D-ala portion of cell wall precursors.

Use:
-gram-positive only (MRSA, enterococci, and PRSP)
-first-line for enterococcal endocarditis.
-orally for pseudomembranous colitis

AE:
-Nephrotoxicity, Ototoxicity, Thrombophlebitis
-red man syndrome (d/t degranulation of mast cells-->flushing)

Front 106

daptomycin

Back 106

Antibiotic

MOA:
-cell-wall synthesis inhibitor
-binds to the cell membrane via calcium-dependent insertion of its lipid tail-->depolarization with K+ efflux-->rapid cell death

Use:
-vancyomycin-resistant strains of enterococci and S. aureus
-inactive against gram-negative
-contraindication: pneumonia (surfactant antagonizes daptomycin)
-complicated skin infections caused by aerobic gram-positive, S. aureus, and right-sided endocarditis.

AE:
-constipation, nausea, headache, and insomnia.
-myopathy (monitor CK levels)

Front 107

bacitracin

Back 107

Antibiotic

MOA;
-inhibits cell wall formation by interfering with dephosphorylation.

Use:
-gram-positive organisms
-used only topically for the treatment of mixed bacterial infections of the skin, wounds, or on mucus membranes.
-S. pyogenes is sensitive
-S. agalactiae is resistant

AE:
-nephrotoxic

Front 108

fosfomycin

Back 108

Antibiotic

MOA:
-inhibits enolpyruvate transferase-->inhibits cell wall synthesis

Use:
-orally for uncomplicated lower UTIs

Front 109

tetracycline, doxycycline, demelocycline, minocycline

Back 109

Tetracyclines

MOA:
-bacteriostatic, bind to the 30S subunit and prevent attachment of aminoacyl-tRNA.

PK:
-doxycycline is fecally eliminated and can be used in patients with renal failure.
-must NOT take with milk, antacids, or iron-containing preparations b/c divalent cations inhibits absorption.

Use:
-most common current use is for severe acne and rosacea.
-drugs of choice for Mycoplasma, Lyme disease, Cholera, anthrax (prophylaxis).
-drugs ability to accumulate intracellularly --> Chlamydia and Rickettsia
-Demelocycline (ADH antagonist): SIADH
-syphilis
-combination regiments for duodenal ulcer by H. pylori, plague, tularemia, and brucellosis.
-doxycycline: against erythrocytic schzionts of all human malaria parasites.

AE:
-GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
-contraindicated in pregnancy (category D) and avoided in children <8 years
-dizziness and vertigo (drugs concentrate in endolymph)

Front 110

tigecycline

Back 110

Glycylcyclines

MOA:
-bind to 30S subunit more tightly than tetracyclines (overcomes resistance of efflux pump and ribosomal protection)
-only Proteus and P. aeruginosa have been reported to have resistance.

Use:
-complicated skin, soft tissue, and intra-abdominal infections.
-MRSA, VISA, and VRE.

PK:
-given IV, eliminated via biliary

AE:
-contraindicated in pregnancy and young children
-same AEs as tetracyclines.
-most commonly nausea and vomiting

Front 111

GNNATS (Gentamycin, Neomycin, Netilmycin, Amikacin, Tobramycin, Streptomycin)

Back 111

Aminoglycosides

MOA:
-bactericidal, inhibit formation of initiation complex and cause misreading of mRNA.
-require O2 for uptake; therefore infeffective against anaerobes.
-binds to 30S subunit, inhibiting translocation and elongation.

Use:
-gram-negative rod infections.
-neomycin: bowel surgery
-gentamicin+penicillin/vancomycin is rug of choice for infective endocaridits
-septicimeia, nosocomial RTIs, complicated UTIs, complicated intraabdominal infections, endocarditis, and osteomyelitis.

PK:
-postantibiotic effect (PAE): even after the antibiotic drug is removed, there is continued suppression d/t irreversible binding of the 30S subunit.
-concentration-dependent killing: higher concentrations cause more killing

AE:
-nephrotoxicity, ototoxicity, NM blockade (myasthenia gravis is an absolute contraindication)
-contraindicated in pregnancy

Front 112

erythromycin, azithromycin, clarithromycin, telithromycin

Back 112

Macrolides

MOA:
-inhibit protein synthesis by blocking translocation
-bind to the 23S rRNA of the 50S ribosomal unit.
-bacteriostatic

Use:
-Atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
-URIs, STDs, gram-positive cocci (streptococcal infections in patients allergic to penicillin), and Neisseria
-soft-tissue infections (H. influenzae, S. pneumoniae, Staphylococci, enterococci)

PK:
-telithromycin is the most highly concentrated in tissue.
-erythromycin should be considered the safest in pregnancy
-azithromycin, clairthromycin, and telithromycin are stable in gastric pH
-inhibitors of cyp 3A4 (except azithromycin)

AE:
-myopathy if macrolides and statins are combined
-prolonged QT interval (clarithromycin, telithromycin, especially erythromycin)
-telithromycin: fatal hepatotoxicity, exacerbations of myasthenia gravis (contraindicated), visual disturbances. Should NOT be used to treat sinusitis or bronchitis.
-GI irritation
-hepatic abnormalities (azithromycin and erythromycin)
-pseudomembranous colitis
-anaphylaxis
-Stevens-Johnson syndrome (hypersensitivity that causes the epidermis to separate from the dermis)
-increases serum concentration of theophyllines, oral anticoagulants

Front 113

chloramphenicol

Back 113

Antibiotic

MOA:
-blocks peptide formation at 50S ribosomal unit (inhibiting the peptidyl transferase step), bacteriostatic

Use:
-Meningitis (SHiN), Bacteroides, Salmonella, and Rickettsia.
-vancomycin-resistant enterococci
-topical treatment of ear and eye infections

AE:
-inhibits cyp p450s
-gray baby syndrome (cyanosis): premature infants lack liver UDP-glucoronyl transferase
-bone marrow depression: dose-related suppression of RBC production-->anemia-->aplastic anemia.

Front 114

clindamycin

Back 114

Antibiotic

MOA:
-blocks peptide formation at 50S subunit, bacteriostatic

Use:
-Anaerobic infections (Can't Breathe Air) in aspiration pneumonia or lung abscesses
-skin and soft tissue infections caused by streptococci and staphylococci, some MRSA.
-used with aminoglycoside or cephalosporin for penetrating wounds of the gut or abdomen
-effective alternative to cotrimoxazole (TMP/SMX) for P. jiroveci in AIDS patients.
-combined with pyrimethamine for AIDS-related toxoplasmosis
-prophylaxis of endocarditis
-treats anaerobes ABOVE diaphragm vs metrodinazole treats it BELOW.

AE:
-diarrhea, nausea, and skin rashes
-pseudomembranous colitis
-hepatotoxicity and neutropenia

Front 115

Quinupristin-dalfopristin

Back 115

Streptogramins

MOA:
-inhibit protein synthesis by binding to the 50S ribsosome.

Use:
-bactericidal for most organisms except Enterococcus faecium, which is killed slowly.
-staphylococci or by vancomycin-resistant strains of E. faecium, but not E. faecalis.

PK:
-given IV and inhibits cyp3A4

AE:
-arthralgia-myalgia syndrome
-GI effects and CNS effects

Front 116

Linezolid

Back 116

Antibiotic

MOA:
-inhibits protein synthesis by binding to the 23S rRNA of the 50S subunit.

Use:
-bacteriostatic
-gram-positive (staphylococci, streptococci, enterococci)
-gram-positive rods (Listeria and M. tuberculosis)
-VRE (vancomycin-resistant enterococcus faecium)
-nosocomial pneumonia by staphylococci or S. pneumoniae
-uncomplicated skin and skin structure infections.
-multi-resistant infections

PK:
-weak reversible inhibitor of monoamine oxidase-->increase toxicity of adrenergic and serotonergic drugs.

AE:
-dont combine with psychiatric medications bc of the MAO inhibition
-long-term administration can cause reversible myelosuppression, optic and peripheral neuropathy, and lactic acidosis.

Front 117

Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, enoxacin (fluoroquinolones), nalixidic acid (quinolone)

Back 117

Fluroquinolones

MOA:
-inhibits DNA gyrase (topoisomerase II) and topoisomerase IV

PK:
-must not be taken with antacids

Use:
-Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram-positive organisms.
-nalidixic acid: 1st generation, gram-negative organisms and uncomplicated UTIs
-ciprofloxacin: 2nd generation, travelers diarrhea, P. aeruginosa (cystic fibrosis), alterative to ceftriaxone and rifampin for prophylaxis against meningococci.
-levofloxacin: 3rd generation, prostatitis by E. coli, STDs (not syphilis), skin infections, acute sinusitis and chronic bronchitis, TB, community-acquired pneumoniae (S. pneumoniae, chlamydiae, mycoplasma, and legionella).
-moxifloxacin, gemifloxacin: 4th generation, atypical pneumonia, along with levofloxacin are called respiratory fluoroquinolones and are used after first-line agents have failed.

PK:
-moxifloxacin can be given to renal failure patients since it is eliminated via biliary excretion.

