Gastrointestinal Medicines Flashcards
learn the GI meds, MOA, SE, contraindications, and considerations. (211 cards)
1
Q
Name one medication to tx gallstones
A
Ursodiol (Actigall)
2
Q
How does urosiol protect cholangiocytes against cytotoxicity of hydrophobic bile acids?
A
- modulation of the composition of mixed phospholipid-rich micelles
- reduction of bile acid cytotoxicity
- decrease concentration of bile acids in cholangiocytes
3
Q
How does ursodiol stimulate hepatobiliary secretion?
A
through Calcium and protein kinase C alpha dependent mechanisms or activation of p38 MAPK and extracellular signal related kinases, which results in insertion of transporter molecules (bile salt export pump (BSEP) or conjugate export pump (MRP3)
4
Q
How does ursodiol protect hepatocytes against bile acid-induced apoptosis?
A
it inhibits mitochondrial permeability transition (MMPT) and stimulates a survival pathway
aka stabilizes hepatocyte canalicular membranes
5
Q
What is ursodiol used for?
A
dissolution of gallstones and decreases hepatic cholesterol secretion
6
Q
What are the side effects of ursodiol?
A
diarrhea, abd pain, HA, dyspepsia, nausea, viral infections
7
Q
Name 2 drug interactions with ursodiol?
A
- aluminum based antacids decrease the effect of ursodiol
2. estrogen and clofibrate negate ursodiol’s effects
8
Q
What are the functions of gastric acids in the body? (3 main)
A
- protein digestion
- absorption of B12, iron, and calcium
- prevents some enteric infections
9
Q
What is the composition of TUMS?
A
calcium carbonate
10
Q
What is the chemical composition of Alka-seltzer?
A
sodium bicarbonate
11
Q
What is the chemical composition of maalox?
A
aluminum hydroxide
12
Q
The condition in which antacids should be used cautiously
A
renal insufficiency
13
Q
What does the aluminum in maalox cause?
A
constipation
14
Q
What does the magnesium in mylanta cause?
A
diarrhea (due to unabsorbed salts)
15
Q
What is the general MOA of antacids?
A
they are weak bases therefore they neutralize acids and raise the pH to greater than 3.5
16
Q
What is the end product of antacids? (2)
A
- sodium and water
or - salt and CO2 (sodium bicarbonate)
17
Q
What are major SE of antacids?
A
metabolic alkalosis, cardiac disease, fluid/electrolyte imbalances
18
Q
Drug interactions of antacids?
A
any - binds with other drugs so take 1-2 hours after taking other meds, also the decrease in gastric acids could cause inefficient absorption
19
Q
What is the result of blocking Histamine 2 receptors?
A
decreased stomach acid production
20
Q
What can the decrease of stomach acid cause?
A
increased bacterial growth in the stomach, leading to increased bacterial colonization in the lungs, and pneumonia in COPD pt
21
Q
SE of IV formulations of H2 receptor antagonists
A
confusion, mental changes
esp. if pre-existing renal or hepatic impairment
22
Q
Famotidine brand name
A
pepcid
23
Q
ranitidine brand name
A
zantac
24
Q
cimetidine brand name
A
tagamet
25
what is the chemical composition of mylanta?
magnesium hydroxide
26
common SE of antacids NOT containing AlOH or MgOH?
eructation
27
what is eructation
bleching
28
Considerations for chronic antacid use in renal compromised pt
monitor ALP, ALT, AST, serum creatinine, BUN
29
What do parietal cells do?
produce gastric acid
30
What stimulates parietal cells?
histamine, acetylcholine, and gastrin receptors
31
What releases histamine, ach and gastrin?
antral G cells and enterochromaffin-like cells (ECL)
32
Examples of H2 antagonists?
famotidine, ranitidine, nizatidine, cimetidine
33
nizatidine brand name
axid
34
endocrine effects associated with cimetidine?
increased prolactin, decreased metabolism of estradiol, and blockage of androgen receptors
35
how does cimetidine block androgen receptors?
