G.I. Drugs Flashcards
Esomeprazole
Proton Pump Inhibitor
Covalently modify the active site of H/K ATPase (IRREVERSIBLE)
Relies on slow turnover of ATPase at apical surface
First line treatment for hyperacidity (80-95% reduction)
Prodrug that requires acid activation to react with proton pump
Acid Labile
Must be absorbed into the blood and can only do so at higher pH so must be administered as:
- Gelatin Capsule
Lowers acid secretions by 90%
- Used for GERD
- Used for erosive esophagitis
- Used for peptic ulcers
- Zollinger- Ellison syndrome (secretion of gastrin from tumors in pancreas and intestine)
- NSAID induced gastric ulcers
- H. pylori treatment
NOT ALL Proton Pumps active at one time, so treatment requires 2-5 DAYS
Clearance through liver
Adverse Reaction
- Hepatic Failure reduces clearance
- Nausea, Abd pain, constipation, flatulence, diarrhea
- Rare: Myopathy arthralgia, headache, skin rashes
- Drug interactions through CYP activity
- Increase serum warfarin concentration
- Decrease activation of clopidogrel
Rebound hypergastrinemia and gastritis can occur (excessive gastrin secretion)
lansoprazole
Proton Pump Inhibitor
Covalently modify the active site of H/K ATPase (IRREVERSIBLE)
Relies on slow turnover of ATPase at apical surface
First line treatment for hyperacidity (80-95% reduction)
Prodrug that requires acid activation to react with proton pump
Acid Labile
Must be absorbed into the blood and can only do so at higher pH so must be administered as:
- Gelatin Capsule
Lowers acid secretions by 90%
- Used for GERD
- Used for erosive esophagitis
- Used for peptic ulcers
- Zollinger- Ellison syndrome (secretion of gastrin from tumors in pancreas and intestine)
- NSAID induced gastric ulcers
- H. pylori treatment
NOT ALL Proton Pumps active at one time, so treatment requires 2-5 DAYS
Clearance through liver
Adverse Reaction
- Hepatic Failure reduces clearance
- Nausea, Abd pain, constipation, flatulence, diarrhea
- Rare: Myopathy arthralgia, headache, skin rashes
- Drug interactions through CYP activity
- Increase serum warfarin concentration
- Decrease activation of clopidogrel
Rebound hypergastrinemia and gastritis can occur (excessive gastrin secretion)
Omeprazole
Proton Pump Inhibitor
Covalently modify the active site of H/K ATPase (IRREVERSIBLE)
Relies on slow turnover of ATPase at apical surface
First line treatment for hyperacidity (80-95% reduction)
Prodrug that requires acid activation to react with proton pump
Acid Labile
Must be absorbed into the blood and can only do so at higher pH so must be administered as:
- Gelatin Capsule
- Enteric coated capsule
- Mixed with bicarbonate
Lowers acid secretions by 90%
- Used for GERD
- Used for erosive esophagitis
- Used for peptic ulcers
- Zollinger- Ellison syndrome (secretion of gastrin from tumors in pancreas and intestine)
- NSAID induced gastric ulcers
- H. pylori treatment
NOT ALL Proton Pumps active at one time, so treatment requires 2-5 DAYS
Clearance through liver
Adverse Reaction
- Hepatic Failure reduces clearance
- Nausea, Abd pain, constipation, flatulence, diarrhea
- Rare: Myopathy arthralgia, headache, skin rashes
- Drug interactions through CYP activity
- Increase serum warfarin concentration
- Decrease activation of clopidogrel
Rebound hypergastrinemia and gastritis can occur (excessive gastrin secretion)
cimetidine
H2 Receptor Antagonist
4-5hr duration
Adverse Reaction:
- <3% incidence of effect overall
- Minor effect: diarrhea, headache, drowsiness, fatigue, muscle pain
- Parenteral administration in the elderly (hallucinations, delirium, confusion, slurred speech, and headaches)
Long term effect decrease testosterone binding to androgen receptor and hydroxylation
