GI Drugs Flashcards
What is the treatment of gastroesophageal reflux and peptic ulcer disease?
- antacids
- H2 receptor antagonists
- Proton pump inhibitors
- mucosal protective agents
What are corroding factors?
Gastric acid
pepsin
bile
H. pylori
What are protective factors?
Secretion of mucus and bicarbonate
Blood flow
Mucosal cellular regeneration
Prostaglandins
How do antacids work?
antacids + HCl –> salt and H20
neutralizes gastric pH and protects esophageal mucosa from reflex corrosion
onset: 5 min
duration of action: 30 min–>1 hr
Types of antacids
Aluminum hydroxide: constipation
Magnesium hydroxide: diarrhea
Calcium carbonate: causes CO2 belching (can cause metabolic alkalosis)
Antacids drug interactions
- binding of other drugs
- tetracyclines, fluoroquiniolones, iron, etc
How does H2 receptor antagonists work?
suppress histamine induced gastric acid secretion
- reduce signal transduction for Ach and Gastrin induced acid production
H2 antagonists act by ___
competitively inhibiting the parietal cell H2 Gs receptor
onset: 2.5 hr
duration of action: 4-10 hr
Tacyphylaxis develops in 2-4 weeks
H2 antagonist drugs
Cimetidine: lots of AE
Famotidine
Nizatidine
H2RAs suppress___
basal gastric acid secretion*
H2RA inidications
- GERD
- PUD
- non ulcer dyspepsia
- prophylaxis
H2RA AE
- myelosuppression
- increased gastric pH
- b12 deficiency
Cimetidine AE
- galactorrhea, male impotence due to anti-androgen and prolactin stimulant
- CNS effects
- inhibits CYP450 increasing conc of warfarin, diazepam, phenytoin
Proton Pump inhibitors MOA
suppress final common pathway of gastric acid secretion
irreversibly bind and inhibit the H-K ATPase pump of gastric parietal cells
PPI suppress
BOTH basal and meal stimulated gastric acid production
PPI
most potent inhibitors
inhibit 90-98% of 24 hr acid secretion
PPI drugs
Omeprazole Esomeprazole Reabeprazole Pantoprazole Lansoprazole
PPI indications
- Gastrinoma
- non ulcer dyspepsia
- prophylaxis
- GERD
- PUD
PPI AE
- pretty safe but can give you diarrhea, AB pain, headache
- b12 deficiency
- increased risk of pneumonia and C.difficile
- hypomagnesemia
- osteopenia
** fractures
Omeprazole may inhibit ___ of ___
CYP450, warfarin diazepam and phenytoin
What prodrug requires activation by hepatic P450 CYPC19 isoenzyme?
Clopidogrel
Omeprazole, Esomeprazole, and Lansoprazole inhibit
CYP2C19 –> reduce clopidogrel activation
H.Pylori treatment
- triple therapy
- quadruple therapy
- both
Triple therapy
2 antibiotics and PPI:
- clarithromycin + amoxicillin + PPI
- clarithromycin + metronidazole + PPI
Quadruple therapy
2 antibiotics with PPI and bismuth subsalicylate
- Bisthmus subsalicylate + metronidazole + tetracycline + PPI
Both therapy
antibiotics given for 10-13 days and the PPI for 1 month
Mucosal protective agents:
Misoprostol
Sucralfate
Bismuth Subsalicylate
Misoprostol
analog of PGE
binds to EP3 receptor to decrease GA secretion
stimulates mucus and bicarb
enhances blood flow
Misoprostol uses and contraindications
- prevention of NSAID induced ulcers in high risk pt
- CI in pregnant ppl
Sucralfate
forms a paste that binds to ulcers
stimulates mucosal prostaglandin and bicarb secretion
initial management of GERD in pregnancy
Bismuth subsalicylate and AE
suppresses H.pylori
no neutralizing action
PEPTO BISMOL
AE:
- blackening of stool
- cause toxicity
- CI in pt with renal failure
Prokinetic drugs are ___
- Motilin agonist
- Serotonin receptor agonist
Prokinetic drugs:
Erythromycin
Cisapride
Metoclopramide
Erythromycin
- antibiotic
- agonist at motilin receptor
indication: diabetic gastroparesis
Cisapride
5HT4 receptor agonist
5HT3 receptor antagonist
- direct smooth muscle stimulant
- used for GERD, gastroparesis
Metoclopramide
5HT4 agonist
