Med classes GI- Quiz 2 Flashcards
What are the 2 main causes of peptic ulcer disease? *
- H. Pylori (H2 blockers)
- NSAIDs (PPI’s)
How is H. Pylori diagnosed?
Diagnosed:
1. EGD or serology
2. Fecal antigen
3. Urea breath tests (patient cant have antacids, PPI, or H2 for 14 days prior) WHY DO I FEEL LIKE THIS IS A TEST ?
What is the regimen of choice for H. Pylori?*
-Quadruple therapy with: Pepto-Bismol, Flagyl, Tetracycline + PPI
Second option is Triple therapy with: PPI, Amoxicillin and Clarythromycin
H2 Blockers*
-“Tidine’s”
-MOA: Act selectively on H2 receptors in the stomach, without effecting H1 receptors — they reduce the secretion of gastric acid
-Uses: PUD/ heartburn (takes longer to work but lasts longer than antacid)
Pharm: Distribute widely across body (including placenta/breast milk)
Half life: ½ life of these drugs are prolonged in renal disease—
dosage adjustments are needed
-ADE’s: Confusion in elderly
Cimetidine= gynecomastia/ galactorrhea
-Ex. Cimetidine, Famotidine, Nizatidine
-NOTE* Cimetidine is PROTOTYPE
for this family but rarely used today d/t ADE’S (inhibits many CYP 450 isoenzymes)*
Compare and contrast Cimetidine, Famotidine, and Nizatidine *
-Cimetidine= gynecomastia, CYP, warfarin phenyntoin clopidogrel cant use
-Nizatidine= Well tolerated
-Famotidine= minimal side effects, MOST potent, NO CYP
H+/K+ ATPase Proton
Pump Inhibitors (PPI’s)*
-“Prazole’s”= more effective at suppressing acid/healing ulcers than H2 blockers
-MOA: work by inhibiting the hydrogen-potassium ATPase enzyme ,the proton pump, which is responsible for the final step in gastric acid secretion.
-Uses: Gerd, esophagitis, active duodenal ulcer, Zollinger-Ellison Syndrome
Pharm: take 30-60 mins before largest meal of day
Half life: only a few hours but duration of action is long (when initiating usually 18-24 hrs to work)
-ADE’s: Increased risk of fractures with >1 year of use, prolonged acid suppression=vitamin B 12 deficiency, supplement with ca citrate, diarrhea, C diff, low mag, increased risk of PNA
-Oral agent of Omeprazole + NaHCO3
that has a faster onset of action
- Nexium, Prevacid, Protonix are IV
-Ex: Lansoprazole, Dexlansoprazole,
Omeprazole, Esomeprazole,
Pantoprazole, Rabeprazole
Prostaglandins*
-Misoprostol (Cytotec) approved for the prevention of NSAID induced ulcers
MOA: PGE-1 produced by gastric mucosa, inhibits secretion of acid and stimulates secretion of mucus and HCO3 (Cytoprotective)
-Can be used prophylactially in those who take a lot of NSAID’s and are at increased risk for ulcer
-A deficiency of prostaglandins is thought to be involved in the pathology of peptic ulcers)
-CI: DO NOT USE THIS DRUG IN PREGNANCY/CHILDBEARING AGE
-ADE: Dose related diarrhea is the most common
Antacids*
-MOA: Weak bases that react with gastric acid to form water and a salt to diminish gastric acidity
-Also decrease pepsin activity
Uses: symptomatic relief of PUD, heartburn, GERD
Pharm: Most effective AFTER meals
-Chem: Varies widely,Efficacy of an antacid depends on its capacity to neutralize gastric HCl and whether the stomach is full or empty— food delays stomach emptying, allowing more time for antacid to react and prolonging action of the medication
ADE: Aluminum hydroxide (constipation) Magnesium hydroxide (diarrhea), accumulation and ADEs can occur in those with renal disease
-Ex: Aluminum hydroxide (constipation), Aluminum hydroxide + magnesium hydroxide (diarrhea), Calcium Carbonate (constipation), Magnesium hydroxide (diarrhea),
Sodium bicarbonate (constipation or diarrhea depending on dose)
Which antacids to avoid with HF, renal failure, HTN, or constipation*
-HF= sodium bicarb (fluid retention)
-Renal=Magnesium (toxicity)
-HTN= sodium bicarb (fluid retention)
-Constipation= aluminum hydroxide
What meds can you NOT take with antacids?*
-Tetracylines
-Flouroquinolones
-Digoxin
-Warfarn
-Phenytoin
-Keoconozale
-Iron
(All these reduce absorption)
-Levothyroxine
(reduces efficacy)
Mucosal Protective Agents*
-MOA: have actions to enhance mucosal protection mechanisms—preventing mucosal injury, reducing
inflammation and healing ulcers
-Cytoprotective compounds
-Ex. Sucralfate, Bismuth subsalicylate (Pepto-Bismol)
Sucralfate*
-Forms a complex gel with epithelial cells by creating a physical barrier that protects the ulcer from pepsin and acid, allowing the ulcer to heal
-Effective to treat duodenal ulcers and prevent stress ulcers—but use is limited due to the need for multiple daily doses, drug- drug interactions.
