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PHARM250 Gastrointestinal System Cheat Sheet by

Covers Nutrition,Constipation, Diarrhea, Nausea, & Vomiting Gastroesophageal Reflux Disease (GERD) and Peptic Ulcer Disease (PUD) Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Pancreatitis, Hemorrhoids. Medications for these diseases and their adverse side effects.

Consti­pation + Diarrhea - Classes of medication

Bulk-f­orming agents
Psyllium, polyca­rbo­phil
Ferment in the colon → gas formation, increased osmotic load, water retention and wall stress → stimulates motility
Swell in intestinal fluid → creates gel → facilitate passage
Osmotic agents
glycerin (suppo­sit­ory), lactulose, polyet­hylene glycol (PEG) 3350, magnesium citrate, sodium phosphate, magnesium hydroxide (milk of magnesia), sorbitol
Contain poorly absorbed ions or molecules that create an osmotic gradient to retain water within the intestinal lumen – the ↑ pressure on the intestinal wall induces gastric motility
Used for bowel evacua­tions before procedures (if high, frequent dosing) or for daily mainte­nan­ce/­pre­vention (if low, daily dosing)
BM within 30 mins (high, frequent doses) -> 3 days (low daily doses)
Stimulants
Senna/sennosides (Senokot®, Senoko­t-S®) Bisacodyl (Dulco­lax®) Sodium picosu­lfate (Pico-­Salex®) Castor oil
Stimulate the smooth muscle to produce rhythmic contractions
May be recomm­ended if osmotic laxatives fail or not tolerated
Sometimes referred to as a “rescue agent”
A dose effective in one individual may cause painful cramping in the next
BM within 6-12 hours (often overnight use)
Stool softeners
Docusate sodium or docusate calcium
Act as a surfactant → better mixing of aqueous and fatty substances to soften the fecal mass
A preven­tative measure rather than a “rescue”
Sometimes added to other laxatives (for the “gentle” touch)
Most recent evidence suggests not better than placebo
What to expect: BM in 1 - 5 days
Lubricants
Lubricates contents of GI tract and keeps water in GI tract
Limited use -> after myocardial infarction or rectal surgery
Mineral oil (heavy) – only one suitable for consumption
Not recomm­ended due to risk of aspiration → lipid pneumonia, binding of fat soluble vitami­ns/­meds, and anal seepage
What to expect: BM in 6-8 hours – avoid lying down or bedtime dosing
Suppos­itories & Enemas
Mineral oil retention enema, Phosphate enema, Tap water enema­Mi­crolax® Enema (sodium citrate, sodium laurel sulfoa­cet­ate)
For acute relief or bowel prep for procedure
Not for management of chronic consti­pation
Presence of object in rectum stimulates defecation reflex
This is in addition to any benefits provided by specific ingredient (i.e. glycerin – osmotic; mineral oil – lubricant)
Patient should try to retain (hold in) product as long as possible (generally a few minutes)
What to Expect: Cleansing of bowel within 1 hour; if no BM – call physician Not pleasant, therefore not the preferred route
Anti­dia­rrh­eals
Adsorbant agents
attapulgite (Kaope­ctate®, Fowler­’s®)
Adsorbs fluid in intestine, reducing stool liquidity
May give some relief, very safe (can use in kids)
Antimo­tility agents
loperamide (Imodi­um®), bellad­onna, diphen­oxy­late
Opioid agonists that do not cross blood-­brain barrier
Dependence and tolerance with long-term use? NOPE
Antise­cretory agents
bismuth subsal­icylate (Pepto­-Bi­smol®)
Stimulates absorption of fluid and electr­olytes across intestinal wall; also bacter­icidal (e. coli)and anti-i­nfl­amm­atory
Not for children (related to ASA  Reye’s)
Good option for travel­ler’s diarrhea
Bulk-F­orming agents
psyllium (Metam­ucil®)
Identical mechanism as with constipation
Creates “gel” using excess fluid in GI tract
Loper­amide (Imodi­um®)
Slows intestinal motility by stimul­ating opioid receptor, which reduces fecal volume and increases viscosity
Very high first-pass effect and poor penetr­ation of blood-­brain barrier
No dependence or tolerance with long-term use
Also useful for radio- or chemo-­induced diarrhea

