GI Part 2 Flashcards
Goals of mild constipation IBS treatment?
Increase dietary fiber and fluid intake
Goals of moderate constipation IBS treatment?
Add bulk forming laxatives with or without antispasmodics
Goals of severe constipation IBS treatment?
Add chloride channel activator
Goals of mild diarrhea IBS treatment?
- Dietary restriction
- Avoid contributing meds
Goals of moderate diarrhea IBS treatment?
-Add loperamide or other antispasmodics
Goals of severe diarrhea IBS treatment?
Add 5HT3 antagonists
IBS diarrhea drug choices
- Loperamide
- Anticholinergics
- Serotonin receptor blockers
IBS constipation drug choices
- Fiber supplements
- Osmotic laxatives
- Cl Channel Activators
- Guanylate Agonist
Describe antispasmodics
- Anticholinergic (anti-SLUD)
- Used for diarrhea
- Side effects are dry mouth, blurred vision, urinary retention, constipation
- Dicyclomine
What are TCAs and what type of IBS are they used to treat?
- Tricyclic Antidepressants
- Anticholinergic action
- Decreases GI secretion and motility
- Used for diarrhea
- May help chronic abdominal pain
- Amitriptyline, desipramine
What are 5HT3 receptor blockers and what type of IBS are they used to treat?
- Serotonin receptor blockers
- Mediate visceral pain
- Inhibits colonic motility
- Used for diarrhea
- Alosetron
What is Alosetron and how is it used?
- Selective 5HT3 blocker
- Used for severe diarrhea IBS in women (efficacy in men not established)
Side effects of Alosetron?
- Constipation (can be severe)
- Ischemic colitis (fatalities reported, black box warning)
Describe bulk forming laxatives
- Anti constipation
- Form bulky emollient gel that distends colon and promotes peristalsis
Describe osmotic laxatives
- Anti constipation
- Nonabsorbable compounds that result in increased stool liquidity (due to obligate increase in fecal fluid)
What are chloride channel activators?
- Approved for constipation IBS in women (efficacy in men not shown)
- Lubiprostone/Amitiza
What is Lubiprostone?
- Chloride channel activator
- For constipation IBS in women
- Works on small intestine
- Enhances Cl-rich secretions and intestinal motility
Contraindications of lubiprostone? Adverse effects?
- Avoid in women of CBP (preg cat C)
- Nausea, diarrhea, HA
What is linaclotide?
- Guanylate agonist-Used for constipation
- Causes rise of cGMP leading to rise of Cl and bicarb into intestinal lumen
- Fluid increases, transit time decreases
Side effects of linaclotide?
- Diarrhea
- Flatulence
- GI upset
What are serotonin 5HT4 receptor blockers?
- Results in release of NTs promoting peristaltic reflex
- Proximal bowel contraction and distal bowel relaxation
- For constipation
- No agent available in US
Drug classes for IBD treatment
- Aminosalicylates
- Glucocorticoids
- Purine analogs
- MTX
- Anti-TNF
- Anti-integrins
Drugs for mild IBD
- 5-aminosalicylates
- Abx
- Topical corticosteroids
- Budesonide
Drugs for moderate IBD
- Azathioprine/6-mercaptopurine
- MTX
- Oral corticosteroids
- TNF blockers
Drugs for severe IBD
- IV corticosteroids
- TNF blockers
- Cyclosporine
- Natalizumab
- Surgery
What is the active compound of all aminosalicylates?
5-ASA
MOA of aminosalicylates?
Unclear
- May affect inflamm mediators
- May interfere w/cytokine production
- May inhibit immune cells
How do aminosalicylates work in IBD treatment?
- Topically on affected areas of GI mucosa
- So must get to affected site
- Pure oral 5-ASA is more than 80% absorbed which means little left over to go to needed area
- Formulations are made to avoid so much absorption
What are the different formulations of aminosalicylates?
- Azo compounds
- Mesalamine compounds
What are the azo aminosalicylate drugs?
- Sulfasalazine
- Olsalzine
- Balsalazide
What are the mesalamine aminosalicylate drugs?
- Pentasa
- Asacol
- Lialda
How do azo compounds work?
- N=N azo bond reduces absorption after oral absorption
- At ileum and colon, bacteria cleave the molecules and release active 5-ASA
How do mesalamine compounds work?
- Each is uniquely formulated to deliver 5-ASA
- Pentasa is timed-release microgranules
- Asacol, apriso, lialda are coated in a pH resin that dissolves in distal ileum and colon
Mesalamine compounds provide ___ concentrations to sites in ___ GI tract
High Lower
What drug class is considered first line in mild to moderate UC?
Aminosalicylates
Sulfasalazine limitations
- Many pts can’t tolerate dosing
- Many ADRs (nausea, HA, arthralgias)
- Hypersensitivity reactions
What supplementation does sulfasalazine require?
Folic acid due to impaired absorption
MOA of glucocorticoids in IBD
Inhibit production of inflammatory cytokines like TNF-a, IL-1, IL-8
How are glucocorticoids used in IBD?
