GI DISEASES Flashcards
ANTACID MECHANISM
weak bases that react with gastric HCl to form salt and water. The end result is an INCREASED pH. Provide QUICK RELIEF OF SYMPTOMS
COMMONLY USED ANTACIDS
1) MAGNESIUM HYDROXIDE (Milk of Magnesia)
2) ALUMINUM HYDROXIDE
3) CALCIUM CARBONATE (TUMS)
ADVERSE EFFECT of
1) MAGNESIUM HYDROXIDE
2) ALUMINUM HYDROXIDE
3) CALCIUM CARBONATE (TUMS)
1) Magnesium hydroxide produces Mg salt, which is very poorly absorbed and causes DIARRHEA
2) ALUMINUM HYDROXIDE: reacts with HCl to form Aluminum chloride, which is insolube and causes CONSTIPATION + HYPOPHOSPHATEMIA
3) CALCIUM CARBONATE: hypercalcemia, nephrolithiasis, and constipation (fecal compaction) -
NOTE FOR ALL 3: note that Ca, Mg, and Al can all CHELATE TETRACYCLINE
FACTORS that ENHANCE GASTIC ACID SECRETION
3 AGONISTS:
1) HISTAMINE
2) ACETYLCHOLINE
3) GASTRIN
- the final pathway of these compounds is activation of the H+/K+ ATPase pump
H2 RECEPTOR BLOCKERS
Names + function
1st Gen: CIMETIDINE =
–> shorter acting and inhibit CYP450
2nd Gen: =
–> longer acting and do not inhibit CYP450
–> anything that ends in “TIDINE” that’s not Lora Fux
1) Famotidine
2) Ranitidine
3) Famotidine
4) Nizatidine
FUNCTION: blocks the Gs mediated increase in cAMP that activates the H+/K+ pump
–> are capable of decreasing nearly 60-90% of basal secretion of gastric acid following a single dose
INDICATION for ANTACIDS
1) GERD
2) GASTRITIS
3) PUD
- provide quick releif for these symptoms
Drug used to treat ACUTE STRESS ULCERS (associated with major trauma and in high-risk patients in intensive car units)
H2 BLOCKERS –> are usually given IV injection
Drus used PREOPERATIVELY to PREVENT ASPIRATION PNEUMONIA
H2 blocker
ADVERSE EFFECTS of H2 BLOCKERS
-H2 second gen: normally all tolerated well
H2 blocker: first gen = CIMETIDINE: presents unwanted endocrinal adverse effects including
1) GYNECOMASTIA, (“Ci-me-tiddies”)
2) ELEVATED SERUM PROLACTIN LEVELS,
3) CONFUSION in ELDERLY
Big tittied confused lady at dinner that’s lactating
CIMETIDINE is also a STRONG INHIBITOR of cytochrome P450
PROTON PUMP INHIBITORS (names)
1) OMEPRAZOLE
2) LANSOPRAZOLE
3) PANTOPRAZOLE
4) ESOMEPRAZOLE
5) RABEPRAZOLE
PPI MECHANISM OF ACTION
-is a PRODRUG that after transporation into the parietal cell canaliculus, is converted to the active form, which reacts with a CYSTEINE RESIDUE of the H+/K+ ATPase, forming a stable COVALENT BOND leading to IRREVERSIBLE INACTIVATION OF ENZYME
PPI INDICATIONS
1) GERD
2) DUODENAL/GASTRIC ULCERS
3) MEN-1/ZOLLINGER-ELLISON SYNDROME
4) Contribute in combo with antibotics to eradicate H. Pylori
5) NSAID INDUCED ULCERS –> they support platelet aggregation and maintain clot integrity –> used in hemorrhagic ulcers
PPI SIDE EFFECTS
- are well tolerated, but can produce nausea/diarrhea
- long term administration of Omeprazole, in ANIMALS, is associated with gastric carcinoid tumors (not seen in humans)
- Omeprazole INHIBITS the metabolism of warfarin, clopidogrel, phenytoin, diazepam, and cyclosporin
- reports of small increase in resp and GI infections; decrease in serum Mg2+ and Hip fractures with long term use of PPI
- rarely pancreatiits, hepatotoxicity, and interstitial nephritis
- prolonged therapeutic use of PPI + H2 blockers may DECREASE BIOAVAILABILITY of
1) VITAMIN
2) DIGOXIN
3) KETOCONAZOLE
this is because the acid is required for their absorption
ANTIMICROBIALS used for H. Pylori eradication
1) CLARITHROMYCIN (crows in sketchy