AE:
-GI distress
-tendinitis and tendon rupture in adults
-QT prolongation (moxifloxacin, gemifloxacin, and levofloxacin)
-CNS effects (headache, dizziness, insomnia)
-leg cramps and myalgia in kids
-superinfections, skin rashes
-abnormal liver function
-contraindicated in pregnancy and children <18y (develop arthropathy)

Front 118

Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine, sulfacetamide, sulfadoxine, sulfasalazine

Back 118

Sulfonamides

MOA:
-PABA metabolites inhibit dihydropteroate synthase, bacteriostatic

Use:
-gram-positive, gram-negative, Nocardia, Chlamydia.
-Triple sulfas or SMX for simple UTI.
-topical agents for ocular or burn infections and oral agents for simple UTIs
-Sulfasalazine for ulcerative colitis, enteritis, and other IBD.

AE:
-hypersensitivity reactions
-hemolysis if G6PD deficient
-nephrotoxicity/crystalluria(tubulointerstitial nephritis)
-photosensitivity, urticaria, fever, skin rashes
-kernicterus in infants
-displace drugs from albumin
-contraindicated in newborns and infants <2 mo

Front 119

Trimethoprim

Back 119

Antibiotic

MOA:
-inhibits bacterial dihydrofolate reductase, bacteriostatic

Use:
-UTIs, bacterial prostatitis, and vaginitis.
-used in combination with sulfonamides.
-Shigella, Salmonella, P. jiroveci pneumonia

AE:
-megaloblastic anemia, leukopenia, granulocytopenia
-contraindicated in pregnancy (d/t antifolate)

Antidote:
-folinic acid aka leucovorin (alleviates symptoms)

Front 120

Cotrimoxazole

Back 120

Antibiotic (SMX-TMP)

MOA:
-blocks folate synthesis, bactericidal

Use:
-drug of choice for uncomplicated UTIs
-drug of choice for PCP (P. jiroveci)
-drug of choice for nocardiosis and toxoplasmosis

PK:
-distributed well including CSF

AE:
-same as TMP-SMX

Front 121

Metronidazole

Back 121

Antiparasitic (Urinary Antiseptics, Antiamebic)

MOA:
-nitro group gets reduced by ferredoxin (found in anaerobic parasites)-->ROIs-->interfere with nucleic acid synthesis.
-bactericidal, antiprotozoal

Use:
-GET GAP (Giardia, Entamoeba, Trichomonas, Gardnerella vaginallis, Anaerobes, H. pylori)
-drug of choice for C. difficile

PK:
-widely distributed including CSF

AE:
-disulfiram-like reaction
-headache, metallic taste
-prolonged use: nausea, diarrhea, stomatitis, and peripheral neuropathy
-leucopenia, dizziness, and ataxia
-contraindicated in pregnancy

Front 122

Nitrofurantoin

Back 122

Urinary antiseptic

MOA:
-reduced by bacteria in the urine-->ROIs-->damage bacterial DNA

Use:
-alternative oral agent for uncomplicated UTIs

PK:
-metabolized and excreted so fast that no systemic antibacterial action is achieved.

AE:
-anorexia, nausea and vomiting
-neuropathies and hemolytic anemia
-contraindicated in pregnancy (38-42 wks) and infants <1 mo

Front 123

Isoniazid (INH)

Back 123

Antimycobacterial

MOA:
-structural analog of pyridoxine (Vit B6). Metabolized by mycobacterial catalase-peroxidase (KatG) to an active metabolite.
-metabolites target enzymes involved in mycolic acid-->inhibiting cell wall synthesis

Use:
-M. tuberculosis. Only agent used for prophylaxis against this.

PK:
-half-life in "fast-acetylators" is 60-90 min, "slow acetylators" is 3-4 hours.
-hence "fast-acetylators" require a higher dosage.

AE:
-Neurotoxicity (peripheral neuritis, restlessness): prevented by pyridoxine supplementation.
-hepatotoxicity
-cyp p450 inhibitor
-lupus-like syndrome
-SAFE in pregnancy

Front 124

rifampin, rifabutin, and rifapentine

Back 124

Antimycobacterial

MOA:
-block transcription by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase.

Use:
-M. tuberculosis
-delays resistance to dapsone when used for leprosy.
-prophylaxis of meningitis.
-in combination with vancomycin for MRSA or PRSP.
-chemoprophylaxis in contacts with children with H. influenza type B
-Rifabutin is less likely to cause drug interactions and thus is the prferred drug for TB in HIV patients.

PK:
-rifampin is an inducer of cyp p450, while rifabutin and rifapentine are less effective inducers and thus are less likely to cause drug interactions.

AE:
-light chain proteinuria
-GI distress
-thrombocytopenia, rashes, enphritis, liver dysfunction
-orange-colored secretions (harmless)
-SAFE in pregnancy

Front 125

ethambutol

Back 125

Antimycobacterial

MOA:
-decreases carbohydrate polymerization of mycobacterial cell wall by inhibiting arabinosyl transferases.

Use:
-M. tuberculosis and M. kansaii

PK:
-dose adjustment required in patients with renal dysfunction.

AE:
-dose-dependent visual disturbances (red-green color blindness, optic neuritis, retinal damage)
-headache, confusion, hyperuricemia
-SAFE in pregnancy

Front 126

pyrazinamide

Back 126

Antimycobacterial

MOA:
-converted to pyrazinoic acid by pyrazinamidase, which lowers the pH of the environment. This helps macrophages more effectively kill TB.
-also blocks mycobacterial fatty acid synthase I, inhibiting mycolic acid production.

Use:
-M. tuberculosis.

PK:
-dose adjustments for hepatic and renal insufficiency

AE:
-hyperuricemia, hepatotoxicity
-non-gouty polyarthralgia
-acute gouty arthritis
-porphyria, rash, photosensitivity, myalgia
-category C in pregnancy.

Front 127

Streptomycin, Amikacin, Levofloxacin, Ethionamide

Back 127

2nd line drugs for TB

-Streptomycin: life-threatening TB, meningitis, miliary dissemination.
-Amikacin: multi-drug resistant strains of TB.
-Levofloxacin: for first-line resistant strains.
-Ethionamide: drug-resistant strains of TB, major side effect is GI irritation and neurologic effects.

Front 128

Dapsone

Back 128

Antimycobacterial

MOA:
-inhibits dihydropteroate synthase, inhibiting folate synthesis.

Use:
-used with rifampin and clofazimine for leprosy.
-alternative in the treatment of AIDS-related PCP.

PK:
-Acedapsone is a repository form of dapsone that provides inhibitory plasma concentrations for several months.

AE:
-hemolysis in G6PD patients
-erythema nodosum leprosum (painful skin lesions on the arms, legs, and face). It can be prevented by corticosteroids or thalidomide.
-fever, methemoglobinemia, hepatitis.
-inhibitor of cyp p450

Front 129

clofazimine

Back 129

Antimycobacterial

MOA:
-phenazine dye that binds to DNA to inhibit replications.

Use:
-bactericidal to M. leprae and some activity against M. avium-intracellulare

AE:
-red-brown discoloration of the skin (harmless)
-GI irritation
-eosinophilic enteritis

Front 130

Cycloserine

Back 130

Antimycobacterial

MOA:
-inhibits mycolic acid synthesis, inhibiting mycobacterial cell wall formation.

Use:
-M. tuberculosis

Front 131

Oseltamavir, Zanamivir

Back 131

Respiratory Antivirals (Neuraminidase inhibitors)

MOA:
-inhibit viral neuraminidase-->prevent viral release.

Use:
-influenza A and B

AE:
-GI disturbances (oseltamavir)
-Airway irritation (Zanamivir)

Front 132

Amantadine, Rimantadine

Back 132

Respiratory Antivirals (Ion Channel blockers)

MOA:
-inhibit viral penetration/uncoating by blocking M2 protein channel.
-also causes the release of dopamine from nerve terminals.

Use:
-Influenza A prophylaxis and treatment.
-Parkinsons (amantadine)

AE:
-Rimantidine does not cross BBB hence has fewer CNS side effects.
-GI disturbances (both)
-CNS effects (amantadine): affects cerebellum - ataxia, dizziness, slurred speech.

Front 133

Ribvarin

Back 133

Respiratory Antiviral (Guanosine Analog)

MOA:
-prevents viral mRNA capping -->inhibition of RNA polymerase.
-inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase.

Use:
-RSV, chronic hepatitis C

AE:
-hemolytic anemia, teratogenic (Cat X), elevated bilirubin

Front 134

Interferons alpha, beta, gamma

Back 134

Hepatic Antivirals (Interferons)

MOA:
-use innate immune response-->inhibit DNA and RNA synthesis.
-glycoproteins synthesized by viral-infected cells blocks replication of DNA and RNA viruses.

Use:
-alpha (2a): HCV, HBV, Kaposi's sarcoma, Hairy cell leukemia, condyloma accuminata.
-beta (1b): multiple sclerosis
-gamma: (1b) Chronic granulomatous disease.

AE:
-flu-like, fatigue, mental depression, neutropenia

Front 135

Lamivudine, Telbivudine, Adefovir, Enecavir

Back 135

Hepatic Antivirals(Nucleotide/Nucleoside analogs)

MOA:
-phosphorylated by cellular kinases-->inhibit HBV DNA polymerase.

Use:
-HBV, HIV (not Telbivudine)

AE:
-well tolerated (headache, dizziness)
-severe hepatitis after discontinuation.

