GI Flashcards

Question

Alprostadil

Answer 1

PGE₁ used for its smooth muscle relazing effects to maintain the ductus arteriosus patency in some neonates awaiting cadiac surgery and in treatment of impotence

Answer 2

AKA acetylsalicylic acid Rapidly absorbed from stomach and upper small intestine, bound to albumin Irreverisbly inhibits COX1 and 2 (antiplatelet effect lasts 8-10 days, the life of the anuclear platelet) Used against TIAs, unstable angina, coronary artery thrombosis with MI, and thrombosis after coronary artery bypass grafting Side effects include gastric upset, gastric and duodenal ulcers. Rarely, hepatotoxicity, asthma, rashes, GI bleeding, and renal toxicity occur Don't use in hemopheliacs (duh) Not effective in treating ankylosing spondylitis (unlike all other NSAIDs)

Answer 3

Selective COX-2 inhibitor. Cox-2 inhibitors have the same analgesic, antipyretic, and anti-inflammatory effects but half of the GI adverse effects. Associated with a higher incidence of cardiovascular thrombotic events Associated with fewer endoscopic ulcers than most other NSAIDs May cause rashes, does not effect platelet aggregation at usual doses, and may also interact with warfarin. Can also cause renal toxicity

Answer 4

A COX-2 inhibitor that is not as selective as celecoxib. It is associated with fewer clinical GI symptoms and complications than piroxicam, diclofenac, and naproxen. Does not effect TXA2 in appreciable levels in vivo

Answer 5

Nonselective COX inhibitor GI ulceration may occur less frequently than with some other NSAIDs. **Often paired with misoprostol to prevent GI effects, but this may lead to diarrhea.** Impairs renal blood flow and glomerular filtration rate. Elevation of serum aminotransferases is more common with this drug than other NSAIDs. Used for postoperative opthalmic inflammation, solar keratoses, and has a rectal suppository for preemptive analgesia and postoperative nausea

Answer 6

Nonselective COX inhibitor Subject to capacity limited metabolism Claimed to be particularly effective for cancer pain due to bone metastases and for pain control in dental surgery Limit dosage with renal impairment

Answer 7

Nonselective COX inhibitor Can be given 3-4 times a day (not many specifics on this one)

Answer 8

Nonselective COX inhibitor Complex MOA: Its S enantiomer inhibits COX, but may also interact with TNF alpha and nitric oxide synthesis Available in topical opthalmic formulation for inhibition of intraoperative miosis, used in ear, neck, and nose surgery Rarely associate with cogwheel rigidity, ataxia, tremor, and myoclonus

Answer 9

Nonselective COX inhibitor derivative of phenylproprionic acid More potent than aspirin in anti-inflammatory effect Effective in closing PDAs in preterm infants just like indomethacin Decreases urine output les than indomethacin Contraindicated in patients with nasal polymps, angioedema, and bronchospastic reactivity to aspirin Use with aspirin decreases both the protective cardiac effects of aspirin and the anti-inflammatory effect of both drugs

Answer 10

Potent Nonselective COX inhibitor May also inhibit phospholipase A and C, inhibit neutrophil migration, and decrease T and B-cell proliferation Used to close PDAs and as pain reliever in numerous conditions Can be given as an epidural injection GI effects include pancreatitits. Headaches can occur along with renal papillary necrosis Probenecid prolongs its half life

Answer 11

Nonselective COX and lipoxygenase inhibitor Probenicid prolongs its half life Not superior to other NSAIDs in clinical efficacy

Answer 12

Nonselective COX inhibitor Used as an analgesic, not as an anti-inflammatory (although it has anti-inflammatory properties) Is often used in conjunction with or to replace morphine for pain control

Answer 13

Only nonacid nonselective COX inhibitor in current use Given as a ketone prodrug that is converted to an acid in the body. Does not undergo enterohepatic circulation; cleared by kidneys May be less damaging to stomach than other NSAIDs Associated with a pseudoporphyria and photosensitivity in some patients Very expensive

Answer 14

Nonselective COX inhibitor Only NSAID marketed as a single enantiomer Used for usual rheumatologic indications Incidence of GI bleeding is low but double that of ibuprofen Rare cases of allergic pneumonitits, leukocytoclastic vasculitits, and pseudoporphyria have been noted

Answer 15

Another propionic acid nonselective COX inhibitor Main difference is very long half life (50-60 hours) Mild uricosuric, meaning it may be useful in gout patients

Answer 16

Nonselective COX inhibitor at high concentrations also inhibits polymorphonuclear leukocyte migration, decreases oxygen radical production, and inhibits lymphocyte function. Used for usual rheumatic indications Has increased incidence of peptic ulcer and bleeding compared to other NSAIDs

Answer 17

A sulfoxide prodrug nonselective COX inhibitor Used for rheumatic diseases, familial intestinal polyposis, and may inhibit development of colon, breast, and prostate cancer. Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranuloctyosis, and nephrotic syndrome have all been observed. It can also elevate serum aminotransferases like diclofenac

Answer 18

Nonselective COX inhibitor Short half-life; not often used ineffective at treating gout, and may cause thrombocytopenic purpura

Answer 19

For renal insufficiency, choose nonacetylated salicylates Use celecoxib plus omeprazole or misoprostol for those patients with the highest risk of a GI bleed. Choice requires a balance of efficacy, cost-effectiveness, safety, and personal factors

Answer 20

**Analgesic, not an anti-inflammatory** Weak COX-1 and COX-2 inhibitor Highly reactive metabolite (N-acetyl-p-benzoquinone) is toxic to both liver and kidneys Does not affect uric acid levels and lacks platelet modifying effects Use in people that can't handle aspirin and children with viral infections Fatal with large doses, antidote is acetylcysteine GI bleeding does not occur