Decrease pepsin and intrinsic factor output
Tolerance can develop in 3 days
Rebound is a problem if discontinued suddenly
Block base level of acid secretion from ECL cells
Useful for nocturnal acid secretion, important for duodenal ulcers (4-8wk)
Use for Zollinger-Ellison syndrome (excessive gastrin secretion)
Not as effective as proton pump inhibitor but decreases acid secretion by 70% for 24 hours with daily dosing
Excretion is renal via organic cation system
famotidine
H2 Receptor Antagonist
10-12hr duration
Adverse Reaction:
- <3% incidence of effect overall
- Minor effect: diarrhea, headache, drowsiness, fatigue, muscle pain
- Parenteral administration in the elderly (hallucinations, delirium, confusion, slurred speech, and headaches)
Long term effect decrease testosterone binding to androgen receptor and hydroxylation
Decrease pepsin and intrinsic factor output
Tolerance can develop in 3 days
Rebound is a problem if discontinued suddenly
Block base level of acid secretion from ECL cells
Useful for nocturnal acid secretion, important for duodenal ulcers (4-8wk)
Use for Zollinger-Ellison syndrome (excessive gastrin secretion)
Not as effective as proton pump inhibitor but decreases acid secretion by 70% for 24 hours with daily dosing
Excretion is renal via organic cation system
ranitidine
H2 Receptor Antagonist
6-8hr duration
Adverse Reaction:
- <3% incidence of effect overall
- Minor effect: diarrhea, headache, drowsiness, fatigue, muscle pain
- Parenteral administration in the elderly (hallucinations, delirium, confusion, slurred speech, and headaches)
Long term effect decrease testosterone binding to androgen receptor and hydroxylation
Decrease pepsin and intrinsic factor output
Tolerance can develop in 3 days
Rebound is a problem if discontinued suddenly
Block base level of acid secretion from ECL cells
Useful for nocturnal acid secretion, important for duodenal ulcers (4-8wk)
Use for Zollinger-Ellison syndrome (excessive gastrin secretion)
Not as effective as proton pump inhibitor but decreases acid secretion by 70% for 24 hours with daily dosing
Excretion is renal via organic cation system
sucralfate
Misc. Drug
Octasulfate of sucrose with Al(OH)3
Forms sticky neutral pH polymer coating that swells and covers the epithelium
Used for STRESS ULCERS (sticks better to duodenal)
Acid activated, take before food and avoid antacids/PPIs
Common Side Effect is constipation (2%)
Block absorption of other drugs through the stomach
aluminum hydroxide
Neutralizing Antacids
Neutralizes pH of gastric contents
Largely supplanted by proton pump inhibitors
Used over the counter
Al is slower than Mg
Adverse effect:
- Rebound acid secretion
- AlOH- Constipation, nausea, possible phosphate loss, binds tetracyclines
Use in combo for H. Pylori Treatment
calcium carbonate
Neutralizing Antacids
Neutralize pH of gastric contents
Largely supplanted by PPIs
Widely used over the counter
Largely supplanted by proton pump inhibitors
Used over the counter
Adverse effect:
- Rebound acid secretion
Use in combo for H. Pylori Treatment
magnesium hydroxide
Antacids
Neutralize pH of gastric contents
Fast Acting
Stimulates gastric emptying and motility while
Largely supplanted by PPIs
Widely used over the counter
Largely supplanted by proton pump inhibitors
Used over the counter
Adverse effect:
- Rebound acid secretion
Use in combo for H. Pylori Treatment
ALSO A LAXATIVE
- Mg stimulates CCK receptors and increases motility
- Avoid in individuals with
- Cardiac Disease
- Renal Insufficiency
- Diuretic Use
- Electrolyte abnormalities
magnesium trisilicate
Antacids
Neutralize pH of gastric contents
Fast Acting
Stimulates gastric emptying and motility while
Largely supplanted by PPIs