5HT3 receptor antagonist
D2 receptor antagonist
Upper digestive tract effects:
- increases LES tone
- Stimulates antral and small intestine contractions
Metoclopramide indications and AE
indications:
- gasteroparesis
- antiemetic
- GERD
AE:
- extrapyramidal effects due to DA antagonism
- galactorrhea
Anti- emetic drugs
- Anti-Histamines
- Cholinergic Antagonists
- D2 Antagonists
- 5-HT3 Receptor Antagonists
- Corticosteroids
- Neurokinin-1 receptor Blockers
- Benzodiazepines
- Cannabinoids
Cholinergic Antagonists
Scopolamine
motion sickness
Anti-Histamines
Diphenhydramine
Meclizine
Cyclizine
motion sickness
D2 Antagonists
Promethazine
Droperidol
Promethazine
motion sickness
Chemo nausea
Droperidol
adverse extrapyramidal effects
- prolonged QT interval
5-HT3 Receptor Antagonists
Ondansetron
Granisetron
- DOC for acute chemo nausea
- DOC for hyperemesis gravidarum (pregnancy)
Corticosteroids
Dexamethasone
Methylprednisolone
- used for nausea in pt with metastatic cancer
NK1 Antagonists
Aprepitant
Fosaprepitant
- used for delayed Chemo nausea
- given with dexamethasone and 5HT R antagonist
- affects metabolism of warfarin and oral contraceptives
Benzodiazepines
Lorazepam
Alprazolam
Diazepam
- reduce anticipatory component
- GABAa action
- AE: CNS depression and dependence
Cannabinoids
Dronabinol (Δ- 9 - tetrahydrocannabinol)
Cannabis sativa
CB1 receptors in brainstem
used for cancer chemo
AE:
- tachycardia
- hypotension
- paranoid
Laxatives
Bulk forming laxatives Cathartics Stool softeners Lubricant laxatives Osmotic laxatives Selective Mu opioid receptor antagonists
Bulk forming laxatives
Methyl cellulose
Psyllium
Bran
non digestible colloids that absorb water to form bulky jelly
Contraindicated in pt that are immobile or using opioid therapy
Cathartics
directly stimulate enteric nervous system to increase motility
Bisacodyl
Senna
Castor oil
Bisacodyl
acts on nerve fibers of mucosa of colon
Senna
natural in plants
water and electrolyte secretion
chronic use can lead to melanosis coli: brown colonic mucosa
Castor oil
broken into ricinoleic acid in small intestine
CI in pregnant pt
Stool softeners
surfactant which allow water and lipids to penetrate
Docusate
Glycerin
Lubricant laxatives
Mineral oil: coals feces to prevent water reabsorption
DO not give with docusate
Osmotic laxatives
Lactulose
Mg Salts
Polyethylene glycol (PEG)
non absorbable sugars or salts which exert an osmotic pull to retain water in lumen
Lactulose
metabolized by colonic bacteria –> AB cramping
Mg salts
dont use for long time in pt with renal problems
Polyethylene glycol (PEG)
creates high osmotic pressure in gut
used for bowel preparations before GI endoscopy
management for chronic constipation
Lubiprostone
stimulates type 2 Cl channels of SI –> increased motility
indicated for chronic constipation and IBS
AE:
- diarrhea
- CI in children
Selective Mu opioid receptor antagonists
Alvinmopan
Methylnaltrexone
normal motility
do not cross BBB
Antidiarrheal drugs
Opioid agonists
Somatostatin analogs
Bismuth compounds
Opioid agonists
Loperamide
Diphenoxylate
Loperamide
does not cross BBB
no analgesia or addiction
CI in kids and pt with colitis
Diphenoxylate
high dose have CNS effects –> dependence
CI in kids and pt with colitis
Somatostatin analogs
Octreotide
indicated in diarrhea due to neuroendocrine tumors, vagotomy, dumping syndrome, short bowel syndrome, and AIDS
Octreotide AE
decreased pancreatic exocrine function (steatorrhea)
inhibition of gallbladder contractility –> gallstones
Bismuth subsalicylate
travellers diarrhea
IBS treatment first line
no meds food diary: - exclude gas producing foods - low diet in fermentable FODMAPs - lactose of gluten free
Constipation type IBS treatment
Psyllium
Lubiprostone
Polyethylene Glycol