inhibits binding of DHT (dihydroxytestosterone)
36
Adverse endocrine effects of cimetidine (2)
glactorrhea in women, gynecomastia in men
37
cautions for H2 antagonists
pregnancy category B, monitor renal or hepatic dysfunction for mental status changes
38
IV administration of H2 antagonists may cause ___ in renally or hepatic impaired pt
mental status changes, confusion, depression
39
What enzymes could cimetidine affect?
cytochrome p450 enzymes
40
drug interactions with cimetidine?
other drugs using the same p450 pathway - warfarin, phenytoin, theophylline, lidocaine
41
examples of proton pump inhibitors
esomeprazole, omeprazole, lansoprazole, pantoprazole, rabeprazole
42
brand name esomeprazole
nexium
43
brand name lansoprazole
prevacid
44
brand name omeprazole
prilosec
45
brand name pantoprazole
protonix
46
brand name rabeprazole
aciphex
47
MOA proton pump inhibitors
directly inhibiting proton pumps, which plays a role in gastric acid production in the stomach
48
adverse effects of OTC PPI? (3)
increase of stomach bacteria, abdominal discomfort, diarrhea
49
adverse effect of high dose, chronic PPI? (3)
atrophic gastritis, osteoporosis related bone fx, magnesium deficiency
50
cautions for PPI
pregnancy category B, liver impaired patients due to the increased half life and impaired metabolism of the drug
51
Drug interactions with PPI's
ketoconazole and atazanavir (decreases the bioavailability of these drugs, since they need a certain pH to work); cyp 2c19 and cyp3A4 metabolized drugs; taking PPI and warfarin inc risk of bleeding
52
How are PPI's metabolized?
cytochrome P450 pathways, CYP 2C19 and CYP2A4
53
2 treatments for H. pylori
1. PPI plus clarithromycin and amoxicillin OR PPI plus metronidazole for 14 days
2. a PPI or H2 antagonist plus bismuth, metronidazole, and tetracycline (bismuth quadruple therapy) for 10-14 days
54
what is an alternative treatment for H. pylori NOT including bismuth-based quadruple therapy?
a PPI plus amoxicillin for 5 days, followed by a PPI plus clarithromycin and tinidazole for another 5 days
55
what is bismuth subsalicylate?
pepto bismol
56
absolute contraindictions for pepto bismol?
never give to children, especially after flu and varicella shots. salicylate is a causative agent of Reye's syndrome
57
How are mucosal protectants different than antacids, H2 antagonists, or PPI's?`
they do not affect gastric acid secretion, rather, shield gastric mucosa
58
MOA of sucralfate
due to limited solubility, becomes thick and sticky in acid solutions. <3% of intact drug absorbed.
utilizes negative charges to adhere to gastric erosions (with positively charged proteins) to protect from further damage and promote healing
59
MOA bismuth subsalicylate
coats stomach lesions and can bind to microbes to provide protection from gastric acids, for diarrhea can bind to and absorb toxins and inhibit intestinal prostaglandin and chloride secretion
60
MOA misoprostol (cytotec)
activates prostaglandin E1 receptors on gastric parietal cells and inhibits gastric acid production via G protein coupled receptor-mediated inhibition of adenylate cyclase. this decreases intracellular cyclic adenosine monophosphate and proton pump activity.
61
what combination of drugs is given to prevent GI erosions ?
NSAID and misoprostol, due to NSAID decreasing prostaglandin synthesis
62
Adverse effects bismith subsalicylate? (3)
dark brown-black stools, constipation or salicylate toxicity with chronic use
63
adverse effects misoprostol? (5)
abdominal discomfort with or without diarrhea, N/V, flatulence, dyspepsia
64
Pregnancy risk categories for sucralfate, bismuth subsalicylate, and misoprostol?
B, C, X
65
Drug interactions with sucralfate?
should not be given with any other drugs bc will bind to them and inhibit their absorption
66
drug interactions with misoprostol?
none
67
drug interactions with bismuth subsalicylate?
chemical reactions with tetracyclines and quinolone antibiotics, decreases antibiotic absorption; may increase hypoglycemic effects of insulins/DM meds, increase risk of bleeding in concurrent warfarin d/t synergistic effects of antiplatelets; decrease effectiveness of probenecid and sulfinpyrazone (for gout); avoid using with other salicylates like aspirin
68
Drugs to stimulate GI motility are called?