2) AMOXICILLIN (amo box in sketchy)
3) METRONIDAZOLE
4) TERACYCLINE
- to document infection with H. Pylori –> do
1) endoscopic biopsy of the ulcer margin,
2) serolgic tests OR
3) Urea breath tests:
- eradication of H. pylori results in rapid healing of active peptic ulcers and low recurrence rates
UREASE BREATH BEST
- used to diagnose Helicobacter Pylori infection
1. Subjects are given urea labelled with 13C orally
2. H. pylori produces UREASE, which hydrolyses the labelled urea to 13CO2 and ammonia
3. 13CO2 is dissolved in the blood and transported to the lungs
4. Exhaled 13CO2 is analyzed –> the presence of H. pylori results in an increase in the ratio of 13CO2: 12CO2 in expired breath
FIRST + SECOND LINE REGIMEN for eradication of H. Pylori
FIRST LINE: TRIPLE THERAPY, regimen for at least 4 WEEKS
1) 2 ANTIBIOTICS
2) PPI
- clathithromycin + amoxicillin, or clarithromycin + metronidazole both = 70=85% eradication rate
SECOND LINE THERAPY: QUADRUPLE THERAPY for 4 weeks
1) BISMUTH (a mucosal protective agent)
2) 2 ABX (Metro + tetracycline)
3) PPI OR RANITIDINE
- second line therapy has a 75-90% eradication rate
MUCOSAL PROTECTIVE AGENTS
1) SUCRALFATE
2) BISMUTH SUBSALICYLATE
3) MISOPROSTOL
“Sugar Latte’s By Mouth and Miso Soup” all help with mucosal protection
SUCRALFATE MOA
“sugar-late” –> binds all the shitty girls = the necrotic tissue –> needs to be ACIDIC (hot) or else they won’t like them (ie can’t be given with an H2 blocker or PPI)
is a mucosal protecting agent that undergoes polymerization and selective binding to NECROTIC TISUE where it acts as a barrier to acid
-it also stimulates PROSTAGLANDIN SYNTHESIS
Note: sucralfate is INEFFECTIVE with action of H2 receptor blockers or PPI
–> it req_uires acidic pH to be activated_ therefore it should NOT be administered simultaneously with H2 blockers, PPI, or other antacids
BISMUTH THERAPEUTIC ACTIONS
-appears to have some antimicrobial effect on H Pylori
–> when it is admisisterd along with metronidazole and tetracycline, ulcer healing rate increases to 90%
MISOPROSTOL
MISO SOUP of PROSTaglandins for Every1
–> AEs include DIARRHEA + ABORTIONS –> soup makes everything come out AND irritates bowel!!!
- a muucosal protective agent that is a PROSTAGLANDIN E1 ANALOGUE that
1) DECREASES ACID SECRETION
2) STIMULATES MUCIN + BICARB PRODUCTION
Clinical Uses: approved for PREVENTION OF GASTRIC ULCERS induced by NSAIDS, but it is L_E_SS EFFECTIVE than H2 blockers or PPI in acute cases
ADVERSE EFFECTS:
1) DIARRHEA in up to 30% of patients
2) ABORTIONS –> d/t induction of uterine contractions during pregnancy, therefore it is contraindicated in pregnancy
3) Exacerbations of inflammatory bowel disease
GERD TREATMENT
NON-PHARMACOLOGICAL:
-small meals, weigh loss, avoid bed-time acid rich drinks, elevate head of the bed to 6-8 inches and lifestyle modifications (smoking, alcohol)
DRUGS:
1) PPI +/- H2 blocker
PROKINETIC DRUGS USED IN GI DISORDERS
1) NEOSTIGMINE/BETHANECHOL
2) METOCLOPRAMIDE
3) CISAPRIDE
4) ERYTHROMYCIN
METOCLOPRAMIDE
“Metro-cop Ride” –> Serotonin3 and Dopamine receptor blocker (blocks the good things b/c is a cop), but allows the “4” to be an agonist
AE: they always PARK, SLEEP, and POOP in the wrong places (parkinsons, sedation, and diarrhea all d/t dopamine
- is a PROKINETIC DRUG that performs as a 5-HT3 and D2 receptor blocker
- The prokinetic activity of metoclopramide is mediated by muscarinic activity via 5-HT4 receptor agonist activity.