-It requires an acidic pH for activation—should not be given with PPIs, H2B or antacids
-Well tolerated; it can bind to other drugs and interfere with their absorption
ADE: Constipation
Which GI meds are CI for pregnant women or childbearing age?*
-Misoprostal
-Tetracyclines
-Flouroquinolones
Antidiarrheals appropriate for pregnant women and children?*
-Pregnant women= Bismuth (limited use) Need oral rehydration
-Children= Loperimide (limited doses) need oral rehydration
Bismuth subsalicylate*
-NAUSEA, Heartburn, indigestion, upset stomach, DIARRHEA- hey! pepto-bismol! ;)
-Used as part of quadruple therapy to treat H. Pylori
-It has antimicrobial actions—it inhibits the activity of pepsin, increases secretion of mucous and interacts with glycoproteins in necrotic mucosa to coat and protect the ulcer
-Prevents travelers Diarrhea
-BLACK TONGUE
-Dont use in children less than 12
What 2 sites in the brainstem play a role in vomiting?*
- Chemoreceptor trigger zone [CTZ]—located outside the blood-brain barrier— can respond directly to chemical stimuli in the blood or CSF (dopamine, serotonin)
- Vomiting center—located in the medulla, coordinates the motor mechanisms of vomiting (histamine, acetylcholine)
Phenothiazines for nausea*
-MOA: These agents act by blocking dopamine receptors in the CTZ in
the brain
-Prochlorperazine [Compazine] is the PROTOYPE in this category
-Used for low or moderately emetogenic chemotherapy agents prophylactically
-Can also be used for post-op n/v and
associated with gastroenteritis
-Not approved for children < 2 years
-Another option is Promethazine [Phenergan] (used for post-operative nausea and vomiting and GI
associated nausea and vomiting; not approved in those < 2 years)
-ADE: ADEs limits high dose, prolonged use (Extrapyramidal symptoms)
5-HT3 receptor blockers for nausea*
-“Tron”
-MOA: These drugs selectively block the 5-HT3 receptors in the periphery and in the CTZ
-This is the superior choice for chemo
-Ondansetron [Zofran]—is the PROTOTYPE drug in the category
-Pharm: Are metabolized by the liver, only Zofran requires dose reduction in those with liver disease
-ADE: QT prolongation can occur with high dose Zofran
-Not recommended in children, but Zofran can be used in those 4 and older on chemo
-Ex: Dolasetron, Granisetron,
Palonosetron
Substituted Benzamides for nausea*
-MOA: work by inhibiting dopamine in the CTZ
-Metoclopramide is the PROTOTYPE
-Because of potential for EPS—this is never recommended long term or high doses
-Uses: n/v treatment of DM gastroparesis (even though lower doses are used—risk of EPS is still concern)
-Other med: Trimethobenzamide
-Used for post-op/ gastroenteritis related n/v
-Very effective, but risk of EPS limits long term use
-Not approved to be used in children
-CI= Parkinsons
NOTE* BB WARNING FOR TARDIVE DYSKINESIA WHEN USED > 12 WEEKS*
Butyrophenones for nausea*
- “peridol”
-MOA: work by blocking dopamine receptors
-Used most often for sedation for EGD and
surgery (not used
commonly for n/v because they may
prolong the QTc, now reserved for those resistant to other anti-emetics)
-Only moderately effective for n/v
-Ex: -Droperidol, Haloperidol
Corticosteroids for nausea
-“one”
-MOA is unknown—may involve
blocking prostaglandins
-Mildly/ moderately effective for chemotherapy induced n/v
-Often used in combo with other agents
-Ex: Dexamethasone,
Methylprednisolone
Substance P/Neurokinin-1 Receptor Antagonists*
-“tant”
-MOA: These drugs target the neurokinin receptor in vomiting
center and block the actions of substance P
-Usually given with dexamethasone and a 5-HT3
-Work well for the LATE phase of
chemotherapy n/v (24 or more hours after the chemo infusion)
-Have CYP34A inhibitor/inducer interactions- avoid giving with
-ADE’s: fatigue, diarrhea, abdominal pain and hiccups
-Ex: Aprepitant, Fosaprepitant injection, Netupitant, Rolapitant
What combination of meds can you give for nausea?*
- Dexamethasone + high-dose Reglan, 5-HT3 antagonists,