Front 136

Acyclovir, Valacyclovir

Back 136

Herpes Antivirals (Guanosine analogs)

MOA:
-monophosphorylated by HSV/VZV thymidine kinase.
-the triphosphate formed, inhibits viral DNA polymerase by chain termination.

Use:
-HSV, VZV, EBV.
-no effect on latent forms of HSV and VZV.
-Valacyclovir: prodrug of acyclovir, better oral bioavailability.

AE:
-renal dysfunction, GI disturbance

Front 137

Cidofovir

Back 137

Herpes Antiviral (purine/pyridimine analog)

MOA:
-phosphorylated by cellular kinases NOT viral kinases.
-triphosphate formed, inhibits viral DNA polymerase.

Use:
-CMV retinitis
-acyclovir-resistant HSV.

AE:
-nephrotoxicity (coadminister with probenecid)

Front 138

Ganciclovir, Valganciclovir

Back 138

Herpes Antivirals (Guanosine analogs)

MOA:
-5' monophosphate formed by CMV viral kinase.
-can be phosphorylated by cellular kinase too.
-triphosphate inhibits viral DNA polymerase.

Use:
-DOC for CMV retiitis.
-Valganciclovir (prodrug with better oral bioavailability): CMV prophylaxis.

AE:
-myelosuppression (leukopenia, neutropenia, thrombocytopenia).
-nephrotoxicity.
-more toxic to host enzymes than acyclovir

Front 139

Penciclovir, Famciclovir

Back 139

Herpes Antivirals (pyrimidine/purine analogs)

MOA:
-phosphorylated by viral kinases, triphosphate inhibits DNA polymerase.

Use:
-Penciclovir: HSV-1 (labialis)
-Famciclovir: Acute VZV and recurrent HSV-2 (genital) in immunocompromised.

AE:
-headache, nausea, diarrhea

Front 140

Vidarabine, Trifluridine

Back 140

Herpes Antivirals (purine/pyridimine analogs)

MOA:
-phosphorylated by viral kinases, triphosphate inhibits DNA polymerase.

Use:
-Vidrabine (adenine analog): herpetic and vaccinal keratitis, HSV keratoconjunctivitis.
-Trifluridine (thymidine analog): DOC for HSV keratoconjunctivitis and recurrent epithelial keratitis.

AE:
-eye irritation, photophobia, palebral edema

Front 141

Fomivirsin

Back 141

Herpes Antiviral (Antisense oligonucleotide)

MOA:
-binds to CMV mRNA blocking viral mRNA translation, hence protein synthesis.

Use:
-CMV retinitis (2nd line)

AE:
-iritis, vitritis, vision changes, increases in IOP

Front 142

Foscarnet

Back 142

Herpes Antiviral (Phsophonoformate)

MOA:
-viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme.
-does not require activation by viral kinase.

Use:
-CMV retinitis when ganciclovir fails, acyclovir-resistant HSV, CMV

AE:
-nephrotoxicity, hypocalcemia, anemia, nausea, fever, CNS effects

Front 143

Ritonavir (RTV)

Back 143

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-PK enhancer/booster of other PI's.

PK:
-inhibitor of cyp 3A4

AE:
-Gi, headache and cirumoral parethesias.

Front 144

Saquinavir (SQV)

Back 144

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-given with low dose of RTV.

PK:
-high-fat meals enhance absorption.
-dont give it with rifampin (cyp 3A4 inducer)

AE:
-headache, fatigue, GI

Front 145

Indinavir (IDV)

Back 145

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-given with RTV

PK:
-least protein bound.
-absorption decreased when taken with meals.
-contraindicated in hepatic insufficiency.

AE:
-well-tolerated (GI, headache)
-nephrolithiasis, hyperbilirubinemia (adequate hydration important)

Front 146

Nelfinavir (NFV)

Back 146

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-cannot be boosted by RTV.

PK:
-metabolized by several CYPs.

AE:
-diarrhea (controlled by Ioperamide), nausea, flatulence.

Front 147

Fosamprenavir (fAPV)

Back 147

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-given with RTV

PK:
-prodrug-->amprenavir
-inhibits CYP

AE:
-headache, fatigue, nausea, vomiting, paresthesias.

Front 148

Lopinavir (LPVr)

Back 148

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-one of preferred PIs, given with RTV.

PK:
-poor bioavailability.
-avoid CYP inducers (St. Johns wort)
-avoid disulfiram or metronidazole (bc oral solution contains EtOH)

AE:
-GI, hyperlipidemia, insulin resistance

Front 149

Atazanavir (ATV)

Back 149

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-inhibits HIV protease resistant to other PIs.

PK:
-well absorbed with food.
-metabolized and inhibits CYP3A4.

AE:
-same with other PIs and rash

Front 150

Tipranavir (TPV)

Back 150

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-inhibits HIV protease resistant to other PIs.
-twice daily with RTV.

PK:
-well absorbed with food.
-inducer of CYP P450

AE:
-same with other PIs and:
-severe and fatal hepatitis
-fatal and nonfatal ntracranial hemorrhages.

Front 151

Darunavir (DRV)

Back 151

Protease inhibitor

MOA:
-inhibit HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into functional parts.
-hence, it prevents maturation of new viruses.

Use:
-ATV+RTV are only once-daily preferred PIs.

PK:
-well absorbed with food
-inhibits cyp3A4

AE:
-same with other PIs and rash

Front 152

Zidovudine (ZDV, formerly AZT)

Back 152

NRTI (nucleoside reverse transcriptase inhibitor)

MOA:
-competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'-OH group).
-must be phosphorylated by thymidine kinase to be active.
-thymidine analog

Use:
-HIV
-general prophylaxis and durign pregnancy to reduce risk of fetal transmission.

AE:
-myelosuppression (can be reversed with G-CSF and EPO)
-insomnia, headaches, GI intolerance
-megaloblastic anemia
-crosses BBB, so some CNS effects

PK:
-cimetidine, indomethacin, lorazepam, acetaminophen, probenecid INCREASE toxicity.
-stavudine and ribvarin DECREASE toxicity.

Front 153

Stavudine (d4T)

Back 153

NRTI (nucleoside reverse transcriptase inhibitor)

MOA:
-competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'-OH group).
-must be phosphorylated by thymidine kinase to be active.
-strong inhibitor of beta and gamma DNA polymerases (decreases mitochondrial DNA synthesis, which can lead to toxicity)
-thymidine analog

Use:
-HIV

AE:
-peropheral neuropathy, lactic acidosis.
-hyperlipidemia, neuromuscular weakness.

Use:
-

Front 154

Didanosine (ddI)

Back 154

NRTI (nucleoside reverse transcriptase inhibitor)

MOA:
-competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'-OH group).
-must be phosphorylated by thymidine kinase to be active.
-adenosine analog

Use:
-HIV

PK:
-absorption best in fasting state (acid labile) or combined with antacid.

AE:
-pancreatitis (esp. alcoholics and patients with hypertriglyceridemia)
-peripheral neuropathy, diarrhea, hepatic dysfunction
-CNS effects
-contraindicated with Stavudine

Front 155

Tenofovir (TDF)

Back 155

NRTI (nucleoside reverse transcriptase inhibitor)

MOA:
-competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'-OH group).
-must be phosphorylated by thymidine kinase to be active.
-guanosine analog

Use:
-HIV

AE:
-GI (nausea, diarrhea, vomiting, flatulence)
-creatine is monitored with renal insufficency
-only NRTI with sig. durg interactions (increases didanosine concentrations, decreases atazanavir concentrations). Give RTV to boost atazanavir.

Front 156

Lamivudine (3TC)

Back 156

NRTI (nucleoside reverse transcriptase inhibitor)

MOA:
-competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'-OH group).
-must be phosphorylated by thymidine kinase to be active.
-DOES NOT affect mitochondrial DNA synthesis or bone marrow precursor cells.
-Cytidine analog

Use:
-HIV

AE:
-headache, dry mouth

Front 157

Emtricitabine (FTC)

Back 157

NRTI (nucleoside reverse transcriptase inhibitor)

MOA:
-competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'-OH group).
-must be phosphorylated by thymidine kinase to be active.
-cytidine analog

Use:
-HIV

AE:
-hyperpigmentation of palms and soles (most frequently in dark-skinned people)

Front 158

Abacavir (ABC)

Back 158

NRTI (nucleoside reverse transcriptase inhibitor)

MOA:
-competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'-OH group).
-must be phosphorylated by thymidine kinase to be active.
-guanosine analog

Use:
-HIV

AE:
-GI, headache, dizziness
-5%: hypersensitivity reaction (rash, malaise, respiratory distress)
-sensitized individuals should NEVER be rechallenged.

Front 159

Nevirapine (NVP)

Back 159

NNRTI (non-nucleoside reverse transcriptase inhibitor)

MOA:
-bind to RT at site different from NRTIs (noncompetive inhibition). Do not require phosphorylation to be active or compete with nucleotides.

