11. Gastrointestinal pathopharmacology 1

anorexia, vomiting, constipation, diarrhea, abdominal pain, GI bleeding

absence of hunger or desire to eat despite the hunger signal being there

- not a disorder with the hunger pathway or satiety, not motivation to respond to signals

- associate w/nausea, abdominal pain, psychological distress

a reflex response triggered by vomiting centre located in the medulla, preceded by series of muscular events relating to the GI tract (retching) + sensation of nausea

PNS

tachycardia

hypersalivation

very subjective

medulla -> if you have a lesion/its removed then you cannot vomit

anticipation, fear, memory,

sensory input

motion sickness -> vestibular system activates it

indirect activation: things absorbed in blood (drugs), don't reach centre directly, but if brain knows they are there it will trigger reflex

feeling dizzy activates centre directly through release of histamine and muscarinic neurotransmitters

its actually a PROTECTIVE mechanism

activate the chemoreceptor trigger zone (CTZ), which is outside BBB

- monitors contents of blood

- opioids and chemo also activate CTZ -> vomiting side effect

1. increase of salivary gland fluid (hyper salivation)

2. deep breath (avoid aspiration)

3. GI retroperistalsis (contraction of GI smooth muscle from small intestine to build pressure in abdomen

4. decreased intrathoracic pressure (create pressure gradient)

5. retching (muscle contractions without fluid ejection)

6. vomiting

7. SNS response (increased HR, sweating)

infrequent or difficult defecation

- significant only if associated with decreased QoL

increase in frequency or fees fluidity

- significant only if associated with decreased QoL

healthy bowel movement is variable -> depends on persons normal

rectal pain + bleeding, anal fissure, hemorrhoid

functional: normal rate but difficult evacuation

- risk factors = sedentary lifestyle; dehydration, poor fibre diet, ↑ Emptying Suppression

slow transit: impaired colon motility or stool block

pelvic: ↓ Pelvic muscle strength or Anal sphincter relaxation

secondary: complications of disorders or Tx

- opioids, pregnancy, aging, neurological/endocrine disorders

dehydration, electrolyte imbalances, anal irritation + pain

osmotic:

- substance malabsorption -> water osmosis into colon -> large volume diarrhea

- ex: celiac, lactose intolerant, laxatives

secretory:

- bacterial endotoxins/viral infection -> ↑ intestinal secretions + ↓ absorption -> large volume diarrhea

- ex: C.diff, E.coli, rotavirus, hormone/fluid secreting tumors

motility:

- intestinal inflammation/shortened length -> ↓ transit time + absorption -> small volume diarrhea

- ex: Crohn's, ulcerative colitis, surgical intestinal bypass

• Mechanical = Stretching & Rapid Distention; Not cutting/tearing

• Inflammatory = Histamine & Bradykinin Nociceptor Sensitization

• Ischemic = Bowel Distention → Blood Flow Obstruction

Parietal (Layer of fat covering organs) Pain

Source: Parietal Peritoneum Localized & Intensity > Visceral

Visceral Pain (dull and hard to describe)

Source: Abdominal Organ Dull & Difficult to describe

Referred Pain

Visceral Pain felt in periphery Well Localized (Dermatome)

- ex: heart attack pain felt in arm

upper GI:

- bright red/coffee ground vomit

- black and foul smelling stool

lower GI:

- bloody diarrhea

occult bleeding (harder to detect):

- chronic low-volume

- iron deficiency anemia

massive blood loss (20-25% of blood volume within hours):

- compensatory constriction of peripheral arteries cause:

