GI Pharm Flashcards

Question

Laxatives - fiber - osmotic

Answer 1

Fiber = carboxymethylcellulose, psyllium, polycarbophil - bulk laxatives --> form gels in the colon causing water retention and distension = increased peristalsis Osmotic = milk of magnesia, na phosphate, polyethylene glycol, Mg salts, lactulose - draws H2O into the intestinal lumen via osmosis resulting in softer/liquid stools and distension induced peristalsis

Answer 2

Stimulant/irritant = bisacodyl, senna - stimulates colonic smooth muscle and causes H2O accumulation in lumen --> exact mechanism unclear Stool softeners - surfactant = docusate --> causes fat/H2O to mix - lubricant = mineral oil --> softens stools, prevents H2O absorption, can inhibit absorption of fat soluble vitamins - glycerin --> enhances H2O retention Cl channel secretion = lubiprostone - activates ClC2 chloride channels causing chloride secretion --> sodium follows to maintain isoelectric equilibrium --> water follows sodium

Answer 3

- investigate the underlying cause - eliminate infection - remove triggers - replace fluids and electrolytes - treat symptoms

Answer 4

Antimotility - opiates - loperamide - diphenoxylate-atropine - tincture of opium Adsorbents - bismuth subsalicylate - fiber - cholestyramine - colestipol Antisecretory - octreotide - somatostatin

Answer 5

Opioid receptor - loperamide, diphenoxylate/atropine, ticture of opium Acts directly on circular and longitudinal intestinal muscles - inhibits peristalsis and prolongs transit time - increases viscosity - diminishes fluid and electrolyte loss Increases anal sphincter tone

Answer 6

Bismuth subsalicylate (peptobismol) - antisecretory - antimicrobial - anti-inflammatory Fiber = bulking agent - most people are familiar with fibers use in constipation --> better to think of it as a stool regulator - in diarrhea, it acts as a bulking agent by absorbing intraluminal water from stool and therefore improving the consistency Cholesteryamine + colestipol = bile acid binding resin - stimulate colonic secretion, causing a secretory diarrhea - bile acids are normally absorbed in the terminal ileum before reaching the colon - when the terminal ileum is diseased or resected, bile acids can be malabsorbed and subsequently enter the colon - cholestyramine forms a nonabsorbable complex with bile acids in the intestines, preventing them from stimulating colonic mucosa to secrete electrolytes and fluid

Answer 7

Octreotide/somatostatin - reduces fluid and electrolyte secretion by stomach and pancreas - mild antimotility effect - promotes intestinal electrolyte absorption - suppresses neuroendocrine tumor release of peptides that cause intestinal hypersecretion of electrolytes and water

Answer 8

Do not give antidiarrheals in the setting of bacterial infection or inflammation Use caution when combining loperamide and tincture of opium with other CNS depressants --> side effects can be additive, including sedation and respiratory depression Remember the "salicylate" in bismuth subsalicylate --> use with caution in patients on aspirin or anticoagulation; reye syndrome Separate cholestyramine from other medications by at least 2 hours --> just as it binds bile acids, it can also bind other meds, decreasing their absorption and therefore their efficacy

Answer 9

Emetic stimuli act at several sites - Emesis provoked by unpleasant thoughts or smells originates in the cerebral cortex, whereas cranial nerves mediate vomiting after gag reflex activation. - Motion sickness and inner ear disorders act on the labyrinthine apparatus. - The area postrema, a medullary nucleus, responds to bloodborne emetic stimuli, and is also known as the chemoreceptor trigger zone. - Many emetogenic drugs act on the area postrema, as do bacterial toxins and metabolic factors produced during uremia, hypoxia, and acidosis. - Gastric irritants stimulate gastroduodenal vagal afferent nerves, which activate the area postrema. These emetic stimuli result in release of neurotransmitters such as histamine and acetylcholine from the vestibular system and 5-HT3 and DA from visceral stimuli and the area postrema, which then activate the nucleus tractus solitarius to coordinate the initiation of emesis involving neuromuscular responses in the gut, pharynx and thoracic and abdominal wall.

