Linaclotide (Linzess) Pharmacology

Questions and Answers

What is the mechanism of action of Diphenoxylate/Atropine in treating diarrhea?

Increasing the viscosity of stool

Inhibiting the release of gastrin and VIP

Inhibiting excessive GI motility and propulsion (correct)

Reducing fluid and electrolyte loss

What is the primary function of Loperamide in treating diarrhea?

Inhibiting the release of serotonin

Inhibiting peristalsis and prolonging transit time (correct)

Increasing the secretion of gastrin and VIP

Reducing the visceral sensation of stool

What is the primary mechanism of action of Sulfate salts in bowel preparation?

Inhibiting peristalsis and prolonging transit time

Reducing the viscosity of stool

Increasing the osmotic effect in the gastrointestinal tract (correct)

Inhibiting the release of gastrin and VIP

What is a common adverse effect of Sucralfate?

Constipation Signup and view all the answers

What is a contraindication for the use of Diphenoxylate/Atropine?

All of the above Signup and view all the answers

What is a serious adverse effect of Loperamide?

Torsades de pointes Signup and view all the answers

What is the mechanism of action of Somatostatin Analogs?

Inhibiting the secretion of gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide Signup and view all the answers

What is a serious adverse effect of Sulfate salts in bowel preparation?

All of the above Signup and view all the answers

Which medication is a chloride channel activator that acts locally on the apical membrane of the gastrointestinal tract to increase intestinal fluid secretion and improve fecal transit?

Lubiprostone Signup and view all the answers

What is the mechanism of action of lactulose in treating constipation?

It promotes stool water content by acidifying intestinal contents Signup and view all the answers

Which medication is used to treat opioid-induced constipation?

Methylnaltrexone Signup and view all the answers

What is the effect of linaclotide on gastrointestinal motility?

It increases intestinal fluid secretion Signup and view all the answers

Which of the following medications is not approved for males with IBS-C?

Lubiprostone Signup and view all the answers

What is the primary mechanism of action of metoclopramide in treating gastrointestinal motility disorders?

It enhances the response to acetylcholine of tissue in upper GI tract Signup and view all the answers

What is the main adverse effect of lactulose?

Flatulence Signup and view all the answers

Which medication is used to treat hepatic encephalopathy?

Lactulose Signup and view all the answers

What is the primary mechanism of action of dicyclomine?

Blocking the action of acetylcholine at parasympathetic sites Signup and view all the answers

What is a common side effect of dicyclomine?

Anticholinergic symptoms Signup and view all the answers

Which of the following medications is used to decrease growth hormone (GH) and IGF-1 in acromegaly?

Octreotide Signup and view all the answers

What is a serious potential complication of octreotide therapy?

Bradyarrhythmia Signup and view all the answers

Which of the following is a contraindication for the use of dicyclomine?

Glaucoma Signup and view all the answers

What is the brand name of octreotide?

Sandostatin Signup and view all the answers

What is the route of administration for dicyclomine?

PO, IM Signup and view all the answers

What is an off-label use of octreotide?

Esophageal varices bleeding Signup and view all the answers

What is the mechanism of action of Polyethylene glycol 3350?

It draws water into the stool, thus softening the stool Signup and view all the answers

What is the indication for Alosetron?

Irritable bowel syndrome with severe constipation-predominant symptoms Signup and view all the answers

Which medication is a guanylate cyclase-C agonist?

Linzess Signup and view all the answers

What is the role of CYP2C19 in the metabolism of certain medications?

It is involved in the metabolism of certain proton pump inhibitors and antiplatelet medications Signup and view all the answers

What is the difference between an osmotic laxative and a stool softener?

Osmotic laxatives increase stool frequency, while stool softeners soften the stool Signup and view all the answers

What is the potential serious adverse effect of Alosetron?

Ischemic colitis Signup and view all the answers

Which medication is used to treat H. pylori infection?

Pylera Signup and view all the answers

What is the precaution when using Alosetron in patients with hepatic impairment?

Use with caution in mild-moderate hepatic impairment Signup and view all the answers

What is the primary mechanism of action of Roflumilast?

Blockage of PDE causing increased cAMP Signup and view all the answers

What is the brand name of the glucocorticoid Methylprednisolone?

Medrol Signup and view all the answers

What is a common side effect of systemic glucocorticoids?

Increased appetite Signup and view all the answers

What is the relative potency of Dexamethasone?