- postural hypotension

- temporary blindness

- dizziness

- renal failure

- liver necrosis

- decreased blood to brain: confusion, coma

- angina, heart attacks, dysrhythmias

blood is not going to your organs anymore

bulk formers: concentrated dose of dietary fiber

- add soluble fiber to intestine to make stool full of soft squishy fiber gel

- make them heavier and easier to pass

- safest to take long term

osmotic: make concentration of salt higher inside intestines

- water pulled inside intestines: create water slide

stimulant: increase # of contractions in intestine walls by stimulating nerves

- stool goes faster, fastest laxatives

lubricant: coat intestinal walls to make them slippery

emollient: stool softeners

- decrease surface tension of fatty stools, allow them to absorb water + soften

group 1: 2-6hr production of watery stool

- osmotic in high doses

- castor oil

- polyethylene glycol-electrolyte solution

group 2: 6-12hr production of semifluid stool

- osmotic in low doses

- stimulant (except castor oil)

group 3: 1-3 days production of soft stool

- bulk forming

- surfactant

Laxative Effect = Slow production of soft stool

Catharsis = Prompt evacuation of bowels

Diagnostic: Stool Hardness > Infrequent Evacuation Best Treatment: ↑ Fluid & Fiber IntakeGood Adjuncts: Mild Exercises & Group III Laxatives

Antihelmintic (Parasites) Therapy Adjunct

Pre-Surgery Bowel Emptying (Group I)

Removing Ingested Poisons

Any GI Inflammation/Injuries

Long-Term management of Constipation

Caution during Pregnancy/Breast-Feeding

Bisacodyl; Senna (Group II) Castor Oil (Group I)

- suppository can act as fast as 15 mins

Stimulate Peristalsis (even small intestines)

Inhibit intestinal absorption & ↑ GI Secretions

Opioid-Induced Constipation

Slow-Transit Constipation

Frequently Abused

- risk:benefit ratio for constipation is not very good

Psyllium / Methylcellulose (Group III)

≈ Dietary Fibers

Non-digestable or absorbable

Colon stretch → ↑ Peristalsis

Best for Mild Constipation

Irritable Bowel Syndrome (IBS) & Diverticulosis

No absorption = No Systemic EffectsMay exacerbate existing intestinal obstruction

Esophageal Obstruction if insufficient Fluid with intake

Docusate Sodium or Calcium (Group III)

↓ Feces Surface Tension → ↑ Water Penetration +Inhibit intestinal absorption & ↑ GI Secretions

Chloride Channel Activator↑ Intestinal Secretions & Motility

Chronic Idiopathic Constipation

IBS with Constipation in women

Opioid-Induced Constipation

GI Distress (Nausea & Vomiting) & Headaches Rare: Chest Pain + Difficulty Breathing

Polyethylene Glycol (PEG) /Magnesium or Sodium Salts

Poorly Absorbed Salts → Osmotic Pull of Water

Stretching of Intestinal Wall → ↑ Motility

Low-Dose = Group II vs. High-Dose = Group I

Poison or Parasite Purge/Evacuation

Pre-Surgery Emptying

also used for chronic constipation

DehydrationKidney Impairment → ↑ Magnesium Imbalances Sodium Imbalances → ↑ Heart Condition

PEG+Electrolyte Solution

Safest option: Isotonic → No dehydration or electrolyte imbalance

Drawback: Requires significant fluid intake

Sodium Phosphate

Discussed under osmotic laxativesAdvantage over PEG: Easier Administration

Drawback: Hypertonic → Dehydration/Electrolyte Imbalances

Salt Combination

Stimulant + Osmotic Laxatives

Advantage over PEG: ↑ Cleansing Efficacy

Drawback: Same as Sodium Phosphate

False belief of mandatory daily bowel movement + Aggressive OTC Laxative Marketing

Bowel emptying inhibits evacuation until ≈ 2-5 days later → Misdiagnosed as Constipation

- without laxatives: your colon is ready to be emptied, some comes out, and then there is a interval until everything moves forward and next section is ready to be emptied

- with laxatives: empties it completely, so you have a longer interval until next emptying, and you think ur constipated but ur not

Inhibition of normal defecation reflex → Laxatives Dependence

Similar to Nasal Spray Dependence

Dehydration; Electrolyte Imbalances; Colitis (inflammation of colon)

