Pharmacology of the GI System Flashcards
(111 cards)
1
Q
which meds are H2 antagonists
A
cimetidine, famotidine, nizatidine
2
Q
how does cimetidine work
A
it blocks h2 receptors in the basolateral membrane of parietal cells
- H2 is a Gs protein coupled receptor
- prevents activation of cAMP pathway
- reversible blockage
3
Q
what’s the clinical use of famotidine and other h2 antagonists
A
gastritis, GERD, PUD
take before eating
4
Q
what are the adverse effects of h2 antagonists
A
crosses BBB → headache, agitation, vomiting in infants
**confusion in elderly, renally impaired
tachyphylaxis with consistent usage
B12 (cobalamin) deficiency with prolonged usage
- CYP450 inhibition → cimetidine
- QT prolongation → famotidine
5
Q
which h2 antagonist is associated with a QTc prolongation
A
famotidine
6
Q
what do antiemetics do
A
mechanism of action → block receptors in the chemoreceptor trigger zone (CTZ) or stomach
7
Q
where is the chemoreceptor trigger zone (CTZ) located and what does it do
A
- CTZ located in area postrema, outside blood brain barrier
- CTZ sends signals to vomiting center (VC) in medulla
8
Q
what are the types of antiemetics
A
5-HT3 receptor antagonists
NK-1 (neurokinin) receptor antagonists
D2 receptor antagonist
H1 and M1 receptor antagonist
9
Q
what 5-HT3 receptor antagonists are there and how do they work
A
ondansetron, granisetron, palonosetron
-SETRON
they block receptors in the CTZ and vagal afferents in the stomach
10
Q
how o NK-1 receptor antagonist work? and which meds fall into that category
A
aprepitant (oral), fosaprepitant (IV)
-PREPITANT
mostly affect the CTZ, also the solitary nucleus → can also cause inhibition of substance P-induced vomiting
11
Q
what meds are D2 receptor antagonists and how do they work
A
metoclopramide, prochlorperazine, domperidone
mostly affect the CTZ
12
Q
which drugs are H1 and M1 receptor antagonists and how do they work
A
cyclizine, promethazine, diphenhydramine, dimenhydrinate (dramamine), scopolamine (butylhyoscine)
they block input from the vestibular nerve
13
Q
which type of antiemetics have the fastest onset of action
A
5-HT3
14
Q
whats scopolamine and what’s its antidote
A
scopolamine is a antiemetic:
- ADME → injected, transdermal patch
- non-specific muscarinic antagonist
- antidote → physostigmine
15
Q
which types of antiemetics can you give for vertigo and motion sickness, give one example of each
A
H1, M1 and D2 antagonists
- cyclizine
- scopolamine
- metoclopramide
16
Q
which types of antiemetics can you give for gastroenteritis and post-operative N/V, give one example of each
A
D2 and 5-HT3 antagonists
- metoclopramide
- ondansetron
17
Q
which antiemetics are used for chemotherapy, name one of each
A
5-HT3 and NK-1 antagonists
- ondansetron
- aprepitant
18
Q
what type of antiemetic do you give in hyperemesis gravidarum
A
5-HT3 antagonist
- ondansetron
19
Q
what are the general and specific adverse effects of antiemetics
A
GENERAL: headache, constipation, diarrhea
- 5-HT3 antagonists → serotonin syndrome, QTc prolongation
- NK-1 antagonists → CYP3A4 inhibition, hiccups
- D2 antagonists → parkinsonian effects, tardive dyskinesia, restlessness, drowsiness
- domperidone crosses the BBB minimally
- H1 and M1 antagonists → dry mouth, dizziness, blurred vision, disorientation, agitation, decreased urination
20
Q
metoclopramide is a D2 receptor antagonist used as an antiemetic, what other uses does it have
A
- apart from working as a antiemetic it can also be used to treat diabetic/post-operative gastroparesis, and GERD
- 1st line for gastroparesis = has prokinetic effects
21
Q
metoclopramide has effects in the D2 receptor, in what other receptor does it have an effect and which effect does that cause
A
- 5-HT4 receptor agonist
- ⭡contractility, LES tone and motility
- promotes gastric emptying
- central (area postrema) and peripheral effects
22
Q
what are the adverse effects of metoclopramide
A
- D2 receptor blockade → extrapyramidal symptoms
- drug interaction with → digoxin, diabetic agents, antipsychotics
- contraindicated in px with small bowel obstruction
- ⭣seizure threshold
- neuromalignant syndrome
- prolactinemia → gynecomastia, galactorrhea, amenorrhea, impotence
23
Q
what’s cinitapride
A