Answer 21

Drugs containing a 5-aminosalicylic acid that are used in the treatment of inflammatory bowel diseases (especially ulcerative colitis). Include sulfasalazine, olsalazine, balsalazide, and mesalamine Thought to work topically, not systemically, in areas of diseased GI mucosa. MOA is potentially through modulation of inflammatory mediators derived both from COX and lipoxygenase pathways. It also inhibits the activity of NF-kB. Azo compounds (S,O, and B) are bound to an inert compound. This bond is broken by bacteria in the terminal ileum and colon, activating drug here Mesalamine compounds are bascially different ways of packaging the 5-ASA to get it to the colon. Includes Pentasa (contains timed release microgranules), Asacol and Apriso, Lialda (all three are pH sensitive). You can also get it there via an enema (Rowasa) or suppositories (Canasa) Sulfasalazine has the highest incidence of adverse effects (especially in slow acetylators) including nausea, GI upset, headaches, arthralgias, bone marrow suppression, and malaise. Hypersensitivity to sulfapyridine (metabolite) can also occur. It also impairs folate absorption, so supplement with folate The rest are well tolerated, but osalazine may induce a secretory diarrhea (different than inflammatory diarrhea)

Answer 22

MOA: inhibit production of inflammatory cytokines and chemokines, reduce expression of inflammatory cell adhesion molecules, and inhibit gene transcription of NO synthase, PLA₂, and NF-kB Used to treat patients with moderate to severe active inflammatory bowel disease. **They are not useful in maintaining remission** **Prednisone and prednisolone** are the most commonly used oral glucocorticoids in GI practice **Hyrdocortisone** enemas, foam, or suppositories are used to treat inflammatory bowel disease (of rectum and sigmoid colon) topically and avoid systemic administration **Budesonide** is a potent synthetic analog of prednisolone that has a huge first pass effect, but is formulated to be released in the distal ileum and colon (site of action) If systemic administration can be avoided, do so, as there are lots of adverse effects to glucocorticoids

Answer 23

Purine antimetabolites that have immunosuppressive properties used in the treatment of inflammatory bowel diseases Azathioprine is a precursor to 6-MP and has a greater bioavailability than does 6-MP. Active metabolite is 6-thioguanine, which has a significantly greater half life than the parent drug due to concentration within cells. **Important for both induction and maintenance of remission (80% effective) of ulcerative colitis and Crohn's disease** Dose-related toxicities include nausea, vomiting, bone marrow depression, and hepatic toxicity. Leukopenia may respond to GSF. TPMT is what catabolizes 6-MP, which can lead to more bone marrow suppression if low levels are present in the patient. May predispose to lymphoma Avoid allopurinol, as both drugs interact with xanthine oxidase (this can lead to severe leukopenia)

Answer 24

Antimetabolite that can **induce and maintain remission in patients with Chrohn's disease** (effect on ulcerative colitis is uncertain) Principal MOA is inhibition of DHFR leading to decreased thymidine and purine production. It may also interfere with inflammatory actions of IL-1, stimulate the release of adenosine (endogenous anti-inflammatory), and stimulate apoptosis and death of activated T-lymphocytes At high doses, causes bone marrow depression, megaolblastic anemia, alopecia, and mucositis. Supplement with folate. Risk of hepatic damage is lower in these patients that those being treated for psoriasis

Answer 25

Used for moderate to severe Chron's disease in patients who have not responded to conventional therapies (**Infliximab is also used for ulceratice colitis**). Used in both induction and maintenance, but eventually they may lose effect due to antibody formation against the antibodies. **Infliximab** (chimeric) and **Adalimumab** (recombinant) are IgG's against TNFalpha that both neutralize soluble/insoluble TNF as well as induce cell death. This second action is due to presence of Fc region of the antibody **Certolizumab** is 95% human and is a pegylated Fab portion of an antibody that still neutralizes TNF but **cannot** induce cell death Effects are due to suppression of TH1 response (TB, hepB, fungal organisms, bacterial sepsis, et c.). Serum sickness and rare acute hepatic failure, demyelinating disorders, hematologic reactions, and new or worsened congestive heart failure may occur. They are also associated with psoriatic skin rashes that resolve after drug discontinuation.

Answer 26

PGE₂ and PGF_2alpha cause longitudinal smooth muscle contraction, circular smooth muscle contraction is caused by PGF_2apha and PGE₁ and is relaxed by PGE₂. Administraction of PGE₂ or PGF_2alpharesults in colicky cramps **LTB₄ is synthesized by human colonic epithelial cells and is substantially increased in patients with inflammatory bowel disease**

Answer 27

Current treatment of hepatitis C is peginterferon alfa and ribaviran (for 48 weeks). Also used in treatment of chronic hepatitis B. Only about 15% effective when used alone. 40% effective in combination with ribavirin Works by activating JAK-STAT signal-transduction pathways which leads to viral resistance via inhibition of protein synthesis, cleavage of cellular and viral RNAs, and inactivation of eIF-2 HCV resistance is through inhibition of the IFN-induced protein kinase Must be given IV Can be pegylated to prolong action (once per week dosing) Adverse Effects: can lead to a **terrible flu-like feeling following initial injection.** Dose limiting toxicities are depression, myelosuppression, cardiotoxicity, neurotoxicity manifested by somnolence, confusion, seizures,