Use:
-HIV

AE:
-potential severe toxicity (dont use in women with CD4+ counts >250 or men >400)
-rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.
-14 day titriation at 1/2 dose is mandatory (was bold in notes)

PK:
-inducer of CYP3A4

Front 160

Delavirdine (DLV)

Back 160

NNRTI (non-nucleoside reverse transcriptase inhibitor)

MOA:
-bind to RT at site different from NRTIs (noncompetive inhibition). Do not require phosphorylation to be active or compete with nucleotides.

Use:
-HIV

PK:
-not as widely used as other NNRTIs b/c of shorter half-life
-inhibitor of cyp 3A4

AE:
-rash, Stevens-Johnson syndrome, toxic epidermal necrolysis
-fever, headache, depression
-teratogenic

Front 161

Etravirine (ETV)

Back 161

NNRTI (non-nucleoside reverse transcriptase inhibitor)

MOA:
-bind to RT at site different from NRTIs (noncompetive inhibition). Do not require phosphorylation to be active or compete with nucleotides.

Use:
-for treatment-experienced patients with HIV

PK:
-cyp 3A4 inducer
-cyp 2c9 and 2c19 inhibitor
-means interactions are unpredictable...

AE:
-rash, nausea, diarrhea
-transanimase elevations

Front 162

Efavirenz (EFV)

Back 162

NNRTI (non-nucleoside reverse transcriptase inhibitor)

MOA:
-bind to RT at site different from NRTIs (noncompetive inhibition). Do not require phosphorylation to be active or compete with nucleotides.

Use:
-preferred NNRTI on DHHS guidelines for HIV

PK:
-once-aday dosing (was bold in notes)

PK:
-inducer of cyp p450 enzymes

AE:
-mostly CNS (dizziness, headache, vivid dreams, loss of concentration)
-pregnancy (cat D)

Front 163

Enfurvitide (T-20)

Back 163

Entry/fusion inhibitor

MOA:
-binds to gp41 subunit of the viral envelope, preventing ability of virion to fuse cell membrane.

AE:
-injection related hypersensitivity
-no drug interactions with other antiretrovirals ahs been noted.

Front 164

Maraviroc

Back 164

Entry/fusion inhibitor

MOA:
-binds specifically and selectively to CCR5, blocking HIV entry

Use:
-only CCR5-tropic HIV strain

PK:
-metabolized by cyp 3A4, reduce dose when given with protease inhibitors.

AE:
-well tolerated, risk of hepatotoxicity.

Front 165

Raltegravir (RAL)

Back 165

INSTI (Integrase Strand Transfer inhibitor)

MOA:
-binds integrase, inhibiting final step in integration of viral DNA into host cell DNA.

Use:
-approved for treatment-experienced and treatment-naive patients with HIV

PK:
-metabolized by UGT1A1-mediated glucorinidation (bold in notes)

AE:
-well tolerated (nausea, headache, diarrhea)
-can increase CK

PK:
-rifampin, tipranavir, efavirenz DECREASE it.
-PPI's INCREASE it.

Front 166

treatment-naive patients with HIV

Back 166

2 NRTIs + (1 NNRTI or PI or INSTI)

-NNRTI-based regimen: Tenofovir+Emtricitabine+Efavirenz

-PI-based regimen: Tenofovir+Emitricitabine+RTV-boosted atazanavir or darunavir

-INSTI-based regimen: Tenofovir+Emitricitabine+Raltegravir

Front 167

Antiretroviral drugs in pregnancy

Back 167

Ritonavir-boosted lopinavir (twice daily) + zidovudine/lamivudine.

Front 168

Antiretroviral drugs in infant born to HIV-infected mother

Back 168

Zidovudine (start immediately after birth and administer for 6 wks)

Front 169

HIV prophylaxis following a needle stick

Back 169

-for less severe (solid and superficial injury): 2 NRTIs

-for more severe (large-bore hollow needle, deep puncture): 3 drugs (2 NRTIs + PI or NNRTI)

Front 170

HIV prophylactic vaccines

Back 170

-S. pneumoniae, hep A, hep B, and influenza are generally recommended for all HIV-infected patients.

-Live vaccines are contraindicated.

Front 171

Amphoteracin B

Back 171

Antifungal (Polyene)

MOA:
-binds ergosterol, forming pores in cell membrane, allowing leakage of electrolytes which leads to death.

Use:
-serious systemic mycoses
-Cryptococcus, Blastomyces, Histoplasma, Candida, Aspergillus, Coccidioides, Mucor
-intrathecally for fungal meningitis (does not cross BBB).
-deep fungal infections during pregnancy

AE:
-fever/chills (bake and shake)
hypotension, arrythmias.
-nephrotoxicity (leads to loss of Mg and K, so supplement these two)
-anemia (d/t reduced EPO production)
-IV phlebitus
-hydration reduces nephrotoxicity.
-liposomal amphoteracin (amp B in lipid carriers) prevents high drug exposure to the PCT of nephron.

Front 172

Nystatin

Back 172

Antifungal (Polyene)

MOA:
-same as amp B
-Topical form because too toxic for systemic use.

Use:
-oral candidiasis
-topical for diaper rash or vaginal candidiasis

Front 173

Flucytosine

Back 173

Antifungal (Pyrimidine analog)

MOA:
-taken by fungal cells via cytosine pemease.
-converted intracellularly first to 5-FU and then to 5-FdUMP, which inhibits thymidylate synthetase, thus blocking synthesis of dTMP.

Use:
-used in combination with amp B for systemic candidiasis and crytptococcosis.

AE:
-nausea, vomiting, diarrhea, myelosuppression.
-toxic enterocolitis can occur

Front 174

Ketoconazole, Miconazole, Clotrimazole

Back 174

Antifungal (Imidazoles)

MOA:
-inhibit the cyp P450 enzyme 14alpha-sterol demetylase, which converts lanosterol to ergosterol.

Use:
-ketoconazole: chronic mucocutaneous candidiasis and dermatophytes.
-Miconazole and Clotrimazole: topical fungal infections.

AE:
-ketoconazole: decreases testosterone, causing gynecomastia, menstrual irregularities.

PK:
-ketoconazole: inhibitor of cyp 3A4

Front 175

Itraconazole, Fluconazole, Voriconazole, Posaconazole

Back 175

Antifungals (Triazoles)

MOA:
-inhibit the cyp P450 enzyme 14alpha-sterol demetylase, which converts lanosterol to ergosterol.

Use:
-fluconazole: DOC in cryptococcal meningitis, Coccidioides, and all types of candidal infections.
-itraconazole: dimorphic fungi Blastomyces, Sporothrix, and Histoplasma; dermatophytoses and onchomycosis; 2nd line for Aspergillus.
-Voriconazole: DOC for Aspergillus; Fusarium.
-Posaconazole: Zygomycetes like Mucor.

PK:
-fluconazole: widest TI of all azoles, oral bioavailability is high, moderate inhibitor of cyp3A4.
-itraconazole: inhibitor of cyp3A4, no affect on steroid synthesis.

AE:
-voriconazole: transient visual disturbances.
-in general, very minor GI upset.

Front 176

Caspofungin

Back 176

Echinocandin

MOA:
-inhibit synthesis of beta-glucan in fungal cell wall. This results in disruption of the fungal cell wall and cell death.

Use:
-invasive aspergillosis who have fialed to respond to amp B or voriconazole.
-disseminated and mucocutneous candida

AE:
-GI upset, flushing

Front 177

Griseofulvin

Back 177

Antifungal

MOA:
-interferes with microtubule function, disrupting mitosis.
-deposits in keratin-containing tissues like nails.

Use:
-oral treatment of sueprficial infections.
-inhibits growth of dermatophytes (tinea, ringworm).
-replaced by newer drugs like itraconazole and terbinafine.

AE:
-teratogenic, carcinogenic, confusion, headaches.
-inducer of p450 and warfarin metabolism.

Front 178

Terbinafine

Back 178

Antifungal (Allylamine)

MOA:
-inhibits squalene epoxidase, which converts squalene to lanosterol, a precursor in ergosterol.

Use:
-dermatophytosis (especially onychomycosis - fungal infection of finger or toe nails).
-tinea cruris or tinea corporis.

AE:
-GI upsets, rash, headache, taste distrubances.
-abnormal LFTs, visual disturbances.

Front 179

1st line therapy for PCP

Back 179

cotrimoxazole (TMP/SMX)

Even though PCP is a fungus, it responds to antiprotozoal drugs rather than to antifungals bc it does not synthesize ergosterol.

Front 180

Tinidazole

Back 180

Antiparasitic

MOA:
-similar to metronidazole, but better tolerated.

Use:
-amebiasis, amebic liver abscess, giardiasis, and trichonomiasis.

AE:
-same as metronidazole, but shorter duration.

Front 181

Diloxanide furoate

Back 181

Luminal Antiamebic

MOA:
-converted in gut to diloxanide freebase active form.

Use:
-sole agent for treatment of asymptomatic amebiasis.
-not available in US, but is the luminal amebicide of choice.

AE:
-mild GI distress

Front 182

Iodoquinol

Back 182

Luminal Antiamebic

Use:
-orally active against luminal trophozoite and cyst forms of E. histolytica.
-alternative to diloxanide for mild-severe infections.

AE:
-rash, diarrhea, dose-related peropheral neuropathy.

