GI Drugs 1 Flashcards
Two major physiological states of gastric acid production:
- Basal
* Meal stimulated
Which drug causes Therapeutic neutralization of low gastric pH protecting esophageal mucosa from reflux corrosion?
Antacids
Time of onset: 5 minutes
Duration of action: 30 minutes to 1 hour
Examples of antacids
Aluminum hydroxide
Magnesium hydroxide
Calcium carbonate
Antacids shouldn’t be co administered with which drugs ? And why ?
tetracyclines, fluoroquinolones, itraconazole and iron
- Increased gastric pH alters dissolution of weakly charged drugs —> decreases the absorption of these drugs
Which antacid causes constipation?
Aluminum hydroxide
Which antacid causes osmotic diarrhea ?
Magnesium hydroxide
____ and ____ often combine to produce no net change in bowel movements
Al and Mg
Which antacid causes Co2 belching and metabolic alkalosis (milk alkali syndrome)?
Calcium carbonate
Functions of H2 Receptor antagonists
- Suppress histamine induced gastric acid secretion
* Reduce signal transduction for ACh and Gastrin-induced acid production
Examples of H2 receptor antagonists
• Cimetidine: prototype with many adverse effects
• Famotidine, Nizatidine: Second generation with no
anti-adrogenic or CNS adverse effects
_________ strongly suppress basal gastric acid secretion and has a modest effect on meal stimulation secretion
H2 Receptor Antagonist
When do you use H2 receptor antagonists
- GERD (Gastro-esophageal reflux disease)
- PUD (Peptic ulcer disease)
- Non-ulcer dyspepsia
- Prophylaxis against stress-related gastritis
Adverse effects of H2 Receptor
Increased gastric pH: B12 deficiency and myelosuppression in long-term use
Adverse effects of Cimetidine only
• Gynecomastia, galactorrhea, male impotence
- Acts as a nonsteroidal anti-androgen and prolactin stimulant
• Crosses the blood-brain barrier
- Confusion, dizziness and headaches
• Potent inhibition of CYP450 system
Cimetidine increases the serum concentration of which drugs
- Warfarin
- Diazepam
- Phenytoin
These drugs Irreversibly bind and inhibit the hydrogen-potassium (H+ - K+) ATPase pump of gastric parietal cells suppressing the final common pathway of gastric acid secretion
Proton pump inhibitors
- Most potent inhibitors of gastric acid secretion
- Inhibit of 90-98% of 24 hour acid secretion
Effect of PPIs on Gastric Acid Secretion
PPIs effectively suppress both basal- and meal- stimulated gastric acid production
Examples of PPI
• Omeprazole • Esomeprazole • Rabeprazole • Pantoprazole Lansoprazole
Which type of drugs should be used under these circumstances
• Gastrinoma(ZES)
• Non-ulcer dyspepsia
• Prophylaxis against stress-related gastritis
• Patients who fail twice-daily H2RA therapy
• Severe symptoms of GERD that impair quality of life
• (PUD) Peptic ulcer disease
- NSAID associated ulcers
- Prevention of peptic ulcer bleeding
PPI
Adverse effects of PPIs
- Vitamin B12 deficiency due to reduced pepsin function
- Increased risk of community-acquired pneumonias and C. difficile colitis
- Hypomagnesemia
- Osteopenia: possibly via reduced CA2+ absorption or osteoclast inhibition.
• All PPIs carry an FDA-marked mandated warning of a possible increase risk of hip, spine, and wrist fractures
Omeprazole: may inhibit the CYP450 metabolism of:
- Warfarin
- Diazepam
- Phenytoin
Omeprazole , esomeprazole and lansoprazole reduce the activation of which drug ?