0.75 mg Signup and view all the answers

What is a contraindication for live vaccines in glucocorticoid therapy?

Serious systemic infections Signup and view all the answers

What is a long-term side effect of glucocorticoid therapy?

Osteoporosis Signup and view all the answers

What is the brand name of Hydrocortisone?

Solucortef Signup and view all the answers

What is a serious side effect of Roflumilast?

Suicidal thoughts Signup and view all the answers

What is the mechanism of action of Inhaled Steroids in the airways?

Inhibition of inflammatory response and increased sensitivity of beta-2 receptors Signup and view all the answers

What is the effect of LABAs on bronchial smooth muscle?

Relaxation of bronchial smooth muscle by action on beta-2 receptors Signup and view all the answers

What is the mechanism of action of Montelukast?

Inhibition of leukotriene receptors Signup and view all the answers

What is the effect of Short Acting Beta Agonist on bronchial smooth muscle?

Relaxation of bronchial smooth muscle by action on beta-2 receptors Signup and view all the answers

What is the mechanism of action of Phosphodiesterase 4 inhibitor?

Increases cAMP levels, leading to a reduction in lung inflammation Signup and view all the answers

What is the effect of Systemic glucocorticoids on the inflammatory response?

Inhibition of inflammatory response and reverses capillary permeability Signup and view all the answers

What is the mechanism of action of Xanthine Derivative?

Blocks PDE causing increased cAMP, which promotes epinephrine release Signup and view all the answers

What is the benefit of combining corticosteroid and LABA?

Improvement in pulmonary function and control over using the products alone Signup and view all the answers

What is the mechanism of action of Long Acting Muscarinic Antagonist?

Induction of bronchodilation via inhibition of the M3 receptor on airway smooth muscle Signup and view all the answers

What is the mechanism of action of Zileuton?

Decreases the formation of leukotrienes, which causes bronchodilation Signup and view all the answers

Which medication acts on the luminal surface of intestinal epithelium to increase intestinal fluid secretion and improve fecal transit?

Linaclotide Signup and view all the answers

What is the mechanism of action of Antihistamine (H1 Receptor Antagonists)?

Block H1 receptors to decrease the actions of histamine Signup and view all the answers

Which medication is used to treat opioid-induced constipation?

Linaclotide Signup and view all the answers

What is the mechanism of action of Proton Pump Inhibitors?

Decrease acid secretion in gastric parietal cells through inhibition of (H+, K+)-ATPase enzyme system Signup and view all the answers

Which medication is a Somatostatin Analog?

Octreotide Signup and view all the answers

What is the mechanism of action of Osmotic Laxative?

Causes water retention in the stool; increases stool frequency Signup and view all the answers

Which medication is used to treat gastroesophageal reflux disease (GERD)?

Proton Pump Inhibitors Signup and view all the answers

What is the mechanism of action of Antidiarrheal (Loperamide)?

Acts directly on circular and longitudinal intestinal muscles, through the opioid receptor, to inhibit peristalsis and prolong transit time Signup and view all the answers

Which medication is used to treat nausea and vomiting?

5-HT3 Antagonist Signup and view all the answers

What is the mechanism of action of Ammonium Detoxicant?

Bacteria in the colon degrade lactulose into lactic acid resulting in an increase in osmotic pressure and acidification of intestinal contents Signup and view all the answers

What is the mechanism of action of Direct Thrombin Inhibitors?

They bind to the active thrombin site of free and clot-associated thrombin Signup and view all the answers

What is the effect of Vitamin K Antagonist on the human body?

It competitively inhibits vitamin K reductase, which reduces Vitamin K epoxide Signup and view all the answers

What is the mechanism of action of ACE-Inhibitors?

They competitively inhibit Angiotensin-Converting Enzyme, which prevents the conversion of Angiotensin I to Angiotensin II Signup and view all the answers

What is the effect of NSAIDS on platelet function?

They inhibit platelet function by acetylation of the platelet cyclooxygenase Signup and view all the answers

What is the mechanism of action of P2Y12 Inhibitors?

They irreversibly inhibit P2Y12 on platelets, which results in inhibition of platelet activation and aggregation Signup and view all the answers

What is the mechanism of action of Angiotensin Receptor Blocker?

They specifically intercept the binding of angiotensin II to the AT(1) receptor Signup and view all the answers

What is the effect of Antidiuretic Hormone Analog on vasodilatory shock?