Front 183

Paromycin

Back 183

Luminal Antiamebic

MOA:
-amebicidal (causes cell membranes to leak)
-interferes with bacterial protein synthesis (binds to 30S ribosomal units)

Use:
-only against luminal forms of E. histolytica and tapeworm.
-altenative agent for cryptosporidiosis in AIDS patient.

AE:
-GI distress and diarrhea
-headaches, dizziness, rashes, and arthralgia

Front 184

Chloroquine

Back 184

Antimalarial, Antiamebic

MOA:
-blocks plasmodium heme polhymerase (this is what the parasite used to prevent itself from being harmed from heme).

Use:
-DOC for non-falciparum and sensitive uncomplicated falciparum malaria.
-used in combination with metronidazole and diloxanide furoate.

AE:
-retinopathy, G6PD hemolysis
-pruritus (common in Africans)
-SAFE in pregnancy and children
-contraindicated in patients with visual abnormalities, psoriasis or porphyria

Front 185

Emetine, Dehydroemetine

Back 185

Antiparasitic (Antiamebic)

MOA:
-inhibit protein synthesis by blocking robosomal movement along mRNA.

Use:
-backup drugs for treatment of severe intestinal or hepatic amebeiasis.

AE:
-pain at injection site
-nausea, cardiotoxicity
-neuromuscular weakness, dizziness, rash

Front 186

Amebiasis: asymptomatic, intestinal infection

Back 186

diloxanide furoate

Front 187

Amebiasis: mild-moderate intestinal infection

Back 187

metronidazole + luminal agent

Front 188

Amebiasis: severe intestinal infection.

Back 188

metronidazole or tinidazole + luminal agent

Front 189

Amebiasis: hepatic abscess + other extraintestinal disease

Back 189

metronidazole or tinidazole + luminal agent

Front 190

Albendazole

Back 190

Antihelminthics (Benzimidazoles)

MOA:
-inhibits microtubule synthesis and glucose uptake.
-ATP production is decreased resulting in worm immobilization and death.

Use:
-cestodal infestations, such as cysticercosis (Taenia solium larvae) and hydatid disease (Echinococcus granulosis)

AE:
-short therapy (1-3 days): headache, nausea
-hydatid treatment (3 months): risk of hepatotoxicity, agranulocytosis or pancytopenia
-CNS effects: headache, vomiting, hyperthermia, convulsions, mental changes.
-contraindicated in pregnancy and children < 2y (Cat C)

Front 191

Mebendazole

Back 191

Antihelminthics (Benzimidazoles)

MOA:
-inhibits formation of helminth microtubules
-irreversibly blocks glucose uptake.

Use:
-DOC for Whipworm (Trichuris trichuria); Pinworm (Enterobius vermicularis); Hookworm (Necator americanus and Ancylostoma duodenale); Roundworm (Ascaris lumbricoides).

AE:
-abdominal pain, diarrhea, headache, dizziness
-contraindicated in pregnancy (cat C)

Front 192

Thiabendazole

Back 192

Antihelminthics (Benzimidazoles)

MOA:
-affects microtubule aggregation

Use:
-strongyloides stercoralis (threadworm), cutaneous larva migrans, and early stages of trichinosis.

AE:
-more toxic than other benzimidazoles (dizziness, anorexia, nausea, vomiting)
-CNS disturbances (dizziness--> seizures)
-erythema multiforme and Stevens-Johnson
-contraindicated in pregnancy (cat C)

Front 193

Ivermectin

Back 193

Antihelminth

MOA:
-GABA agonist
-Cl- influex increases leading to hyperpolarization of nerve/muscle cell.
-death occurs due to paralysis of parasite.

Use:
-DOC for onchocerciasis (Onchocerca volvulus), cutaneous larva migrans and stronyloides.

AE:
-Mazotti-like reactions with onchoceriasis (fever, dizziness, somnolence, hypotension)
-contraindicated in pregnancy (cat C)
-contraindicated in meningitis (may cross BBB)

Front 194

Piperazine

Back 194

Antihelminth

MOA:
-GABA agonist
-expulsion of worm occurs by peristalsis

Use:
-alternative drug for treatment of pinworm and roundworm infections.

AE:
-contraindicated in patients with seizure disorders.

Front 195

Pyrantel Pamoate

Back 195

Antihelminth

MOA:
-acts as a depolarizing, neuromuscular-blocker (causes persistent activation of parasite's nicotinic receptors by release of ACh and inhibition of AChE)

Use:
-roundworms, pinworms, hookworms.

AE:
-nausea, vomiting, diarrhea

Front 196

Diethylcarbamazine

Back 196

Antihelminth

MOA:
-immobilizes microfilariae and renders them susceptible to host defense mechanisms.

Use:
-DOC for treatment of lymphatic filariasis, loiasis, and tropical eosinophilia.

AE:
-fever, malaise, rash, myalgias, arthralgias, headache
-leukocytosis

Front 197

Doxycycline

Back 197

Antihelminth, tetracycline

MOA:
-acts indirectly by killing Wolbachia (intracellular bacterial symbiont of filarial parasites)

Use:
-macrofilaricidal activity against Wucheria bancrofti.
-onchocerciasis.

AE:
-discoloration of teeth and inhibition of bone growth in children, photosensitivity

Front 198

Praziquantel

Back 198

Antihelminth

MOA:
-increases permeability of cell membrane to calcium, causing contracture and paralysis of worm musculature, resulting in detachement of suckers from blood vessel walls.

Use:
-DOC for all forms of schistosomiasis and msot trematode and cestode infections.
-cysticercosis - 2nd line after albendazole

PK:
-extensive first pass metabolism

AE:
-drowsiness, dizziness, malaise, anorexia and GI upsets.
-drug interactions (P450)
-contraindicated in pregnancy and nursing mothers (cat B)
-contraindicated for treatment of ocular cysticercosis

Front 199

Bithionol

Back 199

Antihelminth

MOA:
-inhibition of helminth's ETC (probably)

Use:
-DOC for fasciolosis (sheep liver fluke)
-alternative drug for pulmonary paragonimiasis.

Front 200

Niclosamide

Back 200

Antihelminth

MOA:
-inhibition of the parasite's mitochondrial phosphorylation of ADP. Anaerobic metabolism may also be inhibited.

Use:
-2nd line for treatment of most cestode infections.
-use is uncommon due to excellent efficacy of praziquantel.
-no longer available in US

PK:
-laxative is admin. prior to niclosamide to get rid of all those cestodes.
-alcohol should be avoided within 1 day of dose.

Front 201

Ascaris lumbricoides (roundworm)

Back 201

DOC: albendazole, pyrantel pamoate or mebendazole

Front 202

Enterobius vermicularis (pinworm)

Back 202

DOC: mebendazole or pyrantel pamoate

Front 203

Trichuris trichuria (whipworm)

Back 203

DOC: mebendazole or albendazole

Front 204

Ancylostoma duodenale, Necator americanus (hookworm)

Back 204

DOC: Pyrantel pamoate or mebendazole or albendazole

Front 205

Cutaneous larva migrans (creeping eruption, dog + cat hookworm) - caused by Ancylostoma sp.

Back 205

DOC: Alebendazole or ivermectin

Front 206

Onchocerca volvulus (river blindness)

Back 206

DOC: Ivermectin

Front 207

Visceral larva migrans (Toxocariasis) - caused by Toxocara canis, Toxocara cati

Back 207

DOC: Albendazole

Front 208

Trichinella spiralis

Back 208

DOC: Albendazole or mebendazole; add corticosteroids for severe infection

Front 209

Lymphatic filariasis (Wucheria bancrofti, Brugia malyi)

Back 209

DOC: Diethylcarbamazine

Front 210

Loiasis (Loa loa - African eye worm)

Back 210

DOC: Dietylcarbamazine

Front 211

Strongyloides stercoralis (threadworm)

Back 211

DOC: Ivermectin

Front 212

Fasciola hepatica (liver fluke)

Back 212

DOC: Bithionol

Front 213

Schistosomiasis (S. mansomi, S. japonicum, S. hematobium)

Back 213

DOC: Praziquantel

Front 214

Clonorchis sinensis (oriental liver fluke)

Back 214

DOC: Praziquantel

Front 215

Paragonimus westermani (lung fluke)

Back 215

DOC: Praziquantel

Front 216

Echinococcus granulosus (dog tapeworm)

Back 216

DOC: Albendazole

Front 217

Taenia solium (pork tapeworm)

Back 217

DOC: Praziquantel or Niclosamide

Front 218

Taenia saginata (beef tapeworm)

Back 218

DOC: Praziquantel or Niclosamide

Front 219

Taenia solium larvae

Back 219

DOC: Albendazole or Praziquantel

Front 220

Diphyllobothrium latum (fish tapeworm)

Back 220

DOC: Praziquantel or Niclosamide

Front 221

Giardia lamblia + Trichomonas vaginalis

Back 221

DOC: Metronidazole

Front 222

Trypanosomiasis

Back 222

DOC: Melarsoprol or suramin

Front 223

Hemolymphatic stage of trypanosomiasis and for PCP

Back 223

DOC: Pentamidine

Front 224

Toxoplasmosis

Back 224

DOC: Pyrimethamine + clindamycin or sulfadiazine or folinic acid

Front 225

leishmaniasisis (all stages)

Back 225

DOC: Sodium stibogluconate / amphoteracin B

Front 226

PCP

Back 226

DOC: clotrimoxazole (TMP/SMX)

Front 227

Quinidine and Quinine

Back 227

Antimalarials

MOA:
-depresses O2 uptake and carbohydrate mtabolism.
-inercalates into DNA, disrupting parasite's replication and transcription.