Answer 28

Purine nucleoside analog with a modified base and D-ribose sugar. Used on a wide range of RNA and DNA viruses (HCV). MOA: incompletely understood but relates to alteration of cellular nucleotide pools and inhibition of viral mRNA synthesis Resistance has only occurred in Sinbis and HCV Orally available; taken up in the proximal small bowel Can cause a dose-related **anemia** owing to extravascular hemolysis and suppression of bone marrow; fatigue, cough, rash, et c. Very teratogenic

Answer 29

diester prodrug of adefovir, an acyclic phosphonate nucleotide analog of AMP Clinical use is limited to HBV infections. Used in combination with other anti-HBV nucleosides Can serve as a comptetitive inhibitor of viral DNA polymerases and reverse transcriptases and as a chain terminator Causes a dose-related nephrotoxicity and tubular dysfunction (hypophosphatemia, acidosis, glycosuria, and proteinuria)

Answer 30

Guanosine nucleoside analog with selective activity against HBV polymerase used in treating chronic HBV Requires intracellular phosphorylation. It inhibits base priming, reverse transcription, and synthesis of the positive strand of HBV DNA all by hitting the reverse transcriptase Severe acute exacerbations of Hepatitis B have been reported in people that discontinued therapy. Monitor liver function test following discontinuation.

Answer 31

A nucleoside analog that inhibits HIV reverse transcriptase and the HBV DNA polymerase. Needs cellular enzymes to convert it to triphosphate form which competitively inhibits polymerases and causes chain termination. Point mutations in the YMDD motif of HBV DNA leads to resistance, but this could be overcome by adefovir Well-tolerated; occasional rise in aminotransferase levels following therapy

Answer 32

Synthetic thymidine nucleoside analog with activity against HBV DNA polymerase It is phosphorylated by cellular kinases to active triphophate form (competitive inhibitor and chain terminator, like the others) Generally well-tolerated. Discontinuation can cause increased creatine kinase, nausea, diarrhea, fatigue, myalgia, and myopathy Given orally

Answer 33

nucleotide analog with activity against both HIV-1 and HBV. It is administered orally as the disoproxil prodrug. Will likely supersede most adefovir use due to its safety, efficacy, and resistance profile

Answer 34

Chronic disease: positive HBsAg for 20+ weeks Stages: 1. rep stage with immune tolerance 2. replicative stage with immune clearance 3. non rep stage, HBeAg disappears but HBsAg may remain can progress to cirrhosis and hepatic failure Treatment: 1. multiple antiviral agents: emtricitabine, entecavir, clevudine, telbivudine, tenofovir 2. interferon alpha reserved for patients w/ persistent HBeAg and elevated transmaminase

Answer 35

Hep C seldom clears on its own. It can lead to cirrhosis, hepatic failure, HPC Treatment with **pegylated interferon alpha** and oral **ribavirin**

Answer 36

Diazepam, Chlordiazepoxide, lorazepam Used in acute ethanol withdrawal binds GABA_A receptor

Answer 37

Inhibits the oxidation of acetaldehyde to acetate (Aldehyde dehydrogenase) Deters drinking from those with alchol abuse Causes facial flushing, nausea, vomiting, dizziness, and headache (hangover) Other drugs (metronidazole, cefotetan, trimethoprim) inhibit ALDH as well

Answer 38

opioid antagonist, blocks the mu receptors. studies have found that small doses of opioids increase the appetite for alcohol. Do the math Reduces the rate of relapse and reduces cravings especially when used in combination with behavioral counseling. oral dose but can be given IM for extended release dose-dep hepatotoxicity

Answer 39

Acts on GABA, glutamate, serotonergic, NE, DA receptors weak NMDA antagonist and GABA activator are best effects Adverse: nausea, vomiting, diarrhea, rash. Do not use in patients with renal impairment.

Answer 40

Odansetron: serotonin 5-HT3 receptor antagonist Topiramate: drug used for seizures These drugs have shown efficacy in maintaining abstinence and reducing cravings in chronic alcoholism

Answer 41

90% of alcohol is oxidized in liver; remainder is excreted through lungs and urine. Zero-order kinetics MEOS: used NADPH as cofactor. During chronic alcohol consumption, this enzyme in induced and alcohol is better cleared; however, so are other drugs that use CYP450. Toxins and free radicals are also produced Effects on liver and GI tract: Liver disease in 15-30%, alcoholic fatty liver can progress to hepatitis and cirrhosis, chronic pancreatitis, gastritis, anemia and protein malnutrition (water-soluble vitamins) Drug interactions: enhances metabolism of other drugs, esp important for acetaminophen. In contrast, acute alcohol ingestion can inhibit metabolism of drugs (reduced blood flow) like TCA, phenothiazine, sedative-hypnotics

Answer 42

used in industrial production of organic compounds and solvents absorbed through skin, GI tract, lungs. Eliminated by ox to formaldehye, formic acid, CO2 Early symptoms: gastritis and inebriation. Most characteristic- visual disturbance "like being in a snowstorm" and can progress to blindness. Treatment: 1. support of respiration 2. suppression of metabolism by alcohol dehydrogenase, hemodialysis to remove methanol and toxic products, and alkalinization to balance metabolic acidosis. **Fomeprizole**, ADH inhibitor, is used to treat methanol and ethylene glycol poisioning. Adverse: burning at infusion site, headache, nausea, dizziness Ethanol has higher affinity for ADH so can also be used

Answer 43

Polyhydric alcohol in antifreeze and solvents Sweet taste metabolized to toxic aldehydes and oxalate Stages: 1. excitation followed by CNS depression 2. metabolic acidosis from lactate 3. renal insufficiency due to oxalate in renal tubules Fomepizole in standard of treatment