–> It accelerates gastric emptying and intestinal motility.
USES:
1) DIABETIC + POST-OP GASTROPARESIS
2) ANTIEMETIC (reduces nausea and vomiting associated with chemo agents)
3) RELIEF OF SX OF GERD
-At HIGHER DOSES, 5-HT3 antagonist activity may also contribute to the anti-emetic effect.
ADVERSE EFFECTS: are d/t ANTI-DOPAMINERGIC effects = sedation, diarrhea, and Parkinsonian effects which limit its high-doses and long-term use
CISAPRIDE
“CIS PRIDE” –> like metro cop ride but is the CIS, so can drive fast (4 wheels for HT4 agonist) –> stimulates ACh secretion etc… but because CIS agents work so hard, their adverse effect = arrhythmia
-5-HT4 AGONIST –> stimulates ACh secretion
USES:
1) GASTROPARESIS
2) GERD
3) CONSTIPITION
AEs: ARRYTHMIAS
NEOSTIGMINE
-is a CHOLINOMIMETIC
USES:
1) COLONIC PSEUDO-OBSTRUCTION in hospitalized patients
BETHANECHOL
- a CHOLINOMIMETIC
- is resistant to cholinesterdase, has a long duration of action
USES:
1) POST-OP BOWEL + BLADDER atony
ERYTHROMYCIN
-is a MACROLIDE antibiotic that acts as a PROKINETIC AGENT
–> is a MOTLIN RECEPTOR AGONIST
USES:
1) GASTRIC EMPTYING before upper GI endoscopic procedures
Tolerance may develop in gastroparesis
ANTIEMETIC AGENTS
a) 5-HT3 inhibitors – Ondansetron (Zofran)
b) H1 antihistamines & antimuscarinics –
Diphenhydramine & Scopolamine
- *c) Corticosteroids** – Dexamethasone
- *d) NK1–receptor blocker** – Aprepitant
- *e) D2 Receptor antagonist** – Prochlorperazine f) Benzamide – Metoclopramide
- *g) Marijuana** – Dronabinol (Marinol)
ONDANSETRON
“little chemo girl on the “jumbo-tron” dancing… dancing on 2 legs and has 1 arm up = serotonin 3 receptor
5-HT3 INHIBITOR/ANTAGONIST in the GUT + CNS
USES:
1) CHEMOTHERAPY INDUCED moderate-severe emesis or post-op nausea/vomiting
- usually given IV, for prophylaxis given orally
Note: CORTICOSTEROIDS can be combined with ondansetron to provide a GREATER ANTI-EMETIC EFFECT
DIPHENHYDRAMINE
CYCLIZINE
MECLIZINE
H1 ANTIHISTAMINES
-are moderately effective in motion sickness + chemotherapy induced nausea/vomiting
SCOPOLAMINE
“SCOPE LA MINE” –> as in come scope the mine but it’s shitty travel there so may need some scopolamine for the motion sickness
-anti-emetic that is an ANTIMUSCARINIC
–> is the DOC for emesis d/t MOTION SICKNESS
APREPITANT
FOSAPREPITANT
“A Prepitant” of that New Killer 1 shit –> makes you not feel nautious during chemo brooooo”
-anti-emetic that is an NK1-receptor blocker in the CNS (NK = NeuroKinin)
–> effective in both decreasing the EARLY + DELAYED EMESIS in CANCER CHEMO
APREPITANT = ORAL
FOSAPREPITANT = IV
ADVERSE EFFECTS: dizziness, fatigue, diarrhea, and CYP interaction may occur
CHEMOTHERAPY INDUCED NAUSEA + VOMITING TX
A) Solo DEXAMETHASONE
–> Dex DOES it by itself
OR
B) Combo of
- METHYLPREDNISOLONE +
- ONDANSETRON/APREPITANT
PROCHLORPERAZINE
an ANTI-EMETIC that is a “pro” for “chlorine” vomiting… makes you not vomit –> antagonizes those dopamine receptors and the muscles)