it’s a benzamide → gastroprokinetic and antiemeic
24
Q
what’s the MOA of cinitapride
A
- 5-HT4 agonist → enhances acetylcholine release in the enteric nervous system → prokinetic effect
- 5-HT2 antagonist → reduces visceral hypersensitivity and motility disorders
- D2 receptor antagonist → counteracts dopamine’s inhibitory effect on GI motility → antiemetic effects (via CTZ)
25
what are the uses of cinitapride
uses → GERD, gastroparesis, intestinal pseudo obstruction, refractory severe
26
what are the contraindications of cinitapride and what can happen if there's an overdose
- if overdose → extrapyramidal symptoms and drowsiness
- contraindications → heart problems and prolonged QT
27
what's dronabinol
- it’s a cannabinoid antiemetic
- naturally occurring cannabinoids form cannabis sativa
- ADME → oral or solution
28
whats the mechanism of action of dronabinol
- central effect → stimulation (agonism) of CB1 cannabinoid receptors in neurons of the CTZ and brainstem emetic centers → suppression of emetic reflex
- peripheral → CB2 agonism in the GI tract → inhibits GI motility
29
what are the indications of dronabinol
- nausea
- chemotherapy-induced nausea and vomiting (CINV) for refractory cases of other meds didn’t work
- anorexia and weight loss in px with advanced HIV → appetite stimulants
30
what are the side effects and contraindications of dronabinol
side effects:
- psychotopic effects → euphoria, dysphoria, paranoia, hallucinations
- ataxia, dizziness, dry mouth
- abdominal pain
- paradoxical worsening of nausea and vomiting → cannabinoid hyperemesis syndrome
contraindications → since it has a high affinity for plasma proteins it can displace other drugs
- if discontinuation do an abrupt withdrawal
31
what's cinnarizine and how does it work? when do you give it?
mechanism → antihistaminic H1 and Ca2+ channel blocker → antiemetic
- depressor effects on CNS and antivasoconstrictor
indications: vertigo, prophylaxis of vascular headache and cinnetic dizziness
32
what are the side effects and contraindications of Cinnarizine
- side effects → drowsiness and digestive discomfort, skin reactions, anticholinergic effects
- contraindications → parkinson’s (can lead to stroke)
33
what medications are bulk-forming laxatives
psyllium husk, methylcellulose
34
what's the mechanism of psyllium husk
- contain hydrophilic mucilloid that undergoes significant fermentation in the colon → increase in colonic bacterial mass
- draws water into the gut lumen → viscous liquid formation → stretching of bowel wall → promotion of peristalsis
**essentially they are fiber, they are indigestible compounds
35
first line of laxatives
bulk-forming laxatives
36
side effects of psyllium husk
usually well tolerated → may cause bloating and flatulence
- diarrhea may occur in lactose intolerant px
- constipation can worsen if the px doesn’t drink enough water
37
what meds are osmotic laxatives
magnesium citrate, polyethylene glycol, lactulose, glycerin
38
mechanism of osmotic laxatives
creates osmotic pressure → water into lumen → stimulation of peristalsis
- lactulose is used in hepatic encephalopathy = lactulose → lactic and acetic acid → ⭡nitrogen excretion as NH4+
- polyethylene glycol for maintenance → takes 24-72hrs to work
- magnesium formulations for acute relief → works faster
*** magnesium-containing laxatives may stimulate the release of CCK
39
adverse effects of magnesium citrate and other osmotic laxatives
- diarrhea, dehydration
- bulimics may abuse them
40
name stimulant laxatives
senna (senosides A-B), bisacodyl
41
mechanism of stimulant laxatives
enteric nerve (myenteric) stimulation → colonic contraction
- used for constipation
- fast onset (6-12hrs oral, <1hr rectal)
42
adverse effects of stimulant laxatives
diarrhea, dehydration, hypokalemia
- melanosis coli (colonic cell death) → harmless, it’s a benign hyperpigmentation of colonic epithelial cells
43
what med is an emollient and when is it used
docusate sodium
- used in iron induced stool hardening
- used in low-strain stooling → post partum, post MI, hemorrhoids
44
mechanism and adverse effects of docusate sodium
mechanism → ⭡water and fat incorporation in stool
- slow onset → 12-72 hrs
adverse effects: diarrhea
45