Answer 44

**Muscarinic agonists** increases secretory and motor activity of the gut. Salivary and gastric glands are strongly stimulated. Peristaltic activity is increased and most sphincters are relaxed. **M3** required for smooth muscle contraction **Acetylcholine: ** binds M3 **Methacholine: ** synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system. methacholine challenge test in asthma **Carbachol**: cholinergic agonist **Pilocarpine: ** Like bethanechol, M3 agonist. Treat xerostomia in Sjogren's and glaucoma **Bethanechol: ** stimulates muscarinic receptors without any effect on nicotinic receptors. Unlike acetylcholine, bethanechol is not hydrolyzed by cholinesterase and will therefore have a long duration of action. Treat post op and neuro ileus. Hits M3 on muscle cells and at myenteric plexus synapses **Neostigmine:** intermediate duration cholinesterase inhibitor. IV for treatment of acute large bowel distention

Answer 45

GI tract: blockade of muscarinic receptors has dramatic effects on motility and secretory functions. Dry mouth, gastric secretions is blocked (less acid, pepsin, mucin). Paralysis of motility is temporary; 1-3 days later, enteric nervous system will reestablish some peristalsis. **Atropine**: muscarinic antagonist **Pirenzepine**: Reduce gastric acid secretion with fewer adverse effects than atropine due to selective blockade of M1 innervating the stomach **Telenzepine**: more potent analog of Pirenzepine **Dicyclomine**: antagonistt at M3. Reduces smooth muscle and secretory activity of gut. Treatment of IBS, minor diarrhea. Toxicity: tachycardia, confusion, urinary retention

Answer 46

D2 receptor antagonists inhibits cholinergic smooth muscle stimulation Increase esophageal peristaltic amplitude, increase LES pressure, and enhance gastric emptying. Also block area postrema (CTZ of medulla)- antiemetic and antinausea Treatment of GERD, impaired gastric emptying, nonulcer dyspepsia, prevention of vomiting, postpartum lactation stimulation Adverse: Metoclopramide has CNS effects: restlessness, drowsiness, insomnia, anxiety, EPS, **tardive dyskinesia (main reason you don't give long term)**, elevated prolactin levels (associated with galactorrhea, gyneocomastia, impotence, and menstrual disorders). Domperidone is well tolerated b/c it does not cross BBB very well.

Answer 47

indigestible, hydrophilic colloids that absorb water and distend the colon, promoting peristalsis **Psyllium, Methylcellulose**: natural plant products **Polycarbophil**: synthetic fibers Adverse: bacterial digestion leads to bloating and flatus

Answer 48

Permit water and lipids to permeate Oral or rectal **Docusate** and **glycerin suppository** Docusate common in hospital to minimize straining and constipation **Mineral oil** lubricates fecal material, retarding water reabsorption. Prevents and treats fecal impaction in young children and debilitated adults. Aspiration results in lipid penumonitis Long term use can impair absorption of fat soluble vitamines K,A,D,E

Answer 49

Soluble but nonabsorbable compounds that results in increased stool liquidity due to increase in fecal fluid _Nonabsorbable sugars or salts:_ For acute constipation or prevention of chronic constipation **Magnesium hydroxide** (milk of magnesia) should not be used for prolonged periods in those with renal insufficiency- hypermagnesemia **Sorbitol** and **Lactulose** are sugars that prevent chronic constipation- causes flatus and cramps High doses cause prompt bowel evacuation (purgation) in 1-3 hours. Most commonly used purgatives are **magnesium citrate** and **sodium phosphate**. Important to maintain hydration to compensate for fecal loss Sodium phosphate causes hyperphosphatemia, hypocalcemia, hypernatremia, hypokalemia and can lead to cardiac arrhythmias and renal failure _Balanced Polyethylene Glycol_ PEG is used for colon cleansing before GI endocscope procedures (colonostocopy). No cramps or flatus produced. Isotonic solutions contain inert nonabsorbable sugar (PEG) and no electrolyte shift occurs.

Answer 50

Carthartics Induce bowel movements. MOA unclear but stimulates enteric nervous system and colonic electrolyte and fluid secretion _Anthraquinone Derivatives_ **Aloe, senna, cascara** occur in plants. poorly absorbed and produce bowel movement in 2 hours. Chronic use gives rise to melanosis coli(brown pigment in colon) _Diphenylmethane Derivatives_ **Bisacodyl**- bowel movement in 6-10 hours (oral) or 30-60 min (rectal) used for acute and chronic constipation

Answer 51

chloride channel activator laxative Used for chronic constipation and IBS with predominant constipation stimulates type 2 chloride channel in small intestine, increasing chloride rich secretion shortening transit time CI in pregancy Nausea in 30% due to delayed gastric emptying

Answer 52

These agents dont cross BBB, so don't diminish pain blocking effects of opioids. **Methylnaltrexone** bromide: treatment of opioid induced constipation. Subcutaneous administration **Alvimopan**: *short term* use for those in the *hospital* who have undergone small or large bowel resection. orally and shouldnt be taken more than week. Cardiovascular toxicity