a PHENOTHIAZINE –> an ANTAGONIST at
- D2 RECEPTORS
- MUSCARINIC RECEPTORS
SIDE EFFECTS:
- EXTRAPYRAMIDAL SYMPTOMS,
- HYPOTENSION,
- SEDATION
METOCLOPRAMIDE (MCP)
- PHENOTHIAZINE
- is a PRO-MOTILITY agent and an ANTI-EMETIC
–> Antagonist at D2 receptors and muscarinic receptors
-effective at HIGH DOSES against the highly emetogenic CISPLATIN
AEs: has ANTIDOPAMINERGIC SIDE EFFECTS
–> TARDIVE DYSKINESIA
–> sedation, diarrhea, extrapyramidal symptoms, limit its high-dose use
LORAZEPAM
ALPRAZOLAM
DIAZEPAM
- are BENZO’S
- the antiemetic potency of lorazepam, alprazolam, and diazepam is low
- their beneficial effects may be d/t their sedative, anxiolytic, and amnesic properties
- useful in ANTICIPATORY NAUSEA/VOMITING
INFLAMMATORY BOWEL DISEASE DRUGS
1) Sulfasalzine,
2) glucocorticoids (Budesonide),
3) azathioprine,
4) Methotrexate,
5) Cyclosporine,
6) Infliximab and
7) Natalizumab
SULFASALAZINE
MESALAMINE (5-ASA)
- BALSALAZIDE
- SULFASALAZINE
DRUG FOR IBD
- MOA: inhibits the pro-inflammatory mediators –IL1, and TNF-α
- It is a sulfa derivative. So, it should be avoided in patients with sulfa allergy.
- In the GIT,
- sulfapyridine (antibacterial) and
- 5- Aminosalicylic acid (5-ASA) (anti-inflammatory) released from sulfasalazine by colonic bacteria.
• It is used in mild to moderate Crohn’s disease or ulcerative colitis
ADVERSE EFFECTS: Nausea, vomiting, diarrhea, _hypersensitivity, and *reversible oligospermia*. Bone morrow suppression_ is related to the sulfapyridine release from sulfasalazine.
NOTE: MESALAMINE (5-ASA) = “metabolite”
• Balsalazide: releases mesalamine (5-ASA) in the large intestine at the active site of ulcerative colitis.
–> B for BIG BOWEL –> LARGE INTESTINE –> more for UC (the LARGE INTESTINE)
• Sulfasalazine: Proximal, distal colon and rectum.
6-mercaptopurine(6-MP)
Methotrexate (MTX)
-IMMUNOMODULATORS
- 6-MP may promote apoptosis of immune response. –> Me-Cap’d (ie getting shot… promoting apoptosis)
- MTX blocks dihydrofolate reductase (DHFR)
They cause generalized immune suppression
They are used in moderately severe to severe Crohn’s disease and ulcerative colitis.
AE:
6-MP: mucositis, myelosupression.
–> Hepatotoxicity can occur with 6-MP.
-MTX: Toxicities are rare at low doses.
INFLIXIMAB
ADALIMUMAB
MAB –> can think monoclonal antibody –> MAB the MOBSTER that helps with ACUTE FISTS(ULA’s) and FLARES –> fight That New Fuck ALPHA (TNF-alpha) in town. Test these mobsters for TB before you give them the MAB
MOA: is a MONOCLONAL ANTIBODY that targets TNF-alpha, a principal mediator in Crohns disease
-used in conditions associated with FLARE UP of IBD; particularly in Crohn’s related FISTULAS + ACUTE FLARES
Note: it is also used in RHEUMATOID ARTHRITIS
AEs: reactivationof latent tuberculosis and other infections. It is given IV – fever, chills, urticarial reaction, hypotension may occur. Antibodies to infliximab may develop.
