Mid 2- Gastrointestinal disorders Flashcards
Mucosal protective agent
name them
MOA
Sucralfate
Sulfated disaccharide used in PUD
MOA: drug undergoes polymerization and selective binding to necrotic tissue where it acts as a barrier to acid. It also stimulates endogenous prostaglandin synthesis.
- ineffectiv with action of PPI orH2 receptor blocker or other antacids
Bismuth Subsalicylate: by selectively binding to an ulcer it forms a coating and protects from acid and pepsin.
- antimicrobial effect on H. pylori. When administered along with metronidazole and tetracycline antimicrobial drug–> ulcer healing rate of upto 90%- BMT regimen!!
Misoprostol: Is a prostaglandin E1 anaglogue that decrease acid secretion and stimulates mucin and bicarbonate production.
- approved for prevention of gastric ulcers induced by NSAIDs.
- infrequently used due to AE and minimal benedfits.
Adverse effects of Misoprostol
Diarrhea
Abortions: due to induction of uterine contractions during pregnancy
Exacerbations of inflammatory bowel disease (IBD)
AE of metoclopramide
Side effects are due to anti-dopaminergic- sedation; diarrhea and parkinsonian effects limit its high doses and long term use.
what is Irritable bowel syndrome characterized by
DAC: Diarrhea Alternating Constipation
Drug tx for IBS
Anticholnergics:
- Hyoscyamine Dicyclomine Glycopyrrolate and methscopalamine
5-HT3 antagonists: alosteron
Opioid agonists: loperamide
Chloride channel activators: Lubiprostone
Adverse effects of Magnesium hydroxide aluminium hydroxide calcium carbonate
Mg(OH)3–> Diarrhea
Al(OH)3–> constipation “A & C before M&D”
CaCO3–> Nephrolithiasis and constipation–>fecal impaction
3 fundemental agonists that control gastric secretions
Histamine
Ach
Gastrin
final pathway of these compunds is the activation of the H+/K+ ATPase pump
Important H2 receptor blockers
“NIZA RAN Cement FAMily business”
- Are they reveresible or irreversible?
- Which ones are more potent and longer acting?
Cimetidine Ranitidine Famotidine Nizatindine - they are reversible H2 blockers - Ranitidine Famotidine and Nizatidine are longer acting and more potent than older cimetidine
Adverse effects of H2 blocker cimetidine
Presents unwanted endocrinal adverse effects:
Gynecomastia
elevated serum prolactin levels
Decreasd Libido
Confusion in elderly
Can also cross BBB and placenta
Cimetidine and ranitidine can decrease renal excretion of creatinine.
Examples of drugs that have slowed down biodegradation due to cimetidine use.
all drugs that are metabolized by CYP450: Warfarin Procainamide Phenytoin Benzodiazepines Theophylline Imipramine Quinidine
Drug that inhibits the metabolism of warfarin clopidogrel phenytoin diazepam and cyclosporine MOA? Reversible or irreversible? AE of prolonged use? Rare AE?**
Omeprazole
MOA: PPI-covalent bond formation with cysteine residue of H+/K+ ATPase within parietal canaliculi–> irreversible inactivation
AE:- prolonged use of PPI decreases bioavailability of Vit B12; digoxin and ketoconazole because acid is required fo their absorption.
- small increase in respiratory and GI infections, decrease in serum. Mg++ and hip fractures with long term use.
- Rarely pancreatitis hepatotoxicity and interstitial-nephritis.
what should Sucralflate not be administered with and why?
Sucralfate requires acidic pH to be activated therefore it should not be administered with H2-blockers PPI or other antacids
AE of Misoprostol
Diarrhea and abortions due to induction of uterine contractions during pregnancy.
- excerabations of inflammatory bowel disease (IBD)
Prokinetic drugs
Metroclopramide 5HT4 agonists (cisapride) Cholinomimetics macrolides (erythromycin) "MCM54"
Metoclopromide
MOA:
Use:
AD:
MOA:5- HT3 and D2 receptor blocker-acts as anti-emetic
- Prokinetic activity is mediated via 5-HT4 receptor agonist activity. It accelerates gastric emptying and intestinal motility.
- at higher dose 5HT3 antagonist may contribute to the antiemetic response.
Used n diabetic Post-operative gastroparesis and relief of symptoms in GERD.