Best Tx: Abrupt Laxative Discontinuation

Patient Education:

Anticipate few days without evacuationStool Quality > Daily MovementSuggest Dietary Fiber + Daily ExercisesIf Laxative used again: Short-Term + Lowest Effective Dose

any drugs that are able to prevent or inhibit, or ↓ the nausea felt as well as the vomiting response

1) Manage side effects of: Opioids / General anaesthetics Chemotherapy (CINV)2) Motion sickness prevention

3) Migraine Therapy

serotonin antagonists: ondansetron (Zofran)

- block serotonin receptors on vagal afferents and in CTZ

glucocorticoids: dexamethasone

- unknown

neurokinin antagonist: Emend

- block receptors for neurokinin in brain

dopamine antagonist: prochlorperazine

- block dopamine receptors in CTZ

- EPS !!

cannabinoids: dronabinol

- unknown, probably activate cannabinoid receptors

5-HT3 Antagonists at CTZ & GI Afferent Neurons

Chemotherapy-Induced Nausea & Vomiting (CINV)

Nausea/Vomiting from Radiotherapy & Anesthesia

Headache / Drowsiness / GI Distress

Prolong QT interval

special usage: delayed emetic response thanks to longer half-life

anticholinergics : scopolamine

- block muscarinic receptors in pathway from inner ear to vomiting centre

- most effective

- less toxicity with transdermal patch

- drowsiness side effect

antihistamines : dimenhydrinate

- block H1 receptors in pathway from inner ear to vomiting centre

- less effective

- sedation effects - has to cross BBB

- Gravol!

Efficacy: Prophylaxis >> Reactive Therapy

- before it happens, anticipate it

Chemotherapy-Induced Nausea & Vomiting (CINV)

Severe Nausea & Vomiting → Fluid/Electrolyte Imbalances → Patients discontinue Tx

Anticipatory = Memory from previous CINV

Acute = Minutes to 1 day post treatment

Delayed = >1 day post treatment

Antiemetics most effective for Prevention Administer before chemotherapy

- high risk: aprepitant, dexamethasone, ondansetron

- moderate risk: dexamethasone, palonosetron

- low risk: dexamethasone

just changes dosages depending

1) Non-Drug Behaviors

Eat Small portions Avoid fatty & spicy foods

2) Doxylamine (Antihistamine) + Vit B6 combination

Best & Safest Rx Option

3) Metoclopramide; Odansetron or Methylprednisone

Last resorts - More toxicity – Use with caution

a class of conditions that anything that involves blockage or inhibition of movement of material within the GI tract.

Abnormal Intestinal Chyme Flow

herniation = any abnormal tissue protrusion, forms sac

- could lead to diverticulosis

adhesions = connection of 2 parts of GI tract that should not be connected

- most common

intussusception = part of intestine prolapse into another

- usually small intestine into colon

- rare in adults, common in children

volvulus = twisting of parts of GI tract

- leads to occlusion of blood supply, ischemia, necrosis

paralytic ileus -> usually following surgery (GI tract in state of shock)

-decline in intestinal motility

acute obstruction

chronic obstruction

IO -> distension -> complications

1. resp system: pressure build up on diaphragm -> ↓ rest volume -> pneumonia

2. nausea + vomiting, ↓ nutrient absorption -> changes in electrolytes

3. changes in electrolytes -> alkalosis if IO is at upper GI (stomach acidity doesn't move), acidosis if IO is in lower GI (acid can come into GI tract)

4. prolonged increase in wall tension -> GI bleeding

5. prolonged increase in wall tension -> release of toxins -> peritonitis + fever

4+5 can lead to hypovolemia + septic shock

manifestations: colicky pain, nausea, vomiting, pain, constipation

Upper Stomach Herniation into Thorax

Type 1: Sliding Hernia (90%) (into esophagus)