what medications are antidiarrheals
octreotide
loperamide
cholestyramine
46
what's octreotide and how does it work
antidiarrheal
ADME → subQ and IV
mechanism:
- somatostatin analog
- inhibits secretion of splanchnic vasodilation hormones
- reduces hepatic portal pressures
47
clinical uses of octrotide
- variceal bleeding (portal hypertension) → may present as painless hematemesis
** use this med before endoscopy in this px
- acromegaly → inhibition of GH, glucagon and insulin (more potent inhibitor of this than somatostatin)
- VIPomas, carcinoid tumors, Zolliger-Ellison syndrome
- “dumping syndrome” px after bariatric surgery
48
what are the adverse effects of octreotide
- nausea, cramps, steatorrhea
- CCK inhibition → ⭡risk of cholelithiasis
49
what's loperamide and how does it work
antidiarrheal
mechanism of action → μ-opioid receptor agonist
- slows gut motility → increases intestinal transit time
- poor CNS penetration → low addictive potential
50
clinical use and adverse effects of loperamide
clinical use = diarrhea, IBD, ⭣ileostomy fluid content
- effective against traveler’s diarrhea
adverse effects:
- constipation, nausea
- rash → hives, peeling erythema, SJS, TEN
- QTc prolongation
- if overdose → CNS depression (specially in children) and paralytic ileus
- do not give in children <2yo
- do not give in active IBD → to avoid toxic megacollon
51
how does Cholestyramina work and what are their indications
mechanism → binds to bile acids and bacterial toxins
- bile acid sequestrants → antidiarrheals
indications:
- bile salt-induced diarrhea → excessive concentrations of bile salts reach the colon and stimulate water and electrolyte secretion
- this happens in px w/ resection of the distal ileum or after a cholecystectomy
52
what are the side effects and contraindications of cholestyramine
side effects:
- bloating, flatulence, abdominal discomfort and constipation
- malabsorption of fat-soluble vitamins
contraindications:
- don’t use in steatorrhea → it will aggravate this type of diarrhea
- hypertriglyceridemia >300-500 mg/dL
- drug-drug interactions → reduces the absorption of Warfarin, digoxin and fat-soluble vitamins
53
which medications are anorexigenic
sibutramine
phentermine
rimonabant
SIBU es un PHENdejo RIendose
54
what's sibutramine and how does it work
- anorexigenic → skinny making
- ADME → oral
mechanism → inhibits re-uptake of 5HT and norepinephrine → satiety (central) and increase metabolic rate (peripheral)
indication → obesity
55
what are the side effects and contraindications of sibutramine
side effects:
- increased BP and heart rate
- dry mouth, blushing, headache, insomnia, nausea
- constipation
- depression
contraindications → hypertension, eating disorders, pregnancy, infants and lactating mothers
- this drug is no longer used because of the cardiogenic effects it had !!
56
which anorexigenic was discontinued because of it's cardiogenic effect
sibutramine
57
what's phentermine and how does it work
anorexigenic → skinny maker
ADME → oral
mechanism →
- methamphetamine isomer → stimulates neurons → release of catecholamines (dopamine, epinephrine, and norepinephrine) → appetite suppression and reduction of craving foods
- more metabolic rate → body weight reduction
indications → short-term loss on obesity
58
what medication do you give for short-term loss of obesity
phentermine
59
what are the side effects and contraindications of phentermine
side effects:
- tachycardia, hypertension, palpitations, nervousness, insomnia
- long term → euphoria and addiction
contraindications:
- cardiovascular disease
- hyperthyroidism
- glaucoma
- pregnancy or lactating
60
what's rimonabant and how does it work
anorexigenic → skinny maker
- ADME → oral
mechanism:
- selective antagonist of CB1 → appetite suppression
- increases energy expenditure, improves insulin sensitivity
indications → obesity and weight related disorders (metabolic syndrome and DM II)
61
side effects and contraindications of rimonabant
side effects:
- neurological and psychiatric risks → depression, anxiety, suicidal behaviors
- insomnia
- nausea and vomiting
- back pain and muscle cramps
contraindications → psychiatric disorders, px with liver and kidney impairment
- no longer used !!