Gastroprokinetic drugs
69
How do gastroprokinetic drugs work?
increased frequency of small intestine contractions WITHOUT disrupting rhythm
70
What conditions can be relieved by gastroprokinetic drugs? (11)
IBS, acid reflux disease, gastroparesis, gastritis, functional dyspepsia, abdominal discomfort, bloating, constipation, heartburn, nausea, vomiting
71
2 types of gastroprokinetic drugs?
cholinergic mimetic agents, dopamine receptor antagonists
72
specific MOA of cholinergic mimetic agents? (2)
1. antagonize M1 receptor (which usually inhibits ach release), therefore increasing ach production
2. inhibit acetylcholineesterase (less ach broken down)
3. MAY stimulate muscarinic M3 receptors on muscle cells and myenteric plexus synapses
73
General MOA of gastroprokinetic drugs?
increasing availability of acetylcholine which increases GI peristalsis which increases pressure on lower esophageal sphincter (increases GI motility)
74
Considerations for cholinergic mimetic agents?
never administer IV (fast absorption may lead to heart block or severe hypotension, d/t drug being in the wrong location) , never use if there is a mechanical obstruction of gastric or urinary tracts
75
Example of a cholinergic mimetic agent?
bethanechol (urecholine)
76
SE of cholinergic mimetic agents? (8)
abd discomfort, diarrhea, hypotension, reflex tachycardia, lacrimation, miosis, salivation, urinary urgency
77
General MOA of dopamine receptor blockers
stimulates the GI tract without increasing gastric secretions
78
example of D2 receptor blocker?
metoclopramide (reglan)
79
Adverse effects of D2 receptor blockers? (10)
parkinsonian like symptoms, tardive dyskinesia, acute dystonia, drowsiness, confusion, elevated prolactin levels, galactorrhea, gynecomastia, impotence, menstrual disorders
80
Drug interactions with D2 receptor blockers?
alcohol, tranquilizers, sleep meds, narcotics, use caution with hypertensive pt
81
Types of drugs to control diarrhea? (3)
opioid agonists, bismuth compounds, octredotide
82
opioid agonist monotherapy drug
loperamide (imodium)
83
combination opioid agonists?
diphenoxylate plus atropine (lomotil) and difenoxin plus atropine (motofen)
84
characteristics of loperamide (3 major)
does not cross blood brain barrier, no analgesic properties or potential for addiction, nonprescription
85
characteristics of diphenoxylate (2 major)
prescription only, analgesic properties at higher/nonstandard doses
86
general MOA of opioid agonists?
act directly on intestine to slow peristalsis, allow more fluid and electrolyte absorption in colon, anticholinergic properties of atropine contribute as well
87
Considerations for opioid agonists?
acute tx of diarrhea d/t CNS depression, take with adequate fluids to prevent constipation and electrolyte imbalance, FIRST rule out c. diff
88
SE Lomotil? (4)
dry mouth, abd pain, tachycardia, blurred vision (d/t atropine)
89
Considerations for the patient for opioid agonist users?
if diarrhea continues, fever, abdominal pain or bloody stools occur, contact prescriber asap
90
Drug interactions with opioid agonists?
additive sedation with CNS depressants or alcohol, hypertensive crisis when taken with MAOIs (because they both increase synaptic 5-HT which can be toxic)
91
3 MOA of octreotide (sandostatin)
1. prevents secretion of hormones and transmitters like gastrin, serotonin, and other active peptides causing diarrhea
2. directly inhibits intestinal and pancreatic secretion and enhances absorption
3. slows GI motility
92
Octreotide is usually used to tx diarrhea related to these 5 conditions
cancer, vagotomy, dumping syndrome, short bowel syndrome, AIDS
93
Adverse effects of octreotide (4)
nausea, abdominal pain, flatulence, diarrhea
94
adverse effects of chronic octreotide use (4)
acute cholecystitis, hyperglycemia, hypothyroidism, bradycardia
95
Considerations for octreotide for impaired pancreatic secretion?