Widely used over the counter
Largely supplanted by proton pump inhibitors
Used over the counter
Adverse effect:
- Rebound acid secretion
Use in combo for H. Pylori Treatment
misoprostol
Prostaglandin Analogs
Synthetic analogue of PGE1
Reduce 80-90% of basal or food-induced acid production
Short acting, up to 3 hr
Used to prevent NSAID-induced injury (but PPIs and H2-antagonists more commonly used for this purpose)
Adverse Effect:
- Diarrhea (30%)
- Exacerbate inflammatory bowel disease
- Increase Uterine Contractions during Pregnancy
pirenzepine
Muscarinic Antagonist
Selective for M1 receptor
Blocks neurotransmission in Intramural Ganglia resulting in less stimulation of parietal cells and ECL cells
Reduce basal acid (40-50%)
Significant anticholinergic side effects
Rarely Used
bethanechol
Prokinetic Agent
Activating M receptors do not activate coordinated motility
Selectively activate M2 and M3 receptors
Side Effects:
- Bradycardia
- Flushing
- Diarrhea
- Cramps
- Salivation
- Blurred vision
cisapride
Prokinetic Agent
5-HT4 receptor agonist and adenylate cyclase stimulant
Used for GERD
Stimulate intrinsic sensory neurons
Adverse reaction:
- Fatal Cardiac arrythmia
erythromycin
Imitates Motilin
Increases motility
Macrolide Antibiotic
Cause gastric dumping, moves bezoars and improves gastric emptying with ILEUS, SCLERODERMA, and PSEUDOOBSTRUCTIONS
Fast dumps can be painful so not recommended for chronic use
metoclopramide
Prokinetic Agent
Dopamine receptor antagonist
- DA decreases ACh release so drugs enhance normal ACh response
Long used, increases lower esophageal sphincter tone and upper GI motility
Relieves GERD symptoms but does not promote healing
Used for nausea and vomiting in dysmotility syndromes
Used as AntiEMETIC also
- PREFERRED AGENT IN CHEMOTHERAPY INDUCED NAUSEA
Also a laxative
Adverse effect:
- Extrapyramidal side effects, dystonias, Parkinson’s like symptoms, Tardive dyskenesia with chronic use
neostigmine
Prokinetic Agent
AChE inhibitor (not insecticide) - Commonly used to counter ILEUS
Tegaserod
Prokinetic Agent
Partial 5-HT agonist in gut for FEMALES with Irritable bowel syndrome
Can improve lower bowel motility in cases with chronic constipation and bloating
Adverse Reaction:
- Fatal Cardiac Arrhythmias
USED FOR CONSTIPATION PREDOMINANT IBS
magnesium citrate
Laxative
Osmotic Laxative
- Non absorbable agent
- Cause water retention
Techically a cathartic causing bowel emptying with watery stool, but act as laxative at lower dosages
Mg Stimulates CCK receptors and Increases motility
Avoid in individuals with renal insufficiency
Cardiac Disease
Electrolyte abnormalities
Diuretic Use
magnesium sulfate
Laxative
Osmotic Laxative
- Non absorbable agent
- Cause water retention
Techically a cathartic causing bowel emptying with watery stool, but act as laxative at lower dosages
Mg Stimulates CCK receptors and Increases motility
Avoid in individuals with renal insufficiency
Cardiac Disease
Electrolyte abnormalities
Diuretic Use
polyethylene glycol
Laxative
Osmotic Laxative
Non-absorbable agent
Cause water retention
Cathartics that cause bowel emptying with watery stool, but act as laxatives at lower dosages
lactulose
Laxative
Osmotic Laxative
Sugar
Used for constipation associated with opioid use and vincristine
Bacterial fermentation of lactulose also drops luminal pH and traps NH4 (increased in colons of patients suffering from hepatic disease)
mannitol
Osmotic Laxative
Sugar
Used for constipation associated with opioid use and vincristine
sorbitol
Osmotic Laxative
Sugar
Used for constipation associated with opioid use and vincristine
docusate
Stool wetting agent
Surfactants that allow mixing of fatty substances and water in stool.