Use:
-parenteral treatment of severe falciparum malaria (Quinidine)
-oral treatment of falciparum malaria (alternative in chloroquine-resistant areas) (Quinine)

AE:
-cinchronism: tinnitius, headache, nausea, dizziness, flushing and visual disturbances.
-hypersensitivity: skin rashes, urticaria, angioedema, bronchospasm.
-hypoglycemia: stimulation of insulin release.
-uterine contractions: still DOC for severe malaria in pregnancy.
-hematological: hemolysis (G6PD), leukopenia, agranulocytosis, thrombocytopenia
-severe hypotension (too rapid IV infusion)
-QT prolongation
-blackwater fever: hemolysis and hemoglobinuria

Contraindications:
-heart problems
-visual problems
-severe cinchronism
-dont use with mefloquine
-dont use with warfarin or digoxin
-cat C in pregnancy

Front 228

Mefloquine

Back 228

Antimalarial

MOA:
-destruction of asexual blood forms of malarial pathogens. Details unknown.

Use:
-chlorquine-resistant strains
-chemoprophylaxis against most strains of P. falciparum (only medication for prophylaxis in pregnancy)
-used with artesunate for uncomplicated malaria in Southwest Asia

AE:
-weekly dosing: nausea, vomiting, dizziness, sleep & behavioral disturbances, epigastric pain, diarrhea, abdominal pain, headache, rash
-higher doses: leukocytosis, thrombocytopenia, aminotransferase elevations, arrhythmias, bradycardia.
-serious neuropsychiatric toxicities (depression, confusion, acute psychosis, or seizures)

Contraindications:
-dont give with quinine, quinidine, or halofantrine
-patients with history of epilepsy, arrythmia, or psychiatric disorders.

Front 229

Primaquine

Back 229

Antimalarial

MOA:
-not completely understood - primaquine metabolites believed to act as oxidants, disrupting mitochondria and binding to DNA

Use:
-DOC for eradication of dormant liver forms of P. vivax and P. ovale.
-chemoprophylaxis of all strains.

AE:
-generally well tolerated (nausea, cramps, headaches, epigastric pain).
-hemolysis or methemoglobinemia esp. in G6PD patients.

Contraindications:
-G6PD deficiency
-pregnancy

Front 230

Atovaquone, Proguanil

Back 230

Antimalarial

MOA:
-malarone=atovaquone + proguanil.
-disrupts mitchondrial ETC

Use:
-treatment and prophylaxis of P. falciparum

AE:
-generally well tolerated (cramps, nausea, vomiting, diarrhea, headache)
-safety in pregnancy (cat C)

Front 231

Pyrimethamine, Proguanil, Sulfadoxine

Back 231

Folate synthesis inhibitors

MOA:
-pyrimethamine+proguanil: inhibit plasmodial DHF reductase.
-sulfonamides: inhibit dihydropteroate synthase

Use:
-chemoprophylaxis
-intermittent preventive therapy
-chloroquine-resistant falciparum malaria.
-NOT for severe malaria
-pyrimethamine+proguanil: erthrocytic forms of malaria
-proguanil: hepatic forms of malaria
-sulfonamides: erythrocytic

AE:
-proguanil: mouth ulcers, alopecia
-pyrimethamine-sulfadoxine: erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis.
-Sulfadoxine: hematologic, GI, CNS, dermatologic and renal toxicity.
-SAFE in pregnancy

Front 232

Artemisinin

Back 232

Antimalarial

MOA:
-bindis iron, breaking down peroxide bridges leading to generation of free radicals that damage aprasite proteins.

Use:
-treatment of severe, multi-drug resistant falciparum malaria (given IV)

AE:
-low doses: nausea, vomiting, diarrhea
-high doses: neurotoxicity, QT prolongation
-can't be used in 1st trimester in pregnancy

Front 233

Halofantrine

Back 233

Antimalarial

Use:
-erythrocytic stages of all parasites

AE:
-teratogenic

Front 234

Lumefantrine

Back 234

Antimalarial

Use:
-erythrocytic stages of all parasites

AE:
-minor QT prolongation (clinically insignificant)

Front 235

uncomplicated malaria / P. falciparum or P. malariae

Back 235

DOC: chlorquine / hydrochloroquine

Front 236

uncomplicated malaria / P. falciparum with chloroquine-resistant strain

Back 236

DOC:
a) atovaquone-proguanil
b) artemether-lumefantrine
c) quinidine + doxycycline
d) mefloquine

Front 237

uncomplicated malaria / P. vivax or P. ovale

Back 237

DOC:
a) chloroquine + primaquine
b) hydroxychloroquine + primaquine

Front 238

Uncomplicated malaria / P. vivax and chloroquine-resistant strain

Back 238

DOC:
-a) Quinidine + doxycycline + primaquine
b) atovaquone-proguanil + primaquine
c) mefloquine + primaquine

Front 239

uncomplicated malaria during pregnancy

Back 239

DOC:
-Chloroquine-sensitive: chloroquine/hydrochloroquine
-Chloroquine-resistant (P. falciparum): quinine+/- clindamycin (1st trimester) ; artesunate + clindamycin, quinine + clindamycin (2nd + 3rd trimester)
-chloroquine-resistant (P. vivax): Quinine

Front 240

severe malaria

Back 240

DOC:
a) quinidine + doxycycline, tetracycle, or clindamycin
b) artesunate + atovaquone-proguanil. Doxcycline, or mefloquine.

Front 241

severe malaria in pregnancy

Back 241

DOC:

-1st trimster: quinine or qrtesunate
-2nd or 3rd trimester: 1st option is artesunate, 2nd option is artemether

Front 242

Malaria prophylaxis

Back 242

DOC:
-chloroquine-sensitive: chloroquine
-chloroquine-resistant: mefloquine, doxycycline, primaquine

Front 243

malaria prophylaxis in pregnancy

Back 243

DOC:
-chloroquine-sensitive: chloroquine
-chloroquine-resistant: mefloquine.

Front 244

ABVD regimen for Hodgkin's lymphoma

Back 244

Adriamycin (doxorubicin) - blocks G0, cardiotoxicity.

Bleomycin - blocks G2, pulmonary fibrosis

Vincristine - blocks M2, neurotoxicity.

Dacarbazine - blocks G0, myelosuppression.

Front 245

BEP regimen for testicular cancer

Back 245

Bleomycin -

Etoposide - blocks late S phase and early G2 phase, myelosuppression

Platinum (Cisplatin) - cell cycle nonspecific including G0, nephrotoxicity, ototoxicity

Front 246

Adjuvant chemotherapy

Back 246

chemotherapy is added in addition to surgery or radiotherapy

Front 247

neo-adjuvant chemotherapy

Back 247

chemotherapy given before surgery to decrease the size of tumor.

Front 248

induction chemotherapy

Back 248

chemotherapy given to obtain complee remission from the tumor, usually blood cancers.

Front 249

Cyclophosphamide, ifosfamide, mechlorethamine, melphalan, chlorambucil

Back 249

Anticancer, Alkylating agents (Nitrogen mustards)

MOA:
-covalently X-link (interstrand) DNA at guanine N-7. Require bioactivation by liver.

Use:
-NHL, breast and ovarian carcinoma.
-Mechlorethamine: highly vesicant, used in NHL
-Melphalan: Multiple myeloma
-Chlorambucil: CLL

AE:
-Ifosfamide: has more potential to cause hemorrhagic cystitis (must give mesna prior to each dose)
-myelosuppression
-chlorambucil: mucositis, vomiting

Front 250

Busulfan

Back 250

Anticancer, Alkyl Sulfonate

MOA:
-Alkylates DNA

Use:
-CML
-also used to ablate patient's bone marrow before bone marrow transplanttation.

AE:
-pulmonary fibrosis, hyperpigmentation

Front 251

Carmustine (BCNU), Lomustine (CCNU), Semustine, streptozocin

Back 251

Anticancer, Nitrosureas

MOA:
-require bioactivation
-chloroethyl moeity alkylates nucleic acids and proteins, producing single-strand breaks and interstrand cross-linkage of DNA.
-all cross BBB

Use:
-brain tumors (including glioblastoma multiforme)
-

AE:
-CNS toxicity (dizziness, ataxia)
-delayed myelosuppression
-GI distress

Front 252

Dacarbazine

Back 252

Anticancer, Triazene

MOA:
-requires bioactivation.

Use:
-NHL, soft tissue sarcoma, and melanoma

AE:
-myelosuppression, nausea, and vomiting.

Front 253

Procarbazine

Back 253

Methylhydrazine

MOA:
-n/a

Use:
-Hodgkin's disease

AE:
-teratogenic, mutagenic, leukemogenic.
-nausea, vomiting, myelosuppression
-hemolytic anemia
-pulmonary effects
-peripheral sensory neuropathy
-disulfiram-like reaction

Front 254

cisplatin, carboplatin, oxaliplatin

Back 254

Anticancer, Platinum coordination omplexes

MOA:
-alkylates N7 position of guanine in DNA
-cross link DNA
-cell cycle nonspecific

Use:
-testicular, bladder, ovary, and lung carcinomas.

