GI PHARM 2 Flashcards
Define
Laxative effect
Produce soft, formed stool in 1 or more days
- slower onset
- mild effect
Define
Catharsis
Prompt fluid evacuation from rectum
- fast onset
- intense
Function of the colon
Absorb water and electrolytes
- 1500mL enters the colon
- 90% water is reabsorbed
*minimal nutrient absorption
Function of the colon is defined by…
Consistency of stool (versus stool frequency)
Soft formed stool
Minimal straining
Rome IV Criteria for Constipation
ADULTS
2 or more of the following for past 3 months, 25% of the time
- straining
- lumpy hard stool
- incomplete evacuation
- anorectal blockage
- manual manuever required (digital, pelvic floor)
- </= 3 BM per week
- rarely loose and not IBS
Rome IV Criteria for constipation
CHILDREN
1 month with at least 2 criteria
Children </= 4 years
- </= 2 BM per week
- stool retention
- painful hard stool
- large diameter stool
- 1x per week incontinence
Indication
Laxatives
- reduce painful elimination (hemorrhoids, anal fissures, episiotomy)
- Anthelmintic: obtain fresh stool sample (parasites); empty bowel before parasite treatment; empty colon of dead parasites
- Empty bowel before surgery
- Modify ileostomy/colostomy effluent
- prevent fecal impaction bedrest
- correct constipation (pregnancy, opioid use)
Non pharmacological interventions
Constipation
- increase fluid
- increase fibre
- walk after meals
Laxatives
Infants pregnancy
Infants
- glycerin, ducosate, lactuluose
Children
- bisacodyl, mineral oil, Senna, ducosate, MgOH
Pregnancy
- caution
- can cause pre-term labour
Breastfeeding
- Senna
Older adults
- caution
- dehydration
- everything is safe
Laxative classification
MOA
- Bulk forming
- Surfactant
- Stimulant
- Osmotic agent
Bulk forming laxative
Example
- methylcellulose
- Psyllium
- Polycarbophil
Surfactant Laxative
Example
- ducosate sodium
- ducosate calcium
Stimulant laxative
examples
- Bisacodyl
- Senna
- Caster oil
*cannot be used in infants
Osmotic Laxative
Examples
- polyethylene glycol
- lactulose
- magnesium hydroxide, magnesium citrate, magnesium sulfate
- Sodium phosphate
Classification Laxatives
Therapeutic action
Group I: watery stool in 2-6 hours (bowel prep)
Group II: intermediate semi-fluid stool in 6-12 hours
Group III: slow 1-3 days, soft formed stool (chronic constipation relief)
Example Group I Laxatives
*liquid stool, 2-6 hours
High dose osmotic laxative
- Magnesium salts
- Sodium salts
- Polyethylene glycol
- Caster oil
Example Group II Laxatives
*semi-fluid stool 6-12 hours
Low dose osmotic laxative
- Magnesium salts
- sodium salts
- polyethylene glycol
Stimulant laxatives
- bisacodyl (oral)
- Senna
Example Group III Laxatives
*soft stool, 1-3 days
Bulk forming laxatives
- Methylcellulose
- Psyllium
- POlycarbophil
Surfactant laxative
- decosate sodium
- decosate calcium
Osmotic laxative
- lactulose
MOA
Bulk forming laxatives
Increase stool bulk, form viscous gel in water, increase stretch of GI, and peristalsis
Hasten transit time of stool through GI
*nutrients for GI bacteria
AE
Bulk forming laxatives
Non-digestable
Non-absorbable
*minimal systemic effects
Esophageal obstrution
GI
Patient education: take with water
obstruciton/impaction
Contraindications
Bulk forming laxatives
Narrowed GI
Dysphagia
Can cause GI obstruction and impaction
Indications
Bulk forming laxatives
Soft, formed stool, 1-3 days
Constipation
Diverticulitis
Relief of diarrhea (IBS)
colostomy/ileostomy bags
Surfactant Laxatives
MOA
- Lower surface tension allowing water to easily penetrate feces
- Prevent GI from absorbing water, Promote GI to secrete water and electrolytes into lumen
Indication
Surfactant laxatives
Group III laxative
soft BM in 1-3 days
Full glass of water
Stimulant Laxatives
MOA
- Stimulate GI motility
- increase water and electrolyte secretion into lumen (and reduce absorption)
Group II
Semi-fluid stool in 6-12 hours
SE & Contraindications
Bisacodyl
Contraindications
- do not crush the pill (gastritis)
- do not administer with milk (wait 1 hour)
- not safe in infants
SE
- proctitis
