DR. LEAL - GASTROINTESTINAL DRUGS Flashcards
Weak bases that react with gastric hydrochloric acid to form salt and water.
ANTACIDS
Reduce or neutralize gastric and peptic
acidity.
ANTACIDS
ADVERSE DRUG RXN OF ANTACIDS
CONSTIPATION
● Reacts rapidly with hydrochloric acid (HCl) to
produce carbon dioxide and sodium chloride.
● Gastric distention and belching; metabolic alkalosis;
fluid retention.
SODIUM BICARBONATE
● Less soluble and reacts more slowly than sodium
bicarbonate with HCl to form carbon dioxide and
calcium chloride (CaCl2).
● Belching or metabolic alkalosis
CALCIUM CARBONATE
● React slowly with HCl to form magnesium chloride
or aluminum chloride and water.
● Osmotic diarrhea; constipation; not given to
patients with renal insufficiency.
BRAND NAME MAALOX AND MAALOX PLUS
MAGNESIUM HYDROXIDE OR ALUMINUM HYDROXIDE
● Parietal cells have 3 receptors: M3, H2 for the attachment of Ach, and CCK-B receptors for the attachment of gastrin.
● Histamine 2 (H2) blockers block the attachment of histamine to the H2 receptors to be able not to reach the proton pump, therefore no HCl created.
H2-RECEPTORANTAGONISTS
○ Cimetidine
○ Ranitidine
○ Famotidine
○ Nizatidine
H2 BLOCKERS
HAS THE MOST EFFECTS H2 RECEPTOR ANTAGONIST
CIMETIDINE
● Inhibits binding of dihydrotestosterone to androgen receptors.
● Inhibits metabolism of estradiol, and increases serum prolactin levels.
CIMETIDINE
GYNECOMASTIA OR IMPOTENCE IN MEN
GAACTORRHEA IN WOMEN
PROLONGED USED OF CMETIDINE
MOST POTENT H2 RECEPTOR ANTAGONIST
FAMOTIDINE
○ Omeprazole
○ Esomeprazole
○ Lansoprazole
○ Dexlansoprazole
○ Rabeprazole
○ Pantoprazole
PROTON-PUMPINHIBITORS
● Called PRO DRUGS because they need activation in an acid environment such as the stomach.
● MOA: Irreversibly inhibit gastric parietal cells proton pump secretion.
PROTON PUMP INHIBITORS
ADVANTAGES
● Short serum half-life.
● Concentrated and activated near their site of action.
● Long duration of action. Hence, they are prescribed
(signatura) one tablet once a day 30 minutes before breakfast for two weeks.
PROTON PUMP INHIBITORS
USE OF PPI
GERD
PUD
NONULCER DYSPEPSIA
STRESS RELATED MUCOSAL BLEDING
GASTRINOMA
ACUTE INTERSTITIAL NEPHRITIS
DEMENTIA IF LONG TERM
SUBNORMAL B12 LEVELS
OSTEOPOROSIS
CLOSTRIDIUM DIFFICILE INFECTION
ADVERSE EFFECTS OF PPIs
DRUG INTERACTION OF PPI’S
Inhibit the metabolism of clopidogrel, warfarin, diazepam, and phenytoin.
OMEPRAZOLE
DRUG INTERACTION OF PPI’S
Decrease metabolism of diazepaM
ESOMEPRAZOLE
DRUG INTEACTION OF PPI’S
Enhance clearance of theophylline.
LANSOPRAZOLE
PROSTAGLANDIN ANALOGS
○ Methyl analog of PGE1.
○ Administered 3-4x daily if used as mucosal
protective agent. But if used as an abortifacient, they can use up to 10 tablets inserted in the vagina.
MISOPROSTOL
FOUR-DRUG REGIMENS FOR ERADICATION OF H. PYLORI INFECTION
- PPI2xaday
- Bismuth subsalicylate (2 tablets; 262 mg each)
- Tetracycline (500 mg)
- Metronidazole (500 mg)
○ Taken 4x daily for 10-14 days.
FOUR-DRUG REGIMENS FOR ERADICATION OF H. PYLORI INFECTION
- PPI2xaday
- 3 capsules of a combination (each capsule containing Bismuth subsalicylate 140 mg
Metronidazole 125 mg
Tetracycline 125 mg
○ Taken 4x daily for 10-14 days.