Note: Adalimumab: (HUMIRA) - TNF-α inhibitor
NATALIZUMAB
“nat” LIZ “MAB” –> blocks that integration
blocks leukocyte integrins
- can produce multifocal leukoencephalopathy.
HYDROCORTISONE
PREDNISONE
PREDNISOLONE
CORTICOSTEROIDS
- are gneralized anti-inflammatory drugs used in acute cases
- Inhibit TNF-α, IL-1, IL-8
Age you can start “corting” at is 18 (IL1, IL-8… can be the ALPHA male for TNF-alpha)
BUDESONIDE
CORTICOSTEROID
-controlled release formation in the distal ileum and colon
IBS (Irritable Bowel Syndrome)
IBS Characterized by
- diarrhea (D) or
- constipation (C) or
- alternating (A)
Chronic symptoms with no structural abnormalities
Frequent abdominal pain correlated with following:
- Altered stool frequency
- Pain gets better with defecation
- Alteration in stool appearance
Treatment: symptomatic
ALOSETRON
5-HT3 BLOCKER
Al! Set (up) RON for the 3!
- 5-HT3 antagonist with long duration of action, has high potency
MOA: Reduces smooth muscle activity in the gut (For IBS-D).
USES: Recommended for severe diarrhea associated IBS.
AE: Rare, serious constipation; ischemic colitis and infarction may occur.
DICYCLOMINE
HYOSCYAMINE
GLYCOPYRROLATE
METHSCOPALAMINE
ANTICHOLINERGICS
non-selective action on the gut (IBS-D)
USES: IBS: diarrhea
-Chronic symptoms with no structural abnormality
LUBIPROSTONE
CHLORIDE CHANNEL ACTIVATOR in IBS
“lubey up my prostone” bro, i need to shit”
-used in CONSTIPATION-associated IBS (IBS-C)
LOPERAMIDE
DIPHENOXYLATE
ANTI-DIARRHEAL, OPIOID AGONISTS
-are both opiate derivatives that SLOW GUT MOTILITY with NEGLIGABLE CNS EFFECTS
–> acts via GI mu-opioid receptors
- INHIBITS ACH release + decreases perstalsis!!
DIPHENOXYLATE: is formulated with ATROPINE to REDUCE ABUSE POTENTIAL –> High doses can cause CNS EFFECTS
AE: risk of TOXIC MEGACOLON in children or patients with severe colitis
CHOLESTYRAMINE
COLESTIPOL
COLESEVELAM
-prevent diarrhea of IBS + IBS by blocking osmotic and irriating actions of bile salts (ie PREVENT SECRETORY DIARRHEA)
–> BILE SALTS stimulate Cl- secretion in the colon (cAMP) –> Resins form insoluble complexes with bile acids that are no longer able to stimulate this excess secretion
- they form INSOLUBLE COMPLEXES with BILE ACIDS in the intestine
- also used in LOWERING CHOLESTEROL
LAXATIVES
- classified by mechanism of action as
1) STIMULANTS
2) OSMOTIC AGENT
3) BULK FOMRING AGENTS
4) STOOL SOFTENERS
SENNA
BISACODYL
CASTOR OIL
LAXATIVE STIMULANT
–> can thing SENNA for STIMULANT, and that CODYL which kind of soudns like CASTOR OIL which casts off the poop (b/c is a laxative)
- may cause cramping
- chronic use may lead to habit of perceived need for laxitives
Note: Senna is used with docusate for opioid induced constipation
METHYCELLULOSE
PSYLLIUM
BRAN
BULK FORMING AGENT LAXITIVES
- if pack cells full of methyl will get bulky, as well if you go to a psyllium, you get bulky as well, and we all know bran makes bulk occur too
- these are insolube indigestible derivatives form fruits and vegetables (are hydrophilic colloids)
- they are NON-ABSORBABLE —> increase water retention and stool becomes BULKY
- the distention of bowel leads to peristaltic stimulation of the gut
MAGNESIUM CITRATE
MAGNESIUM HYDROXIDE
LACTULOSE
POLYETHYLENE GLYCOL
OSMOTIC AGENTS used as LAXATIVES
- the magnesium ones are “magnetic” –> help draw the water out (as does the lactose)