Adverse effects of medication for the GI tract

Bulk-f­orming Agents
flatul­ence, bloating are common
Osmotic Agents
nausea, abdominal bloating, cramping, diarrhea, flatul­ence, skin rashes­/hives
Stimulants
: bloating, abdominal discom­fort, flatul­ence, diarrhea
Highest incidence of crampi­ng/pain (due to muscle contra­ctions)
Caution:
Avoid in pregnancy if possible (do not stimul­ate!)
Avoid if sensitive to electr­olyte or fluid abnorm­alities
Stool softeners
bloating, abdominal discom­fort, flatulence
Lubricants
allergic reactions, anal seepage, alteration of vitami­ns/­min­era­ls/­drugs
Suppos­itories & Enemas
discom­fort, bloating, cramping, allergic reactions
Loperamide (Imodium®)
cramping, discom­fort, skin rash, dry mouth; Possible CNS usually only if compro­mised BBB = drowsi­ness, dizziness, confusion (rare)
Dimenh­ydr­inate (Gravol®)
drowsiness + antich­oli­nergic effects
Doxylamine + Pyridoxine (Dicle­ctin®)
drowsi­ness, fatigue
Domper­idone
headache, menstrual irregu­lar­ities, dry mouth, diarrhea, abdominal discomfort
Ondans­etron (Zofran®)
headache, dizziness, drowsi­ness, consti­pation, diarrhea (all rare)
H2-Ant­ago­nists
headache, dizziness, drowsiness Difficult to differ­entiate between heartburn symptoms and some adverse effects (nausea, vomiting, consti­pation, diarrhea)
Very rare – reduction in RBC, WBC, and platelets; bradyc­ardia, allergic reactions
Because of reduction in acidity, it can potent­ially interact with absorption of drugs or vitamins (like B12) that need an acidic enviro­nment to absorb
Separate as much as possible, while also unders­tanding that we want prolonged reduction in acidity
Proton Pump Inhibitors (PPIs)
very well tolerated; limited to headache, diarrhea, flatul­ence, nausea, abdominal pain
Long-term (years): decrease in bone mineral density + others via post-m­ark­eting survei­llance
Sucralfate
consti­pation or diarrhea, nausea, headache, indige­stion, dry mouth
Bezoars have been reported in people treated with sucralfate (most had comorb­idities that contri­buted such as low gastric motility)
May increase blood glucose due to high carboh­ydrate content
Antacids
Calcium – consti­pating
Magnesium & aluminum – diarrhea, and can make stool a whiter colour
Misopr­ostol
headache, abdominal cramps, diarrhea, vaginal bleeding, uterine cramping
Aminos­ali­cylates
5-ASA (Asacol®)
nausea, diarrhea, abdominal pain, headache, rash, rhinitis, photos­ens­itivity
Meds are well tolerated; can be difficult to discern adverse effects from condition
Immuno­-su­ppr­essants
Methotrexate (MTX)
ulcerative stomat­itis, leukop­enia, nausea, abdominal distress, malaise, fatigue, chills & fever, dizziness, decreased resistance to infection
Pancreatin (Creon®)
Rare - nausea, vomiting, diarrhea
Local anesth­etics (dibuc­aine, pramoxine)
Use > 7 days: possible CNS effects (restl­ess­ness, excite­ment, nervou­sness, parest­hesias, dizziness, tinnitus, blurred vision, nausea and vomiting, muscle twitching and tremors, convul­sions) and cardio­vas­cular effects (hypot­ension, bradyc­ardia)
Cortic­ost­eroids (hydro­cor­tisone)
Use > 14 days, mucosal atrophy
 