Answer 10

Anticholinergic --> scopolamine Antihistamine --> meclizine + dimenhydrinate DA-antagonist --> prochlorperazine + promethazine 5HT3 antagonist --> ondanestron, dolasetron, granisetron Cannabinoid --> dronabinol Neurokinin antagonist --> aprepitant

Answer 11

Blocks action of Ach at M1 - scopolamine is effective in preventing motion sickness, but not significantly in treating it - can also be effective in preventing chemo induced nausea - transdermal patch applied every 72 hours Side effects - dry mouth - sedation - blurred vision - confusion and urinary retention in the elderly

Answer 12

Anti-histaminic (H1) and anticholinergic - Meclizine, dimenhydrinate (dramamine) - effective in treatment of motion sickness - tablet, oral suspension, IM dimenhydrinate - anticholinergic side effects - meclizine may be less sedating than dimenhydrinate

Answer 13

D2 receptor blockers, some anticholinergic effect - promethazine + prochlorperazine - effective antiemetic in multiple settings --> motion sickness, toxic and metabolic induced nausea, and is often used for preoperative prophylaxis - available formulations include oral tablet or suspension, rectal suppository, IM and IV Adverse effects - sedation - extrapyramidal symptoms --> pseudoparkinsonism, acute dystonic reactions, and tardive dyskinesia - QT prolongation - anticholinergic side effects

Answer 14

Selective 5HT3 receptor antagonist, vagal nerve terminals, and chemoreceptor trigger zone - ondansetron, dolasetron, granisetron - effective anti-emetic in multiple settings, including chemotherapy induced nausea and vomiting Adverse effects - QT prolongation

Answer 15

CNS cannabinoid (CB1) receptor agonist, likely interacts with multiple neurotransmitters - delta-9-tetrahydrocannabinol (THC) - oral tablet - approved for chemotherapy induced nausea/vomiting, and as an appetite stimulant in HIV/AIDS Adverse effects - euphoria - paranoia - CNS depression - abuse potential

Answer 16

Substance P/neurokinin-1 receptor antagonist - aprepitant + fosaprepitant - effective in prevention of acute and delayed chemotherapy induced and postoperative nausea/vomiting, especially as adjunctive therapy - oral capsule or IV before chemo chemo or anesthesia Adverse effects - hiccups - fatigue - increased risk of severe infection

Answer 17

Migraine related nausea --> DA antagonists, 5HT3 antagonists Motion sickness --> anticholinergics, antihistamine Chemo induced nausea/vomiting --> 5HT3 antagonists, corticosteroids, NK antagonists - others = cannabinoids, benzodiazepines Postoperative nausea/vomiting --> DA antagonist, 5HT3 antagonists, NK antagonists Hyperemesis gravidarum --> ginger, B6, antihistamines, DA antagonists, 5HT3 antagonists

Answer 18

In the GI world, these medications are most often used to treat inflammatory bowel disease. In general, inflammatory bowel disease or IBD is comprised of 2 major disorders– Crohn’s disease and ulcerative colitis. They are chronic autoimmune inflammatory conditions that affect the GI tract. The goals of therapy in IBD are both managing symptoms as well as preventing complications of disease. Drugs - aminosalicylates - glucocorticoids --> predinsone, methylpredisolone, budesonide - immunomodulators --> 6mercaptopurine, azathioprine, methotrexate - bioogics --> infliximab, adalimumab, certolizumab pegol, natalizumab

Answer 19

Topical anti-inflammatory effect via multiple mechanisms - Sulfasalazine: prodrug reduced in the colon - 5-aminosalicylate: mesalamine, balsalazide, olsalazine - -> Effective in ulcerative colitis (UC) and Crohn’s disease (CD) of the colon 5-ASA is the active component in all of these agents. However, >75% of unconjugated 5-ASA is absorbed in the jejunum, leaving little to act in the colon. Sulfasalazine is a prodrug of 5-ASA linked to sulfapyridine by an azo bond; in the colon, bacteria produce azoreductase which breaks the bond and releases 5-ASA. Different mechanisms to allow delivery of 5-ASA to the colon have been developed. There are delayed and controlled-release formulations of mesalamine that consist of 5-ASA molecules within an enteric coating or a semipermeable membrane that resists breakdown in the stomach.