Extrinsic innervation of the digestive tract is made up of the
sympathetic AND parasympathetic system (via the vagus nerve and the pelvic nerve
SC- SYMPATHETIC - CRANIOSACRAL
PT - PARASYMPATHETIC - THORACOLUMBAR
specialized, spindle-shaped cells located in the gut wall that function as pacemaker cells and help regulate slow-wave peristalsis of the gut
Interstitial cells of Cajal (ICCs)
Controlling muscle activity along the length of the
gut with specific effects:
○ Increased muscle tone
○ Increased intensity of the rhythmical
contractions
○ Increased velocity of conduction of excitatory waves along gut wall, causing more rapid movement of gut peristaltic waves.
MYENTERIC PLEXUS
AUERBACH’S PLEXUS
Composed of excitatory as well as an inhibitory neuron.
MYENTERIC PLEXUS
AUERBACH’S PLEXUS
● Controlling function within the inner wall of each minute segment of intestine such as:
○ Local intestinal secretion
○ Local absorption
○ Local contraction of submucosal muscle
that causes various degrees of infolding of
GI mucosa.
SUBMUCOSAL PLEXUS
MEISSNER PLEXUS
● Composed mainly of excitatory neurons.
SUBMUCOSAL PLEXUS
MEISSNER PLEXUS
○ Increase esophageal peristaltic amplitude.
○ Increase lower esophageal sphincter
pressure.
○ Enhance gastric emptying.
○ No effect on small intestine or colonic
motility.
METOCLOPRAMIDE AND DOMPERIDONE
Dopamine D -receptor Antagonists
Also block dopamine D2 receptors in the
chemoreceptor trigger zone of the medulla (area postrema), resulting in potent antinausea and antiemetic action.
METOCLOPRAMIDE AND DOMPERIDONE
Dopamine D -receptor Antagonists
CLINICAL USES
● Gastroesophageal Reflux Disease ● Impaired gastric emptying
● Nonulcer dyspepsia
● Prevention of vomiting
● Postpartum lactation stimulation
METOCLOPRAMIDE AND DOMPERIDONE
Dopamine D -receptor Antagonists
ADVERSE EFFECTS
● Extrapyramidal effects (dystonias, akathisia,
parkinsonian features) due to central dopamine
receptor blockade.
● Elevated prolactin levels.
METOCLOPRAMIDE AND DOMPERIDONE
Dopamine D -receptor Antagonists
● Stimulate muscarinic M3 receptors on muscle
cells and at myenteric plexus synapses.
● Multiple cholinergic effects.
BETHANECHOL
CHOLINOMIMETICAGENTS
● Acetylcholinesterase inhibitor.
○ Acetylcholine increases since the degrading enzyme is inhibited.
● Enhance gastric, small intestine, and colonic emptying.
● Acute Colonic Pseudo-obstruction or Ogilvie’s syndrome.
NEOSTIGMINE
CHOLINOMIMETICAGENTS
● Stimulate motilin receptors.
● Gastroparesis: 3 mg/kg.
● Upper gastrointestinal bleeding (UGIB): promote
gastric emptying of blood before endoscopy.
ERYTHROMYCIN
MACROLIDES
● Indigestible, hydrophilic colloids that absorb water, forming a bulky, emollient gel that distends the colon and promotes peristalsis.
● Examples:
○ Psyllium
○ Methylcellulose
○ Polycarbophil
BULK-FORMINGLAXATIVES
Examples:
○ Docusate (oral or enema)
○ Glycerin suppository
○ Mineral oil
● Long-term use can impair absorption of fat-soluble vitamins (A,D,E,K).
STOOLSURFACTANTAGENTS (SOFTENERS)
● Soluble but non-absorbable compounds that result in increased stool liquidity due to an obligate increase in fecal fluid.
OSMOTICLAXATIVES
Examples:
○ Non Absorbable Sugars or Salts
- Magnesium hydroxide (milk of
magnesia)
- Sorbitol and lactulose
- Magnesium citrate, sulfate
solution
- Sodium phosphate
○ Balanced Polyethylene Glycol
OSMOTICLAXATIVES
● Aloe, Senna, and Cascara
● Occur naturally in plants.