Nausea, & Vomiting - Classes of medication

Dimen­hyd­rinate (Gravol®)
An antihi­stamine (with antich­oli­nergic activity){{nl{{ Only effective for nausea & vomiting caused by motion sickness (vesti­bular apparatus)
Used for all types of nausea (like a virus…..) inappr­opr­iately (sedation may provide benefit)
Doxyl­amine + Pyridoxine (Dicle­ctin®)
Prescr­iption product specif­ically for nausea and vomiting during pregnancy
Mechanism of action largely unknown
Doxylamine = antihi­sta­mine; pyridoxine = vitamin B6
Safe for baby
Used when concerned about proper nutrition
Effect ~ 8 hours after dose
Dompe­ridone
Mechanism of action: a peripheral dopamine antago­nist, that blocks dopamine receptors in the GI tract; also has pro-ki­netic proper­ties, which increases perist­alsis to improve gastric emptying rates
Also stimulates release of prolactin – used to enhance milk production while breast­feeding (see Module 8)
Primary use: antiemetic for multiple GI condit­ions, prevention of nausea & vomiting with concurrent medica­tions (chemo), enhance milk produc­tion, GERD
Ondan­setron (Zofran®)
Mechanism of action: serotonin receptor antagonist in chemor­eceptor trigger zone and along GI tract (CTZ)
Primary use: chemot­herapy induced nausea & vomiting
Occasi­onally used in severe nausea & vomiting in pregnancy (concerned about baby nutrition)

PUD + GERD - classes of medication

H2-A­nta­gonists
-tidine
Blocks H2 receptors which prevents acid secretion; reduces the volume and acidity of secretions  allowing a lesion to heal
Can take up to 3 months to heal a lesion
Cimetidine was first drug  lots of signif­icant drug intera­ctions via CYP450 enzymes and signif­icant adverse effects (gynec­oma­stia) not widely used anymore but still available
Ranit­idine (Zantac®), famoti­dine, nizati­dine
Most effective if taken regularly (every day) to consis­tently reduce acid and allow lesion to heal
Can also be used as needed (PRN) for heartburn by anyone
Very safe, Smoking decreases the effect­iveness of H2-ant­ago­nists (encourage smoking cessation)
Proton pump inhibitors (PPIs)
-prazole
Proton pumps = cells that are present in the lining of the stomach; their job is to ‘pump’ protons (H+) into the stomach for acid secretion
PPIs inhibit this, preventing acid secretion, creating a less acidic enviro­nment for a lesion to heal
↓ acidity more than H2-ant­ago­nists (more effective)
Also very safe; recently OTC
A longer duration of action than H2-ant­ago­nists = less frequent dosing
Omepr­azole, esomep­razole, lansop­razole, pantop­razole, rabepr­azole
Have a longer onset of action than H2-ant­ago­nists (don’t work as quickly) – would not be effective to use PRN (as needed) for heartburn
Sucr­alfate
A cytopr­ote­ctive agent that adheres to and then protects ulcerated gastric or duodenal mucosa
Product also contains aluminum, which lowers acidity of gastric contents
Anti­biotics
Must be specific for h. pylori – breath tests confirm presence
We attempt to completely eradicate the bacteria, due to extremely high rate of recurrence
Eradic­ation of h. pylori allows ulcers to heal more rapidly and remain in remission longer, often perman­ently
Otherwise, organism may survive for life
We always give at least 2 antibi­otics to:
Increase effect­iveness of therapy
Reduce chance of resistance
Also give with H2-ant­agonist or a PPI to allow for healing
amoxi­cillin, clarit­hro­mycin, metron­ida­zole, tetrac­ycline
Specific for h. pylori
As with all antibiotic therapy, complete course must be finished – at least 1 week
Anta­cids
Neutralize acid that is already present – do NOT have an effect on future acid secretion – supportive role only
Most approp­riately used as needed (PRN)
Very safe and can be used for long periods of time (years) with few conseq­uences – Tums® are also used as a calcium supple­ment! – but long term use for recurring heartburn indicates underlying problem
Can interfere with absorption of many medica­tions – separate by 2 hours
Miso­pro­stol
Arthr­otec® = diclofenac + misopr­ostol
A mucosal protective agent, occasi­onally used to prevent GI adverse effects of long-term NSAID use
A synthetic prosta­glandin E analogue, increasing mucous production
ALSO used for medica­lly­-in­duced abortions, and to evacuate uterus after miscarriage
DO NOT USE FOR PREGNANT PATIENTS

