W13 Pharmacology Flashcards
Examples of bulk laxatives
Bran, apples, broccoli
Methylcellulose (citrucel), psyllium husk (Metamucil)
Mechanism of action of bulk laxatives
Indigestible water absorbing molecules
Intestinal distension leading to ENS stimulation of peristalsis
What are osmotic laxatives
Poorly absorbed molecules
- salts
- sugars
Mechanism of action of osmotic laxatives
Poorly absorbed salts
Retain/ draw water back into colon by osmosis
Increased stimulation of peristalsis
Some soften stools
Examples of stimulant/contact laxatives
Sennosides (Ex-Lax) Diphenylmethane derivatives (bisacodyl)
Mechanism of action of stimulant/contact laxatives
Direct stimulation of myenteric plexuses in ENS
Increased smooth muscle motility and evacuation of contents
What type of laxative is acid sensitive ?
Stimulant
What type of laxative is indicated for bowel evacuation?
Osmotic
When are laxatives contraindicated?
Known/suspected GI blockage
Pregnancy (stimulant (castor oil))
Side effects of bulk laxatives
Bloating
Flatulence
Side effects of osmotic laxatives
Bloating, flatulence
Cramping, diarrhea
Electrolyte imbalance
Side effects of stimulant laxatives
Cramping, diarrhea
Colon pigmentation
Examples of stool softeners (emollients)
Glycerin
Docusate
Mechanism of action of stool softeners
Lower surface tension —> increase lubrication
Contraindications and side effects of stool softeners
Known or suspected GI blockage
Rectal irritation
What is methylnaltrexone?
An opioid receptor antagonist
Mechanism of action of opioid receptor antagonists
Relieve opioid-mediated inhibition of GI tract —> stimulatory effect on GI motility
Pharmacokinetics of opioid receptor antagnists
Subcutaneous administration
Doesn’t readily cross BBB —> peripherally selective effect
Treatment of opioid induced constipation
- Laxatives and stool softeners
- PAMORAs (mu-opioid receptor antagonists )
- Chloride channel activators (lubiprostone)
Indications and contraindications of opioid receptor antagonists
I: opioid induced constipation
C: known or suspected GI blockage
Side effects of opioid receptor antagonists
Abdominal pain and/or cramping
Diarrhea and/or flatulence
Nausea
Example of an antimotility agent
Loperamide
- selective mu opioid receptor agonist
Mechanism of action of loperamide
Inhibition of neural activity of the GI tract —>
Increased colonic transport time and water absorption
Pharmacokinetics of loperamide
Doesn’t readily cross BBB
Doesn’t appear to produce tolerance with chronic use
Indications, contraindications and side effects of loperamide
I: symptomatic relief of acute and chronic diarrhea
C: worsening diarrhea while on drug
SE: constipation
Mechanism of action of bismuth subsalicylate
Antisecretory effects
Subsalicylate mediated reduction of
- intestinal prostaglandin production —> reduced motility
- chloride secretion —> reduced liquidity
Antimicrobial effects
Drugs used to reduce inflammation in IBD
Aminosalicylates Glucocorticoids Immunosuppressants Anti-TNFa therapy Anti-integrin therapy
Mechanism of action of 5-ASA
Anti-inflammatory:
- NSAID like inhibition of prostaglandins ?
- interfere with cytokine production ?
- reduced leukocyte activity ?
Pharmacokinetics of 5-ASA
Acts topically
Up to 80% absorbed in small intestine
5 ASA formulations that are absorbed primarily in large intestine
Sulfasalazine, balsalazide, olsalazine
Azo conjugation
Prevents absorption until bacterial cleavage in large colon
5-ASA indications and contraindications
I: UC - induction and maintenance of remission
C: children <2 (Reye’s syndrome), aspirin allergies
5-ASA side effects
Nausea Headaches Impaired folate absorption Hypersensitivity (rare) Kidney inflammation (rare)
Glucocorticoids examples
Prednisone
Prednisolone
Glucocortioids mechanism of action
Anti-inflammation:
- inhibition of chemokine/cytokine production
- inhibited transcription of several pro-inflammatory mediators
Pharmacokinetics of glucocorticoids
Enema and suppository formulations
Indications and contraindications of glucocorticoids
I: induction of remission in IBD
C: peptic ulcer disease, heart disease or hypertension with HF, osteoporosis
Side effects of glucocorticoids
Peptic ulcer disease
Adrenal suppression
Fewer with budesonide
Example of an immunosuppressant
Azathioprine (purine analogue)
Mechanism of action of azathioprine
Converted it guanine analogue that halts DNA/RNA synthesis
Somewhat selective for rapidly dividing cells
Mechanism of action of methotrexate (immunosuppressant)
Inhibition of a key enzyme required for nucleotide synthesis
Inhibition of cell proliferation unlikely at doses used in IBD treatment
Indications and contraindications for immunosupressants
Azathioprine
- UC, CD —> induction and maintenance of remission
- Con: adjust dosing in TPMT deficient individuals
Methotrexate
-CD —> induction and maintenance of remission
side effects of immunosuppressants
Nausea and vomiting
Bone marrow suppression
Hypersensitivity to azathioprine
- fever, pancreatitis, hepatitis, diarrhea
What is infliximab
Anti-TNF-a drug
Mechanism of action of Anti-TNF-a drugs
Monoclonal antibody against tumour necrosis factor
-major pro-inflammatory cytokine in IBD
How is infliximab administered and what is its half life
IV
8-10 days
Indications for infliximab
Induction and maintenance of unresponsive to previous therapies moderate to severe CD and UC
Contraindications of Anti-TNF-a
Current infecctions Latent infections (TB, Hep B)
Side effects of anti-tNF-a
Opportunistic infections
Hypersensitivity
What is a drug used for anti-integrin therapy ?
Vedolizumab
Mechanism of action of anti-integrin therapy
Prevent leukocyte adhesion to endothelium via integrin antagonism
Indications for anti-integrin therapy
Moderate to severe UC and CD unresponsive to other therapies
- carefully monitored IV at 0,2,6,14 weeks
Side effects of vedolizumab
Nasopharyngitis
Headache
Arthralgia