AE:
-nephrotoxicity and acoustic nerve damage.
-severe nausea and vomiting (d/t stimulation of CTZ)
-carboplatin and oxaliplatin has a more acceptable toxicity profile than cisplatin, but has more myelosuppression.

Antidote:
-amifostine (inactivates free radicals by giving thiol (-SH)) for prevention of cisplatin-induced nephrotoxicity.
-osmotic diuresis with mannitol
-chloride diuresis with NaCl

Front 255

6-mercaptopurine (6-MP), 6-thioguanine (6-TG)

Back 255

Anticancer, Antimetabolites, Purine antagonists

MOA:
-Purine (thiol analog) --> decreases de novo purine synthesis.
-activated by HGPRTase
-6-MP is converted to TIMP which blocks formation of AMP and GMP.

Use:
-6-MP: leukemias (ALL), lymphomas (not CLL or Hodgkins)
-6-TG: AML, ALL

AE:
-allopurinol will increase toxicity since it inhibits xanthine oxidase.
-6-TG can be given with allopurinol
-myelosuppression, hepatotoxicity, nausea, vomiting.

Front 256

5-Flurouracil (5-FU)

Back 256

Anticancer, Antimetabolite, Pyramidine antagonist

MOA:
-bioactivated to 5F-dUMP, which covalently complexes with folic acid.
-this complex inhibits thymidylate synthase, inhibiting dTMP synthesis.

Use:
-colon cancer and other solid tumors.
-basal cell carcinoma (topical)
-synergy with MTX

AE:
-myelosuppression that is not reversible with leucovorin, instead give thymidine.
-mucositis, alopecia
-photosensitivity: skin exfoliation on palm and feet "hand-foot syndrome"

Front 257

Capecitabine

Back 257

Anticancer, Antimetabolite, Pyramidine antagonist

MOA:
-onverted to 5-FU by thymine phosphorylase inside tumor cells.

Use:
-metastatic breast cancer
-colorectal cancer

AE:
-same as 5-FU

Front 258

Gemcitabine

Back 258

Anticancer, Antimetabolite, Pyramidine antagonist

MOA:
-same as 5-FU

Use:
-pancreatic cancer, non-SCLC, ovarian cancer

AE:
-myelosuppression, alopecia, flu like symptoms and elevation of liver enzymes.

Front 259

Cytarabine (ara-C)

Back 259

Anticancer, Antimetabolite, Pyramidine antagonist

MOA:
-ara-C is transformed to ara-CTP that competitively inhibits DNA polymerase.

Use:
-AML for induction, ALL, high-grade non-Hodgkin's lymphoma.
-CML in blast crisis

AE:
-leukopenia, thrombocytopneia, megaloblastic anemia

Front 260

Vincristine, Vinblastine, Vinorelbine

Back 260

Anticancer, Vinca alkaloids

MOA:
-bind to tubuilin M-phase and block polymerization of microtubules so that mitotic spindle cannot form.

Use:
-Vinristine: Hodgkin's lymphoma
-Vinblastine: testicular cancers
-Vinorelbine: NSCLC
-Wilm's tumor, choriocarcinoma, ALL

AE:
-Vincristine: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus. Bone marrow sparing drug (myelosuppression is minimal)
-Vinblastine: myelosuppression
-Vinorelbine: granulocytopenia.

Front 261

Paclitaxel, Docetaxel

Back 261

Anticancer, Taxanes

MOA:
-hyperstabilize polymerized microtubules in M-phase so that mitotic spindle cannot break down (cells arrested in M-phase)

Use:
-ovarian and breast carcinoma

AE:
-Paclitaxel: severe allergic reaction to attributed to cremophor EL (castor oil), neutropenia, and alopeica is unviersal.
-Docetaxel: skin toxicity and fluid retention leading to pleural and peritoneal effusions.

Front 262

Etoposide (VP-16), Tenoposide

Back 262

Anticancer, Epipodophyllotoxins

MOA:
-inhibits topoisomerase II--> prevents re-ligation of DNA strand breaks --> increases DNA degradation.
-act at late S and early G2 phases.

Use:
-germ cell tumor (testicular carcinoma)
-small cell carcinoma of lung and prostate
-AML

AE:
-myelosuppression, alopecia
-GI irritation
-some correlation b/w etoposide use and leukemia

Front 263

Topotecan, Irinotecan

Back 263

Camptothecins

MOA:
-inhibit Topoisomerase I

Use:
-Topotecan: metastatic ovarian cancer (cisplatin-resistant)
-Irinotecan: colon and rectal cancer

AE:
-Topotecan: enutropenia, thrombocytopenia, anemia
-Irinotecan: severe diarrhea, myelosuppression (caution in patients with Gilbert's syndrome)

Front 264

Bleomycin

Back 264

Antitumor Antibiotics

MOA:
-induces free radical formation, which causes breaks in DNA strands.
-acts at G2 phase
-reduced iron mediates the reduction of molecular oxygen into damaging free radicals.

Use:
-testicular cancer
-Hodgkin's lymphoma
-Kaposi's sarcoma

AE:
-pneumonitis followed by pulmonary fibrosis
-skin changes, Raynaud's phenomenon
-retroperitoneal fibrosis
-minimal myelosuppression

Front 265

Doxorubicin (Adriamycin), Daunorubicin

Back 265

Antitumor antibiotics, Anthracyclines

MOA:
-inhibition of topoisomerase II, leading to DNA breaks.
-also form free radicals that damage DNA.
-alters membrane fluidity and ion transport.

Use:
-AML, Hodgkin's lymphomas, sarcomas, myelomas.
-solid tumors (breast, ovary, and lung)

AE:
-cardiotoxicity (dilated cardiomyopathy)
-myelosuppression
-nausea, vomiting, alopecia, mucositis.
-erythema at sites of prior radiation (radiation recall reaction)
-highly vesicant (causes blisters)

Antidote:
-Dexrazoxane (iron chelating agent), is used to prevent cardiotoxicity.

Front 266

Dactinomycin (actinomycin D)

Back 266

Antitumor antibiotic

MOA:
-binds to DNA noncovalently, intercalates with it.
-cell cycle nonspecific

Use:
-Wilm's tumor, Ewing's sarcoma, rhabdomyosarcoma.
-used for childhood tumors

AE:
-myelosuppression
-radiation recall reaction
-highly vesicant

Front 267

Dexamethasone, Hydrocortisone, prednisone, Prednisolone

Back 267

Hormonal agents, Glucocorticoids

MOA:
-bind to intra cyctoplasmic receptor, the steroid-receptor complex binds to nuclear receptor modualting protein expression.

Use:
-ALL, Hodgkins lymphoma, non-hodgkins lymphoma, multiple myeloma, etc.
-palliative care
-spinal cord compression d/t metastasis to relieve edema.
-management of autoimmune anemia and thrombocytopenia.

AE:
-immunosuppression leading to infections
-mood swings, osteoporosis, hyperglycemia, poor wound healing, etc.

Front 268

Diethylstilbestrol, Ethinylestradiol

Back 268

Hormonal agents, Estrogens

MOA:
-binds to cytoplasmic receptor, the receptor-drug complex then moves to nucleus to modulate protein expression.

Use:
-prostate cancer
-contraindicated in patients with breast and endometrial cancers.

AE:
-increased risk of thromboembolism, migraine, cholestasis, and mood changes.
-gynecomastia and impotence when administered to men.

Front 269

Tamoxifen, Raloxifene

Back 269

Hormonal agents, SERM (selective estrogen receptor modulators)

MOA:
-Tamoxifen: antagonist effect on breast tissue but agonist on endometrium and bone.
-Raloxifene: antagonist at breast and endometrium but agonist at bone.

Use:
-breast cancer (esp. ER positive)
-prevent osteporosis

AE:
-hot flushes and thrombosis
-fluid retention
-risk of endometrial cancer for tamoxifen

Front 270

Aminogluthethimide

Back 270

Hormonal agent, Aromatase inhibitor

MOA:
-inhibitor of adrenal steroid synthesis at the first step, conversion of cholesterol to pregnelone.
-inhibits the extra-adrenal synthesis of estrone and estradiol.
-inhibits the enzyme aromatase that conversts androstenedione to estrone.

Use:
-ER positive metastatic breast cancer.

AE:
-adrenal insufficiency
-dizziness, lethargy, visual blurring, rash

Front 271

Anastrozole, Letrozole

Back 271

Hormonal agent, Aromatase inhibitor

MOA:
-selective non-steroidal inhibitor of aromatase enzyme.

Use:
-ER positive breast cancer that is tamoxifen resistant.

AE:
-hot flushes, headache

Front 272

Exemestane, Formestane

Back 272

Hormonal agents, Aromatase inhibitors

MOA:
-steroidal irreversible inhibitors of aromatase.

Use:
-ER positive breast cancer

AE:
-mood changes, acne, and hair growth

Front 273

Hydroxyprogesterone, Megestrol

Back 273

Anticancer, Progestins

MOA:
-n/a

Use:
-endometrial cancer
-palliative care: to improve appetite in terminally ill cancer patients.