- Magnesium citrate, Magnesium hydroxide = SALINE CATHARTICS
- Lactulose + Sorbitol = NON-DIGESTIBLE SUGARS
- they OSMOTICALLY DRAW WATER into the lumen of GIT, which then stimulate motility
USES:
1) SIMPLE CONSTIPATION
2) BOWEL PREP FOR ENDOSCOPE
LACTULOSE
OSMOTIC LAXATIVE
- is a semi-synthetic disaccharid sugar that acts as an OSMOTIC LAXITIVE
- large doses are degraded by colonic bacteria to form lactic, formic, and acetic acid –> this increases osmotic effect too
- is also used in HEPATIC ENCEPHALOPATHY: it helps to “draw out” ammonia (NH3) from the body and is useful for PREVENTING HYPERAMMONIA
PEG (Polyethylene glycol)
OSMOTIC LAXATIVE
- “draws you out” like a “PIG” (for peg)
- used for COLONIC LAVAGE for ENDOSCOPIC and RADIOLOGICAL PROCEDURES
MINERAL OIL
DOCUSATE SODIUM
STOOL SOFTENERS
-mineral oil + docusate sodium –> together they EMULSIFY STOOL and SOFTEN IT –> lubricate it and make it wasy to pass
SENNA –> is used in combo with a DOCUSATE (make stools softer and easier to pass) –> used to treat cases of OPIOID-INDUCED CONSTIPATION
LUBIPROSTONE
CL- CHANNEL ACTIVATOR LAXATIVE
- prostanoic acid derivative
- stimulate chloride secretion into GI –> increases fluid content
ALVIMOPAN
METHYLNATREXONE
-blocks GI mu-receptors but do not enter CNS
–> useful in OPIOID INDUCED CONSTIPATION
PANCRELIPASE
DRUGS FOR IBS: PANCREATIC ENZYME
- a replacement enzyme from animal pancreatic extract
- improve the digestion of dietary fat, protein, and carbs (increases A, D, E, K vit absorption)
USE:
1) Patients with CHRONIC PANCREATITIS
2) AFTER PANCREATECTOMY
3) STEATORRHEA
4) CYSTIC FIBROSIS associated insufficiences
URSODIOL
BILE ACID THERAPY FOR GALLSTONES
- has enterohepatic circulation
- it reduces cholesterol absorption by breaking up micelles containing cholesterol
- used in patient who refuses or not eligible for surgery
AE: DIARRHEA
OCTREOTIDE
SOMATOSTATIN ANALOGUE
-is a LONG ACTING somatostatin analogue
USE:
1) CARCINOID TUMORS: note if tumor is in GIT there are no symptoms noticed at 5-HT is metabolized in the liver
2) VIPoma
3) ACUTE VARICEAL BLEEDING
4) ACROMEGALY
AE: abdominal cramps, nausea, steatorrhea, gallstones
TREATMENT OF CARCINOID TUMOR
OCTREOTIDE (somatostatin analogue)
TREATMENT OF VIPoma (Vasoactive Intestinal Polypeptide)
A non α and β islet cell pancreatic tumor that secretes VIP, produce copious diarrhea.
- Source: PANS in sphincters, gall bladder & small intestine
- Increase water and electrolyte secretion, relax intestinal smooth muscle and sphincters
- Treatment with Somatostatin analog: octreotide
TX OF VARICEAL HEMORRHAGE
1) Octreotide: I.V.
A somatostatin derivative with uncertain MOA
Alter portal blood flow and variceal pressure.
Uses: bleeding varices or high risk of repeat bleeding.
Adverse effect: reduce endocrine and exocrine pancreatic activity.
2) NON-SELECTIVE B-BLOCKERS –> Propanolol + Nadolol)
–> are effective in reducing portal pressures
–> β1 & β2 blockade result in ↓CO &↑VC Improves GI blood vessel tone↑systemic vasoconstriction & ↓vasodilation
TX OF REYE’S SYNDROME
- Reye’s syndrome is associated with fatty liver, hypoglycemia, and coma – childhood hepatic- encephalopathy.
This is linked to viral infection treated with aspirin.
Therefore, acetaminophen may be advised in place of aspirin.