It stimulates V1 to increase systemic vascular resistance and mean arterial blood pressure Signup and view all the answers

What is the mechanism of action of Fibrinolytics?

They break down clots by binding to fibrin in a thrombus and converting plasminogen to plasmin Signup and view all the answers

What is the effect of ADH Inhibitor on the human body?

It inhibits ADH-mediated water reabsorption in the distal tubule Signup and view all the answers

What is the primary function of insulin in glucose metabolism?

Facilitates glucose uptake by cells Signup and view all the answers

Which process is directly involved in the conversion of glucose to glycogen?

Glycogenesis Signup and view all the answers

What triggers the release of glucagon from the pancreas?

Low blood glucose levels Signup and view all the answers

What defines the homeostatic response to high blood glucose levels?

Insulin secretion to lower blood glucose Signup and view all the answers

In glycolysis, which phase involves the phosphorylation of glucose using ATP?

Investment Phase Signup and view all the answers

What is the primary role of glycogen in the body?

To store excess glucose for later use Signup and view all the answers

What process does glucagon primarily stimulate in the liver?

Glycogenolysis Signup and view all the answers

Which mechanism helps maintain stable blood glucose levels?

Negative feedback involving insulin and glucagon Signup and view all the answers

Study Notes

Linaclotide (Linzess)

Used to treat IBS with constipation and opioid-induced constipation
Acts locally on the apical membrane of the gastrointestinal tract to increase intestinal fluid secretion and improve fecal transit

Lubiprostone (Amitiza)

Used to treat IBS with constipation and opioid-induced constipation
Chloride channel activator that increases intestinal fluid secretion and improves fecal transit
Not approved for males with IBS-C

Lactulose

Used to treat constipation (osmotic laxative)
Bacteria in the colon degrade lactulose into lactic acid, increasing osmotic pressure and acidifying intestinal contents
Softens stool by promoting stool water content
Alters colonic flora to decrease ammonia production
Used to treat hepatic encephalopathy

Metoclopramide (Reglan)

Used to treat GERD, diabetic gastroparesis, and hiccups
Dopamine antagonist that blocks dopamine receptors and enhances the response to acetylcholine in the upper GI tract
Contraindications: GI obstruction, perforation or hemorrhage, history of seizure, use with other drugs causing EPS
Side effects: drowsiness, insomnia, extrapyramidal symptoms, depression, neuroleptic malignant syndrome, tardive dyskinesia

Sucralfate (Carafate)

Used to treat duodenal ulcers
Antiulcer activity is the result of formation of an ulcer-adherent complex that covers the ulcer site and protects it against further attack by acid, pepsin, and bile salts

Sodium/Potassium/Magnesium (Suprep Bowel Kit)

Used for colonoscopy preparation
Sulfate salts provide sulfate anions, which are poorly absorbed, causing water retention in the GI tract
Contraindications: GI obstruction, bowel perforation, gastric retention, ileus, toxic colitis
Side effects: discomfort, abdominal distention/pain, N/V, fluid/electrolyte abnormalities, cardiac arrhythmia, seizure

Diphenoxylate/Atropine (Lomotil)

Used to treat diarrhea
Diphenoxylate inhibits excessive GI motility and GI propulsion
Contraindications: obstructive jaundice, diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria
Side effects: drowsiness, euphoria, N/V, flushing, paralytic ileus, toxic megacolon, anaphylaxis, anticholinergic effects, respiratory depression

Loperamide (Imodium)

Used to treat diarrhea
Acts directly on circular and longitudinal intestinal muscles to inhibit peristalsis and prolong transit time
Reduces fecal volume, increases viscosity, and diminishes fluid and electrolyte loss
Demonstrates antisecretory activity
Contraindications: children younger than 2 years, abdominal pain without diarrhea, acute dysentery, active ulcerative colitis, bacterial enterocolitis
Side effects: dizziness, abdominal pain, constipation, torsades de pointes

Esomeprazole (Nexium)

Used to treat difficile infection
Somatostatin analog that inhibits serotonin release and the secretion of gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide
Interacts with Pylera, Risedronate DR, CYP2C19 inx, Clopidogrel, Atazanavir, and Rilpivirine

Dexlansoprazole (Dexilant)

Interacts with Pylera, Risedronate DR, CYP2C19 inx, Clopidogrel, Atazanavir, and Rilpivirine

Polyethylene glycol (Miralax)