• Risk Factors = Short Esophagus; Fibrosis; ↑ Vagus Activity; Pregnancy

• Associated with GERD, eased by standing

Type 2: Paraesophageal Hernia (beside esophagus)• GERD uncommon• Mucosal Blood Flow Compression → Ulcers & Gastritis

• Extreme Cases: Hernia Strangulation → Hemorrhage

Type 3: Mixed

mis of type 1 + 2

Type 4:

severe type 3

lower esophageal sphincter doesn't close all the way

- contents of stomach back up esophagus

- acid irritates = heartburn

Worsened by:

Lying Down;↑ Abdo Pressure; Alcohol/Acidic Foods; ↓ Gastric Emptying;↑ Acid Secretion

Risk Factors:

Obesity; Hiatal hernia; Lower Esophageal

Sphincter(LES)-relaxing substances

esophagitis

esophageal stricture

stomach acid into lungs: asthma, chest congestion, wheezing, hoarseness, laryngitis, pneumonia

Heart burn, Nausea, Problems swallowing, Bad breath, Sore throat, Hoarseness, Regurgitation

Pregnant, overweight, smoking, meds (allergies, high BP, antidepressants, hiatal hernia

group of conditions characterized by difficulty swallowing

- neuromuscular problems: phase 1+2 of swallowing

- myasthenia graves, MS, stroke, impaired coordinating

- narrowing of throat problems: phase 3 of swallowing

- cancers, GERD, scars

• Timing of discomfort depends on level of dysfunction

2-4 s = Upper Esophagus

10-15s = Lower Esophagus

o   Choking

o   Pulmonary aspiration

o   Not enough nutrition

o   Muscle exercises

o   Change in neck/head position

o   Soft/thickened food/water

o   Surgery

o   Tube feeding

Mucosal Barrier Injury caused by:

• Chemicals (Alcohol)• Drugs (NSAIDs)• H. Pylori Bacteria

Common Symptoms• Abdominal discomfort

• Bleeding

Acute Inflammation

source removed

Antacids or ↓ HCl secretions

Chronic Inflammation

• Gastric Mucosa Atrophy → ↓ Secretions

• Duodenal Ulcers; Pernicious Anemia (insufficient B12)• ↑ Risk of Gastric Cancer

Peptic ulcers = acid secretion

• Duodenal Ulcers

• Gastric Ulcers

stress ulcers

break through the submucosa and into the tunica muscularis, muscularis at the very least

if just breaks mucosa, it's called an erosion.

Excessive acid Secretion or Muscle Spasm → Chronic Intermittent Pain

Most Common; Affects Younger Individuals (20-50 y.o.)

Meal or antacids relieve Pain

Main Manifestations• Intestinal Hemorrhage/Perforation

• Common Nocturnal Pain• No ↑ Cancer Risk• Remission-Exacerbation Pattern

• 1◦ defect is NOT ↑ HCl Secretions - Most often defective mucosa barrier

• Older Onset (55-65)

Main Manifestations:• Similar to Duodenal• Vomiting/Nausea & Anorexia• No Remission-Exacerbation Pattern (slow gradual decline)

• ↑ Gastric Cancer Risk

have a tumor in cells of stomach that release gastrin

- stimulates more acid secretion

- breaks down mucosal barrier

Acute Mucosal Disease caused by severe physiological stress

• Several Ulcers along Gastric & Duodenal Wall

Complication of Severe Illness/Multisystem Organ Failure

Ischemic Ulcers: Within Hours

Curling Ulcers: Following Severe Burn Injuries

Cushing Ulcers: ↑↑ Vagal Activity Following Brain Surgeries or Head Trauma

Main Manifestations:

Severe Bleeding

Exacerbated by concomitant Coagulopathy

Sudden & Severe Inflammation of Appendix → Surgical Emergency Happens most often in 20-30 years old