may cause steatorrhea, leading to fat soluble vitamin deficiency
96
Types of stool according to Bristol Stool Chart (7)
1. separate hard lumps like nuts (hard to pass)
2. sausage shaped but lumpy
3. sausage but with surface cracks
4. sausage or snake, smooth and soft
5. soft blobs with clear cut edges (passed easily)
6. fluffy pieces with ragged edges (mushy stool)
7. watery, no solid pieces, entirely liquid
97
Normal frequency of bowel movements?
once per week to 2-3 times per day
98
Subcategories of laxatives (5)
bulk forming laxatives, stimulant laxatives, stool softeners/surfactants, osmotic laxatives, miscellaneous
99
Considerations for prescribing laxatives
sufficient fluids must be consumed, take a thorough hx of laxative use d/t potential to cause fecal impaction, adequate fiber and fluid intake
100
Examples of bulk forming laxatives?
calcium polycarbophil (fibercon), psyllium mucilloid (metamucil)
101
MOA of bulk forming laxatives?
absorb water to form a bulky emollient gel that distends the colon to promote peristalsis
102
Characteristics of bulk forming laxatives
indigestible, hydrophillic colloids, safest class, produce less abdominal cramping, but more flatulence or bloating
103
Drug interactions of bulk forming laxatives?
may decrease absorption of warfarin, digoxin, nitrofurantoin, antibiotics, salicylates
104
examples of stimulant laxatives
bisacodyl (dulcolax), castor oil (emulsoil)
105
Pregnancy categories dulcolax and emulsoil?
C and X
106
General MOA of stimulant laxatives?
activate bowel movement by irritating mucosa and enteric nervous system in the colon and altering intestinal electrolyte and fluid absorption
107
Concern for stimulant laxatives?
more abdominal cramping and depletion of fluid and electrolytes, potential dependence and destruction of myenteric plexus MAY be safe for long term use
108
drug interactions for stimulant laxatives?
do not give with milk or dairy, as this will dissolve enteric coating and cause dyspepsia, take on empty stomach for faster action and to avoid decreased absorption
109
example of stool softener/surfactant?
docusate sodium (colase)
110
general MOA of colase?
soften stool by absorbing water and lipids, take with 6-8 oz water
111
Colase is commonly used in these (3) situations to prevent constipation?
recent surgery, traumatic injury, MI
112
adverse effects of colase? (2)
abdominal cramping, diarrhea, caution with elderly d/t risk of nutritional deficits
113
pregnancy category of colase?
C
114
Drug interactions with Colase?
do not use in sodium restricted patients, do not give concurrent with mineral oil (increases systemic absorption of docusate), long term use may impair absorption of fat soluble vitamins ADEK (decreased contact time in GI tract)
115
Examples of osmotic laxatives?
magnesium hydroxide (milk of magnesia), polyethylene glycol (miralax), sodium biphosphate (fleet phospho-soda)
116
general MOA of osmotic laxatives?
attract water and create more fluid stools, cause a concentration gradient
117
considerations for milk of magnesia?
very potent, so only use in fecal impaction where bowel obstruction has been ruled out
118
Adverse effects of osmotic laxatives?
abdominal cramping, diarrhea
119
Use osmotic laxatives with caution in these patients
elderly d/t dehydration and electrolyte imbalance, renal impairment d/t risk of hypermagnesemia (decreased ability of mg elimination)
120
Drug interactions with osmotic laxatives?
Milk of magnesia may decrease absorption of histamine2 receptor antagonists, iron salts, phenytoin, digoxin and tetracyclines
121
Collection of medications to control IBS? (5)
antidiarrheal, laxatives, anticholinergics, serotonin 5HT receptor antagonists/agonists, chloride channel activators
122
What are anticholinergics used to treat in IBS?
reduce bowel motility, prevent painful cramping spasms
123
Commonly used anticholinergic/antimuscarinics for IBS?
dicyclomine (bentyl) and hycosamine
124
general MOA of anticholinergics in IBS?
bind to muscarinic receptors in GI mucosa, relaxing intestinal spasms, may inhibit intestinal gland secretion (reduce diarrhea)
125
Anticholinergic effects (4 examples)
dry mouth, visual disturbance, urinary retention, constipation
126
Examples of 5HT3 antagonists (5)
alosetron, ondansetron, graisetron, dolasetron, palonosetron
127
Which 5HT antagonist was removed from market due to cardiovascular deaths?