Answer 53

For mild to moderate acute diarrhea and IBS and IBD. Not for bloody diarrhea, high fever _Opioid Agonists_ **Loperamide** doesnt cross BBB and no analgesics (no addictive potential) **Diphenoxylate** opioid agonist that does have analgesic effects at high doses. commercial preps add atropine to prevent overdosage _Bile Salt-Binding Resins_ **Cholestyramine, Colestipol, Colesevelam** may decrease diarrhea caused by excess fecal bile acids. Diseases of the terminal ileum lead to malabsorption of bile salts Colsevelam doesnt affect the absorption of other drugs Adverse: bloating, flatulence, constipation, fecal impaction _Octreotide_ **Octreotide** has similar actions to somatostatin (inhibits gastrin, CCK, slows motility, reduces blood flow) Useful for treating carcinoid and VIPomas diarrhea; pancreatic fistula b/c it inhibits pancreated secretion Octreotide increases motility at low doses but at high doses it does the opposite Adverse: steatorrhea (with KADE deficiencies), gallstones in 50%, blood glucose imbalances, bradycardia. **Kaolin, Pectin, Subsalicylate, Bismuth** are also used for treatment of diarrhea

Answer 54

Exocrine pancreatic insufficiency - cystic fibrosis, pancreatitis, pancreatic resection and leads to steatorrhea, vitamin malabsorption and weight loss supplements contain amylase, lipase, and protease **Pancreatin**: alochol derived extract of hog pancreas with low conc. of lipase and proteolytic enzymes **Pancrelipase**: enriched preparation. 12 times lipolytic activity and 4 times proteolytic activity of pancreatin. Pancrelipase rapidly inactivated by gastric acids. Enteric-coated preparations dont need to be given with an acid inhibitor Well tolerated; capsules should not be chewed b/c it can cause oropharyngeal mucositis. diarrhea and abdominal pain

Answer 55

Bile acid therapy for gallstones oral administration. After conjugation in liver and excretion in bile, it undergoes hepatic recirculation with a 100 hour half life Decreases cholesterol content by reducing hepatic cholesterol secretion Used for dissolution of small cholesterol gallstones in patients with gallbladder disease who refuse surgery or are poor surgical candiates. Adverse: Bile salt induced diarrhea (unlike chenodeoxycholate, it is not associated with hepatotoxicity)

Answer 56

Vomiting center in lateral medullary reticular formation. Acts through CN VIII and X and nucleus tractus solitarius Area postrema is outside BBB and rich in D2 receptors Vestibular system is rich in M1 and H1 Vagal and spinal afferents rich in 5-HT3 are stimulated by radiation, chemotherapy, distention

Answer 57

Antiemetic by blockade of receptors on extrinsic vagal and spinal afferents **Ondansetron, Granisetron, Dolasetron, Palonsetron** Palonsetron is a newer IV with greater affinity and longer half life Used for Chemotherapy induced nausea and vomiting (effect enhanced by combination with glucocorticoids like **dexamethasone** or **methylprednisolone**) and postoperative and postradiation nausea and vomiting **Alosetron**– IBS w diarrhea (AE – constipation) Adverse: headache, dizziness, **QT prolongation (mainly dolasetron)** metabolized by P450

Answer 58

Neurokinin receptor antagonist Antiemetic NK1 antagonism at area postrema Aprepitant (oral) is highly selective and crosses BBB Fosaprepitant is IV and converted to aprepitant in 30 minutes after infused Aprepitant is metabolized by CYP3A4 – Increased aprepitant plasma level by ketoconazole, ciprofloxacin, clarithromycin, nefazodone, ritonavir, nelfinavir, verapamil, quinidine) – Decreases the INR in patients taking warfarin with corticosteroids for prevention of acute and delayed nausea and vomiting from chemotherapy Adverse: fatigue, dizziness,diarrhea, and drug interactions all from Aprepitant

Answer 59

Antipyschotic agents that are used for their inhibition of dopamine and muscarinic receptors to prevent emesis Sedation through anti Histamine action **Prochlorperazine, Promethazine, Thiethylperazine** **Droperidol** (IM or IV) extremely sedating and EPS occurs, QT prolonged

Answer 60

Antiemetic via dopamine receptor blockade Trimethobenzamide has antihistmaine activity Used for prevention and treatment of nausea and vomiting, metoclopramide may be given in high doses EPS effects: restlessness, dystonia, parkinsonian symptoms.

Answer 61

**Diphenhydramine** and **Dimenhydrinate** are first generation H1 antagonists that have anticholinergic properties. **Meclizine** is H1 antihistamine and causes less sedation used for motion sickness and vertigo due to labyrinth dysfunction **Scopolamine** (Hyoscine) muscarinic antagonist used for preventing motion sickness High incidence of anticholinergic effects orally, better tolerated as a transdermal patch

Answer 62

Cannabinoid to reduce vomiting THC from marijuana Oral appetite stimulant and antiemetic Adverse: euphoria, dysphoria, dry mouth, hallucinations, hungry, tachycardia **Nabilone** is a closely related THC analog

Answer 63

Prokinetic agents are drugs that can selectively stimulate gut motor function Drugs that increase LES are useful for GERD; drugs that improve gastric emptying may be useful for gastroparesis and postsurgical gastric emptying delay; stimulate small intestine to treat ileus and intestinal pseudo-obstruction; enhance transit for constipation **Bethanecho**l: stimulates M3; treat GERD and gastroparesis **Erythromycin**: macrolide that stimulates motilin receptors on smooth muscle and promotes the migrating motor complex. Useful in those with gastroparesis and acute upper GI hemorrhage to promote emptying of blood (**cisapride** was increased with QT prolongation, as is erythromycin) **Metoclopramide:** D2 antagonist. Dopamine normally inhibits cholinergic smooth muscle stimulation **Domperidone**: D2 antagonist like Metoclopramide **Neostigmine**: acute large bowel distention treatment **Octreotide**: somatostatin analog that inhibits pancreatic secretion among other effects **Tegaserod**: serotonin 5-HT4 partial agonist which binds the receptors on the presynpatic terminal of submucosal intrinsic primary afferent nerves. Ultimately this promotes peristaltic reflex and proximal bowel contractions and distal bowel relaxation. Used to treat chronic constipation and IBS Pulled from market b/c of cardiovascular adverse effects **Lubiprostone**: activates type 2 chloride channel Guanylate cyclase C agonist: ** Linaclotide** – activates CFTR