Lumen Obstruction (Stool, Tumors, etc.) → ↑ Intraluminal Pressure → Ischemia → Bacterial Infection & Inflammation

Acute Pain (right lower quadrant)INTENSEFeverNausea/VomitingSerious Complications = Abscess & Perforations

at beginning of rectum, close to junction of small/large intestine

- hosting a lot of the bacteria within the GI tract responsible for helping us digest certain parts of food BUT optional

surgery

Crohn's

- transmural inflammation spanning whole layers

- can affect any part, multiple parts at same time

- surgery not option

ulcerative colitis

- continuous lesion usually affecting distal section closest to rectum of large intestine

- surgery option: remove entire affected area

Mouth Ulcers; Skin Lesions; Osteoporosis; Gallstones; Arthritis

Increase in the coagulation process due to the inflammation activating clotting factors -> ↑ DVT + lethal microthrombi

Inner lining of large intestine is inflamed

o   Causing open sores or ulcers

o   Usually only affects mucosa and submucosa layers

o   Abdominal pain

o. Persistent diarrhea

o   Mucus blood in stools

o   Fecal urgency

o   Fecal incontinence

o   Tenesmus

o   Extra-intestinal: Arthritis, Dermatitis, Uveitis

o   Systemic: Weight loss, Nausea, vomiting, Fatigue, Fever

o   Proctitis

§  Rectum only

§  Mildest

§  Normal stool but might have blood

o   Proctosigmoiditis

§  Rectum + sigmoid colon

o   Left sided colitis

§  Rectum + sigmoid colon + descending colon

o   Pancolitis

§  Entire colon

§  Most severe

§  Stools become more watery

o   Increased risks for colon cancers

o   Toxic colitis = inflammation extends into smooth muscle layer, paralyzes colon muscle

§  High fever

§  Abdominal pain

§  Signs of peritonitis

§  Colon dilation + perforation

o   Mostly based on symptoms

o   Stool tests excludes infection

o   Colonoscopy to exclude cancer

o   Dietary management : Avoid RAW fruits/veggies, no dairy

o   Antidiarrheal : Loperamide (not for acute though)

o   Suppository (only if rectum involved) or oral 5-ASA :Mild to moderate

o   Corticosteroids, immunomodulators: Azathioprine, mercaptopurine, for extensive UC

o   IV corticosteroids: Severe cases

o   High dose IV corticosteroid + antibiotics + emergency surgery: Toxic colitis

o   About 1/3 patients with extensive UC will need surgery

inflammation anywhere in GI tract

-   Is immune related: Triggered by pathogen

§  Mycobacterium paratuberculosis

§  Pseudomonas

§  Listeria

o   Immune response is large and uncontrolled

§  Leads to destruction of cells in GI tract

o   Pathogen activates immune system

o   T helper cells release cytokines

o   Call macrophages, which release proteases, free radicals, platelet activating – A LOT of these in Crohns

o   One of the steps is dysfunctional

§  Leads to unregulated inflammation

Pathogens should not be able to just enter but in Crohn's it is thought that there is a defect in epithelial barrier so pathogens can enter

o   immune system invades deep mucosa

§  Organizes itself in granulomas

·       Big masses of immune cells

§  Ulcers form because of this

o   Pain = Most common right lower quadrant

o   Diarrhea + blood in stool = Due to damage in intestine, unable to absorb H20 -> diarrhea

o   Malabsorption

o   Anti-inflammatory

o   Antibiotics = Helps control gut bacteria, Reduce immune response

o   Immunosuppressants = Corticosteroids

o   Surgical removal = But DOESN’T cure disease

antibiotics -> when ulcer caused by infection

antisecretory agents -> reduce acid secretion

- H2 receptor antagonists

- proton pump inhibitor

antisecretory agent that enhances mucosal defenses

- misoprostol

Alleviate Sx + Promote healing + Prevent complications & relapse

• H.pylori-induced ulcers: Antibiotics + PPI or H2RAs• NSAIDs-incuded ulcers prophylaxis: PPI or Misoprostol• NSAIDs-incuded ulcers treatment: PPI + NSAID discontinuation