Also used in nausea and vomiting associated with chemotherapeutic agents.
AE: Anti-dopaminergic- sedation diarrhea and parkinsonian effects. This limits its high doses and long term use.
Cisapride
MOA:
Use:
AD:
Prokinetic MOA: 5HT4 agonist Use: gastroparesis GERD and constipation via stimulating Ach AD: arrhythmias
Cholnomimetics:
Use?
Neostigmine:
Use: in colonic pseudo-obstruction in hospitalized patients.
Bethnechol:
Use: resistant to cholinesterase; long duration of action used in post operative bowel and bladder atony.
Macrolides
USE?
prokinetic: Erythromycin acts on motilin receptors of GIT used I.V.
- used for gastric emptying before uper GI endoscopic procedures.
- tolerance may develop in gastroparesis
ANTIEMETIC AGENTS
major categeories
1) 5HT3 inhibitors- setrons.
2) H1 antihistamines and antimuscarinics- sopolamine
3) NK1- receptor blockers
4) corticosteroids
5) D2 receptor antagonist
6) benzamide-derivative of metonidazole
7) metoclopramide
8) cannabinoids- marijuana
Name 5-HT3 inhibitor used in the gut and CNS
MOA?
USE?
Admin?
Ondansetron
MOA: block 5HT3 in the gut and CNS
USE: indications of the antiemetics are:
- Chemotherapy induced- moderate to severe emesis or post-operative nausea and vomiting.
- route of admin: IV usually and for prophylaxis given orally.
H1 antihistamines and antimuscarinics
H1 anthistamines- Diphenhydramine cyclizine and Meclizine effective in motion sickness and chemo.
Antimuscarinics- scopolamine (motion sickness antemetic)
NK1 receptor blocker
AE?
Aprepitant: in CNS (a receptor to substance P). Effective in both decreasing the early and delayed emesis in cancer chemotherapy.
- PO administration
Fosaprepitant is IV
AE: dizziness fatigue diarrhea CYP interaction may occur.
Corticosteroids
Name 2
what can you coadminister with and why
Dexamethasone or Methylprednisolone
- can be coadministered with Ondansetron to provide greater anti-emetic effect.
- choice CINV (Chemotherapy Induced nausea & vomiting)
D2 Receptor antagonists:
AE?
Phenothiazines- prochlorperazine
- Antagonist at D2 receptors and muscarinic receptors
AE: Extrapyramidal symptoms hypotension and sedation.
Also Promethazine and Droperidol
Phenothiazines D2 Receptor antagonists:
Promethazine:
Promethazine: anti-dopaminergic and anticholinergic. used as antiemetic (decreases motion sickness) antipsychotic effects and sedative.
Phenothiazines D2 Receptor antagonists:
Droperidol:
Droperidol: anti-dopaminergic antiemetic antipschotic and neuroleptic analgesic agent
“Anti-DEP”
Cannabinoids-
Dronabinol: acts on CB1 receptors as an agonist.
Antidiarrheals
AE:
Opioid agonists:
Loperamide (imodium)
Diphenoxylate (lomotil)- formulated w/ atropine to reduce abuse potential.
AE: toxic megacolon in children or pt.s with severe colitis.
Somatostatin analogs:
octreotide: hypersecretory conditions like vipoma
Bismuth compounds:
Bismuth subscalicyate: binds with toxins microbes and inflammatory areas decreasing their effects
LAXATIVES- stimulants
Caster oil; Senna and Bisacodyl - “CBS”
- may cause cramping
- chronic use may lead to habit of perceived need for laxatives
LAXATIVES- bulk formers
Methylcellulose; Psyllium; Bran “BP uses Methyl gas for Bulk”
- increase water retention and stools become bulky. bowel distention leads to peristaltic stimulation of gut.
LAXATIVES- Osmotic agents
Magnesion citrate; Magnesium hydroxide; Lactulose
-osmotically draw water into lumen–> stimulates motility
- simple constipation
- Lactulose also used in hepatic encephalopathy.
PEG (polyethylene glycol) used for colonic lavage.
Glycerine: hyperosmotic effect
LAXATIVES- Stool softeners
Mineral oil and docusate sodium (Colace)
can be used with senna to treat cases of opioid-induced constipation.
- emulsify stool and soften it, lubricate - making it easy passage.
