Gastro Intestinal Flashcards
Proton Pump Inhibitors
MOA: irreversible blockade of the gastric proton pump (H+-K+-ATPase) in parietal cells
→ reduced H+ secretion (by 99 %)
- acid-activated prodrugs (convert to sulfenic acids/sulfenamides → covalent binding to cysteines from the luminal surface of ATPase: their inhibitory effects > plasma half-life!
- PPIs enter the parietal cell from the blood!
- Indication:
+ gastritis, PUD, GERD
+ Zollinger-Ellison syndrome (gastrin producing tumor)
+ prevention of upper GI bleeding in high risk patients
+ eradication of helicobacter - CI: - anaphylaxis due to PPI
- ADR:
short-term: well tolerated (increased intestinal gas, headache, nausea)
long-term (> 8 weeks):
+ risk of GI infections (Salmonella, Campylobacter, Clostridium difficile)
+ risk of pneumonia
+ micronutrient deficiencies (Vit B12, Mg, Ca, Fe)
Omeprazole
Proton Pump Inhibitor
- Ind: gastritis, PUC, GERD and others
- all PPIs: lower bioavailability of acid-activated prodrugs
→ TDM in critical drugs
- all PPI but pantoprazole: inhibition of CYP2C19
→ interactions with phenprocoumon, clopidogrel…
→ pantoprazole is best choice in patients taking more than just the PPI!
Pantoprazole
Proton Pump Inhibitor
- Ind: gastritis, PUC, GERD and others
- all PPIs: lower bioavailability of acid-activated prodrugs
→ TDM in critical drugs
- all PPI but pantoprazole: inhibition of CYP2C19
→ interactions with phenprocoumon, clopidogrel…
→ pantoprazole is best choice in patients taking more than just the PPI!
H2-Antihistamines
MOA: antagonism at H2 receptors → lower acid production ► IND - gastritis, PUD, GERD ► ADR - constipation - unspecific H1 antagonism - Vit B12 deficiency
Histamine System: H1-Receptor - bronchoconstriction - NO release in endothelium (lower RR ) - vasoconstriction (higher RR) - higher blood vessel permeability - adrenal medulla: secretion of epinephrine → higher RR , tachycardia/ arrhythmia - nausea/vomiting - increased vigilance
H2-Receptor - higher gastric acid secretion - higher intestinal motility - higher heart rate → dementsprechend ADR bei Blockade: constipation
Antacids
Bsp: Al(OH)3 + Mg(OH)2, CaCO3
► MOA: alkaline ions chemically neutralise stomach acid (no effect on acid production, poor efficacy)
► IND: occasional heartburn (minor symptoms only!); not: gastritis, PUD, GERD
► ADR:
- constipation (Al3+), diarrhoea (Mg2+)
- meteorism (CaCO3) = farting
- hypophosphataemia (→ cramps, osteoporosis, haemolytic anaemia)
► CI: GFR < 30 ml/min (→ Al3+-induced encephalopathy)
► IA:
high risk of drug-drug interactions (ionic IAs, renal IAs)
Ranitidine
MOA: antagonism at H2 receptors → lower acid production ► IND - gastritis, PUD, GERD ► ADR - constipation - unspecific H1 antagonism - Vit B12 deficiency ► IA - cimetidine: inhibits CYP1A2, CYP2C19, CYP2D6, CYP3A4 - raniditine: no interactions -> Warum überhaupt Cimetidine nehmen??
less effective than PPIs but (because of remaining acid): → only low risk of B12 deficiency → marginal risk of GI infections → if sufficient for symptom control, H2Bs might be prefered!
Ranitidine
MOA: antagonism at H2 receptors → lower acid production ► IND - gastritis, PUD, GERD ► ADR - constipation - unspecific H1 antagonism - Vit B12 deficiency ► IA - cimetidine: inhibits CYP1A2, CYP2C19, CYP2D6, CYP3A4 - raniditine: no interactions -> Warum überhaupt Cimetidine nehmen??
less effective than PPIs but (because of remaining acid): → only low risk of B12 deficiency → marginal risk of GI infections → if sufficient for symptom control, H2Bs might be prefered!
Methylnaltrexone
= MNTX
Ind.: opioid-induced constipation (OIC)
► MOA: peripherically acting μ-opioid receptor antagonists (PAMORAs)
→ antagonising opioid effects outside the CNS (mainly in GI tract)
→ limited ability to cross blood-brain barrier
= analgesic effects of opioids in the CNS are not impaired
Methylnaltrexone
= MNTX
Ind.: opioid-induced constipation (OIC)
► MOA: peripherically acting μ-opioid receptor antagonists (PAMORAs)
→ antagonising opioid effects outside the CNS (mainly in GI tract)
→ limited ability to cross blood-brain barrier
= analgesic effects of opioids in the CNS are not impaired
Stimulant Laxatives
Bsp: bisacodyl (Dulcolax®); sodium picosulfate (Laxoberal®), herbal anthracenediones (Aloe vera, rhubarb)
MOA:
prodrugs of BHPM (formed by colonic microbiota)
1. stimulation of enteric nerves → more peristalsis
2. increased H2O & salt secretion into gut lumen → more peristalsis
► ADR
- abdominal pain, cramps
- habituation, dependency (vicious circle)
► CI: hypertension, arrythmias, IBD, ileus…
► IA: lower bioavailability of other drugs
Saline Laxatives
Bsp.: sodium sulfate, magnesium sulfate (“Epsom salt“) - obsolete! besser: Macrogol ► MOA: hyperosmotic → binds H2O in intestinal lumen → higher stool volume → more peristalsis ► ADR: - impaired electrolyte balance - Na+: hypertension, renal damage ► CI - GFR < 30 ml/min, CVD, IBD, ileus... ► IA: - ionic IA, renal IA
Macrogol
same MOA wie Saline Laxatives (binds water due to osmosis), but without electrolyte ADR
= polyethylene glycol = PEG
- biologically inert (biologisch träge/reagiert nicht), no colonic fermentation
→ 1st line in patients with indication for permanent laxative use
Vicious circle of laxative use
Constipation → Use of Laxative → increased loss of H2o, Na+ und K+ → Hypokalemia → decreased GI motility → Constipation
then again use of laxatives, but higher dose, more ADR!
zusätzlich: durch loss of H2O and Na+ → more Aldosterone secretion → renal loss of K+ (über ROMK im Tubulus) → verstärkt Hypokalemia
Chronic abuse:
Hyperaldosteronism (Hypokalemia + Hypertension + metabolic alkalosis)
Diarrhoea
- 3rd leading cause of child mortality globally
- oral rehydration therapy (ORS) = fluid + electrolyte replacement
- if not infective: Loperamide
Loperamide
= Imodium akut
- MOA: peripherically acting μ-receptor agonist
(bioavailability = 0)
→ inhibition of intestinal motility
take for max. 2 days (severe constipation)
- CI: infective diarrhoea (bacteria remains in the body!)