AE:
-weight gain, depression
-edema, acne
-decreased HDL

Front 274

Fluoxymesterone, testosterone

Back 274

Anticancer, Androgens

MOA:
-n/a

Use:
-palliative care to improve feeling of well being and appetite.

AE:
-n/a

Front 275

Leuprolide, Goserelin

Back 275

Anticancer, Androgen inhibitors

MOA:
-continuous dose (not pulsatile) will produce reversible medical castration.
-continuous administration leads to decreased release of LH and FSH.
-initial flare-up of androgen dependent cancer may occur.

Use:
-prostate cancer
-sometimes for fibroid uterus

AE:
-decreased bone mass, hot flushes, initial tumor flare up, impotence

Front 276

Flutamide

Back 276

Anticancer, Androgen receptor blocker

MOA:
-antagonizes androgenic effects.

Use:
-prostate cancer
-given with GnRH agonists to prevent initial tumor flare-up

AE:
-gynecomastia and GI distress

Front 277

Hydroxyurea

Back 277

Anticancer, miscellaneous

MOA:
-analog of urea
-inhibits ribonucleotide reductase, resulting in depletion of deoxynucleoside triphosphate pools, inhibiting DNA synthesis.
-acts at S phase

Use:
-melanoma, CML
-sickle cell disease (by increasing HbF)

AE:
-leukopenia, mild GI toxicity
-mild dermatologic changes with prolonged therapy.

Front 278

L-Asparagniase

Back 278

Anticancer, miscellaneous

MOA:
-enzyme isolated from bacteria
-causes catabolic depletion of serum asparagine to aspartic acid and ammonia.
-this results in reduced blood glutamine levels and inhibition of protein synthesis.

Use:
-childhood acute leukemia

AE:
-hypersensitivity reactions (anaphylactic shock)
-hemorrhage, hyperglycemia
-headache, pancreatitis

Front 279

Arsenic trioxide

Back 279

Anticancer, miscellaneous

MOA:
-in PML/rAR-alpha positive AML, it causes differentiation of leukemic cells.

Use:
-APL

AE:
-headache, cardiac dysrhythmias
-fluid retention, increases risk of skin cancers

Front 280

Interferon 2 alpha, Interferon 2 beta

Back 280

Anticancer, miscellaneous

MOA:
-INF-alpha stimulates NK cells.
-increases the expression of HLA molecules on tumor cells.

Use:
-INF-2 alpha: CML, hairy cell leukemia, Kaposi's sarcoma, etc.
-INF-2 beta: melanoma, follicular lymphoma, AIDS-related Kaposi's sarcoma, etc.

AE:
-fever, myalgia, headache, loss of appetitie, depression, etc.

Front 281

Imatinib

Back 281

Anticancer, Signal transduction inhibitor

MOA:
-inhibits tyrosine kinase

Use:
-BCR-ABL positive CML, ALL, and GIST

AE:
-fluid retention, edema, hepatotoxicity, thrombocytopenia, etc.

Front 282

Gefitinib

Back 282

Anticancer, Signal transduction inhibitor

MOA:
-inhibits epidermal growth factor receptor signal transduction.

Use:
-NSCLC

AE:
-acne-like skin lesions, nausea, diarrhea, etc.

Front 283

Cetuximab

Back 283

Anticancer, Signal transduction inhibitor

MOA:
-inhibits EFGR signaling

Use:
-colorectal cancer, head and neck cancer

AE:
-infusion reaction, skin rash, fatigue.

Front 284

Trastuzumab

Back 284

Anticancer, Signal transduction inhibitor

MOA:
-epdermal growth factor receptor protein 2

Use:
-breast cancer

AE:
-congestive heart failure and infusion related side effects.

Front 285

Bortezombib

Back 285

Anticancer, Signal transduction inhibitor

MOA:
-inhibits proteosome which has chymotrypsin like activity

Use:
-multiple myeloma and mangle cell lymphoma

AE:
-thrombocytopenia, neuropathy

Front 286

Sunitinib

Back 286

Anticancer, Signal transduction inhibitor

MOA:
-multiple receptor kinase inhibition like VEGF-1, 2, and 3, PDGFR.

Use:
-renal cell cancer and GIST

AE:
-skin rash and bleeding

Front 287

Erlotinib, Lapatinib

Back 287

Anticancer, Signal transduction inhibitor

MOA:
-EGFR tyrosine kinase inhibitor

Use:
-NSCLC, pancreatic cancer

AE:
-skin rash, interstitial lung disease.

Front 288

Sorafenib

Back 288

Anticancer, Signal transduction inhibitor

MOA:
-multiple receptor kinase inhibition like VEGF-2 and 3, PDGFR

Use:
-renal cell cancer, HCC

AE:
-skin rash, fatigue

Front 289

Cyclosporine

Back 289

Immunosuppresant

MOA:
-binds to intracellular protein "cyclophilin". Complex blocks the differentiation and activation of T cells by inhibiting calcineurin-->preventing NFAT activation-->preventing the production of Il-2 and its receptor.

Use:
-suppresses organ rejection after transplantation

PK:
-metabolized by cyp3A4
-grapefruit juice increases absorption.

AE:
-predisposes patients to viral infections and lymphoma.
-nephrotoxic (preventable with mannitol diuresis)
-gout
-hyperkalemia, hyperglycemia, dyslipidemia, hypertension, hepatotoxicity.
-gum hyperplasia and hirsutism.

Front 290

Tacrolimus (FK506)

Back 290

Immunosuppressant

MOA:
-binds to FK-506 binding protein and the complex inhibits calcineurin.

Use:
-potent immunosuppressive used in organ transplant recipients.

AE:
-significant nephrotoxicty
-no gum hyperplasia or hirsutism
-more likely to cause neurological defects than cyclosporine (e.g. peripheral neuropathy)
-hypertension, pleural effusion, hyperglycemia.

PK:
-absorption is bile dependent
-metabolized by CYP3A4

Front 291

Sirolimus (rapamycin)

Back 291

Immunosuppressant

MOA:
-inhibits mTOR (mammalian target of rapamycin) and inhibits the ACTION of IL-2.

Use:
-immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids.
-also used with drug-eluting stents (sirolimus-eluting coronary artery stents are effective in preventing restenosis after angioplasty)

AE:
-hyperlipidemia, thrombocytopenia, leukopenia
-nephrotoxic when combined with cyclosporine.

Front 292

Mycophenolate mofetil

Back 292

Cytotoxic drug

MOA:
-converted to mycophenolic acid.
-inhibits IMP DHse (an enzyme necessary for guanosine synthesis)
-this suppresses both B and T-cells.

AE:
-diarrhea and myelosuppression

Front 293

Muromonab-CD3 (OKT3)

Back 293

Monoclonal antibody

MOA:
-binds to CD3 (epsilon chain) on the surface of T cells. Blocks interaction with CD3 protein responsible for T-cell signal transduction.
-only affects cell mediated immunity.

Use:
-immunosuppression after kidney transplantation.
-acute graft rejection

AE:
-cytokine release syndrome
-hypersensitivity reactio

Front 294

Daclizumab, Basiliximab

Back 294

IL-2 receptor antagonists

Use:
-peri-operative use during transplantation.

Front 295

Rh (D) Immunoglobulin (Rho GAM)

Back 295

Polyclonal antibody

MOA:
-prevents primary immune response to Rh antigen on fetal RBCs in Rh negative mothers.

Use:
-hemolytic disease of the new born.
-should be administered to Rh negative patients within 72 hours of delivery.

Front 296

Aldesleukin

Back 296

Monoclonal antibody

MOA:
recombinant IL-2, activates cytotoxic T cells and NK cells.

Use:
-renal cell cancer

Front 297

Rituximab

Back 297

Monoclonal antibody

MOA:
-antibody against CD20 antigen.

Use:
-CD20 tumors like non-hodgkins lymphoma, CLL

Front 298

Bevacizumab

Back 298

Monoclonal antibody

MOA:
-antibody against VEGF.

Use:
-colorectal, breast, renal, and non-small cell lung cancer.

AE:
-skin rash and hypersensitivity

Front 299

Hyperimmune globulins

Back 299

Polyclonal antibodies

MOA:
-Igs from pool of selected human donors or animals.

Use:
-tetanus, rabies, snake bite, digoxin overdose
-prevention of HBV in new born.

Front 300

BCG (Bacillus Calmette-Guerin)

Back 300

Vaccine

MOA:
-live attenuated vaccine against TB.

Use:
-TB
-administered intravesically after resection of superficial bladder cancer.
-contraindicated in immunocompromised.

Front 301

Thalidomide

Back 301

Immunomodulator

MOA:
-decreases TNF-alpha production, enhances cell mediated immunity.
-has anti-angiogenic effect

Use:
-first line drug in the treatment of multiple myeloma.
-aphthous ulcers, lepra reaction and wasting syndrome in AIDS and terminal cancer patients.

AE:
-teratogen, causes Phocomelia (sealed limbs deformity or "flipper" limbs)
-neuropathy, constipation, DVT, and sedation

Front 302

Antithymocyte globulin

Back 302

Polyclonal antibody

MOA:
-against T-cells

Use:
-acute transplant rejection
-aplastic anemia