IBD, IBS, pancre­atitis + Hemorr­hoids - Meds

Infl­amm­atory Bowel Disease (IBD)
key treatment includes anti-i­nfl­amm­atories + also an auto-i­mmune component
Aminos­ali­cylates
5-ami­nos­ali­cylic acid (5-ASA), sulfas­ala­zine, mesala­mine
Anti-i­nfl­amm­atories (a GI topical effect)
Inhibit production of inflam­matory mediators prosta­gla­ndins and leukot­rienes
For mild symptoms, would not treat an exacer­bation
Used to lengthen times between exacer­bations
Can be given orally (formu­lated for minimal systemic absorp­tion) or rectally (if lesions are more present in lower tract) – all work topically
Cortic­ost­eroids
Useful because of both anti-i­nfl­amm­atory and immuno­sup­pre­ssant activity
Auto-i­mmune & inflam­matory components to IBD
Used to treat exacer­bations to send disease into remission
Short term therapy, at high doses (pulse therapy) To minimize adverse effects
Budes­onide (Entoc­ort®)
A unique cortic­ost­eroid used specif­ically for IBD
Encaps­ulated to avoid signif­icant absorption in stomach or duodenum, then released slowly in lower tract
In direct (topical) contact with lesions (ulcers)
Any absorption that does occur is almost entirely removed by first-pass metabolism
Avoids most long-term cortic­ost­eroid adverse effects (would still monitor)
Immuno­-su­ppr­essants
Metho­tre­xate, azathi­oprine, mercap­top­urine
Suppresses auto-i­mmune component of disease only
For more severe disease, where aminos­ali­cylates are not enough to prevent exacer­bations
Takes ~3 months for onset of action
Can increase time between exacer­bations
Metho­trexate (MTX)
Folate antago­nist, interf­ering with DNA synthesis, repair, and cellular replic­ation – most active against rapidly dividing cells
Used in many auto-i­mmune diseases (rheum­atoid arthritis, IBD)
Due to the mechanism of action, we must replace folic acid that is being inhibited
Biologics
Infli­ximab (Remic­ade®)
tumour necrosis factor (TNF)-α inhibitor (a cell signaling protein involved in inflam­mation and immune response)
Adali­mumab (Humira®)
also TNF-in­hibitor
Irri­table Bowel Syndrome
Abdominal pain or discomfort with altered bowel habits which occur over a period of at least 3 months
“Altered bowel habits” = bloating, cramping, mucous in stool, consti­pation, diarrhea
Antisp­asm­odics
dicyclomine & hyoscine
reduce muscle spasms of GI tract by blocking muscarinic receptors (antic­hol­inergic effects!)
Calcium channel blockers (CCB)
pinaverium
very specific for GI smooth muscle, reduces muscle contra­ctions by inhibiting calcium influx (hypot­ens­ion!)
Opioid agonists
loperamide
doesn’t cross blood-­brain barrier; trimeb­utine – also has anti-s­ero­tonin activity
Antide­pre­ssants
TCAs & SSRIs
address neurol­ogical connection (serotonin receptors in CNS and GI) and overlap of neurol­ogical conditions with IBS
~55% patients given TCA or SSRI saw benefit compared to ~35% placebo
Osmotics & stool softeners
used for prevention or as needed
Panc­rea­titis
Acute or chronic inflam­mation of the pancreas (very painful)
Usually caused by gallst­ones, heavy alcohol use, or cystic fibrosis (CF)
Pancr­eatin (Creon®)
Enzymes are not absorbed
Capsules formulated to release in duodenum
Hemo­rrh­oids
Commonly seen with consti­pation, diarrhea, pregnancy, advancing age and possibly physical exertion
Symptom relief only – no meds are curative
Products can provide short-term relief of pain, burning, itch, discomfort and irritation while swelling subsides and healing occurs
Local anesth­etics
dibucaine, pramoxine
to relieve pain
Safe if < 7 days of continued use
Cortic­ost­eroids
hydrocortisone
to reduce itch and inflam­mation
Safe if < 14 days of continued use
Astrin­gents
hamamelis
dries out skin to relieve burning, itching, and pain
Anti-i­nfe­ctives
framycetin
if concerned about infection
Protec­tants
glycerin, petrol­atum
to provide barrier for healing
Vasoco­nst­rictors
phenylephrine
to relieve inflam­mation and limit bleeding; short term only
                   
 

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