Gastro-oesophageal

PPI, H2A

LES relaxants: nitrates, calcium antagonists (nifedipine, amlodipine)

GORD: LES incompetence, impaired oesophageal mucosa resistance, decreased esophageal clearance

GABA_B agonist baclofen (short term trials: reduce TLESRs, increases LOS pressure, reflux episodes, and reflux-related symptoms, increase gsatric emptying). Side effects such as drowsiness and dizziness should be monitored while on baclofen therapy. (TLESR  on manometry: swallow LES pressure declines >3mmHg to <2 mmHg above intragastric pressure for >5s post  OR LES relaxations>10s)

neuromodulation: tricyclics (amitriptyline or nortriptyline if drowsiness)

Prokinetics

challenges:  a) little correlation found between the gastric emptying accelerating effects of various agents and symptom responses. b) factors other than measurable gastric emptying are involved in symptoms in affected individual, c) effective but non-selective agents have been abandoned eg. cholinergics caused intolerable bladder spasms, cisapride lead to hERG channel-mediated cardiac arrhythmias, such as Torsades de Pointes and ventricular tachycardia even without risk factors or tegasarod and cardiac effects d) "safety first” policy for non-life threatening conditions stifles drug development for severely disabling disorders, such as gastroparesis, pseudo-obstruction and severe IBS. e) In the management of the more complex and multifactorial disorders, while the search for highly specific agent is logical given the problems that have arisen as a consequence of unexpected adverse events, there may be some advantages to a “dirty” drug. For example, a drug with 5-HT4 agonist (promotility) and 5-HT3 antagonist (visceral analgesic) would seem attractive in IBS. In another arena, the unexpected but apparent anti-nociceptive effects of the pro-secretory agent, linaclotide, may contribute to its benefits on pain in constipation-predominant IBS and the neuroprotective effects of prucalopride may have significant implications for the long-term outlook of enteric neuropathic disorders. Antihistamines (Bendadryl diphenhydramine), antidepressants (amitriptyline, citalopram, mirtazapine, doxepin), antipsychotics (haloperidol, quetiapine), antibiotics/antifungals (macrolides, metronidazole with alcohol, azoles) all can prolong QTc f) Combination therapy addressing symptoms (i.e. nausea), pain, abnormal gastric function, and psychological therapy for more refractory patients; g) differential diagnoses might show a similar presentation eg. peptic ulcer disease, gastric cancer, coeliac disease, abdominal angina for gastroparesis, anastomotic ulcers, internal herniation and gallbladder disease for early dumping syndrome and insulinoma, surreptitious use of glucose-lowering medication for late dumping

 

cholinergics- muscarinic M2-type receptor agonist: Neostigmine for Ogilvie’s syndrome and pyridostigmine for pseudo-obstruction;

dopamine agonists  metoclopramide (DA, 5HT3/4 antagonist, modest anticholinesterase activity; SE fatigue, sleepiness, depression, akathisia, anxiety, hyperactivity, dyskinesia), domperidone 10-20mg qid (DA2 - breast tenderness and galactorrhea, cardiac - needs close monitoring)

serotonin agonists:  mosapride (selective 5HT4/3: minimal affinity for 5-HT_1/2, dopamine D₂, or adrenergic receptors) 5 mg tds 8 weeks or i CR (loose stools, dry mouth, malaise and headache <5% of patients, does not cause QT prolongation); Prucalopride (highly selective 5-HT₄ agonist, very low affinity for other 5-HT receptors and for the hERG-K⁺ cardiac channels . Its high affinity for the 5-HT₄ receptor confers greater efficacy for prucalopride while low affinity for the hERG-K⁺ channel explains why it has not been shown to be arrhythmogenic; together they confer a major therapeutic advantage for prucalopride over cisapride); Mirtazapine 15mg 6pm (tetracyclic antidepressant -5-HT 1a/2a+c/3 -functional dyspepsia -central and peripheral 5-HT1A receptors - theoretically leads to gastric fundus relaxation, 5-HT3 receptors  antiemetic effect, 5HT2 anti-anxiety)

Macrolide: motilin receptor agonist intravenous erythromycin  (3 mg/kg every 8 hours) and continues with oral administration (250 mg three times a day) for 5 to 7 day, Azithromycin similar; tachyphylaxis within 4 weeks, slowed with lower dosages; P-450 3A inhibitors, Less QTc prolongation and drug interactions with azithromycin

Botulinum toxin (Botox®)