phenothiazines, butyrophenones or a benzodiazepine - Antihistamines (Dramamine) + with high dose Reglan to reduce EPS reactions
- Antihistamines (Dramamine) + with
corticosteroids to reduce Reglan induced diarrhea
What nausea medications are safe in pregnancy?*
-Pyroxidine (Vitamin B6) First line
-Zofran relatively safe
-Phenergan relatively safe
What nausea medications are safe in children?*
-Zofran older than 4 on chemo
-Phenergan older than 2
Antimotility Agents (Antidiarrheal)*
-MOA: They activate presynaptic opiate receptors in the to inhibit acetylcholine release and decrease peristalsis
-Are analogs of Demerol and have opioid like actions on the gut [no analgesic effects at usual dosages]
-Uses: Imodium is first line to treat acute diarrhea, traveler’s diarrhea
-Both of these agents can cause TOXIC MEGACOLON, so they should not be prescribed in young children OR those with severe colitis
-NOTE* BB WARNING TO TAKE AS INSTRUCTED, HIGH DOSE= EUPHORIA
-Lamotil= Less likley to be abused d/t atropine qualities
-Ex: [Lomotil], [Imodium]
Adsorbents (Antidiarrheals)*
-MOA: act by absorbing intestinal toxins or bacteria and/or by coating
the intestinal mucosa
-Less effective than antimotility drugs
-They CAN interfere with
absorption of other drugs (separate by 2 hours)
-Ex: Aluminum hydroxide,
Methylcellulose, bismuth (fluid and electrolyte modifier)
Irritant and Stimulant Laxatives*
- Senna: Stimulant, cramping
- Bisacodyl: Stimulant, cramping
- Castor Oil: Irritant, tastes bad, severe GI side effects
-Avoid in pregnancy—it could
stimulate contractions
Bulk Laxatives*
-MOA: Form gels in the large colon, causing water retention and intestinal distention
-Psyllium can reduce the absorption of other oral drugs
-Other drugs should be separated from Metamucil by at least 2 hours
-ADE:s Bloating
-Ex: Methylcellulose, Psyllium [Metamucil]
Saline and Osmotic Laxatives*
-MOA: Nonabsorbable salts that hold water in the gut by osmosis
-Ex. Magnesium citrate, Magnesium hydroxide
-Polyethylene glycol
-PEG powder solution without electrolytes is also used as a laxative (Thought to cause less cramping and flatus than others)
-Lactulose:
-Acts as an osmotic laxative—not
-Can also be used for hepatic encephalopathy
Stool softeners*
-Surface active agents that soften stools and ease passage through gut
-Should not be used with mineral oil because of the potential to absorb the mineral oil
-Better for preventing constipation than treating it– takes days to work
- Ex: Docusate sodium [Colace], Docusate calcium
Lubricant Laxatives*
-Mineral oil, Glycerin suppositories
MOA: Lubricants that facilitate the passage of hard stools
-Patient should take mineral oil orally in an upright position for at least 30 mins (worry about asp pna)
Chloride Channel Activators (Laxatives)*
-Lubiprostone
-Activates Cl- channels to increase fluid secretion in the gut causes little change in electrolytes
-Used to treat chronic constipation and IBS-C because there is no evidence of dependency and tolerance to this medication and min drug-drug interactions
Laxatives that can be used on pregnant women and children?*
-Pregnant women= psyllium, metamucil, melthycellulose, colace, magnesium, lactulose
-Children= metamucil, citrucil, water, glycerin suppositories, miralax, mineral oil
Irritable Bowel Syndrome*
-Syndrome of chronic abdominal pain and altered bowel habits in the absence of pathology
-Classified as either constipation predominant [IBS-C], diarrhea predominant [IBS-D] or combined IBS
-Type of meds you can give:
IBS-C → Laxatives, secretagogues, fiber
IBS-D → Antidiarrheals, bile acid binders, 5-HT3 antagonists
Inflammatory Bowel Disease*
-IBD is a group of immune mediated GI disorders— inflammation in the intestine in response to bacterial
antigens in the lumen of the bowel
-Ulcerative Colitis [UC] (usually involves rectum)
-Crohn’s Disease [CD] (Can involve any part of the bowel from mouth to the anus)
5-Aminosalicylates for IBD:
AZO/ MESALAMINE AGENTS*
-“Zi’s”
-Actions: antiinflammatory and immunosuppression properties
-Uses: workhorses for UC
-The PROTOYPE drug is Sulfasalazine
-MOA: unknown
-Pharm: Absorption of 5-ASA increases with severity of disease and decreases with decreased pH
-Absorption and systemic exposure depends on length of rectal retention
-Sulfasalazine reversibly impairs male fertility, and inhibits intestinal folate absorption (supplements are needed when taking this chronically)
-ADE: headache, nausea, fatigue,
-Rare: hemolysis, myelosuppression,
hepatitis, nephrotoxicity, fever, rash and SJS syndrome
-Ex: Balsalazide, Mesalamine, Olsalazine
-NOTE* avoid taking with PPIs, H2Bs, antacids cause increased systemic
absorption and premature release of 5-ASA before it gets to site of action
Corticosteroids for IBD considerations*
-Effective in inducing remission in IBD—but long-term maintenance should be avoided because of marked ADEs
-Rectal formulas have fewer ADEs than systemic steroids—but they
are only effective in left sided disease
-Enteric released drugs of oral budesonide deliver the steroid to a portion of inflamed bowel—few ADEs
-Delayed release budesonide is used in ileocecal CD
-ER budesonide delivers drug troughout the colon and is used in UC patients that have pancolitis—
although effective, is not used in long term maintenance of remission because of risk of ADEs of steroids
What are the general biologics groups?*
- TNF-ἀ inhibitors
- ἀ-4 integrin inhibitors
- L 12/23 inhibitor
-Used in the management of IBD
-Are associated with increased risk of infections
-Patients MUST be checked for TB and treatment for latent TB should be considered BEFORE these drugs are initiated
TNF-α Inhibitors for IBD*
-All end in “mab” for monoclonal antibody
-Infliximab [PROTOTYPE drug]
-Effective at both induciotn and maintenance of remission in IBD
-Are first line drugs for CD for moderate disease or risk for progression
-Are 2nd line in those with UC who have failed 5- ASA, are unresponsive to or dependent upon steroids or who present w more severe disease
-Are associated with development of
immunogenicity and antidrug antibodies that can result in loss of response in large number of patients
-Ex: AdalimumaB, Certolizumab,
* GolimumaB
α-Integrin Inhibitors for IBD*
-Only one drug approved for this:
-Vedolizumab
-Adhesion molecules that promote WBC migration to sites of inflammation
-These drugs reduce WBC migration into the intestine mucosa and also inflammation
-Exhibits specific binding to α-4/ß-7 integrin and is indicated for refractory UC and CD for induction of remission and maintenance
-ADE: HA, arthralgia, nausea, fatigue, MSK pain
IL-12/23 Inhibitors for IBD*
-Inhibits cytokines IL-12 and IL-23 involved in lymphocyte activation
-Uses: psoriasis, psoriatic arthritis, induction and maintenance of remission in CD in those refractory to
or intolerant to an TNF-α , immune modulators or steroids
-Only one drug in this group: Ustekinumab
-ADE: HA, arthralgia, infection, nausea and nasopharyngitis
Immune modulators for CD:
Methotrexate*
-Structural analogue of folic acid that inhibits the production of folinic acid
-MOA in CD is unknown
-Only IM or SQ MTX works in CD
-It is recommended as monotherapy for maintenance of remission in CD, but is NOT recommended in UC
-Daily folic acid supplement helps reduce GI SE and is recommended
-ADE: —headache, n/v, abdominal discomfort, elevated LFTs, rash
Thiopurines for IBD*
-“prine”
-Oral meds that have steroid sparing effects in those with UC or CD
-1 st line as monotherapy to maintain remission
-Use of these agents in IBD is limited due to concerns regarding toxicity, including BM suppression and liver
toxicity
-Monitoring of CBC and LFTs is necessary
-Ex: Azathioprine and 6-mercaptopurine a
What are the 3 main immune modulators used for IBD?*
- Methotrexate (MTX is also used in cancer, RA and psoriasis)
2.Azathioprine (sometimes used in kidney transplant) - 6-Mercaptopurine