Answer 64

Nitroimidazole compound used in the treatment of *E. histolytica* infections, *Giardia lamblia* infections. Also has antibacterial activity against all **anaerobic** cocci and anaerobic Gram-negative bacilli, including *Bacteroides*, *Clostridium, H.pylori, and Campylobacter* It is a pro-drug that is activated by susceptible organisms via their ferredoxins that are capable of donating electrons to metronidazole. PFOR's keep the ferrodoxins reduced. Oxygen is inhibitory. Degrades DNA Resistance is due to decreased oxygen scavenging (higher O₂) and lowered levels of PFORs. Resistance can also occur via a reducing reaction in *Bacteroides* and via multiple pathways by *H. pylori* Well absorbed in the gut, so therapeutic levels may not be reached in the colon; it is also not as effective against the cyst form of *E. histolytica*. Metabolized by liver; can be excreted by kidneys and can cause a reddish brown urine Toxicities: Well-tolerated, but can cause headache, nausea, dry mouth, metallic taste, and diarrhea. Furry tongue, glossitis, and stomatitis can be associated with exacerbation of candidiasis. Can cause peripheral neuropathies and Steven-Johnson syndrome. **Acts like disulfuram upon consumption of ethanol** Often combined with a luminal agent such as **paromomycin** or **iodoquinol** for treatment of *E. histolytica* infections **Tinidazole** is an analog used for the same purposes, and is more effective than metronidazole in the treatment of *Giardia lamblia* infections. Has less GI toxicity, hence its use in treating diarrheal Giardiasis

Answer 65

Used for treatment of trophozoites of *E. histolytica* infections and giardiasis; and oocytes of **C. parvum.** Can also treat helminths such as *T. trichiura, A. lumbricoides, E. vermicularis, A. duodenale,* and *S. stercoralis* Interferes with PFOR enxyme-dependent electron-transfer reaction (essential to anaerobic metabolism in protozoan and bacterial species) Main treatment for cryptosporidiosis, especially in immune competent children Toxicities are rare, but include a greenish tint to the urine

Answer 66

An aminoglycoside used as a **luminal agent** in treatment of *E. histolytica* infections in combination with metronidazole for liver abscesses or amebic colitis, or as a solo drug for asymptomatic patients Binds to 30S subunit of rRNA. Does not seem to be absorbed (100% fecal recovery). Parenteral administration carries same risks of ototoxicity and nephrotoxicity as the other aminoglycosides. Also used in pregnant women for treatment of giardiasis Another luminal agent is **iodoquinol**

Answer 67

An antimalarial that works on DHFR (pyramethamine) and also hits the incorporation of PABA into synthesis of dihydropteroic acid (sulfadiazine) Slowly but completely absorbed orally Adverse Effects: occasional skin rashes and reduced hematopoiesis. Excessive doses can mimic a folate deficiency. It is teratogenic

Answer 68

A halogenated 8-hydroxyquinoline that is used as a **luminal agent** to eliminate intestinal colonization with *E. histolytica*. At high doses over long periods of time can lead to **subacute myelo-optic neuropathy** (can also lead to milder peripheral neuropathy) Can be used in combination with metronidazole to treat amebic colitis or amebic liver abscesses and can be used alone to treat asymptomatic colonization

Answer 69

Anti-helminthics used in treatment of STH infections (ascariasis, enterobiasis, trichuriasis, and hookworm) Includes **thiabendazole, mebendazole, and albendazole** MOA: inhibits microtubule polymerization by binding to parasitic B-tubulin Resistance can occur through site-directed mutagenesis of the B-tubulin gene Especially effective at treating GI nematodes, where absorption is not necessary. None are recommended for use during pregnancy **Albendazole:** More effective than Mebendazole at curing hookworm, strongyloidiasis, tissue-dwelling helminths, and trichuriasis infections in children. Treatment of choice for *Echinococcus granulosus* and neurocysticercosis of *Taenia solium.* Like mebendazole, it is poorly water soluble. Fatty foods increase absorption. Can cause mild GI symptoms; causes liver dysfunction in long term use. Also have to watch out for inflammatory reactions brought about by dying cysts of neurocysticercosis. **Thiabendazole:** Not used as often due to less toxic effects of mebendazole and albendazole, but is still used topically for cutaneous larva migrans (creeping eruption). Toxicities include anorexia, nausea, vomiting, and dizziness. **Mebendazole:** Seems like its not used as often as albendazole. No significant systemic toxicity due to low systemic bioavailabitily

Answer 70

Used mostly for treatment of lymphatic filariasis caused by *Wuchereria bancrofti* and *Burgia malayi* MOA not well characterized Does not fix lymphatic damage, only prevents future lymphatic damage Do **not** use for onchocerciasis or loiasis because of severe reactions related to microfilarial destruction Toxicities include anorexia, nausea, headache, and vomiting. Major adverse effects relate to host response to dead parasites Not sure why this is a drug for this phase?