tegaserod, is now used in emergency situations for short term treatment in women with IBS with predominant constipation
128
What is the difference between alosetron and tegaserod?
alosetron is a highly potent and selective 5HT3 antagonist with a longer duration of effect (higher affinity and slower dissocation from receptors), tegaserod is a 5HT4 receptor partial agonist
129
Considerations for alosetron
restricted to women with diarrhea-predominant IBS who have not responded to conventional therapies (due to ischemic colitis and constipation risks), be very aware of sx of lightheadedness and chest pain due to cardiovascular risks associated with this and tegaserod
130
Adverse effects of tegaserod
angina, heart attack, stroke (pt must register with the manufacturer when they receive this medication)
131
Strict duration of treatment for alosetron and tegaserod
4-6 weeks ONLY
132
Example of a chloride-channel activator for IBS
lubiprostone
133
Lubiprostone target
type 2 volume regulated chloride channel located in gastric parietal cells, small intestinal and colonic epithelia
134
Restrictions for lubiprostone
used in women with constipation-predominant IBS
135
Lubiprostone MOA
prostanoic acid derivative from a metabolite of prostaglandin E1, activates selective type 2 volume regulated Cl channel to accelerate small bowel and colon transit times to increase secretion of fluid and electrolytes
136
Adverse effects of lubiprostone
diarrhea, nausea, DO NOT use for known or suspected bowel obstruction
137
Drug interactions with lubiprostone
none
138
What stimulates nausea and vomiting?
center of medulla stimulated when receives input from digestive tract, inner ear, or chemoreceptor trigger zone (in postrema)
139
6 classes of antiemetics
1. 5HT3 receptor antagonists
2. corticosteroids
3. neurotonin 1 receptor antagonists
4. dopamine receptor antagonists
5. antihistamines/anticholinergics
6. cannabinoids
140
Examples of 5HT3 receptor antagonists (4)
ondansetron (zofran), granisetron (kytril), dolasetron (anzemet), palonosetron (aloxi)
141
What effect do cytotoxic drugs or radiation have on GI cells?
causes release of serotonin from enterochromaffin cells in the GI mucosa, which stimulates 5HT3 receptors on sensory nerve terminals peripherally, initiating emesis or cause sensory nervous system to initiate emesis
142
5HT3 antagonists work on the receptors to create an antiemetic response through selective antagonism at ____?
peripheral 5HT3 receptors
143
Mild SE of 5HT3 antagonists? (5)
mild HA, dizziness, constipation, diarrhea, transient elevation of hepatic aminotransferase levels (AST, ALT)
144
drug interactions with 5HT3 antagonists?
none
145
Examples of corticosteroids used to treat N/V (2)
dexamethasone (decadron), methyprednisolone (solu-medrol)
146
Long term effects of corticosteroids? (5)
risk for DM2, hypertension, osteoporosis, hyperadrenalism, hypoadrenalism
147
Cautions for corticosteroids
avoided or monitored in hyperglycemic or diabetic pt
148
adverse events in dexamethasone specifically (7)
insomnia, indigestion, epigastric discomfort, agitation, increased appetite, weight gain, acne
149
example of neurokinin-1 (NK1) receptor antagonist
aprepitant (emend)
150
MOA of NK1 RA?
inhibits substance P, which is involved in the emesis reflex centrally and peripherally
151
What is substance P?