● Poorly absorbed and after hydrolysis in the colon
● “Melanosis coli”
STIMULANTLAXATIVES/CATHARTICS
ANTHRAQUINONE DERIVATIVES
Bisacodyl: dulcolax (brand name).
● Induces a bowel movement within 6-10 hours when
given orally and 30-60 minutes when taken
rectally.
● Safe for acute and long-term use.
DIPHENYLMETHANE DERIVATIVES
STIMULANTLAXATIVES/CATHARTICS
● Prostanoic acid derivative labeled for use in chronic
constipation and irritable bowel syndrome (IBS)
with predominant constipation.
LUBIPROSTONE
CHLORIDESECRETIONACTIVATORS
increases chloride-rich fluid secretion into the intestine, which stimulates intestinal motility and shortens intestinal transit time.
LUBIPROSTONE
● Minimally absorbed, short amino acid peptides
● Stimulate intestinal chloride secretion by binding to and activating guanylate cyclase-C on the luminal surface that leads to increased intracellular and extracellular cGMP
LINACLOTIDE AND PLECANATIDE
can decrease motility of the intestine, leading to constipation.
● Commonly in post-cesarean patients.
OPIOID RECEPTOR ANTAGONISTS
EX.METHYLNALTREXONE BROMIDE
OPIOID RECEPTOR ANTAGONISTS
● Orally within 5 hours before surgery and twice
daily after surgery until bowel function has recovered, but for no more than 7 days.
ALVIMOPAN
high affinity for 5-HT4 receptors
● Approved for the treatment of patients with chronic
constipation AND IBS WITH PREDOMINANTSconstipation
TEGASEROD
SEROTONIN 5-HT4-RECEPTOR AGONISTS
SEROTONIN 5-HT4-RECEPTOR AGONISTS
treatment of chronic constipation
in women.
PRUCALOPRIDE
● An opioid but nonprescription opioid agonist.
● Does not cross the blood-brain barrier and has no analgesic properties or potential for addiction
LOPERAMIDE
OPIOD AGONISTS
● Prescription opioid agonist that has no analgesic properties in standard doses.
● Higher doses have CNS effects.
● Prolonged use can lead to opioid dependence.
DIPHENOXYLATE
OPIOD AGONIST
● Prescription opioid agonist with high affinity for the
mu receptor (as well as low affinity for the delta
receptor).
● When taken orally, it binds to gut opioid receptors,
resulting in :
—slower colonic transit
—increased fecal fluid absorption.
● Approved for diarrhea-predominant IBS at a dose of 75-100 mg twice daily.
ELUXADOLINE
OPIOD AGONISTS
Conjugated bile salts are normally absorbed in the terminal ileum.
● Crohn’s disease (disease of the terminal ileum) or surgical resection leads to malabsorption of bile salts, which may cause colonic secretory diarrhea.
BILESALT-BINDING RESINS
Adverse Effects:
○ Bloating
○ Flatulence
○ Constipation
○ Fecal impaction
○ Exacerbation of fat malabsorption
BILESALT-BINDING RESINS
___ & ___bind a number of drugs and reduce their absorption; hence, they should not be given within 2 hours of other drugs.
Cholestyramine and colestipol
14-amino-acid peptide that is released in the GIT and pancreas from paracrine cells, D cells, and enteric nerves as well as from the hypothalamus.
SOMATOSTATIN
- INHIBITS SECRETION OF NUMEROUS HORMONES
- REDUCES INTESTINAL FLUID SECRETION AND PANCREATIC
- SLOWS GI MOTILITY
- INHIBITS GALLBLADDER CONTRACTION
- REDUCES PORTAL AND SPLANCHNIC BLOOD FLOW
- INHIBITS SECRETION OF ANT. PIT. HORMONES
SOMATOSTATIN
Synthetic octapeptide with actions similar to
somatostatin.
OCTREOTIDE
- Inhibition of gastrointestinal neuroendocrine tumors (carcinoid, VIPoma) symptoms.
- Effective in diarrhea due to vagotomy or dumping syndrome; short bowel syndrome or AIDS.