Clopidogrel
- because it requires P450 CYP2C19 isoenzyme to be activated and these drugs inhibit CYP2C19
How to treat H pylori
• Triple therapy: two antibiotics with a PPI
- clarithromycin + amoxicillin + PPI OR
- clarithromycin + metronidazole + PPI
• Quadruple therapy: 2 antibiotics with a PPI and bismuth subsalicylate
- Bisthmus subsalicylate +metronidazole +tetracycline +PPI
• Both regimens: antibiotics given for 10-13 days and the PPI for 1 month
This drug is an analog of PGE1; binds the EP3 receptor stimulating the GI pathway to decrease gastric acid secretion; Stimulates mucus and bicarbonate secretion and Enhances mucosal blood flow
Mucosal Protective Agents: Misoprostol
Properties of misoprostol
- Approved for prevention of NSAID-induced ulcers in high-risk patients
- Diarrhea, abdominal pain and/or cramps occur in 30% of patients
- Contraindicated in pregnancy due to abortifacient effects
Forms a viscous paste that binds selectively to ulcers
Mucosal Protective Agents: Sucralfate
Properties of sucralfate
Sucralfate: salt of sucrose + sulfated aluminum hydroxide
Forms a viscous paste that binds selectively to ulcers
Negatively charged sucrose sulfate binds positively charged proteins forming a physical barrier
Restricts further caustic damage
Stimulates mucosal prostaglandin and bicarbonate secretion
Limited to the initial management of gastroesophageal reflux disease in pregnancy
This drug
- Suppresses H. pylori
- Used in quadruple antibiotic therapy of H. pylori-positive ulcers
Bismuth subsalicylate
• Pepto-Bismol is widely used for dyspepsia and acute diarrhea
Adverse effects of bismuth
Harmless blackening of stool
Salicylate toxicity
Contraindicated in patients with renal failure
Prokinetic drug groups
- Motilin Agonist
* Serotonin(5HT4) Receptor Agonist
Properties of prokinetic agents
Should enhance coordinated GI motility
• Act ‘upstream’ of ACh at receptor sites on the enteric neuron, or higher
• Activation of muscarinic (M1) receptors enhance contraction in a relatively uncoordinated fashion
- This produces little or no net propulsive activity
- Thus, the cholinomimetic agent, bethanechol and the Ach-esterase inhibitor neostigmine are not currently preferred for treating GI motility disorders
Which prokinetic agent is an
- Antibiotic
- Agonist effects at the motilin receptor
- Rapid down-regulation of motilin receptors leads to early tolerance of this drug. (Use is limited to short courses)
- Best established indication: diabetic gastroparesis
Erythromycin
Which prokinetic drug is a
- 5-HT4 receptor agonist; 5-HT3 antagonist
- Direct smooth muscle stimulant
- Was commonly used for gastroesophageal reflux disease, gastroparesis
- No longer available in the US because of potential to induce serious and occasionally fatal cardiac ventricular arrhythmias
Cisapride
Which prokinetic drug is a
• 5-HT4 receptor agonist
• Vagal and central 5-HT3 antagonist
• Dopamine (D2) receptor antagonist
• Effects confined to the upper digestive tract
- Increases lower esophageal sphincter tone
- Stimulates antral and small intestinal contractions
Metoclopramide
When to use metoclopramide
- Gastroparesis
- Antiemetic
- GERD for symptomatic relief
Adverse effects of metoclopramide
Extrapyramidal effects due to Dopamine antagonism
Galactorrhea by blocking the inhibitory effect of dopamine on prolactin release
Anti emetic drug list
- Anti-Histamines
- CholinergicAntagonists
- D2Antagonists
- 5-HT3ReceptorAntagonists
- Corticosteroids
- Neurokinin-1 receptor Blockers
- Benzodiazepines
- Cannabinoids
Antimuscarinics- Scopolamine
- Treatment and prevention of motion sickness
* May have some activity in postoperative nausea and vomiting
H1 Antagonists examples
Diphenhydramine
Meclizine
Cyclizine
Function of h1 antagonists
- Histamine H1 antagonists act on vestibular afferents and the brainstem
- Useful for motion sickness and postoperative emesis
This drug is
- Weak D2 receptor antagonism at the CTZ
- Sedative Properties are due to antihistaminic and anticholinergic properties effectively treat motion sickness
- Low to moderately effective in CINV
Promethazine
D2 Antagonists- Phenothiazines
This drug is a
- Central Dopaminergic Blockade
- Potential for adverse extrapyramidal effects
- Prolongation of QT Interval
Droperidol
D2 Antagonists-Butyrophenones
Who are the 5HT3 antagonists
- Ondansetron
* Granisetron
5HT3 receptors are present in several critical sites involved in emesis including;
- vagal afferents
- the solitary tract nucleus (STN)
- chemorecptor trigger zone (CTZ)
- area postrema (AP)
_______________ are the drug of choice for prophylaxis against Acute CINV
5HT3 receptor antagonists are the drug of choice for prophylaxis against Acute CINV
5-HT3 antagonists are Effective against_________
And Not effective against: ________________
Effective against hyperemesis gravidarum
Not effective against: Delayed CINV, motion sickness
These drugs work via suppression of peritumoral inflammation and prostaglandin production. They are also highly effective adjuvants in the treatment of nausea in patients with metastatic cancer
Dexamethasone
Methylprednisolone
These drugs are
Antagonists of the NK1 receptors for substance P
• Indicated for prophylaxis against delayed CINV cause by moderate to highly emetogenic drugs
• Given orally in combination with dexamethasone and 5HT3 receptor antagonist
- Aprepitant
* Parenteral formulation: Fosaprepitant
___________ undergoes extensive CYP3A4 metabolism and may affect the metabolism of warfarin and oral contraceptives
Aprepitant
These drugs
- Do not have intrinsic antiemetic effects
- Useful adjuncts due to sedative, amnesic, and anti-anxiety effects which reduce the anticipatory component of nausea and vomiting
- Facilitate GABAA action in the CNS by increasing the frequency of chloride channel opening
- Lorazepam
- Alprazolam
- Diazepam
Adverse effects of benzodiazepines
CNS depression and dependence
Adverse effects of cannabinoids
- Palpitations
- Hypotension
- Tachycardia
- Conjunctival injection (bloodshot eyes)
- Vasodilation
- Paranoid reactions and thinking abnormalities
- Abrupt withdrawal of dronabinol, abstinence syndrome