a neuropeptide that acts as a NT by preferentially binding to NK1 receptor that is involved in the emesis reflex
152
common SE of aprepitant (6)
fatigue, HA, anorexia, diarrhea, hiccups, mild transaminase elevation
153
Drug interactions with NK1 RA
induces CYP3A4 and CYP 2C9, and dexamethasone is a substrate of CYP2C9, so decrease dexamethasone 50%; warfarin, phenytoin, itraconazole, terfenadine, oral contraceptives (synergistic effects on same CYP 450 subtype system)
154
Categories of dopamin-receptor antagonists (3)
1. phenothiazine, butyrophenones, substituted benzamides
155
examples of phenothiazines (3)
promethazine (phengergan), prochlorperazine (compazine), thiethylperazine
156
examples of butyrophenones (1)
droperidol (inapsine)
157
examples of substituted benzamides (2)
metoclopramide (reglan), trimethyobenzamide (tigan)
158
General MOA of central dopamine antagonists
inhibits dopamine and muscarinic receptors, selective for D2 receptors
159
Adverse effects of central dopamine antagonist long term use? (5)
sedation, extrapyramidal symptoms (restlessness, dystonias, parkinsonian symptoms)
160
Additional adverse effects of droperidol (inapsine) (2)
hypotension, prolonged QT interval
161
Pregancy class of the phenothiazines?
C
162
Pregnancy class of metoclopramide
B
163
Drug interactions with phenothiazines
synergistic with streptomycin, erythromycin, oleandomycin, spectinomycin, levofloxacin, azithromycin, amoxicillin-clavulanic acid
164
Contraindications of metoclopramide
pt who take antipsychotics, HIGH LIKELIHOOD of tardive dyskinesia with long term use
165
Drug given for motion sickness, and type of drug
scopolamine (hyoscine), anticholinergic
166
Examples of H1 antihistamines
diphenhydramine (benadryl), dimenhydrinate (dramaine), meclizine (antivert)
167
MOA for H1 antihistamines and anticholinergics for antiemesis?
inhibits H1 and muscarinic cholinergic M1 receptors
168
Adverse effects of antihistamines and anticholinergics?
dizziness, sedation, dry mouth, confusion, cycloplegia, urinary retention
169
Cannabinoids used as antiemetics
dronabinol (marinal), nabilone (cesamet)
170
What is dronabinol (marinal) used to tx? (2)
appetite stimulant, antiemetic
171
Hypothesized MOA of cannabinoids?
modulates 5HT3 receptor activation in nodose ganglion and substance P release in the spinal cord
172
Effects of cannabinoids? (9)
euphoria, dysphoria, sedation, hallucinations, dry mouth, increased appetite, tachycardia, conjunctival injection, orthostatic hypotension
173
What is IBD?
inflammatory bowel disease, combines ulcerative colitis and Crohn's Disease
174
IBD drugs that affect the immune system (6)
immunosupressants, purine analogs, methotextrate, monoclonal antibodies, antitumor necrosis factor agents, anti-integrin agents
175
Categories of IBD drugs (3)
aminosalicylates, corticosteroids, immune system drugs
176
Two subtypes of aminosalicylates
5-ASA/mesalamine and azo compounds
177
Drugs with azo compounds (3)
sulfasalazine, balsalazide, olsalazine
178
Drugs with 5-ASA formulations (6)
pentasa, asacol, apriso, lialda, rowasa, canasa
179
Primary MOA of salicylates and NSAIDS
blockage of prostaglandin synthesis by inhibiting COX
180
Potential MOA of salicylates in the GI tract (4)
1. modulation of inflammatory mediators derived by COX and lipoxygenase pathways
2. interference with the production of inflammatory cytokines
3. inhibitory effects on nuclear factor kB
4. other inhibitory effects on NK cells, mucosal lymphocytes, and macrophages
181
SE of olsalazine (4)
secretory diarrhea, subtle renal tubular changes, rare interstitial nephritis, rare hypersensitivity reactions
182
SE of sulfasalazine (15)
nausea, GI upset, HA, malaise, arthralgias, myalgias, bone marrow supression, hypersensitivity reactions causing fever, exfoliative dermatitis, pancreatitis, pneumonitis, hemolytic anemia, pericarditis, hepatitis
183
Drug interactions with sulfasalazine
may interfere with folic acid absorption and processing, take 1mg/day folic acid
184
examples of glucocorticoids used to treat IBD (4)
prednisone, prednisolone, topical hydrocortisone, budesonide
185
MOA of glucocorticoids
inhibits production of inflammatory cytokines and chemokines like TNFalpha, interleukin 1 (IL-1) and interleukin 8 (IL-8)