Pain alleviation & ulcer healing often do not correlate

• H.Pylori test to determine eradication• Radiologic or endoscopic exam for ulcer healing

• Diet: Consumption of 5-6 small meals (instead of 3 large) → ↓ stomach acidity fluctuation

• No evidence of efficacy of ‘ulcer diet’ or exacerbation by coffee and tea

• Other measures: Avoid ulcer-inducing agents• Ex.: NSAIDs (except low-dose aspirin) / Smoking /Anxiety-Stress / Alcohol (debated evidence)

Establish H.pylori involvement before initiating + never use an antibiotic alone

- look at table w/different regimens, there's always a PPI in there

Clarithromycin

Very effective but high resistance

Amoxicillin

Highly efficient & Low resistance↑ efficacy at neutral pH (ex. with meal or PPI)

Bismuth

Risk of stool discoloration (Often misdiagnosed as gastric bleeding!)

Avoid long-term use (neural injuries)

Tetracycline

Very low resistance

Avoid during pregnancy

Metronidazole & Tinidazole

Very effective but high resistance

Disulfiram-like reaction with alcohol

promote protection of GI

block acid secretion

H2 antagonist

Uses

• Gastic & Duodenal Ulcer• Treatment + Prevention

• Gastroesophageal Reflux Disease

• Sx alleviation only

• Zollinger-Ellison Syndrome (gastrin-secreting tumor)

Action

• Selective H2 receptor antagonist• ↓ gastric secretion volume & acidity

• No anti-allergy effects (H1 receptors)

Adverse Effects low incidence and mostly benign• CNS excitation & confusion• Small increase in pneumonia risk (↑ gastric pH = ↑ bacteria colonies)

• Mostly patients with renal or hepatic impairments

Interactions

Most important toxicity factor

• CYP450 inhibition of warfarin, phenytoin & lidocaine

• Antacids ↓ cimetidine absorption (avoid combo)

Better option = Ranitidine

• Higher potency• Fewer ADRs• Fewer interactions

Proton Pump Inhibitor (PPI)

• PPIs superior to H2-RA in HCL ↓ and onset speed

• PPIs are equivalent in terms of safety & efficacy• Select based on $

Uses

Short-term ulcer & gastric reflux Tx

Long-term Zollinger- Ellison syndrome mgmt

Action

• Irreversible H+/K+ ATPase inhibitor• Prodrugs with short T1/2 but long duration• Very efficient, 97% ↓ HCl within a few hours

Adverse Effects

• Minimal with short-term therapy• Rebound acid hypersecretion• Increased risk of C.diff, report signs of diarrhea

Interactions

↓ absorption of antiviral & antifungal Rx

with clopidrogel:

↓ GI bleeding risk (beneficial)but also ↓ clopidogrel activation (adverse)

• Combine in patients with bleeding risk factors only, ex: NSAIDs use; advanced age

mucosal protectant

Use

• Acute + maintenance therapy of duodenal & gastric ulcers

Action

• PO available acid barrier

• Promotes ulcer healing

• Efficacy ≈ H2-RA

No serious ADRS

• Constipation in 2% of patients

Interactions

• Antacids: ↓ efficacy if pH ≥ 4

• ↓ absorption of other Rx

• Administer 2h apart

ionic compounds

Aluminum ex. aluminum hydroxide

- constipation increase

- no effect on pH

Magnesium ex. magnesium hydroxide

- diarrhea increase

- no effect on pH

Aluminum + Magnesium ex. magraldate

Calcium ex. calcium carbonate

- constipation increase

- no effect on pH

Sodium ex. sodium bicarbonate

- no effet on bowels

- increase systemic pH

Efficacy ≈ H2-RAs but more toxicity

• No curative therapies/Sx relief only

• IBD ≈ Excessive immune response

- most drugs used will be immunomodulators, immunosuppressants

Non-Rx Measures for all:

Exercise, Healthy Diet; Avoid Smoking & Alcohol

5-aminosalycylates - very close to aspirin

- ↓ Inflammatory Prostaglandin synthesis

Best for mild-moderate acute ulcerative colitis episodes

not for Crohn's disease.