OCTREOTIDE
- Carcinoid and VIPoma cause secretory diarrhea and systemic symptoms such as flushing and wheezing.
- Inhibits intestinal secretion and has dose-related effects on bowel motility.
OCTREOTIDE
- STEATORRHEA
- ALTERATIONS IN GI MOTILITIY
- SLUDGE OR GALLSTONES (ACUTE CHOLECYSTITIS)
- ALTERS BALANCE AMONG INSULIN AND GLUCAGON
- HYPOTHYROIDISM
- BRADYCARDIA
ADVERSE EFFECTS OF OCTREOTIDE
● Idiopathic chronic, relapsing disorder.
● Abdominal discomfort (pain, bloating, distention,
or cramps) in association with alterations in bowel
habits (diarrhea, constipation, or both)
IRRITABLE BOWEL SYNDROME
● Episodes of abdominal pain or discomfort, patients note a change in the frequency or
consistency of their bowel movements.
● Abnormal contractions in the large intestine.
IRRITABLE BOWEL SYNDROME
● Inhibit muscarinic cholinergic receptors in the
enteric plexus (Auerbach) and on smooth muscle
(Miesner).
DICYCLOMINE and HYOSCYAMINE
ANTISPASMODICS (ANTICHOLINERGICS
Most commonly in pediatric patients.
DICYCLOMINE and HYOSCYAMINE
○ Dry mouth
○ Visual disturbances
○ Urinary retention
○ Constipation
Anticholinergic effects:
● Antiemetic drugs used in chemotherapy but not in motion sickness. Chemotherapy can induce vomiting.
ALOSETRON
SEROTONIN5HT3-RECEPTOR ANTAGONISTS
● Treatment of patients with severe IBS with diarrhea.
ALOSETRON
CONSTIPATION
ISCHEMIC COLITIS
ALOSETRON ADVERSE EFFECTS
● Prevention and treatment of nausea and vomiting.
● Potent antiemetic properties that are mediated in
part through central 5-HT3 receptor blockade in the
vomiting center and chemoreceptor trigger zone
● Do not inhibit dopamine or muscarinic receptors.
● Do not have effects on esophageal or gastric motility
but may slow colonic transit.
-SETRON
ONDANSETRON, GRANISETRON, DOLASETRON, AND PALONOSETRON
Clinical Uses
1. Chemotherapy-induced vomiting
- Postoperative and Post-radiation nausea
and vomiting.
-SETRONS
SEROTONIN 5HT3-RECEPTOR ANTAGONISTS
prevention of acute and delayed nausea and vomiting in patients receiving moderately to highly emetogenic chemotherapy
regimens.
DEXAMETHASONE
METHYLPREDNISOLONE
● Antiemetic properties that are mediated through central blockade in the area postrema.
● No affinity for serotonin, dopamine, or corticosteroid receptors.
APREPITANT, NETUPITANT, ROLAPITANT AND FOSAPREPITANT
NEUROKININ RECEPTOR ANTAGONISTS
● Used in combination with 5-HT3-receptor antagonists and corticosteroids for the prevention of acute and delayed nausea and vomiting from highly emetogenic chemotherapeutic regimens.
This combination is also used for prevention of irritable bowel syndrome.
APREPITANT, NETUPITANT, ROLAPITANT AND FOSAPREPITANT
decreases the incidence of acute and delayed nausea and vomiting with highly emetogenic chemotherapeutic regimens by 15–30%.
OLANZAPINE
For patients unable to tolerate oral therapy, IV _________ 115 mg may be given as a single intravenous dose 1 hour before chemotherapy.
FOSAPREPITANT
ADVERSE EFFECT AND DRUG INTERACTIONS
- WEL TOLERATED
- LOW INCIDENCE OF FATIGUE AND DIZZINESS
- INHIBIT METABOLISMOF OTHER DRUGS
- DECREASES THE INR IN PATIENTS TAKING WARFARIN
APREPITANT, NETUPITANT, ROLAPITANT AND FOSAPREPITANT
NEUROKININ RECEPTOR ANTAGONISTS
used in the treatment of irritable bowel syndrome.