62
which anorexigenic was discontinued because of it's psychiatric effect
rimonabant
63
what medications are antipasmodics
pinaverium
flunarizine
64
how does Pinaverium work
mechanism → selective Ca2+ channel blockers on smooth muscle of the GI tract
- inhibits calcium influx in intestinal smooth muscle
- reduces GI motility and spasms
65
when is pinaverium indicated
- treatment for pain and intestinal discomfort like IBS
- can also be used for biliary and intestinal spasms
66
side effects and contraindications of pinaverium
side effects:
- GI → abdominal pain, diarrhea, dysphagia
- skin → rash and pruritus
contraindications → interactions w/ anticholinergic drugs
67
how does flunarizine work
mechanism → NON-selective Ca2+ channel blocker with antihistaminic and vestibular effects
- blocks T-type calcium channels
- has anti-vasospastic and neuroprotective properties
68
when is flunarizine indicated
- neurological and vestibular conditions
- can be used for the GI tract (IBS) but mostly used for the CNS
69
what are side effects of flunarizine
drowsiness, depression, weight gain, extrapyramidal symptoms (specially in the elderly)
70
whats Cyproheptadine and how does it work
appetite stimulant and antihistaminic
5-HT2 receptor antagonist and H1 receptor antagonist → serotonin and histamine antagonist
significant increase in appetite, body weight and
linear growth
71
indications for Cyproheptadine
- allergic symptoms → pruritus, anaphylactic reactions, etc.
- appetite stimulation
- serotonin syndrome
72
side effects and contraindications of Cyproheptadine
side effects → dizziness, sedation, paresthesia, hallucinations, photosensitivity
contraindications:
- breastfeeding
- acute asthma attacks
- PUD
- prostatic hyperthropy
73
what medications are PPIs
omeprazole, pantoplazole, landoprazole
74
best PPI to give in pregnant women
pantoprazole
75
clinical use of PPIs
- peptic ulcers, GERD, Zollinger-Ellison syndrome
- part of combination therapy for H. pylori
- GI bleeds
- MALT lymphoma → stages 1 and 2
76
adverse effects of PPIs
- abdominal pain, nausea, diarrhea (well-tolerated)
- ⭡risk of pneumonia → chest pain caused by a pulmonary infection is confused w/ GERD so the disease progresses to pneumonia
** also → since there’s reduced acidity the can be increased bacterial growth, and if gastric contnets are aspirated there’s a bigger risk of pneumonia
- ⭣iron, B12, Ca2+, and Mg2+ with prolonged use
**⭡risk for osteoporosis and osteoporotic fractures
- ⭡risk of C. difficile associated diarrhea
- CYP450 inhibition
** omeprazole and esomeprazole → CYP2C19 inhibition → CYP2C19 metabolizes clopidogrel into active form
77
what meds are antacids
aluminium hydroxide, magnesium hydroxide and calcium carbonate (Tums)
78
how do antacids work
- neutralization of HCl directly
- ⭣pepsin absorption and activity
79
clinical uses of antacids
- flares of GERD, gastritis
**aluminium hydroxide → constipation
- mouthwash for chemotherapy related mucositis
**magnesium hydroxide → diarrhea
80
what are the specific and general adverse effects of antacids
all can affect drug bioavailability and renal excretion via pH alteration → ex. tetracyclins
aluminium hydroxide:
- ⭣K+, Mg2+, phosphate → renal caution needed
- seizures, encephalopathy, osteomalacia
calcium carbonate :
- hypercalcemia/milk-alkali syndrome → hypercalcemia, metabolic alkalosis and acute kidney injury
- rebound acid production
magnesium hydroxide:
- hyporeflexia, hypotension
- ⭣K+, arrhythmias
81
what medications are salicylates
bishmuth subsalicylate and sulfasalazine
82
mechanism of action of bismuth subsalicylate
- mechanism of action → reacts in low ph and forms Bismuth oxychloride + salycylic acid → binds ulcer base → physical protection +⭡HCO3-retention in mucus layer
- anti-secretory, antiinflammatory and antimicrobial effects
83
clinical use of bismuth
- traveler’s diarrhea
- ulcer healing, quadruple therapy for H pylori gastritis (bismuth, tetracycline, metronidazole and PPI)
84
adverse effects and contraindications of bismuth
adverse effects → constipation, grey-black tongue, tarry stools
- neurotoxicity (confusion), tinnitus, tremor
- Reye syndrome, salicylate allergies
contraindications → pregnancy, lactancy, pediatric px, renal or liver impairments
85
MOA of sulfasalazine
mechanism of action = sulfasalazine → colonic bacteria breaks it down→ sulfapyridine, 5-aminosalicylic acid
- sulfapyridine → locally antibacterial
- 5-ASA inhibits COX, LOX, cytokines (IL-1, TNF-a)
86
clinical use of Sulfasalazine
- IBD → chron’s and ulcerative colitis → uses as a MAINTENANCE drug
- ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis
87
adverse effects of Sulfazalazine