ADRs: nausea, fever, agranulocytosis, complete blood count

- due to toxic metabolite sulfapyridine

Glucocorticoids

PO for mild-moderate cases / IV for severe

High systemic toxicity with long-term use

Methotrexate

Promotes short-term remission when Glucocorticoid Tx is too long

Dosage much lower than anticancer dosage → Milder toxicity

Thiopurines

High toxicity → Only if aminosalicylates & GCC failed

Delayed-onset → Up to 6 months!!

Cyclosporine

More powerful than Thiopurines

IV admin for severe Crohn’s & ulcerative colitis

Watch for nephrotoxicity / neurotoxicity / immunity ↓

Monoclonal Antibodies against:• TNF-α: Infliximab, adalimumab, certolizumab

• α4-Integrins: Natalizumab & vedolizumab• IL-12&IL-23: Ustekinumab

- these are all proteins

Old guidelines:

2nd-line agents for moderate to severe IBD

New guidelines:

Use as 1st-line to ↑ remission duration

Serious toxicity with long-term use:

Severe ↓ immune functions -> ↑ infections, Lymphoma & Tuberculosis risk Infusion reactions: rash + fever

KGF Agonist (growth factor receptor on epithelial cells)

• Unique indication: Severe Oral Mucositis (OM)

• Only for patients with hematologic cancer on high-dose chemotherapy + radiation therapy

- KGF receptors promote growth + aren't expressed on blood cells

it reduces

- Oral Mucositis incidence & duration Palifermin

- Need for opioid analgesia

- Supplemental parenteral nutrition

Adverse Effects

• Skin rash in <1% of patients• Concern for vision loss, but no data yet

Drug Interactions

• Reacts with Heparin• Increases severity of oral mucositis if administered too close to chemotherapy

Ø Leave at least 24h buffer

Oral Mucositis relief

Usually contains 3 of the following:

An antibiotic to kill bacteria around the sore

An antihistamine or local anesthetic to ↓ pain

An antifungal to ↓ fungal growth

A corticosteroid to treat inflammation

An antacid that helps ensure the other ingredients

adequately coat the inside of mouth

Possible ADRs

• Nausea

Diarrhea or constipation

Burning / tingling sensation in mouth

promote movement or transit in GI

- metoclopramide

Antiemetic

• Inhibits 5HT and dopamine at CTZ

Prokinetic

• Increases Ach release on upper GI smooth muscles

- like activating PNS

PO

GERD & Gastroparesis

IV

• Reduces nausea & vomiting (cancer & post-op)

• Facilitation of bowel intubation

• Facilitation of radiologic examination

Serious toxicity with high-dose & long-term use

Sedation & diarrhea

Irreversible tardive dyskinesia

opioids

Can induce constipation, cancelling out diarrhea

Drugs like Loperamide (Imodium) were designed to not cross BBB, limiting toxicity & CNS effects

Opioid antidiarrheal dosage < Analgesia

opioid effect on GI system

GI Opioid Receptor Effects:

Less intestinal motility

Less fluid secretion

More fluid & electrolyte

absorption

Most infections mild and self-limiting

Only use antibiotics for severe infections (ex.: C.diff / Salmonella)

Best therapy: Fluid & Electrolyte formulations + good hygiene

Travellers’ Diarrhea E.coli

Only treat if prolonged & severe

Ciprofloxacin preferred

Loperamide relieves Sx but prolongs

infection

C.Difficile-associated Diarrhea

Vancomycin PO & Mitromidazole IV