Used to treat constipation
Osmotic laxative that causes water retention in the stool, increasing stool frequency

Docusate (Colace)

Used to treat constipation
Stool softener that draws water into stool, softening the stool and achieving ease in bowel movement

Alosetron (Lotronex)

Used to treat irritable bowel syndrome
Selective 5-HT3 receptor antagonist
Contraindications: constipation, colitis, intestinal obstruction, Crohn's disease, severe hepatic impairment
Side effects: constipation, abdominal pain, ischemic colitis### Acromegaly Treatment
Octreotide (Sandostatin) decreases growth hormone (GH) and IGF-1 in acromegaly, available in IV and PO forms
Common side effects of octreotide include hyperhidrosis, abdominal pain, and headache
Serious side effects of octreotide include bradyarrhythmia, hyper/hypoglycemia, and cholelithiasis

Antispasmodic

Dicyclomine (Bentyl) blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS
Dicyclomine is used to treat functional bowel/IBS, available in PO and IM forms
Contraindications of dicyclomine include obstructive disease of GI tract, severe ulcerative colitis, glaucoma, Myasthenia gravis, and breast feeding in infants
Common side effects of dicyclomine include anticholinergic effects and lightheadedness
Serious side effects of dicyclomine include tachyarrhythmia, psychosis, and dyspnea

COPD Treatment

Roflumilast (Daliresp) is used to treat COPD, available in PO form
Common side effects of roflumilast include weight loss, diarrhea, nausea, and decrease in appetite
Serious side effect of roflumilast is suicidal thoughts
Contraindication of roflumilast is moderate-severe liver impairment (Child Pugh B or C)

Systemic Glucocorticoids

Systemic glucocorticoids cause inhibition of inflammatory response, suppress neutrophil migration, and decrease inflammatory mediators
Glucocorticoids reverse capillary permeability and have immunosuppressive effects
Dexamethasone (DexPak) is available in PO, IV, and ophthalmic forms
Hydrocortisone (Cortef, Solucortef) is available in PO, rectal, and injectable forms
Methylprednisolone (Medrol, Solumedrol) is available in PO and injectable forms
Prednisone (Deltasone) is available in PO form
Prednisolone (Millipred) is available in PO and ophthalmic forms
Common side effects of systemic glucocorticoids include increased appetite, weight gain, Na/H2O retention, hypokalemia, CNS effects, indigestion, HTN, and hyperglycemia
Chronic side effects of systemic glucocorticoids include Cushing's syndrome, dermal thinning, diabetes, glaucoma, cataracts, amenorrhea, growth retardation, acne, and pancreatitis
Relative potency of glucocorticoids: dexamethasone 0.75 mg, methylprednisolone 4 mg, hydrocortisone 20 mg, prednisone/prednisolone 5 mg

Respiratory Agents

Inhaled steroids inhibit inflammatory responses in airways and increase beta-2 receptor sensitivity
ICS/LABA combination improves pulmonary function and control by combining corticosteroid and LABA
Corticosteroids have anti-inflammatory, immunosuppressive, and antiproliferative actions
LABAs relax bronchial smooth muscle by acting on beta-2 receptors
Short-acting muscarinic antagonists work on M3 receptors, decreasing secretions and causing bronchodilation
Long-acting muscarinic antagonists induce bronchodilation by inhibiting M3 receptors on airway smooth muscle
Short-acting beta agonists relax bronchial smooth muscle and inhibit mediator release from mast cells by activating beta-2 receptors
Leukotriene modifiers, such as montelukast, inhibit leukotriene receptors, facilitating bronchodilation
Phosphodiesterase 4 inhibitors increase cAMP levels, reducing lung inflammation

Thyroid Hormones and Antithyroid Agents

Thyroid hormones increase cellular metabolism and play a role in growth, development, CNS, and bone functions
Antithyroid agents inhibit the synthesis of thyroid hormones