- yellowing of skin/urine, nausea, vomiting, headache, oligospermia
- severe allergic reactions → sulfa drug
- hepatic/renal impairment
- ⭡infection risk
- hemolytic anemia in G6PD deficiency
88
what meds are mucosal barrier protectants
sucralfate and misoprostol
89
what's sucralfate and what's its MOA
mucosal protectant
- ADME → oral or rectal enema
* since it’s activated by acid take the oral dose before foods
mechanism of action → protects mucosa from acid, pepsin and bile
- sucralfate transforms due to the acidic environment → sucrose octasulfate, aluminium hydroxide
- sucrose octasultate polymerizes using HCl → viscous polymer coats ulcers
- ulcer bases contain acidic protein exudate
- should not use alongside PPIs/H2 antagonists
- it also has cytoprotective effects → stimulation of local production of PGs and epidermal GF
90
clinical use of sucralfate
peptic ulcer disease, esophageal ulcers
91
initial treatment for GERD in pregnancy
sucralfate
92
what are the adverse effects and contraindications in sucralfate
- adverse effects → constipation and bezoars
- contraindications → renal failure
93
what's the MOA and clinical use of misoprostol
mechanism of action → prostaglandin analog
- PGE1 analog → ⭡production mucosal barrier, ⭣acid production
clinical use → NSAID-induced peptic ulcer disease
** labor induction (cervical ripening)
94
adverse effects of misoprostol
diarrhea, abdominal cramping, abortion
95
what's azathioprine and how does it work
purine analog
mechanism:
- purine analog (antimetabolite of 6-mercaptopurine) → ⭣nucleotide synthesis → ⭣proliferation of lymphocytes
- direct inhibition of PRPP amidotransferase → normally catalyzes the conversion of PRPP to 5-phosphoribosylamine (purine synthesis)
96
what's 6-mercaptopurine and how does it work
- immunomodulator
- ADME → oral
- mechanism → less nucleotide synthesis → less proliferation of lymphocytes
97
when is 6-mercaptopurine indicated
in moderate to severe chron
98
what are side effects of 6-mercaptopurine
- malignancies → lymphoma
- pancytopenia
99
what's methotrexate and how does it work
mechanism → folic acid antagonist (antimetabolite) → inhibition of dihydrofolate reductase (DHFR) → ⭣pyrimidine and purine nucleotide synthesis → ⭣DNA synthesis
- blocks tetrahydrofolate (THF) synthesis
- suppression of cell mediated and humoral response
100
what's the indication of methotrexate regarding IBD
in moderate to severe chron
- as monotherapy or with infliximab
- and as maintenance
101
what's Mesalamine (aka 5-aminosalicylic acid) and how does it work
- active drug
- acts locally in the colon and has less adverse effects
- ADME → oral, rectal and enemas
mechanism:
- anti-inflammatory effects are targeted topically to the mucosa, not that deep → local effects
- inhibitory cyclooxigenase and lipoxigenase → responsables of forming PGE precursors and leukotrienes
102
first line tx for mild to moderate CUCI
mesalamine
103
side effects and contraindications of mesalamine
- oral → headache, rash, vomiting, diarrhea, flatulence, constipation, nausea, dyspepsia, abdominal pain, fever, arthralgia, flu syndrome
- rectal → gas/flatulence, fever, dizziness, rectal pain, rash, leg/joint pain, flu syndrome
- acute intolerance syndrome → cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis, pruritus, rash
- pancolitis → rare
contraindications → hypersensitivity to salicylates; renal impairment
104
MOA of prednisone
- inhibition of intracellular NFkB → inhibition of various inflammatory mediators (IL-1, IL-6) → suppression of B cells and T cells
- increased T cell apoptosis
105
indication of prednisone regarding IBD
induction to remission in moderate to severe Chron or CUCI
106
adverse effects of prednisone
- osteoporosis, Cushing syndrome, hyperglycemia, amenorrhea, avascular necrosis of femoral head, growth retardation in children, increased risk of infection, poor wound healing, cataracts and hypertension
- additional = leukocytosis, iatrogenic adrenal insufficiency with abrupt discontinuation
107
contraindications of prednisone
NSAIDs -> GI upset
108
what's infliximab and how does it work
- anti TNF-a antibodies
- ADME → IV
- mechanism → binds to TNF-a with high affinity and prevents cytokines from binding to it’s receptor
109
what's adalimumab and how does it work
- ADME → subQ
- binds with high affinity TNF-a → prevents cytokine from binding to it’s receptor
110
Immunomodulators (azathioprine, 6-MP, methotrexate) are for ...
maintenance, not suitable for rapid symptom control.
111
Biologics (infliximab, adalimumab) are used in moderate-severe or refractory disease; require screening for ...
TB and hepatitis B prior to initiation.