SE & Contraindications
Senna
Contraindications
- not safe in infants
SE
- yellow, brown or pink urine
Caster oil
MOA
Stimulant laxative
Group I: liquid stool in 2-6 hours
Acts on the small intestine, rapid evacuation
Intestinal lipase converts to ricinoleic acid 1. surfactant 2. stimulate motility 3. increase secretion water, electrolytes into GI (prevent absorption)
MOA
Osmotic laxatives
High dose laxative salts are poorly absorbed
Draw water into lumen, fecal swelling, stimulation peristalsis with GI wall stretch
Dosage and MOA
Osmotic laxative salts
Low dose
Group II
semi-fluid stool 6-12 hours
High dose
Group I
Fluid stool 2-6 hours
AE
Osmotic Laxative Salts
Magnesium toxicity
Sodium stimulated fluid volume overload: HF, HTN, edema
Kidney failure, HTN, Heart failure, Edema
Dehydration
Contraindications
Osmotic Laxative salts
Dehydration
Kidney failure
Heart failure
HTN
Edema
ACE inhibitors, diuretics, ARBs –> dehydration –> Kidney failure
SE
Polyethylene glycol
not absorbed systemically
Nausea
abdominal bloating
cramping
flatulence
diarrhea at high dose
Indication
PEG
osmotic laxative
chronic constipation
17g daily in 4-8oz of water
Lactulose
MOA
Group III: Osmotic laxative
disaccharide of galactose and fructose
*not absorbed or digested by GI enzymes
Digested by colon bacteria
Conversion to lactic acid, formic acid, acetic acid
pull water into intestine, soft, formed stool, 1-3 days
excrete ammonia
Lactulose
Indications
Group III: osmotic laxative, soft stool, 1-3 days
Chronic liver disease: hepatic encephalopathy, excretion ammonia
Contraindiciations
Laxatives
- appendicitis
- enteritis
- c diff
- diverticulitis
- ulcerative colitis, Crohn’s disease
- acute abdominal surgery
- fecal impaction
- bowel obstruction
- caution pregnancy
- magnesium and sodium salts: kidney disease, heart disease
Patient instructions
Laxatives
lowest dose, shortest duration
can diminish deification reflex
drink water
Laxative abuse
Cycle
Laxative clears bowel
takes 2-5 days for another BM
*think constipated and repeat the dosage
Diarrhea
Definition
Increase
1. volume
2. frequency
3. fluidity
of stool
Diarrhea
Causes
- infectious
- malabsorption
- Inflammation
- Bowel disorders (IBS, IBD)
- Drugs
Management of Diarrhea
- diagnose cause (infectious, malabsorption, inflammation, disorder)
- Treat cause
- reverse dehydration, electrolyte imbalances
- reduce passage of stools
- reduce cramping
Two types of anti-diarrheal drugs
- Specific
- treat the cause - Non-specific
- treat the frequency of passage of stools
- Ex. opioids
Opioid Anti-Diarrheal
Examples
- Diphenoxylate (lomotil)
- Loperamide (Imodium)
Opioid anti-diarrheal
MOA
- Bind mu receptors in GI tract, slow motility, increase Sphincter tone, decrease secretions, increase absorption water, electrolytes, decrease stool volume and frequency
- Promote absorption water and electrolytes in small intestine (prevent excretion water, electrolytes)
SE
Opioid anti-diarrheals
- Toxic megacolon IBD
- High dose = morphine like effects
- Prevent passage of infection (increase duration disease)
High doses diphenoxylate
Equate to morphine
CNS supression
Respiratory suppression
constipation
urinary retention
Euphoria
hypotension, bradycardia
*Atropine included in diphenoxylate (lomotil) to prevent abuse
Why is loperamide not regulated
It is too large to cross the BBB
Management of Infectious Diarrhea
Majority self limiting - resolve in 24 hours
Anti-diarrheals prolong disease
Infections requiring antibiotics:
- Salmonella (gram negative)
- Shiegella (gram negative)
- Campylobacter (gram negative)
- Clostridium dificile (+ anaerobe)
- sometimes E. coli
Traveller’s Diarrhea
Etiology
E. coli (gram negative bacilli)
Most common
Usually self limiting
- drinking water
- eating local unwashed food
- do not take anti-diarrheal if moderate or severe
Prevention Traveller’s Diarrhea
- boil, cook, peel or forget it
- avoid raw, uncooked meat, fish, seafood, dairy
- don’t drink tap water, ice cubes
- ground grown greens, vegetables, fruits (untreated water)