Effective as stool softeners
Do not increase frequency of defecation
bisacodyl
Irritant laxative
Used orally or rectally
Generally safe but overdose causes catharsis
Warn patients not to chew tablets or mix with milk or antacids to ensure that the tablet reaches the site of action in the small intestine and avoid gastric irritation
castor oil
Irritant laxative
Smooth muscle stimulant
Used as cathartic
- laxative
- induce labor
- Purge
- Neolid
Made from castor bean
4 ml will produce laxative effect in 4 hours
16 ml for cathartic effect
glycerin
Irritant glycerin
Suppository that acts as hydroscopic agent and lubricant
Increased water retention
Stimulates peristalsis and produces an evacuation reflex
Rectal admin can produce a bowel movement in a hour
methylcellulose
Bulk-forming laxative
Fiber based
Great for regular soft stools
May exacerbate intestinal obstructions
May absorb other drugs
polycarbophil
ulk-forming laxative
Fiber based
Great for regular soft stools
May exacerbate intestinal obstructions
May absorb other drugs
Psyllium
ulk-forming laxative
Fiber based
Great for regular soft stools
May exacerbate intestinal obstructions
May absorb other drugs
bismuth subsalicylate
Antidiarrheal
Also used in H. pylori treatment
Suspended in magnesium aluminum silicate and oil of wintergreen
Naturally pink
Salicylate is released in stomach and absorbed systemically
diphenoxylate
Antidiarrheal
Opioid
Piperidine derivative
Can have CNS effects
Packaged with atropine to discourage abuse
loperamide
Antidiarrheal
Opioid
mu opioid receptor agonist that stops bowel motility
40-50X more potent than morphine
Does not enter CNS
octreotide
Antidiarrheal Agent
Same as Somatostatin
Parenteral octapeptide
Used to combat secretory diarrhea of hormone secreting tumors
Used for post-surgical gastric dumping syndrome
Diarrhea associated with chemotherapy
Used to rest the pancreas in pancreatitis
Adverse reactions:
- Nausea
- Bloating
- injection site pain
Long term therapy may result in gallstones
chlorpromazine
Antiemetic Agent
Dopamine Receptor Antagonist
Phenothiazines
Originally used as antipsychotics
Preferred use is anti-nauseants and anti-emetic
Mechanism targets D2 receptors in CTZ and H1 receptors
Good for motion sickness
Can be useful in chemotherapy induced nausea
cyclizine
Antiemetic
Antihistamine
Also has anticholinergic effects used in patients with abdominal cancer
H1 receptor antagonist
Used for post-operative emesis
Act primarily on brainstem and vestibular apparatus
diphenhydramine
Antiemetic
Antihistamine
Also has anticholinergic effects used in patients with abdominal cancer
H1 receptor antagonist
Used for post-operative emesis
Act primarily on brainstem and vestibular apparatus
dimenhydrinate
Antiemetic
Antihistamine
Dosed from of diphenhydramine
Also has anticholinergic effects used in patients with abdominal cancer
H1 receptor antagonist
Used for post-operative emesis
Act primarily on brainstem and vestibular apparatus
dolasetron
Antiemetic
5-HT3 antagonist
Used in chemotherapy and antiemesis
Oral or parenteral
Excretion through liver
hydroxyzine
Antiemetic
Antihistamine
Also has anticholinergic effects used in patients with abdominal cancer
H1 receptor antagonist
Used for post-operative emesis
Act primarily on brainstem and vestibular apparatus
granisetron
Antiemetic agent
metoclopramide
Prokinetic agent
Also a Antiemetic agent and Laxative
Dopamine receptor antagonist
Increases forward motility
Stops emesis, promotes defecation
Preferred agent for chemotherapy induced nausea
ondansetron
Antiemetic
5HT3 antagonis
5HT3 promotes gut motility
Act centrally at the CTZ and the STN
Act peripherally in small intestine
Most widely used for chemotherapy induced emesis and nausea
3.9 hours
palonosetron
Antiemetic
Given parenterally only
5HT3 antagonis
5HT3 promotes gut motility
Act centrally at the CTZ and the STN
Act peripherally in small intestine
Most widely used for chemotherapy induced emesis and nausea
Excretion via kidney
40 hours
prochlorperazine
Antiemetic Agent
Dopamine Receptor Antagonist
Phenothiazines
Originally used as antipsychotics
