Gastrointestinal Drugs II Flashcards
Causes of gastroesophageal reflux
- Lower esophageal sphincter - inappropriate relaxation, low resting tone, anatomical alteration
- Acid hypersecretion
- Decreased acid clearance due to impaired peristalsis or abnormal saliva production
- Delayed gastric emptying and/or duodenogastric reflux of bilee salts and pancreatic enzymes
GERD lifestyle Tx
- Elevate head of bed
- Avoid food/liquid 2-3 hrs before bedtime
- Avoidance of fatty or spicy food
- Avoidance of cigs/alcohol
- Weight loss
- Liquid antacid
- Pregnancy
Tx of GERD in patients w/o Esophagitis
- Alginic acid antacids
- Promotility drugs - cisapride, metoclopramide
- H2 blockers - cimetidine, ranitidine, famotidine, nizatidine
Tx of GERD of patients w/ esophagitis
- H2 blockers
- OR
- H2 recceptor blockers + promotility agent
- OR
- PPI
- OR
- Anti-reflux surgery
MOA of promotility drugs to treat GERD?
Promotility drugs prevent acid from sitting in stomach too long
What are the promotility drugs?
Metochlopramide, cisapride
SE of promotility drugs?
Tremor
What is vomiting mediated by?
Chemoreceptor Trigger Zone and Vomiting Center in the Medulla
What is vomiting stimulated by?
Local irritation or CNS stimulation
Metabolic consequences of vomiting?
- Dehydration
- Hypochloremic metabolic alkalosis
- Hypokalemia (Kidney reuptake of acid results in K+ loss)
What are the classes of antiemetics?
- Phenothiazines
- Benzamide
- Tetrahydrocannabinol
- Serotonin (5HT3) receptor antagonists
What are the phenothiazines?
The neuroleptic class
- Prochlorperazine
- Promethazine
MOA of Phenothiazine? Promethazine?
- Prochlorperazine - Dopaminergic receptor antagonist
- Promethazine - H1 anticholinergic
SE of prochlorazine and promethazine?
- Prochlorperazine - Torticollis
- Promethazine - Somnolence
Adverse effects of Benzamide derivatives?
Extrapyramidal Syx (but ont as severe phenothiazines)
What are the Benzamide derivatives?
- Trimethobenzamide
- Metochlopramide
MOA of Trimethobenzamide and Metochlopramide?
- Trimethobenzamide - unknown effects on CRTZ
- Metochlopramide - CNS and peripheral dopaminergic receptor antagonism
MOA of THC?
Suppress the CRTZ by probable anticholinergic mechanism
What are the 5HT3 blockers?
Ondansetron, Granesitron, Dolasetron
Adverse SE of 5HT3 antagonists?
Headache, dizziness, somnolence
Tx strategy for gastroparesis?
Metochlopramide, cisapride, domperidone
5 Types of diarrhea?
- Secretory - Na and Cl secretion/decreased reabs
- Osmotic - Nonabs molecules in gut lumen
- Inflammatory absorptive surface - Destruction of mucosa, impaired abs, outpouring of blood, mucus
- Decreased abs - impaired reabs of electrolytes
- Motility disorder - Increased motility/decreasd motility with bacterial growth
What are the goals to treat diarrhea?
Decrease GI secretion and decrease GI motility
What are the classes for diarrhea Tx?
- Anticholinergics
- Opioid Agonists
- Colloids
- Pectins
Anticholinergic drugs to treat diarrhea?
Atropine sulfate
MOA of loperamide?
Immodium! increase rectal tone and disrupt peristalsis via mu receptor
MOA of diphenoxylate and codeine sulfate?
Mu-R agonist causing contraction of circular muscle “segmentation”
What are the colloids and pectins and what is their MOA?
- Colloid - Metamucil
- Pectin - Kaopectate
Bulk up stool
What is the treatment for constipation?
Laxatives or cathartics
What are the classes of treatments for constipation?
- Irritants/Stimulants
- Osmotic cathartics
- Bluk-forming (hydrophilic colloids)
- Lubricants and fecal softeners
What are the irritants/stimulants?
Castor oil, cascara sagrada/aromatic fluid extract, senne extract, bisacodyl, phenolphthalein
What are the osmotic cathartics?
Magnesium citrate solution, magnesium sulfate, sodium sulfate, milk of magnesia, sodium phosphate, lactulose
What are the bulk forming colloids?
psyllium seed (metamucil), methycellulose, sodium carboxymethylcellulose
What are the lubricant and fecal softeners?
Mineral oil, dioctyl sodium sulfo-succinate, poloxalkol
What is the likely the etiology of the inflammatory bowel diseases?
Likely autoimmune
What are the acute treatments for inflammatory bowel diseases?
- Anti-inflammatories
- Cortiocsteroids
- Antibiotics
What are the antiinflammatory drugs, and what do they target?
- Mesalamine - delayed release for terminal ileum, colon
- Sulfasalazine - ulcerative colitis (colon)
- Olsalazine - ulcerative colitis
What is the mechanism of sulfasalazine? What causes its SEs?
Sulfasalazine is hydrolyzed into 5-ASA (mesalamine - active drug) and sulfapyridine. Sulfapyridine causes side effects
What makes olsalazine so special?
It is a dimer of mesalamine and has few side effects!
What are the drugs used to treat ulcerative colitis and chron’s disease (chronic Tx)?
Immunosuppressive agents:
- Azathiprine - purine antimetabolite that interferes with DNA synth
- Corticosteroids
- Infliximab - binds to and neutralizes TNFalpha
- Cyclosporine - suppresses T helper and T suppressor lymphocytes
What are the drugs used to treat Irritable Bowel syndrome?
- Bulking agents (metamucil)
- Opioids - loperamide
- Anticholinergics - antispasmodics - Dicyclomine hydrochloride, hyoscyamine sulfate
- Antidepressants
What antidepressant is used for diarrhea predominant irritable bowel syndrome? Constipation predominant?
- Alosetron for diarrhea predominant (5HT3 antagonist)
- Tegaserod maleate for constipation predominant (5HT4 agonist)
What conditions affect the large bowel? Small bowel?
- Large - Ulcerative colitis, granulomatous (Chron’s) colitis
- Small - Chron’s disease