- street vendors unless hot
Anti-biotic treatment in Thailand, India, Nepal, Indonesia
Azithromycin
*resistance to fluroquinolones is high
Definition and Treatment
Mild to Moderate
Traveller’s Diarrhea
E. coli.
up to 3 BM per day
No blood
No fever
First line
Loperamide (opioid)
Bismuth subsalicylate (antibiotic)
Should resolve 24 hours
Definition and Treatment
Moderate to Severe
Traveller’s Diarrhea
Moderate
3-5 BM per day
no blood or fever
Severe
3-5 BM per day
blood and/or fever
First line
Fluroquinolones: norfloxacin, ciprofloxacin, levofloxacin
Second line
Azithromycin (first line children, pregnant)
Rifaximin (no blood, not pregnant)
Indications
Prophylaxis treatment
Traveller’s Diarrhea
Anti-biotics:
start day 1 high risk area
continue 1-2 days upon return home
maximum: 3 weeks
Probiotics
- lactobacillus
- Saccharomyces
Vaccination (Dukoral)
- high risk, short term travel
- children > 2 years
- chronic illness
- greater risk (hypochlorhydria, immunocompromised, history repeat travellers diarrhea)
Non pharmacological treatments
Traveller’s Diarrhea
Fluid
- clear fluid
- salted crackers
- electrolyte solutions
- pedialyte (children)
Contraindications
Moderate to Severe Traveller’s Diarrhea
Anti-motility agents
increase curation of infection
Clostridium Difficile
Diarrhea
Gram positive anaerobic bacteria
Spore forming
Toxin A and B attack GI mucosal membrane
inflammation, edema, pus
Complications
Clostridium Difficile Infections
Mild infection
- abdominal pain, nausea, vomiting, anorexia, diarrhea, fever
Severe infection
- toxic megacolon, pseudomembranous colitis, colon perforation, sepsis, death
Treatment
Clostridium Difficile Infections
- ORAL
- Antibiotic therapy
- Vancomycin OR
- Metronidazole
30% Re-occurance rate
1. Vancomycin, QID, 10 days
2. Rifaxamin TID, 20 days
Etiology
Clostridium Difficile
- fluroquinolones
- tetracyclines
- cephalosporins
- PPIs
- can occur up to 6 weeks after D/C
- proton pump inhibitors
- ingestion spores
MOA
Fluroquinolones
Inhibit DNA gyrase (supercoils DNA for replication) and DNA topoisomerase (daughter strands cannot separate)
Indication
Fluroquinolones
Indication
moderate-severe traveller’s diarrhea
Abx. Spectrum
Gram positive, gram negative, pseudomonas
SE/AE
Fluroquinolones
Prolonged QT interval
C. Diff infections: N/V/D
Phototoxicity
Tendon ruptures
- greater risk elderly, glucocorticoids, children, transplants
Teratogenic
MOA
Azithromycin
Macrolide antibiotic
Inhibits 50S ribosomal subunit, bacteriostatic, prevents replication
Indication
Azithromycin
Moderate-Severe Travellers diarrhea
Antibiotic spectrum
Gram positive and gram negative bacteria
SE/AE
Azithromycin
Prolonged QT interval
N/V/Metallic Taste in mouth
Ototoxicity
MOA
Vancomycin
Binds cell wall precursors, preventing synthesis of cell wall
bacteria cell lysis and death results
Indication
Vancomycin
Gram positive bacteria and MRSA
C. diff infection
SE/AE
Vancomycin
Nephrotoxic
Ototoxicity
Bleeding risk
*safe in pregnancy
MOA
Metronidazole
Antibiotic spectrum
anaerobic bacteria - convert prodrug into active form which damages DNA
Indication
Metronidazole
Anaerobic bacterial infections and protozoa
C. difficile
Quadruple therapy for PUD
Amox/meteonidazole + clarithromycin/levooxacin + ppi
Bismuth + tetracycline + metronidazole + ppi
SE/AE
Metronidazole
N/V/HA/Dizziness
Disulfram reaction with alcohol
Inhibits aldehyde dehydrogenase
Hepatitis
Crohn’s Disease
Treatment Pathways
- Mild Disease
