Exam 3 - GI Part 2 Flashcards
Anti-Emetic Drugs
Anti-Emetic Drugs
Indications for use of Anti-Emetic Drugs:
Severe N/V
Motion sickness
Post-op N/V
N/V post-chemotherapy
Two initiation centers of N/V:
Direct stimulants on GI tract
CNS - chemoreceptor trigger zone (CTZ)
What anti-muscarinic is used for motion sickness?
Scopolamine
MOA: Blocks Ach from binding to musc. receptors in CTZ.
Patch applied every 3 days, behind ear
ADR: Wash hands! - Can cause midriasis in one eye.
SE: dry mouth, blurred vision, urine retention
What antihistamines are used as anti-emetics?
Dimenhydrinate (Dramamine)
Promethazine (Phenergan)
MOA: H1 receptor blockers
Antimuscarinic
Inhibit N/V, cause sedation
Phenergan comes as a suppository! YAY
What are anti-seritonergic medications used to treat N/V?
Odansetron (Zofran)
Dolasetron (Anzemet)
Granisetron (Kytril)
Block 5HT-3 receptors (Serotonin) in stomach and brain.
Well tolerated, minus headache, diarrhea, constipation, and QT PROLONGATION, which he ALWAYS asks
What anti-serotinergic drug is used for severe N/V from chemotherapy?
Granisetron (Kytril)
How do you treat severe N/V due to pregnancy?
Doxylamine (Unison) + B12
If refractory, may use Zofran, but not enough data to know if it has teratogen effects.
Anti-dopaminergic drugs used to treat N/V?
Metoclopramide (Reglan)
Phenothiazines - Prochlorperazine (Compazine), Chlorpromazine, Fluphenazine, Haloperidol
Block D2 receptor antagonist in CTZ (dopamine receptors).
Parkinson’s have decreased dopamine levels, these drugs can trigger those symptoms.
Block muscarinic receptors, so might see dizziness, fatigue, seizures.
When you block dopamine receptors, what can occur?
Neuroleptic malignant syndrome
High potency dopamine blockers - skeletal muscle will contract and not let go leading to hyper-rigidity of the arm and legs. Produces heat and acid, leads to metabolic acidosis and rhabdomyolysis.
Cannabinoids
Dronabinol (Marinol)
Similar to Cannabis. Derivate of delta-9-THC.
Treats N/V associated with chemotherapy when other agents have failed. Stimulates appetite.
What is a substance P antagonist?
Aprepitant (Emend)
Antagonist at NK1 substance P receptor
A P receptor is a NT stimulated when you eat spicy foods (pain), stimulates GI tract to cause N/V. Drug inhibits P receptor to stop nausea or vomiting.
Stops N/V from cisplatin and other chemotherapy drugs.
Interacts with CYP3A4!
Treatment for acute and delayed phase of N/V?
First 24hrs?
36-72hrs?
Acute phase: 5HT3 receptor antagonist (Zofran)
Delayed phase: Substance P antagonists (Aprepitant)
This is why we give both drugs together.
Prokinetic Drugs
Metoclopramide (Reglan)
Stimulate GI tract for those with delayed gastric emptying or gastroporesis.
Common in type 2 diabetics.
Blocks D2 (dopamine) receptors to suppress release of Ach. Increases gastric emptying, GI motility, and increases LES tone to help push food along.
What prokinetic drug was removed from the market due to QT prolongation and CYP3A4 interaction?
Cisapride (Propulsid)
Works on 5HT4 and 5HT3
What is used in addition to metoclopramide (Reglan)?
Erythromycin; macrolide abx that interacts with motilin receptors on GI tract to increase motility.
Used for gastroporesis and peds with delayed gastric emptying.
Toxicity may cause cramps or impair motility.
Laxatives
Laxatives
Laxative Mechanisms:
Increase motility
Increase water content of stool
Decrease colonic water and NaCl absorption
Indications for laxatives
Preparation for bowel surgery Hasten bowel excretion of toxins Post-op constipation Minimize straining in CV disease Relieve constipation
CI laxatives
Bowel disease
Long list of side effects for laxatives
Acute - nausea, abd cramps, diarrhea
Chronic - Cathartic colon syndrome
Leads to mucosal inflammation, atrophy of outer muscle layers, damage to nerve plexus, malabsorption, dehydration, protein loss, disruption of gut flora — b/c tract was dependent on drug.
