Drugs for Lower GI Flashcards
What are the 3 groups of treatment for Constipation?
Laxatives
opioid receptor antagonists
stool softeners
What are the three types laxatives
Bulk
osmotic
stimulant
What are bulk laxatives MOA?
MOA:
introduce indigestiable . water absorbing molecules
Intestinal distention leads to ENS stimulation of Peristalsis
What are the three types of bulk laxatives?
Dietary fiber- apples
Supplemental intake-
methykcellulose Citucel
Psyllium husk metamucil
What is the MOA of Osmotic laxatives
Poorly abosorbed moleucles like salts (MgO2) and sugars (lactulose polyethylene glycol 3350) retain and draw water into colon via osmosis , increase stimulation of peristalsis
may also help as stool softener
What are the Stimulant /contact laxatives? (2)
1) Sennosides (Senna spp. Derivatives Ex-lax)
2) Diphenylmethane derivatives
What is MOA of Stimulant/contact laxatives
Direct stimulation of myenteric plexuses in the ENS
Increase smooth muscle motility and evacuation of contents
Pharmacokinetics of bulk, osmotic laxatives
Minimal systemic absorptions
subject to GI transit rates
Pharmacokinetics of stimulant laxatives?
Minimal systemic absorptions
subject to GI transit rates
Need acid sensitive coating
Which type of laxative is used for bowel execution pre-surgery
osmotic
CI for bulk and osmotic laxatives
Known/suspected GI blockage
CI for Stimulant laxatives
Castor oil- Pregnancy- uterine contractions
Side effects for bulk laxatives
Bloating and flatulence
Side effect for Osmotic laxatives
Bloating and flatulence
cramping and diarrhea
electrolyte imbalances- salts.sugars
Side effect for stimulant laxatives
bloating and flatulence
cramping and diarrhea
Colon pigmentation (melanosis coli)
What are the two Stool softeners?
Glycerin
Docusate
MOA of stool softeners
Lowers surafce tnesion and increases lubrication of feces
reduces effort of excertion
Pharmacokinetics
Oral and rectal formaulations
CI of stool softeners
Known or suspected GI blockage
Side effects Stool softeners
rectal irritation
Name of Opioid receptor antagonists
methylnatrexone
MOA of Opioid receptor antagonists
selective competitive block of mu (u)-opiod receptors
Relieve opiod mediated inhibition of GI tract
Net stimularoty effect of GI motility
Pharmacokinetics of Opioid RAs
Subcutaneous administration
does not cross BBB-> preipherally selective effect
minimal effect on opioid induced analgesia
Opiod constipation treatment
Indication for opioid receptor antagonists
Opioid induced constipation
pain
palliative-care patients non-responsive to other treatment
Contraindication for Opioid receptor antagonists
Known or suspected GI blockage
Side effects of Opioid receptor antagonists
What are the two treatments for diarrhea pharm?
Opioid receptor agonists- loperamide
and
bismuth subsalicylate
also absorbants and anti-infectives
What is MOA of loperamide?
selective mu-opioid receptor agonist
inhibition of neural activity in GI tract leading to increase colonic transport time and water absorption
Pharmacokinetics of Loperamide
Does not easily cross BBB-> peripherally selective effect
does not appear to produce tolerance with chronic use
Contraindications of loperamide
worsening diarrhea while on drug
Side of effects of loperamide
Constipation
What ios MOA of bismuth subsalicylate
Antisecretory effect
1) reduces intestinal prostaglandin production->educed motility (reduced smooth muscle stim)
2) reduces chloride secretion
3) Antimicrobial effect
What are the 5 drug classes to reduce the inflammatory activity of IBD?
Aminosalicylates
Glucocorticoids
immunosuppresants
anti-TNF alpha therapy
Anti-integrin therapy
Name of the one Aminosalicytes that we know :) and the other 4 random ones
5-aminosalicylate
(5-ASA)
Azo-conjugated
sulfasalazine
balsalazide
olsalazine(dipendum)
the granule release- Mesalamine
What is the MoA of 5-ASA
Anti-inflammatory
Nsaid like inhibition of production
interfere with cytokine production
reduced leukocyte activity
Pharmacokinetics of 5-ASA
Acts topically at the site of diseased mucosa within the ileum and or large intestine
don’t need or want systemic absorption and distribution not required
up to 80% absorbed in small intestine
formulation designed to increase drug exposure to the distal small and large intestinal tissue
indications for 5-ASA
UC induction and maintenance of remission
is used in Crohns but unproven use but still 1st line
Contraindication for 5-ASA
Due to similarity to asprin
Children under 2 (risk of Reye’s syndrome)
Aspirin allergies
Side effects of 5-ASA
Nausea and or GI upset
Headaches
impaired folate absorption-> supplement recommended
Rare
Hypersensitivity
inflammation of kidney rare- do functional tests 6 wks, 6 months, and the anually
Names of the Glucocorticoids we know
Prednisone
prednisolone
budesonide
MOA of Glucocorticoids
Anti-inflammation through
inhibition of chemokine/cytokine production
inhibition transcription of several pro-inflammatory mediators
Glucocorticoids pharmacokinetics
Low oral bioavailability (1st pass metabolism)
controlled release formulations for increased delivery to distal ileum and colon
Indications for use of Glucocorticoids
Induction of remission in inflammatory bowel disease
CI for Glucocorticoids
PUD
Heart disease
Hypertension with heart failure
Osteoporosis
Side effects of Glucocorticoids
PUD
Adrenal suppression
Fewer side effects with budesonide
Name of the 2 immunosuppressants we know
Azathioprine
Methotrexate
MOA of Azathioprine?
Converted to guanine analogue that halts DNA/RNA synthesis
Somewhat selective for cells dividing rapidly such as immune cells
MOA methotrexate?
Inhibition of a key enzyme required for nucleotide synthesis
inhibition of cell proliferation unlikely at does use in IBD treatment
Indications for Azathioprine
UC and Crohns disease
induction and maintenance of remission
Indications for methotrexate
Crohn’s disease
induction and maintenance of remission
uncertain efficacy in UC
Contraindications of immunosuppressants
Adjusted azathioprine dosing in TPMT deficient individuals
thiopurine metabolism
Side effects of immunosupressents
Nausea and vomiting
Bone marrow suppression-> anemia, leukopenia
Azathioprine-> hypersensitivity
fever pancreatitis hepatitis diarrhea
What is the name of the anti-TNF alpha therapy we know
Infliximab
MOA of Anti-TNF alpha therapy
Mab against tumor necrosis factor
tumor necrosis factor is a major pro-inflammatory cytokine particularly in IBD
Pharmacokinetics of Anti-TNF-alpha therpay
IV administration
8-10 days half life
Indications for Anti-TNF alpha therapy
Induction and mainenance of unresponsive to pervious therapies
moderate to severe Crohn’s disease
Moderate to severe UC
CI for Anti-TNF-alpha
current infections
latent infections TB hep B
Reactivation risk may be able to proactive reat
Side effects of anti-TNF-alpha therapy
Opportunistic infections
hypersensitivity
Anti-integrin therapy name of drug we know
vedolizumab
MOA of anti-integrin therapy
Prevent leukocyte adhesion to endothelium via integrin antagonism
sorta selective for gut endothelial cell adhesion molecules
Indications for Anti integrin therapy
Moderate to sever UC and Crohns unrepsponsive to other therapies
Carefully monitored IV at 0 ,2 6, 14 weeks ,discontinues if no benefit
Side effects
of anti-integrin therapy
Nasopharyngitis,headache and or arthralgia in 10%