- Induction and maintenance remission 5-ASA (sulfasalazine, methalazine) - Mild-Moderate Disease
- Induction remission budesonide
- maintenance remission 5-ASA - Moderate to severe disease
- Induction and maintenance remission
Tumour necrosis factor alpha (infliximab, adalimumab) + Methotrexate OR Thiopurine (Azathiopurine/Mercaptopurine)
5-ASA
Examples
- Sulfasalazine (metbaolized to 5-ASA and sulfapyridine)
- Mesalazine (no sulfa moiety, less SE)
5-ASA
MOA
- Inhibit COX formation of prostaglandins
- Inhibit migration of inflammatory cells to site of action
5-ASA
Indication
Induction and maintenance of remission mild-moderate IBD
5-ASA
SE/AE
Locally acting
Inactivated by first pass effect
Sulfa moiety: nausea, fever, rash, arthralgia
5-ASA
Prescriber considerations
Safe in pregnancy and breast feeding
Monitor CBC and diff
Budesonide
MOA
Anti-inflammatory and immunosupression
Prevents transcription of inflammatory genes and inhibits formation of cytokines (TNF, IL)
Inhibits activation of pro-inflammatory cells: macrophages, neutrophils, T cells, dendrites, etc.
Budesonide
INdication
Enterocort EC
release in ileum and cecum
induction of remission in mild-moderate collitis not responsive to first line 5-ASA
Budesonide
SE/AE
Minimal systemic effects
inactivated by first pass effect
Anti-Tumour Necrosis Factor alpha (TNF alpha)
Examples
Infliximab
Adalimumab
Anti-TNF alpha
MOA
Block the effect of TNF alpha
pro-inflammatory cytokine
responsible for recruitment inflammatory cells and immune response (fever)
Anti TNF alpha
SE/AE
BLACK BOX WARNING:
- increase risk for serious and fatal infections
- bacterial
- fungal
- TB and HBV
Infusion reactions:
- flu like symptoms
- fever, HA, chills, dyspnea, hypotension, anaphylaxis
Rare:
- heart, liver failure
- cancer
- allergic reactions
Prescriber considerations
anti TNF alpha
- no live vaccinations
- screen for opportunistic infections (HBV, TB)
Methotrexate
Indication
Induction and maintenance of remission with anti-TNF alpha therapy of moderate-severe CDM
Methotrexate
MOA
folate anatonist
inhibition of B and T cells
onset: 3-6 weeks
Methotrexate
SE/AE
Hepatic fibrosis
bone marrow supression
pneumonitis
GI ulceration
Teratogenic
Reduced life expectancy: CVE, cancer, infection
Prescribing considerations
Methotrexate
Monitor
- CBC and diff
- Kidney and liver function
- lung function
- screen for pregnancy
- screen for TB, HBV, infections
- no live vaccines
- no alcohol
Thiopurines
Examples
- Azithioprine (pro drug)
- Mercaptopurine (active drug)
Thiopurine
Indication
Maintenance of remission with anti-TNF alpha, moderate to severe disease
Onset delayed: 6 months
Thiopurine
SE/AE
hepatitis
blood dyscaria
malignancy
Ulcerative Colitis (UC)
Treatment Pathways
- Mild disease
Induction 5-ASA
rectal suppository: proctitis
enema: L sided colitis
oral: pancolitis - Mild-moderate disease
Induction 5-ASA with oral budesonide MMX
Second line: prednisone systemic corticosteroid - Moderate-Severe Disease
Induction and maintenance: anti-TNF alpha + Thiopurines
Induction and maintenance: Vedolizumab (integrin blocker, monoclonal antibody) + thiopurine
Which drug is not used in Ulcerative Colitis
Methotrexate
5-ASA is more effective in which disease?
Ulcerative colitis
Special population
UC and CD treatment in pregnancy
Continue 5-ASA and suppliment with folic acid
Methotrexate is teratogenic
Budesonide has minimal systemic effect and is safe
Infliximab and adalimumab are safe in pregnancy