Others for nausea and vomiting:

complementaries: ginger, peppermint drops, and some homeopathic remedies;  melatonin, and herbal medications such as iberogast (STW5, derived from Iberis amara) and capsaicin (component of red pepper)  some benefit in adults with FD
Selective serotonin 5HT3 antagonists: ondansetron ( 4-8 mg tds po, IV, PR) and granisetron
Phenothiazines: most commonly prochlorperazine (Stemetil®)
Antihistamines: cyclizine, diphenhydramine (H1A),  Cyproheptadine (Periactin™ - H1A/muscarinic, HT antagonist, CBB)

neurokinin-1 receptor NK1 RA: aprepitant  125mg daily

anticholingeric - antimuscarinic agent - Scopolamine patch

benzodiazepine - lorazepam (anecdotal chemotherapy studies- anticipatory nausea)

Others for abdominal/chest pain modulation:

Psychosocial therapies (particularly for severe pain, impaired QOL, mood/anxiety disorders): stress management, cognitive behavioral therapy, relaxation therapy, gut directed hypnotherapy, biofeedback, social worker to assist with home/work/education/financial modifications/support
Neuromodulators reduce visceral hypersensitivity (normal motility/FD/EPS subtype) Tricyclics (amitriptyline, nortriptyline), mirtazapine (nausea/weight loss) or Gabapentinoids
Cyproheptadine (younger PDS subtype with early satiety)
Proton pump inhibitors (pantoprazole, omeprazole, lansoprazole, rabeprazole, esomeprazole);  particularly helpful in patients with overlapping symptoms of dyspepsia and gastro-oesophageal reflux disease

Others for abdominal bloating:
Antifoaming/surfactants (alter elasticity of gas bubbles,  ease gastric gas passage): simethicone and activated charcoal
Erythromycin
Metoclopramide
Antibiotics: Metronidazole (Flagyl ®) or Trimethoprim/sulfamethoxazole (TMP/SMX Bactrim®) or  Rifaximin (antibiotic that lacks intestinal absorption and is highly active against aerobic and anaerobic bacteria which may overpopulate digestive tract)

Probiotics:  Bifidobacterium infantis has demonstrated positive effects in RCTs.16 RCTs, B. infantis 35624 reduce intestinal inflammation and showed significant improvement in the composite score for abdominal pain/discomfort, bloating/distention and/or bowel movement difficulty compared with placebo

 

 

Diet:

gastroparesis (Postprandial fullness, early satiety, bloating, abdominal distension, nausea, and vomiting, abdominal pain, and dysphagia): "fork mashable"foods (low particle size diet), Low fat, low fiber foods small frequent meals

anti-dumping diet if rapid GE (

Early dumping syndrome (within 1 h after meal ingestion Gastrointestinal symptoms: Abdominal pain, epigastric fullness, diarrhea, nausea, vomiting, borborygmi, and bloating Vasomotor symptoms: desire to lie down, palpitations and tachycardia, fatigue, faintness, syncope, perspiration, headache, light-headedness, hypotension, flushing, and pallor

Late dumping syndrome (1–3 h after meal ingestion) Neuroglycopenia: fatigue, weakness, confusion, hunger and syncope Autonomic reactivity: perspiration, palpitations, tremor and irritability

(20% of patients suffer from symptoms of dumping syndrome after vagotomy and pyloroplasty,  40% after Roux-en-Y bypass and sleeve gastrectomy, and peak at 50% after esophagectomy): Eat small, frequent meals at least 6 times a day; Lie down as soon as you finish eating. Avoid: simple sugars such as sweets,high sugar soft drinks, cakes, and cookies. Avoid foods that are very hot or very cold. . These can trigger dumping syndrome symptoms. Do not drink liquids with your meal. Instead, drink liquids at least a 30 minutes to an hour after eating solid food. Encourage high-fibre, high-protein food

Prunes. Dried plums (prunes) not only contain fiber but also sorbitol and fructans, non-absorbable carbohydrates that, when fermented by colonic bacteria, create an osmotic load that can dramatically alter stool frequency and consistency. In an 8-week single-blind, randomized study with 40 constipated subjects, the number of CSBMs per week and stool consistency scores improved significantly (P < 0.05) with prunes when compared to psyllium. Straining and global constipation symptoms did not differ significantly between treatments.⁸⁷

Kiwi. In a recent study from Asia, 41 IBS-C patients and 16 healthy adults consumed 2 Hayward green kiwifruits per day for 4 weeks. Another 13 IBS-C patients served as controls. IBS-C patients that consumed kiwi fruit had a significantly faster colonic transit time than controls (P = 0.026). The IBS-C kiwifruit group also reported increases in defecation frequency and improvements in bowel function

Safe prescription of drugs which prolong the QTc interval