Don’t use them chronically :)
Types of Laxatives
Stimulants or irritants
Bulk forming - dietary fiber
Stool softeners
Osmotic agents
Stimulant Laxatives
Castor oil
Bisacodyl (Dulcolax)
Senna (Senokot)
MOA: increases motility, water, and electrolyte secretion
SE: abd cramps, diarrhea, muscle weakness
Do not use a lot or patient will lose the natural urge to go. As needed basis only.
Bulk forming, non-digestable dietary fiber
Can be used safely every day to regulate normal defecation.
Psyllium (Metamucil)
Methylcellulose (Citrucel)
Mix with water before taking.
Increase bulk and water content of stool to increase motility.
Increased volume augments peristalsis.
Binds drugs, flatulence, and cramps.
Can bind to iron, FQ
Cause cramps/flatulence
Stool Softeners
Emulsify stools to make them easier to pass. Good for those with dry, hard stools.
Mineral oil
Glycerin
Docusate sodium (Colace)
Osmotic Agents
Magnesium Sulfate (Causes diarrhea) Magnesium Hydroxide (Milk of Magnesia) Lactulose Mannitol Polyethylene glycol (MiraLax and GoLYTELY)
Increase water content and motility.
MiraLax
occasional relief of constipation
GoLYTELY
Flush; used for irrigation of drug packets (Cocaine smugglers)
Anti-diarrheal agents
Enhance water absorption and decrease GI motility locally.
Opioids:
- Diphenoxylate (Lotomil)
- formulated with atropine
- Doesn’t cross BBB
- Loperamide OTC
Common side effect of opioids is that they slow GI tract and cause constipation.
SE - constipation, cramping, flatulence, megacolon
Not for infectious diarrhea.
Why is diphenoxylate formulated with atropine?
Worried IVDA injecting it. Atropine causes IVDA to get sick when injecting it.
Abuse deterrent.
Megacolon
Blockage from overuse of antidiarrheal agents
Drug abusers and Loperamide
Doesn’t cross blood-brain barrier due to P-glycoprotein, which prevents absorption.
PGP inhibitor like grapefruit juice allows levels to go up of drug. Pt overdosed on cytomegaline and loperamide. by doing this, inhibit PGP for loperamide to be absorbed and cause a high.
Torsades induced coma as a result.
Bismuth subsalicylate (Pepto-bismol)
Used as an antidiarrheal to inhibit intestinal secretions.
Effective in infectious diarrhea.
Can turn stools black.
Why don’t we use Loperamide or Dyphenyloxate in infectious diarrhea?
Want patient to get rid of infection.
IBS/IBD
IBS/IBD
Crohn’s disease vs. Ulcerative Colitis
Crohn’s affects entire GI tract; UC affects colon/rectum.
test question
Etiology of Crohn’s and UC
Cause unknown, thought to be polygenic on chromosome 12.
More prone when on NSAIDs.
Smoking decreases UC.
UC
Inflamamtion confined to rectum and colon
Primary lesion: crypts of lieberkuhn
Pseudopolyps, collar-button ulcer
Crohn’s
Inflammation of GI tract, terminal ileum is most common.
Discontinuous inflammation - sip lesions.
UC common sxs
Diarrhea, Abd pain, Weight loss
Passage of mucus/pus
Blood in stool
Fever, Tachycardia, Hypotension, increased WBC and ESR
Crohn’s common sxs
Diarrhea, Abd pain, Weight loss
Fatigue
Fever
Abd mass
GI bleeding, perianal/rectal lesions, and increased WBC and ESR
What is the purpose of probiotics?
Help restore normal gut flora
Are rectal suppositories better for UC or Crohn’s?
UC - can get away with rectally administered meds, bc they work locally.
Crohn’s - systemic tx
Aminosalicylates
Sulfasalazine (Azulfidine)
-Prodrug - Broken down to form two active components: sulfapyridine and 5-ASA.
Mesalamine (5-ASA) Asacol Lialda Pentasa Canasa Rowasa
Helps reduced inflammation by inhibiting COX and LOX.
ADR: Anorexia, diarrhea, blood dyscrasia (thrombocytopenia)
Mesalamine
Less side effects than sulfasalazine; used more frequently
Rowasa
Aminosalicylate
Enema can be applied
What aminosalicylate is apropriate for UC?
Lower rectum and colon Suppository tx (Canasa)
Why don’t suppositories work for Crohn’s?
They only affect lower colon and rectum; Crohn’s is all over the GI tract.
Tablets preferred for Crohn’s.
Canasa
Rectal suppository; give before bedtime.
Benefits of rectal suppossitory?