Preferred use is anti-nauseants and anti-emetic
Mechanism targets D2 receptors in CTZ and H1 receptors
Good for motion sickness
Can be useful in chemotherapy induced nausea
promethazine
Antiemetic
Antihistamine
Also has anticholinergic effects used in patients with abdominal cancer
H1 receptor antagonist
Used for post-operative emesis
Act primarily on brainstem and vestibular apparatus
scopolamine
Antiemetic
Anticholinergic
Muscarinc ACh receptor antagonist
Used parenterally but most commonly used as trans-dermal patch
Effective for short or long-term prevention of motion sickness
Used for post-operative emesis
Acts on vestibular apparatus
Not effective for chemotherapy induced nausea, minimal CTZ effects
Adverse effects:
- Blurred Vision
- Outburst of uncontrolled behavior when used in presence of pain or anxiety
apomorphine
Emetic
Acts on CTZ
Given Sub-Q
Largely superceded by activated charcoal
ipecac
Emetic
Acts on CTZ
Given Sub-Q
Largely superceded by activated charcoal
6-mercaptopurine
Irritable bowel disease therapy
Thiopurine
Derivative of chemotherapy
Prodrug
Converted to 6-thioguanine to inhibit DNA synthesis
Rapidly proliferating immune cells targetd
Used to maintain remission in both UC and Crohns disease
May help treat fistulas
Effective in 66% of patients but may require weeks/months
Adverse reactions:
- Pancreatitis
- Fever
- Rash
- Arthralgia
- N/V are common
adalimumab
IBD immune modulation
Fully human antibody
used to maintain remission
May gain use in acute UC must be given parenterally
Used for both Crohn’s and UC
Adverse effects:
- Increased respiratory infections
- Lack of effective response to TB
alosetron
IBS treatment
Used for diarrheal predominant IBS
Focuses on motility of gut
azathioprine
IBD treatment
Thiopurine
Protypical drug
Converted to 6-mercaptopurine which is converted to 6-thioguanine
Inhibits DNA synthesis
Rapidly proliferating immune cells targeted
Maintain remission in UC and Crohn’s disease
May help treat fistulas in Crohns disease
Effective in 66% of patients but may require weeks/months for clinical response
Adverse effects:
- Pancreatitis
- Fever
- Rash
- Arthralgias
Nausea and vomiting are common
Bone marrow suppression
budesonide
IBD treatment
Glucocorticoids
Target immune and inflammatory response
Indicated for acute exacerbations and severe disease
200 more potent that hydrocortisone but is only 10% bioavailable and most of that is removed in hepatic first pass
Topical treatment inside the bowel (enema)
Adverse reaction:
- Immunosuppresion
- Endocrine disruption
- Steroid psychoses
- Other effects typical of steroid treatments
infliximab
IBD treatment
Anti-TNF antibody
Humanized mouse antibody to TNF-a, interferes with inflammatory response
Used in maintaining remission
May gaine use in UC.
Must be used parenterally
Used for both Crohn’s and UC
Adverse effect:
- Increased respiratory infections
- Lack of effective response to TB
mesalamine
IBD treatment
5-ASA based therapy
5-aminosilicyclic acid
DO not act through COX inhibition
Act though inhibition of TNF-a
Delivered as pro-drug or as enteric coated tablet
Delayed release in the jejunum
UC: treatment for acute flare-ups
Crohns: useful for flare-ups, must select dosage to target part of colon involved
olsalazine
IBD treatment
5-ASA based therapy
5-aminosilicyclic acid
DO not act through COX inhibition
Act though inhibition of TNF-a
Delivered as pro-drug or as enteric coated tablet
Activated in the colon
UC: treatment for acute flare-ups
Crohns: useful for flare-ups, must select dosage to target part of colon involved
prednisone
IBD glucocorticoid
Oral is prototype
Target immune and inflammatory response
Indicated for acute exacerbations and severe disease
sulfasalazine
IBD treatment
5-ASA based therapy
5-aminosilicyclic acid
DO not act through COX inhibition
Act though inhibition of TNF-a
Delivered as pro-drug or as enteric coated tablet
Activated in the colon
UC: treatment for acute flare-ups
Crohns: useful for flare-ups, must select dosage to target part of colon involved
Has most side effect due to sulfa group
Headache Nausea Fatigue Allergic reactions Contraindicated in pregnancy