Gastrointestinal Agents

Antihistamines (H1 receptor antagonists) block H1 receptors, decreasing histamine actions
Histamine (H2) receptor antagonists competitively inhibit histamine at H2 receptors, reducing gastric acid secretion
Proton pump inhibitors decrease acid secretion by inhibiting (H+, K+)-ATPase enzyme system
Osmotic laxatives, such as polyethylene glycol, cause water retention in stool, increasing stool frequency
Selective 5-HT3 receptor antagonists block 5-HT3 receptors on enteric neurons in the GI tract
Guanylate cyclase agonists bind to guanylate cyclase-C, increasing intracellular and extracellular cGMP, and decreasing GI transit time
Chloride channel activators increase intestinal fluid secretion and improve fecal transit
Ammonium detoxicants, such as lactulose, soften stool by promoting stool water content
Dopamine antagonists block dopamine receptors, enhancing tissue response to acetylcholine in the upper GI tract
Sucralfate has antiulcer activity, forming an ulcer-adherent complex that protects against acid, pepsin, and bile salts
Bowel prep agents, such as sulfate salts, provide sulfate anions that cause water retention in the GI tract
Antidiarrheal agents, such as diphenoxylate and loperamide, inhibit excessive GI motility and propulsion
Somatostatin analogs mimic natural somatostatin, inhibiting serotonin release and secretion of various hormones
Antispasmodics block the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS

Cardiovascular Agents

Direct thrombin inhibitors directly inhibit thrombin, binding to the active thrombin site
Factor Xa inhibitors reversibly and selectively inhibit Factor Xa, resulting in decreased thrombin generation and thrombus formation
Glycoprotein IIb/IIIa inhibitors specifically bind to GPIIb/IIIa, preventing fibrinogen-mediated platelet aggregation
Unfractioned heparin binds to antithrombin, which inactivates thrombin and Factor Xa
Low molecular weight heparin binds to antithrombin, inhibiting Factor Xa more than thrombin
Vitamin K antagonists competitively inhibit vitamin K reductase, reducing vitamin K epoxide and depleting clotting factors
NSAIDS inhibit platelet function by acetylating platelet cyclooxygenase, blocking thromboxane A2 formation
P2Y12 inhibitors irreversibly inhibit P2Y12 receptors on platelets, preventing platelet activation and aggregation
Fibrinolytics break down clots by binding to fibrin and converting plasminogen to plasmin
Antidiuretic hormone analogs stimulate V1 to increase systemic vascular resistance and mean arterial blood pressure, and V2 to increase water permeability in renal tubules

Insulin Regulation

Insulin is a hormone secreted by pancreatic beta cells, essential for reducing blood glucose levels.
It promotes cellular glucose uptake, particularly in muscles and fat tissues.
Insulin facilitates glycogenesis, converting glucose to glycogen in the liver and muscles for storage.
It enhances lipid storage and suppresses gluconeogenesis, the process of generating glucose from non-carbohydrate substrates.
Insulin release is triggered by increased blood glucose levels following meals.

Glycogen Storage

Glycogen serves as the stored form of glucose, primarily found in liver and muscle tissues.
Glycogenesis, the conversion of glucose into glycogen, is stimulated by insulin.
The liver's glycogen acts to maintain blood glucose levels, while muscle glycogen is utilized for energy during physical activity.
Glycogen stores are depleted during fasting, exercise, and when glucose availability is low.

Glucagon Function

Glucagon is produced by alpha cells in the pancreas and acts to elevate blood glucose levels.
It stimulates glycogenolysis, the process where glycogen is broken down into glucose in the liver.
Glucagon encourages gluconeogenesis, creating glucose from non-carbohydrate sources like amino acids.
Its secretion is triggered by low blood glucose levels and during fasting states.

Homeostatic Feedback Mechanisms

A negative feedback loop regulates blood glucose levels: high levels stimulate insulin secretion, lowering glucose and subsequently decreasing insulin release.
Conversely, low glucose levels trigger glucagon secretion, raising glucose and leading to reduced glucagon production.
This feedback ensures blood glucose remains stable within a narrow range, typically between 70-100 mg/dL.

Glycolysis Pathway

Glycolysis is a key metabolic process that converts glucose into pyruvate, yielding energy in the form of ATP.
It consists of three phases:
- Investment Phase: ATP is utilized to phosphorylate glucose, enhancing its reactivity.
- Cleavage Phase: The 6-carbon glucose molecule is split into two 3-carbon molecules.
- Payoff Phase: Produces ATP and NADH, converting the 3-carbon derivatives into pyruvate.
Under aerobic conditions, pyruvate enters the Krebs cycle; under anaerobic conditions, it is converted to lactate in animals or ethanol in yeast.
Glycolysis is crucial for energy production and plays a significant role in cellular respiration.

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Description

This quiz covers the mechanism of action, effects, and side effects of Linaclotide (Linzess) in treating IBS with constipation.