ANTIPSYCHOTIC AGENTS
PHENOTHIAZINES
● Prochlorperazine, Promethazine, and
Thiethylperazine
BUTYROPHENONES
● Droperidol
THIENOBENZODIAZEPINE
● Olanzapine
● Antiemetic properties are mediated through
inhibition of dopamine and muscarinic receptors.
● Sedative properties are due to their antihistamine
activity.
PHENOTHIAZINES
● Prochlorperazine, Promethazine, and
Thiethylperazine
● Antipsychotic, also possess antiemetic properties due to their central dopaminergic blockade.
● Extrapyramidal effects and hypotension may occur.
● May prolong the QT interval.
BUTYROPHENONES
● Droperidol
● Antiemetic properties may be attributable to inhibition of dopamine D2 and serotonin 5-HT1c and 5-HT3 receptors.
THIENOBENZODIAZEPINE
● Olanzapine
● Primary mechanism of antiemetic action is believed to be dopamine-receptor blockade.
F. SUBSTITUTED BENZAMIDES
Adverse effects:
○ Extrapyramidal: restlessness, dystonias,
and Parkinsonian symptoms.
SUBSTITUTED BENZAMIDES
For prevention and treatment of nausea and vomiting: 10–20 mg orally or IV every 6 hours.
METOCLOPRAMIDE
● Has weak antihistaminic activity.
● 300 mg orally, or 200 mg by IM injection.
TRIMETHOBENZAMIDE
● Weak antiemetic activity.
● Useful for the prevention or treatment of motion
sickness.
● Use may be limited by dizziness, sedation,
confusion, dry mouth, cycloplegia, and urinary retention.
H1 ANTIHISTAMINES & ANTICHOLINERGIC DRUGS
Sedating properties, used in conjunction with other antiemetics for treatment of emesis due to chemotherapy.
FIRST-GENERATION H1 ANTAGONISTS ● Diphenhydramine
○ Minimal anticholinergic properties that
also cause less sedation.
○ Used for the prevention of motion
sickness and the treatment of vertigo due to labyrinth dysfunction.
Dimenhydrinate Meclizine
○ Prototype of antihistamine and anticholinergic drugs.
○ Best agents for the prevention of motion sickness.
○ Very high incidence of anticholinergic effects when given orally or parenterally
○ Better tolerated as a transdermal patch.
MUSCARINIC RECEPTOR ANTAGONIST ● Hyoscine (Scopolamine)
treatment of IBDs.
● Differs from salicylic acid only by the addition of an amino group at the 5 (meta) position.
SULFASALAZINE, OLSALAZINE, BALSALAZIDE AND MESALAMINE
- FIRST LINE AGENT FOR TREATMENTOF MILD TO MODERATE ACTIVE ULCERATIVE COLITIS
- FIRST LINE THERAPY FOR MILD TO MODERATE DISEASE INVOLVING COLON AND DISTAI ILEUM
SULFASALAZINE, OLSALAZINE, BALSALAZIDE AND MESALAMINE
contains timed-release
microgranules that release 5-ASA throughout the small intestine
Mesalamine Compounds
○ Pentasa
have 5-ASA coated in a pH-sensitive resin that dissolves at pH 6–7 (the pH of the distal ileum and proximal colon).
Asacol and Apriso:
uses a pH-dependent resin that encases a multimatrix core; on dissolution of the pH-sensitive resin in the colon, water slowly penetrates its hydrophilic and lipophilic core, leading to slow release of mesalamine throughout the colon.
LIALDA
delivered in high concentrations to the rectum and sigmoid colon by means of enema formulations.
ROWASA
suppository
CANASA
Treatment of patients with moderate to severe active IBD.
GLUCOCORTICOIDS
oral controlled-release formulationS
BUDESONIDE
● Purine antimetabolites that have immunosuppressive properties.
● Important agents in the induction and maintenance of remission of ulcerative colitis and Crohn’s disease.
AZATHIOPRINE AND 6-MERCAPTOPURINE (6-MP)
ADVERSE EFFECT
- BONE MARROW SUPPRESSION
- HEPATIC TOXICITY
PURINE ANALOGS
AZATHIOPRINE AND 6-MERCAPTOPURINE(6-MP)
cannot be used together because it will lead to leukopenia.
