gastrointestinal pharmacology - lower GI tracts Flashcards
what does the lower GI tract consist of - 4
small intestine
large intestine
mix of differentiated and stem cells
2kg of intestinal flora
what does the lining of the small intestine consist of
millions of microscopic projections called vili that inc sa for absorption of food particles
the intestinal walls contain __ and ___ receptors that allow intestine to response to food within it and propel food along
tension
stretch
drugs that affect motility of GI tract - 4
purgatives
agents that inc motility of GI smooth muscle
antidiarrhoel drugs (dec motility)
antispasmodic drugs (dec smooth muscle tone)
which type of drugs that affect motility of GI tract specifically treat constipation - 2
purgatives
agents that inc motility of GI smooth muscle
which type of drugs that affect motility of GI tract specifically treat diarrhoea - 2
antidiarrhoel drugs (dec motility)
antispasmodic drugs (dec smooth muscle tone)
constipation cause
dec movement of fecal matter along GI tract
dec freq of bowel movements
constipation general treatments - 2
usually dietary modification
if fails, laxatives used (unless obstruction of bowel) (also abuse of laxatives is number 1 cause of constipation)
morphine can contribute to constipation
laxatives types/ constipation pharmacological therapies - 4
bulking agents
osmotic laxatives
stimulant laxatives
faecal softeners
bulking laxative agents examples - 4
agar
bran
methylcellulose
ispaghula husk
bulking laxative agents admin
insoluble and non absorbable, non digestive so must be taken with lots of water unless will worsen constipation
saline and osmotic laxatives mechanism of action
fluid is drawn into bowel by osmotic force, increasing volume and triggering peristalsis
used to purge large intestine after surgery and poisioning
fast acing - 1-3 hours
saline and osmotic laxative agents are usually ___
nondigestible
saline and osmotic laxative agent example
non digestable sugars and alcogols e.g lactulose
lactulose
semi synthetic disaccharide, broken down by bacteria in GI tract to acetic and lactic acid which cause osmotic effect
saline and osmotic laxative salts examples - 5
milk of magnesia (Mh(OH)2)
epsom salt (MGSO4)
glauber’s salt (Na2SO4)
sodium phosphates (admin as enema)
sodium citrate (admin as enema)
saline and osmotic laxative other examples (not sugars, salts, or alcohols) - 2
polyethylene glycol and vitamic c
saline and osmotic laxative side effects - 2
flatulence
cramping
emollients
faecal softeners
emollient examples - 4
docusate sodium (surfactant and stimulant) suppositories
glycerin suppositories (mildly irritable, inc movement)
groundnut oil, peanut oil
liquid paraffin oral solution
liquid paraffin side effect - 2
anal seepage
granulomatosis of GI - which is necrotizing vasculitis
irritant/ stimulant laxatives mechanism of action
inc peristalsis, inc intestinal motility by stimulating enteric system nerves
irritate GI mucosa and pulls water into lumen
indicated for severe constipation where more rapid effect is required (6-8 hrs)
irritant/ stimulant laxatives/ cathartics examples - 4
castor oil
bisacodyl
lubiprostone
anthraquinones
lubiprostone
PGE1 derivative that srimulates chloride channels, producing chloride like secretions, helps fecal matter being propelled
anthraquinones examples - 3
plant derivatives senna
co-danthramer
co-danthrusate
co-danthramer
co-danthrusate
genotoxic in long term so only given as last resort in terminally ill patients
laxative abuse
most common cause of constipation
after laxative use, longer interval needed to refill colon post faeces expel, is misinterpreted as constiptation
enteral loss of water and salts causes release of aldosterone
laxative abuse - release of aldosterone effects
stimulates reabsorption in intestine, but inc renal excretion of K+ ions
double loss of K+ ions causes hypokalemia, which thus reduces peristalsis
constipation cycle continues
diarrhoea cause - 4
toxins
microorganisms
psychological factors like anxiety
antibiotic associated colitis
microorganisms that can cause diarrhoea - 5
salmonella
e.coli - common in travellers as good at surviving in stomach acid
campylobacter
clostridium difficile
algae
____ children die each year due to acute diarrhoea
1-2 million
approaches for treating severe acute diarrhoea - 3
maintain fluid/ electrolyte balance
use anti infective agents
use spasmolytic or other anti diarrhoeal agents
anti-diarrheal agents are
anti motility/ spasmolytic agents
aka reduce peristalsis by stimulating opioid receptors in bowel
allow time for more water to be absorbed by gut
firms stool consistency
anti-diarrheal agent first line treatment
loperamide hydrochloride or imodium
loperamide hydrochloride/ imodium mechanism of action
ant-diarrheal agent first line treatement
poor cns penetration
inc transit time and sphincter tone
antisecretory against cholera toxin and some e. coli toxin
loperamide hydrochloride/ imodium side efefcts
overdose, can cause paralytic ileus (muscles of the intestines are temporarily paralyzed, preventing food from passing through) or CNS depression
loperamide hydrochloride/ imodium admin
and halflife
4mg daily followed by 2 mg doses
T1/2 11 hrs
other anti diarrheal agents that are less used than loperamide hydrochloride- 4
morphine ( 50 x less potent than first line treatment)
codeine
dipheoxylate (also an opioid)
racecadotril (adjunct to rehydration for uncomplicated acute diarrhoea)
clostridium difficile infection
gram positive
colonises GI tract
major cause of diarrhoea and colitis in patients exposed to antibiotics
clostridium difficile infection symptoms - 4
alteration of normal fecal flora
colonic colonization of C. difficile