Docusate
Diarrhea type IBS
Opioid agonist like loperamide
5HT antagonist alosetron
IBS anticholinergics
Hyoscyamine
Dicyclomine
Glycopyrrolate
Methscopolamine
Mild IBD
no systemic disease
no bowl obstruction
< 10% weight loss
Moderate to severe IBD
Nausea or vomiting
fever
AB pain
anemia
Severe fulminant disease
high fever
persistant vomiting
obstruction
cachexia
IBD drug groups
Triple A GI: Aminosalicylates Glucocorticoids Immunosuppressants Anti TNFa drugs Anti-integrins
Aminosalicylates
Sulfasalazine
Balsalazide
Mesalamine
long term maintenance IBD remission
active group is 5-ASA
Aminosalicylates MOA
modulate COX and LOG pathway
inhibition of NF-KB
inhibition of cellular immunity
Sulfasalazine
passes into colon is reduced by azoreductase
Aminosalicylates AE
unable to tolerate due to nausea, headache, GI upset, etc
Balsalazide
5 ASA linked to carrier molecule
well tolerated
Mesalamine
packaged 5 ASA that release drug to the desired place
well tolerated
Glucocorticoids
Prednisone
Prednisolone
Budesonide
Glucocorticoids use
• remission of acute exacerbations of IBD
• Not indicated for maintaining remission
• Immunosuppressive and anti-inflammatory effects via:
- Interaction with intracellular glucocorticoid response elements
- Inhibition of phospholipase A2 and COX
- Inhibition of NF-κB
Prednisone & Prednisolone
choice for oral therapy
hydrocortisone is in enema for sigmoid and rectal IBD flares
AE: adrenal suppression, hyperglycemia, immunosuppression
Budesonide
topical effects
less AEs
undergoes rapid first pass metabolism –> low bioavailability
Immunosuppressants
Mercaptopurine (6-MP)
Azathioprine
Methotrexate
Cyclosporine
- maintenance of IBD remission
- Steroid-sparing effect
AE:
- Nausea
- Bone marrow depression
- Vomiting
- Hepatotoxicity
Mercaptopurine (6-MP) & Azathioprine drug interactions
Allopurinol:
- reduces xanthine oxidase activity –> increase serum concentration 6-thioguanine
Methotrexate
- Inhibits dihydrofolate reductase, an
- Reduces the inflammatory actions of IL1
- Stimulates increase release of adenosine
AE:
- bone marrow depression
- megaloblastic anemia
- mucositis
AE reduced by folate
Cyclosporine
calcinurin is needed to activate NFAT–> cytokine genes
Cyclosporine inhibits calcineurin
AE: • Nephrotoxicity • Neurotoxicity • Hypertension • Hyperkalemia • GI complaints • Hyperglycemia
Anti TNF a drugs
Infliximab- moderate to severe colitis
Adalimumab
Indicated in acute and chronic treatment of IBD**
• inactivate TNF
• TNF is a key mediator of:
- Release of proinflammatory cytokines
- Stimulation of hepatic acute phase reactants
- Upregulation of endothelial adhesion molecules
promoting leukocyte migration
Anti TNF a drugs AE
• Suppression of Th1 activity:
- Severe infections including invasive fungal disease
- Reactivation of latent tuberculosis
• Antibodies may develop against these biologics:
- Elimination of clinical response to therapy
- Acute or delayed infusion reactions
• Increased risks of lymphoma, acute hepatic failure and
congestive heart failure have also been reported
Anti-integrins
Natalizumab
Natalizumab
monoclonal antibody targeting several integrins on
circulating inflammatory cells
- moderate to severe, unresponsive Crohn’s disease
AE:
- infusion rx
- opportunistic infections
- reactivation of HPV
How to treat mild IBD
5 ASA
antibiotics
Budesonide
corticosteroids
How to treat severe IBD
IV corticosteroids TNF antagonists Cyclosporine Natalizumab Surgery
Pancrelipase
Pancreatic Enzyme Supplements
• Combination of amylase, lipase and proteases which are rapidly
degraded by gastric acids
• Enteric-coated formulations should be used or non-coated
forms given with acid suppression therapy
• Given by mouth with each meal
AE:
- diarrhea
- AB pain