Answer 20

Sulfasalazine - Frequent GI, CNS, and hematologic side effects - Agranulocytosis is a rare side effect. - Decreases folic acid absorption– supplement with folic acid 1mg daily 5-aminosalicylates - mild GI side effects - hypersensitivity reactions = pancreatitis, pneumonitis - paradoxical worsening of disease - chronic interstitial nephritis

Answer 21

Conventional --> predisone + methylpredinsolone - Effective in inducing remission in both UC and CD, generally reserved for moderate to severe disease - Should be used as a short-term induction therapy, not a chronic maintenance agent - Cannot be abruptly stopped, requires taper to avoid secondary adrenal insufficiency Non-systemic --> budesonide - controlled ileal release vs. extended colonic release - high first pass hepatic metabolism** - induction agent in CD, not effective for long term maintenance - lower incidence of adrenal suppression, but still requires taper

Answer 22

- eurphoria - buffalo hump - hypertension - thinning of skin - muscle wasting - poor wound healing - easy bruising - increased abdominal fat - moon face with red cheeks - cataracts

Answer 23

- Azathioprine is a purine antimetabolite - 6-mercaptopurine is the active metabolite of azathioprine - 6-MP is metabolized by thiopurine methyltransferase, or TPMT, into 6-MMP; and by hypoxanthine phosphoribosyl transferase (HPRT) into the precursor of 6-TGN which is the active metabolite. - 6-TGN inhibits nucleotide synthesis, which results in decreased numbers of circulating B and T lymphocytes as well as decreased proinflammatory cytokine production. A very small proportion of the general population can have low or no TPMT enzyme activity, which would cause 6-MP to preferentially be shunted towards the active metabolite 6-TGN.

Answer 24

Maintenance of remission in CD and UC - These mechanisms suppress autoimmune-medicated inflammation in the GI tract in both Crohn’s disease and ulcerative colitis - However, it is effective as only maintenance, does not induce remission. - As a result, we use it in combination with an induction agent such as a glucocorticoid - It typically takes about 3 months to achieve therapeutic levels Adverse effects - leukopenia and thrompocytopenia** (6-TGN) - hepatotoxicity (6-MMP) - infection - increased risk of malignancy - avoid use with allopurinol**

Answer 25

Folate antimetabolite, competitively inhibits the binding of dihydrofolic acid to dihydrofolate reductase. - It is thought to induce apoptosis of peripheral T cells, thereby suppressing autoimmune-mediated inflammation in the GI tract. Effective in maintenance of remission in CD - oral or IM Adverse effects - hepatotoxic --> avoid alcohol - myelosuppression - interstitial lung disease - give folic acid 1mg daily to all patients - teratogenic --> contraindicated in pregnancy

Answer 26

Monoclonal antibodies against TNF alpha = inflammatory cytokine that plays a significant role in IBD - effective for induction and maintenance of remission in CD and UC Adverse effects - infection --> screen for latent TB and hepB before initiation - myelosuppression - increased risk of malignancy - psoriasis, drug induced lupus, demyelination Drugs - infliximab - adalimumab - certolizumab - golimumab

Answer 27

Infliximab - chimeric AB --> Human constant region and mouse variable region - IV - every 8 weeks - CD and UC Adalimumab - humanized AB --> Human constant and variable regions - SC - every 2 weeks - CD and UC Certolizumab pegol - PEG Fab --> Fab’ fragment bonded to polyethylene glycol, increases its half-life - SC - every 4 weeks - CD only Golimumab - humanized AB --> Human constant and variable regions - SC - every 4 weeks - UC only

Answer 28

Natalizumab --> blocks leukocyte migration from blood vessels to sites of inflammation - increased risk of progressive multifocal leukoencephalopathy (PML) --> JC-virus reactivation resulting in severe demyelination, progressive neurologic dysfunction. It is associated with a 20 percent mortality rate and a high degree of disability among survivors.

Answer 29

Induction - 5-ASA - glucocorticoids - biologics Maintenance - 5-ASA - 6MP/AZA - MTX - biologics

GI Pharm Flashcards

(53 cards)