growth and production of toxins e.g. toxin a and toxin b, damage lining of colon
infection can lead to formation of colitis and toxic megacolon
clostridium difficile infection pharmacological treatment - 4
discontinue offending antibiotic
for c. difficile:
metronidazole (contraindicated in patients
with liver or renal impairment)
vancomycin (contraindicated in patients with liver or renal impairment)
bezlotoxumab
antiflatulants
relive painful gas symptoms/ flatulence
antiflatulant example
simethicone is a detergent contain gel
alters elasticity of mucous coated bubbles, causing them to break in large intestine
smaller bubbles = less pain
simethicone admin
can be used in babies - no known side effects
oral admin
there are two types of chronic bowel disease. what are they
irritable bowel disease ibs
inflammatory bowel disease ibd
irritable bowel syndrome symptoms - 5
nausea
diarrhoea/ constipation
bloating
flatulence
abdominal pain/ discomfort
irritable bowel syndrome - general info and prevalence
functional GI disorder
over >10% prevalence, common
oversensitivity of bowel
aetiology uncertain but brain-gut link
more common in women than men so potentially hormone linked but not menstrual linked so more research needed
can present different symptoms
ibs treatments - 4
peppermint oil supplement
antispasmodic drugs
fibre in diet/ supplements
antidepressants
peppermint oil supplement example in ibs
supplements containing L-menthol
relaxes GI smooth muscle by reducing calcium influx
antispasmodic drugs example treating ibs
135 mg Mebeverine
antidepressants example treating ibs - 2
TCAs
SSRIs
(but at lower doses than used for depression)
inflammatory bowel disease
severe, progressive autoimmune inflammatory disorders
long term
can be associated with smoking but not always
usually people diagnosed before age
40
relatively rare
what are the two types of ibd
ulcerative colitis
chron’s disease
ulcerative colitis
diffuse mucosal inflammation that is limited to the colon
bloody diarrhea, colicky pain, urgency to peepee
chron’s disease
inflammatory disease
can affect any part of GI tract
patchy transmural inflammation
abdominal pain diarrhea, weight loss, intestinal obstruction
drugs treating ibd - 4
(just symptom management):
glucocorticoids to prolong remission and reduce inflammation
5-aminosalicytlates (5-ASAa)
immunosuppresant meds
(actually may treat):
biologics/ monoclonal antibodies
non pharma treatments of IBD - 2
surgery to remove parts of bowel
fecal transplants to inc microbiota diversity- used following c. difficile infection
bezlotoxumab
human monoclonal antitoxin antibody
binds to c. difficile toxin b and neutralises its activity
prevents recurrance, passive immunity
examples of glucocorticoids for ibd treatment - 2
prednisolone
budenoside
examples of aminosalicylates for ibd treatment - 2
sulfasalazine
mesalazine
examples of immunosuppressants for ibd treatment
azathrioprine
examples of monoclonal antibodies for ibd treatment - 2
infliximab
adalimumab
prednisolone
budenoside
glucocorticoids
reduce inflammation
short term
ibd treatment
sulfasalazine
mesalazine
aminosalicylates
inhibits prostaglandin production
ibd treatment
azathrioprine
immunosuppressant
for severe cases
ibd treatment
infliximab
adalimumab
monoclonal antibodies
expensive but good
against TNF-alpha
ibd treatment
what drug can contribute to constipation
morphine can contribute to constipation
how do faecal softeners/ emollients work
faecal softeners lubricate stool
dec surface tension in intestine, allowing intestinal fluid to penetrate matter
usually oil based
how do bulk laxatives work
inc in bowel content/ stool bulk volume triggers stretch receptors in intestinal wall, causing peristalsis to propel bowel content forward
fibre acts as bulking
how do stimulant laxatives work
inc peristalsis
laxatives
inc bowel content movement through intestine
when should loperamide hydrochloride not be amdinistered
severe abdominal pain/ inflammatory bowel condition
what is ulcerative colitis
long-term condition where the colon and rectum (large intestine or large bowel) become inflamed.
what is toxic megacolon
rare but life-threatening condition that occurs when the colon becomes inflamed and swollen, often due to a severe infection or colon disease
dietary modification can be used to initially treat constipation. example of this?
fiber supplement - psyllium husk inc stool bulk, stimulates peristalsis
flatulence meaning
the passing of gas from the intestines through the anus
tricycline antidepressant for treating ibs example
amitriptyline - can modulate pain perception so helps
shit we gaf - 5
constipation
diarrhoea
chronic bowel disorder - ibs or ibd
c. difficile infection
flatulence - gas hurty
types of drugs we gaf - 10
purgatives - cons
agents that inc motility of GI smooth muscle - cons e.g. laxatives (bulking agents, osmotic, stimulant, faecal softeners)
emollients/ faecal softeners - cons
antidiarrhoel drugs (dec motility) - dia
antispasmodic drugs (dec smooth muscle tone) - dia
c. difficile infection antiinfections- dia
antiflatulance
ibs treatment - peppermint oil supplement, antispasmodic drugs fibre in diet/ supplements
ibd - immunosuppresant meds (just symptom management), (actually may treat):
biologics/ monoclonal antibodies
examples of gaf drugs - 18
bulking agents - agar, bran, ispaghula husk
osmotic - milk of magnesium, lactulose, epsom salt
stimulant laxative - lubiprostone
anti diarrhoeal - loperamide hydrochloride or imodium
discontinue offending antibiotic
for c. difficile: metronidazole, vancomycin
–
antiflatulence - simethicone
–
ibs - antispasmodic Mebeverine, antidepressy ssri
–
ibd immunosuppressant - Methotrexate, glucocorticoids like budenoside
ibd monoclonal antibody - bezlotoxumab