Answer 71

An anti-helminth that immobilizes affected organisms by inducing a tonic paralysis of the musculature via activation of a family of glutamate-gated chloride channels that are found only in invertebrates. Resistance can occur via pumping out the drug via and ATP-dependent P-glycoprotein or by changing the drug target Metabolized by liver Used to treat onchocerciasis, lymphatic filariasis, **strongyloidiasis**, and other intestinal nematodes including ascariasis, enterobiasis, trichuriasis, and hookworm infections. Well tolerated by uninfected humans, but can cause a big inflammatory reaction due to dying parasites

Answer 72

A pyrazinoisoquinoline derivative use to treat schistosomiasis, liver and lung fluke infections, and tape worm infections Causes increased muscular activity and spastic paralysis of affected worms as well as damaging tegument leading to more exposed antigens. Causes direct toxicities of nausea, diarrhea, headache, dizziness, and drowsiness. Causes indirect effects of fever, pruritus, uricaria, rashes, et c. that are tied to dying organisms Contraindicated in ocular cysticercosis

Answer 73

An organophosphate used initially as an insecticide, now as an anthelmintic Works on cholinesterases of ***Schistosoma mansoni* and *S. haematobium***

Answer 74

Used as second line to treat *Schistosoma mansoni* infections (second to praziquantel) Not really used in US

Answer 75

Second-choice drug to praziquantel for treatment of tape worms (*Taenia saginata, Diphyllobothrium latum, Hymenolepis nana*) Contraindicated in *Taenia solium* infections because it can lead to cysticercosis. No longer approved for use in the US

Answer 76

Not really used much, as it was replaced by the benzimidazoles It can treat *Ascaris lumbricoides* and *Enterobius vermicularis* Works on a GABA-receptor to paralize worms

Answer 77

Open nonselective cation channels and induce persistent activation of nicotinic acetylcholine receptors and spastic paralysis of worm. Used against hookworm, pinworm, and roundworm, but is ineffective against *Trichuris triciura* Poorly absorbed, hence its use in only intralumenal GI nematodes Its an alternative to mebendazole or albendazole in treatment of ascariasis and enterobiasis Do not use with piperazine

Answer 78

highly active Beta lactam antibiotic that works against gram positive organisms MOA: the last step in peptidoglycan synthesis is inhibited (in both beta lactam and vancomycin) where transpeptidase unites two glycopeptides Resistance: 1. structural differences in PBP (target of the drugs) 2. inability of agent to penetrate to site of action 3. active efflux pumps \*High yield: Penicillins with good oral absorption: **Penicillin V** (phenoxymethyl ether group)**, Oxacillin, Amoxicillin, Cloxacillin, Dicloxacillin, Ampicillin,** **Carbenicillin** S. aureus has penicillinase so penicillin G and V are inactivated. Penicillinase resistant are oxacillin, cloxacillin, dicloxacillin

Answer 79

Antibiotic against broad spectrum of gram-positive bacteria MOA: Inhibits the synthesis of cell wall by binding with high affinity to the D-alanyl-D-alanyl terminus of cell wall precursor units (inihbits transglycosylase) Used to treat osteomyelitis, endocarditis, and other infections like **C. difficile that cause pseudomembranous colitis** Resistance: Enterococcus faecium and faecalis via plasmid transposon. Organisms can alter D-ala D-ala target to D-ala D-lactate or D-ala D-serine **poor oral absorption**, IV injection only. Not highly protein bound, unlike teicoplanin. 90% excreted by renal filtration Adverse: hypersensitivity, flushing can cause red-man syndrome, auditory impairment

Answer 80

Similar to vancomycin in its structure (has different R groups), MOA, spectrum of activity, route of elimination (renal) Active against methicillin susceptible and resistant staph **IM and IV**, not orally active

Answer 81

MOA: Inhibits the synthesis of bacterial cell wall by inhibiting the dephosphorylation of a lipid transport molecle of cell wall peptidoglycan subunits Active orally *only* for antibiotic associated diarrhea due to C. difficile because it is not absorbed by the gut (has been replaced by oral vancomycin) Toxicity: serious nephrotoxicity from parental use, hypersensitivity from topical use

Answer 82

Bacteriostatic antibiotic active against broad range of aerobic and anaerobic (Bacteroides) gram positive and negative MOA: binds 30S subunit and inhibits protein synthesis. Prevents access of aminoacyl tRNA to A site on mRNA ribosome Uses: doxycycline eradicates Vibrio cholerae within 48 hours Enterohepatic circulation in the bile so they are around for a long time (weeks) Incomplete oral absorption ranging from 30-95% High absorption for minocycline and doxycycline on empty stomach. Absorption mainly takes place in the stomach and upper small intestine. **Absorption impaired by dairy and bases; chelated by di/trivalent cations** (antacids) Toxicity: toxic metabolite gets into the kidney and causes nephrotoxicity (but not with doxycycline). GI irritation (administer with food), pseudomembranous colitis, hepatic toxicity, Renal excretion except for Minocycline, which has hepatic clearance

Answer 83

Not appreciably absorbed from GI tract. Parenteral use only with wide and rapid distribution into tissues Glycycline, derivative of tetracycline **Effective against tetracycline resistant bacteria** (no resistance due to efflux pumps or ribosomal alterations) Little nephrotoxicity

Answer 84

MOA: inhibits protein synthesis by binding to 50S subunit. Prevents tRNA to bind to A site. Also inhibits mitochondrial protein synthesis in human cells. Erythropoietic cells are particularly sensitive Mostly used to treat pregnant women with Rocky Mountain Spotted fever (they cant take doxycycline). It is also used for bacterial meningitis Resistance: plasmid encoded acetyltransferase inactivates the drug; decreased permeability; ribosome mutation Inhibits the action of clindamycin; inhibits CYP Rapidly absorbed from the GI tract Dose related anemia, and potentially fatal idiopathic aplastic anemia. Can also cause a "gray baby syndrome."because they cant glucoronidate it. Idiosyncratic response of aplastic anemia (fatal pancytopenia)