- Moderate to severe disease
- Helpful in early treatment but not to maintain remissions
What is the MC oral glucocorticoid used for IBD?
Prednisone
What is budesonide and how is it used?
- Oral prednisolone analog
- Used in mild to moderate Crohn’s
Side effects of glucocorticoids
- Hyperglycemia
- Adrenal suppression
- Peptic ulcers
- Immunosuppresion
Describe purine analogs
- Oral
- Delayed onset of action of several weeks due to metabolic conversions
- Azothioprine to 6-MP to 6-thioguanine
How do purine analogs work in IBD?
- Provide immunosuppressive action
- Used to induce and maintain remissions in both UC and Crohn’s
- Often used with steroids to reduce steroid dose
ADRs of purine analogs
- NV
- Bone marrow suppression
- Liver toxicity
- Hypersensitivity reactions
Which med should be avoided when taking purine analogs?
- Allopurinol
- Can cause leukopenia
What is methotrexate?
- Folic acid analog
- Anti-inflamm in low doses (cytotoxic at high doses)
- Used to induce or maintain remission in Crohn’s (unknown effect in UC)
ADRs of MTX
- Myelosuppression, mucositis, alopecia
- Liver toxicity
How do anti-integrins work?
- Prevent inflamm cells from using integrins to bind to vascular cells
- Used for refractory Crohn’s
What is natalizumab and how is it used?
- Anti-integrin
- Mod to severe Crohn’s
- Requires pt enrollment in CD touch due to adverse effects
What should happen if patients are on steroids and then given natalizumab?
Taper once response is observed
Major ADR of natalizumab
Progressive multifocal leukoencephalopathy
- A/w exposure to JC virus
- Occurs in IC pts
- Increased duration of med increases risk
What are the MC causes of cirrhosis and hepatocellular carcinoma?
HBV and HCV
Goal of hepatitis treatments?
Suppressive rather than curative
HAV treatment
- NONE
- Vaccine to prevent
Drug classes for HBV treatments
- Nucleoside/tide analogs
- Interferons
How are nucleoside/tide analogs used in HBV treatment?
Usually combined with interferon
What is lamivudine?
- Nucleoside/tide analog
- Inhibits HBV DNA pol
- Requires phosphorylation to become activated
What is adefovir dipivoxil?
- Nucleoside analog
- Inhibits HBV DNA pol
- 2nd line treatment
- Less toxic than other nucleosides
What is entecavir?
- Nucleoside analog
- Inhibits HBV DNA pol
- Effective in lamivudine-resistant strains
- Take on EMPTY stomach
What is telbivudine?
- Nucleoside analog
- Inhibits HBV DNA pol
- Requires phosphorylation to active form
- Give with or w/o food
What is tenofovir?
- Nucleotide analog of adenosine
- Inhibits reverse transcriptase
Describe interferons
- Family of cytokines, provide antiviral action
- Alfa (2a and 2b), beta, gamma available
IFN alfa 2a is used to treat:
HBV AND HCV
IFN alfa 2b is used to treat:
ONLY HCV
Treatment options for HCV:
- IFN alfa 2a or 2b
- Ribavirin
- Telapravir
- Boceptrevir
How is treatment of HCV directed?
Based on genotype
Describe IFN used to treat HCV
- Genotypes 3-6
- Often used w/ribavirin
- Were once cornerstone of treatment but now newer agents available
Describe ribavirin
- Guanosine analog for HCV
- Blocks RNA dependent RNA pol
- Available oral or IV
- Combined with IFN
Describe simeprevir
- Inhibits HCV NS3/4A protease
- 1st line treatment w/other agents
What is currently recommended as 1st line treatment w/other agents for HCV?
Simeprevir (NS3/4A protease inhibitor)
Describe paritaprevir
- HCV NS3/4A protease inhibitor
- Often 1st line w/other agents
- E.g. viekira pak
What is ledipasvir and sofosbuvir?
-NS5A inhibitors for HCV tx-1st line agent
How are HCV genotypes 5 and 6 treated?
Peg-IFN alfa 2a WITH ribavirin for 48 weeks
What are the protease inhibitors used to treat HCV?
- Simeprevir
- Paritaprevir
- Boceprevir
What are the NS5A protein inhibitors used to treat HCV?
- Ledipasvir/Sofosbuvir
- Ombitasvir
- Sofosbuvir and Dasabuvir
What is 1st line to treat ascites?
Diuretics
Meds for variceal bleeding prophylaxis?
-Nonselective B blockers (propranolol, nadolol)
Meds for acute variceal hemorrhage?
- Vasoconstrictors (octreotide, vasopressin)
- Abx
Meds for spontaneous bacterial pritonitis?
-Abx (cefotaxime)
Treatment of hepatic encephalopathy?
- Targeted to decrease NH3 blood concentration (via abx)
- Neomycin and metronidazole
- Rifaximin