LAXATIVES- Lubriprostone
Prostanoic acid derivative. Chloride channel activator increased secretion into GI-increased fluid content.
LAXATIVES- Opioid receptor antagonists
Alivmopan and Methylnatrexone
- block GI mu-receptors but do not enter CNS
- useful in opioid induced constipation
Drugs used in Crohn’s disease and ulcerative colitis
Aminosalicylates Glucocorticoids Immunosuppressants Anti-TNF-a drugs Anti integrins
Aminosalicylates:
MOA?
USE?
Sulfasalazine; Balsalazide and mesalamine
MOA: inhibits proinflammatory mediators-IL1 and TNF apha
- sulfa derivative.
- sulfapyridine (antibacterial) and 5-aminosalicylic acid (5-ASA) released from sulsalazine by colonic bacteria
USE: Mild to moderate crohns or ulcerative colitis
Sulfasalazine
site of action
and AE
Effects on proximal distal colon and rectum
AE: Nausea/vommiting/diarrhea/hypersensitivity and reversible oligospermia/Bone marrow suppression is related to the sulfpyridine release from sulfasalazine.
Balsalazide USE?
Prodrug; releases mesalamine (5-ASA) in the large intestine at the site of ulcerative colitis.
Glucocorticoids inhibit?
TNF-a
IL-1
IL-8
Immunosuppressants:
AE:
6-mercaptopurine
Azathiopurine- a prodrug of 6-MP
Methotrexate (MTX)
- 6-MP may promote apoptosis of immune response
- MTX blocks dihydrofolate reductase (DHFR)
AE: GI Mucositis myelosupression. Hepatotoxicity can occur with 6-MP.
Anti TNF-a drugs
name 2
Infliximab and Adalimumab (patients w/ fistulas)
Infliximab
MOA
USE
AE
MOA Infliximab: Monoclonal AB targets TNF-a a principle mediator in Crohn’s disease.
USE: conditions associated with flare up of IBD-particularly in Crohn’s related fistulas and acute flares. Also Rheumatoid Arthritis.
AE: *Reacitvation of latent tuberculosis and other infectios. Urticarial reaction hypotension may occur. ABs to infliximab may develop.
Adalimumab
MOA
TNF-a inhibitor
Anti-integrins:
MOA
Natalizumab
blocks leukocyte integrins. can produce *multifocal leukoencephalopathy
Opioid agonist in IBS
MOA
Loperamide (Imodium):
Acts via GI mu-opioid receptors.
- *Inhibit acetylcholine release and decrease peristalsis
- Used in IBS w/ diarrhea.
5-HT3 antagonist in IBS
MOA
AE?
Alosetron
- long duration of action and has high potency
- reduces smooth muscle activity in the gut (For IBS-D)
- Recommended for severe diarrhea associated IBS.
- Rare serious constipation; Iand infarction ISCHEMIC COLITIS may occur
Chloride channel activator in IBS
Lubiprostone
- Used in constipation associated IBS (IBS-C)
drug used in Pancreatic insufficiency
- USE?
Pancrelipase:
- replacement enzyme from animal pancreatic extract.
- Improve digestion of dietary fat protein and carbs.
- Increased ADEK vit absorption
‘USE: pts with chronic pancreatits; after pancreatomy steatorrhea and cystic fibrosis associated insufficiencies.
Orlisatat: USE
Gastric and pancreatic lipase inhibitor used in weight loss. decreases ADEK vit absorption
Antichlinergics MOA
- Non-selective action on the gut can be used in IBS
- Anticholinergic effects on GI, UT, RT, Eye, secretions and on the heart.
What drug causes Oligospermia and bone marrow suppression as an adverse effect?
Sulfsalazine
Antacids increase and decrease absorption of which drugs?
weak bases like quinidine?
Weak acids like warfarin?
ions like Ca++, Mg++, Al++?
increase
decrease
decrease
preoperatively, H2 blockers are used to prevent?
Aspiration pneumonia
Acute stress ulcers associated with major trauma and in high risk patients in intensive care units are treated with?
the drugs are also used as prophylaxis:
H2 receptor blockers
what drug should be used in NSAID-induced ulcers (hemorrhagic ulcers) and why?
PPIs
- they support platelet aggregation and maintain clot integrity!
H2 blockers
GERD Rx.
Antacids for quick relief!
PPI +/- H2 blockers
Pirenzepine
Anticholinergic