ALUPURINOL ABD AZATHIOPRINE
INSTEAD OF ALLUPURINOL IN COMBI WITH AZATHIOPRINE
USE:
FEBUXOSTAT
● Used to induce and maintain remission in patients with Crohn’s disease.
METHOTREXATE
Inhibition of dihydrofolate reductase, an
enzyme important in the production of
thymidine and purines.
METHOTREXATE
○ High doses: used for chemotherapy,
methotrexate inhibits cellular
proliferation.
○ Low doses: treatment of IBD (12–25
mg/wk).
METHOTREXATE
A dysregulation of the helper T cell type 1 (Th1) response and regulatory T cells (Tregs) is present in IBD, especially Crohn’s disease.
ANTITUMORNECROSISFACTOR THERAPY
Four monoclonal antibodies to human TNF are approved for the treatment of IBD:
(I-A-G-C)
○ Infliximab
○ Adalimumab
○ Golimumab
○ Certolizumab
Adverse effects
○ Infection due to suppression of the Th1
inflammatory response.
ANTITUMOR NECROSIS FACTOR THERAPY
family of adhesion molecules on the surface of leukocytes that may interact with another class of adhesion molecules on the surface of the vascular endothelium known as selectins.
INTEGRINS
monoclonal antibodies directed against integrins are available for the treatment of IBD.
NATALIZUMAB
VEDOLIZUMAB
○ Humanized IgG 4 monoclonal antibody targeted only against the α4 subunit.
○ Blocks several integrins on circulating inflammatory cells
NATALIZUMAB
○ Humanized IgG 4 monoclonal antibody targeted only against the α4 subunit.
○ Blocks several integrins on circulating inflammatory cells
VEDOLIZUMAB
● Most commonly caused by cystic fibrosis, chronic pancreatitis or pancreatic resection.
● Fat and protein digestion is impaired when secretion of pancreatic enzymes falls below 10% of normal.
● Can lead to steatorrhea, azotorrhea, vitamin malabsorption, and weight loss.
EXOCRINEPANCREATIC INSUFFICIENCY
● Administered with each meal and snack.
● Dosing should be individualized according to the age and weight of the patient, the degree of pancreatic insufficiency, and the amount of
dietary fat intake
PANCREALIPASE
SHORT BOWEL SYNDROME
BIRTH -
ADULT -
BIRTH - (200-250 CM)
ADULT - (300-800 CM)
IN SHORT BOWEL SYNDROME
CM IF WITH ILEOCECAL VALVE
CM IF WITHOUT ILEOCECAL VALVE
WITH - 15 CM
WITHOUT - 20 CM
CONGENITAL SHORT BOWELSYNDROME
CIG
C- CONGENITAL SHORT BOWEL
I- INTESTINAL ATRESIA
G- GASTROSCHISIS
Binds to enteric neurons and endocrine cells,
stimulating release of a number of trophic hormones (including insulin-like growth factor) that stimulate mucosal epithelial growth and enhance fluid absorption.
TEDUGLUTIDE
● <10 cm gallstones only.
● Decreases the cholesterol content of bile by reducing hepatic cholesterol secretion.
● Used for dissolution of small cholesterol gallstones.
URSODIOL (URSODEOXYCHOLIC ACID)
● First-line agent used for the treatment of early primary biliary cirrhosis (PBC).
URSODIOL (URSODEOXYCHOLIC ACID)
● Reduces portal blood flow and variceal pressures.
● Activity may be mediated through inhibition of release of glucagon and other gut peptides that
alter mesenteric blood flow.
SOMATOSTATIN
OCTREOTIDE
○ Polypeptide hormone secreted by the
hypothalamus and stored in the posterior pituitary (oxytocin and vasopressin are stored in this part).
○ Potent arterial vasoconstrictor.
VASOPRESSIN
Vasopressin analog.
TERLIPRESSIN
Reduce portal venous pressures via a decrease in
portal venous inflow.
● Due to a decrease in cardiac output (β1
blockade) and to splanchnic vasoconstriction (β2 blockade) caused by the unopposed effect of systemic catecholamines on α receptors.
β-RECEPTORBLOCKINGDRUGS
Nonselective β blockers such as ____ & ____ are more effective than selective β1 blockers in reducing portal pressures.
PROPANOLOL
NADOLOL