reduction of expression of adhesion molecules, inhibition of gene transcription of nitric oxide synthesis, phospholipase A2, COX2, and NF-kB
186
Examples of purine analogs
azathioprine, 6-mercaptopurine (6-MP)
187
When are purine analogs used
when IBD patients are unresponsive to aminosalicylates or glucocorticoids, or who relapse when glucocorticoids are withdrawn
188
Proposed MOA of purine analogs
metabolized to nucleotide 6-thioinosinic acid, thioguanylic acid, and 6-methylmercaptopurine ribotide. these are thought to inhibit purine ribonucleotide synthesis, which then impedes DNA synthesis and proliferation of fast growing cells (T and B lymphocytes)
189
Dose dependent adverse effects of purine analogs
nausea, vomiting, bone marrow suppression, hepatic toxicity, hypersensitivity reactions with fever, rash, pancreatitis, diarrhea, hepatitis
190
considerations for purine analogs
monitor CBC and hepatic function tests
191
Drug interactions with purine analogs
allopurinal reduces xanthine oxide catabolism of purine analogs, increasing active 6-thioguanine nucleotides, increasing risk for leukopenia
allopurinol inhibits xanthine oxidase (which breaks down 6-MP)
192
MOA of methotrexate
inhibits dihydrofolate reductase, which participates in tetrahydrofolate synthesis, and therefore inhibits production of purines and thymidines; may interfere with inflammatory actions of IL-1, simulate release of adenosine, and induce apoptosis of activated T-lymphocytes
193
Adverse effects methotrexate
with lower dose, don't see bone marrow suppression, megaloblastic anemia, alopecia, and mucositis, and low risk of hepatic damage.
194
Interactions with methotrexate
caffeine (coffee, tea, soda, chocolate) (effectiveness is reduced), alcohol (liver dysfunction), NSAIDS can increase blood levels of methotrexate
195
Anti-tumor necrosis factor drugs approved for IBD tx (3)
infliximab, adalimumab, certolizumab
196
When are anti-TNF drugs used?
pt with IBD who have shown inadequate response to conventional treatment
197
What is TNF?
important pro-inflammatory cytokine in the pathogenesis of IBD
198
MOA of anti-TNF agents
bind to soluble and membrane bound TNF and prevents the binding of TNF to TNFr that are present on helper T cell type 1 and other innate immune/non-immune cells
-binding of anti-TNF to membrane bound TNF induces reverse signaling, suppressing cytokine release
199
Adverse effects of anti-TNF agents
due to suppression of helper T cell type 1 (TH1), this immunosuppression may allow infections to flourish, like bacterial sepsis, TB, invasive fungal organisms, reactivation of Hep B, listeriosis, and opportunistic infections
200
considerations for anti-TNF agents
test for TB before starting, administer prophylactic tx for positive TB, may increase the risk of lymphoma
201
Why does anti-TNF cause drug resistance?
production of antibodies to TNF antibodies (ATA) or non-ATA mechanisms
202
Reactions to drug resistance/TNF antibody development
acute or delayed infusion reactions = fever, HA, dizziness, urticaria, mild cardiopulmonary sx
203
Delayed infusion reactions to anti-TNF agents
myalgia, jaw tightness, rash, edema
| may occur 1-2 weeks after therapy is initiated
204
Example of anti-integrin therapy
natalizumab
205
What are integrins
integrins are adhesion molecules located on the surface of leukocytes, which interact with selectins on the surface of vascular endothelial cells. this allows circulating leukocytes to adhere to the vascular endothelium and move though blood vessel wall into the tissue
206
MOA of natalizumab
humanized IgG4 monoclonal antibody targets the alpha-4 subunit of integrins and blocks the interaction of integrins with selectin, therefore preventing leukocyte migration into the surrounding tissue
= prevents IBD progression in chronic disease process
207
Risk of natalizumab
induces progressive multifocal leukoencephalopathy due to the reactivation of a human polyomavirius in pt receiving concurrent immunomodulators
aka do not take with immunomodulators/immune suppressants
208
pregnancy class of milk of magnesia?
B
209
pregnancy class of miralax?
B
210
pregnancy class of colase?
C
211
pregnancy class of dulcolax
C