You bypass first pass effect
Good absorption
Good for patients who can’t take it orally
Good, locally, for UC.
Enema
Liquid preparation, inserted into rectum
Patient lays on side, expel product into colon
Drug Therapy options for IBD:
Olsalazine
-Dimer of mesalamine (prodrug)
Balsalazide
-Prodrug that contains 5-ASA and inert carrier molecule
Corticosteroids for IBD
Topical (Anusol, Colocort)
-for UC
Oral (Budenoside, Prednisone)
-Chron’s
IV (Hydrocortisone, Prednisone)
AE: Weight gain, diarrhea, nausea, glucose intolerance, osteoperosis, Cushing’s
Immunosuppressants: Thiopurines
Decrease metabolism of purines and inhibit DNA and RNA synthesis
Prevent replication of cells
Azathioprine (Imuran)
6-mercaptopurine (Purinethol)
AE: Myelosuppression, secondary infections
Immunosuppressants: Cyclosporine
Inhibit release of IL-2 limiting T-cell act.
AE: nephrotoxic, HTN, hirsutism
Immunosuppressants: Methotrexate
Inhibits folic acid
AE: stomatitis, myelosuppression, hepatotoxicity
Monoclonal antibodies (MAB’s): Infliximab
Chimerical mab targeted at TNF-alpha
AE: infections, secondary malignancy
Monoclonal antibodies (MAB’s): Adalimumab
Chimeric mab against TNF-alpha
AE: Secondary malignancy
Both are produced in bacteria, targeted against specific antigen.
Antibiotics
Decrease bacteria
Used for fistulas in CD
-Cipro, Flagyl
Treatment for UC:
Basically,
- Topical 5-ASA (Mesalamine)
- Topical/Oral corticosteroid
- Oral 5-ASA/AZA, 6-MP
- MAB
Treatment for extensive UC:
- Oral 5-ASA
- AZA or 6-MP
- MAB
Treatment for CD:
- Oral 5-ASA + Oral abx + Oral CS
- IV CS
- AZA/6-MP
- MAB
Maintenance therapy:
UC: Sulfasalazine, 5-ASA, AZA/6-MP, MAB
CD: Same but + Methotrexate and abx
NO CS.
IBS Non-pharm therapy:
Education, diet (keep dairy, avoid caffeine, dietary triggers, increase fiber)
Exercise
Psychotherapy
Pharm therapy for IBS 3 forms:
IBS-C:
- Bulk-forming laxatives
- Osmotic laxative
- Lubiprostone
- TICA/SSRI
- 5HT4 partial agonist
IBS-D:
- Loperamide/Cholestyramine
- 5HT3 antagonist
IBS-U:
- Probiotics
- Antispasmodic
Small intestine bacterial overgrowth:
Rifaximin
IBS: Bulk Forming Laxatives
Absorbs water
Metamucil, Citrucel, Fiber Lax
IBS: Osmotic Laxatives
Increases water retention
Milk of Magnesia
MiraLax
IBS: Chloride channel activator
PGE1 derivative: Increases intestinal secretion secondary to Cl channel act.
Lubiprostone (Amitiza)
IBS: Tricyclic antidepressants (TCA’s)
Effects on muscarinic receptors and serotonin reuptake
Amitriptyline
Imipramine
Not used often
IBS: 5HT4 partial agonist
Hard to get, only for women
Zelnorm
Postmarket warnings about ischemic colitis and diarrhea severe
IBS: Anti-diarrheals
Loperamide (Imodium)
Cholestyramine (Questran)
-For refractory pt’s
IBS: 5-HT3 Antagonists
Hard to get, only for women
Lotronex
Restricted use due to ischemic colitis and DEATH!
Dangerous AF don’t take.
IBS: Antispasmodic agents
Decrease GI smooth muscle and motility
Anti-Ach
Use PRN, due to tachyphylaxis
Bentyl, Robinul, Librax, Donnatal
IBS: Antibiotics
Bacterial overgrowth contributes to IBS
Rifaxamin
Tx IBS-C:
- Bulk laxative
- Osmotic laxative
- Lubiprostone
Tx IBS-D:
- Bulk laxative
- Loperamide/Cholestyramine
- TCA/SSRI
Tx IBS-U:
- Probiotics
- TCA/SSRI
- Antispasmodic
Summary IBD:
IBD tx depends on inflammation and severity
Aminosalicyclates and CS - Mild/mod dz
IV CS, thiopurines, infliximab, adalimumab, cyclosporine, tacrolimus, MTX - Severe IBD