Answer 85

**Sulfisoxazole, Sulfamethoxazole** MOA: competitive inhibitors of dihydropteroate synthase, used for incorporation of PABA into dihydropteroic acid, a precursor for folate acid trimethoprim exerts synergism Absorbed rapidly from the GI tract 70-100% Sulfisoxazole: tasteless and preferred for oral use in children. Fewer than .1% had toxic reactions Sulfamethoxazole: oral for systemic and urinary tract infections (this is the one that is always used in combination with trimethoprim) Resistance is by altering target enzymes and active extrusion Toxicity: Older sulfanamides lead to crystaluria (bladder damage). Newer ones don't crystallize. All of them cause anorexia, nausea, vomitting in 2%. Some can cause hemolytic anemia

Answer 86

Macrolide antibiotic Bacteriostatic by inhibiting protein synthesis. Binds 50S ribosome subunit so no translocation Resistance: efflux pumps, methylase enzymes, esterases (enterobacteriaaceae), alter 50S subunit Oral and is rapidly absorbed and distributes widely throughout the body , except to the brain and CSF. aluminum and magnesium hydroxide antacids decrease peak serum concentrations. Dont take with food Gastroenteritis from Campylobacter is treated with Erythromycin and H. pylori is treated with clarithromycin with omeprazole. Not sure

Answer 87

Similar spectrum of activity as Azithromycin. **Can withstand macrolide resistance mechanisms (overcomes methylation of target)** so better against S. aureus and S. pneumoniae Oral absorption is 60%. 60-70% protein bound and concentrates in macrophages and white blood cells. 9.8 hours half life, can be given once daily Doesn't induce methylase

Answer 88

Macrolide antibiotic: binds 50S Resistance: ribosome methylation, **but not a substrate for macrolide efflux pumps (big benefit)** Fully absorbed Kills all gut flora, except for C. difficile High incidence of diarrhea (20%) and **pseudomembranous colitis** should limit its use to treat infections. Colitis: watery diarrhea, fever, elevated WBC. Skin rashes are common

Answer 89

Don't give to children, they get some form of arthritic pain **Ciprofloxacin, Levofloxacin** These agents are first line treatment for typhoid fever, patients with severe diarrhea. Used IV if patient is vomitting GI distress common in 17% of patients **Ciprofloxacin:** DNA gyrase inhibitor GI distress in 17% Causes joint swelling in patients under 17 **Levofloxacin:** Increased risk of tendon tearing heralded by joint swelling

Answer 90

acts on two steps of synthesis of tetrahydrofolic acid. Sulfonamide inhibits the incorporation of para aminobenzoic acid (PABA) into folic acid via dihydropteroate synthase. Trimethoprim prevents the reduction of dihydrofolate to tetrahydrofolate via dihydrofolate reductase Trimethoprim is highly selective for DHFR of lower organisms, and humans get their folate from food sources. 100,000X dosage is needed to inhibit human enzyme Resistance: plasmid encodes a different dihydrofolate reductase Uses: Gram-negative infections, Urinary tract infections, GI infections for Shigellosis, Salmonella typhi, enteropathogenic E. coli Adverse: maybe can induce folate deficiency, megaloblastosis, leukopenia, thrombocytopenia

Answer 91

Campylobactor, Shigella: Ciprofloxacin C. difficile: Methronidazole V. cholera: Tetracycline Traveler's diarrhea: Ciprofloxacin Giardia lamblia: Metronidazole Entamoeba histolyica: Metronidazole

Answer 92

Inhibits bacterial cell wall synthesis similar to penicillin 3rd generations are less active than 1st gen against gram positive. They are more active against Enterobacteriaceae Resistance: alterations of PBP or inability to reach site of action 2nd gen can treat E. coli. 3rd gen for Enterobacteriaceae Adverse: hypersensitivity, cross-reactivity with penicillins, nephrotoxic, diarrhea \*High yield: Oral absorption: 1st gen: **Cephalexin, cefadroxil**, **2nd gen: cefaclor** (most widely used second generation), **loracarbef**. 3rd: **Cefpodoxime proxetil**

Answer 93

**_Salmonella:_** Nontyphoid: ciprofloxacin or levofloxacin for 5-7 days Typhoid: ciprofloxacin or ceftriaxone. For children: azithromycin **_Shigella:_** Ciprofloxacin or Levofloxacin or TMX-sulfa **_Campylobacter jejuni:_** Azithromycin or ciprofloxacin **_E. coli:_** Ciprofloxacin or levofloxacin. No treatment for enterohemorrhagic E. coli **_Vibrio parahemolyticus:_** no treatment **_Vibrio cholera:_** ciprofloxacin or doxycycline **_Yersinia entercolitica:_** doxycycline plus gentamicin **_C. difficile:_** metronidazole or for severe colitis, Vancomycin (risk of superinfection so limit usage) **_H. pylori (not diarrhea)_** Omeprazole, amoxicillin, metronidazole, clarithromycin \*avoid agents that slow peristalsis, as these can prolong fever and bacteremia

Answer 94

– Create protective layer, may stimulate PG, mucus, bicarbonate secretion – Bismuth has direct antimicrobial effects and binds enterotoxins Clinical uses – Dyspepsia, acute diarrhea, prevention of traveler’s diarrhea – Bismuth-based quadruple therapy against H pylor Adverse: – Coloring (black stool, darkening of the tongue) – Short-term use only, avoided in renal insufficiency – Prolonged usage may lead to bismuth toxicity resulting in encephalopathy (ataxia, headaches, confusion, seizures) – High dosage of bismuth salicylate (salicylate toxicity)