GI medications Flashcards
When is early PONV?
within 6 hours
When is late PONV?
6-24 hours
What is the ASA’s recommendation for PONV?
treat only high risk groups but not routine use; use patient’s risk to guide prophylactic therapy
What are some patient factors that increase risk for PONV?
women, non-smokers, hx motion sickness, previous incidence of PONV
What are some surgical factors that increase risk for PONV?
length of procedure, laparotomies, gyn surgery, lap surgery, ENT, breast, ortho
What are some anesthesia factors that increase risk for PONV?
inhalation agents, N20, Neo, narcs, etomidate
Where is the vomiting center located?
medulla oblongata
What are the 4 areas that trigger the vomiting zone?
CTZ, vestibular apparatus (muscarinic 1 receptor), thalamus/cerebral cortex (CNS), and neurons in GI tract
Describe how the vomiting center is triggered.
NT regulate activity in vomiting center. Once activated, efferent signal sent via cranial nerves to vagal parasympathetic fibers and sympathetic chain
What NTs are associated with PONV?
dopamine, serotonin, acetylcholine, histamine, substance P
What NTs act at CTZ?
dopamine, serotonin
What NTs are intrinsic within vomiting center?
substance P, acetylcholine, and histamine
What NTs are in CNS within vomiting center?
???
What NTs are at the vestibular apparatus within the vomiting center?
acetylcholine, histamine (H1 and M1 receptors)
What NTs act on GI tract within vomiting center?
acetylcholine, histamine, serotonin, substance P, and mechanoreceptors.
What are the drug classes used to treat PONV?
anticholinergics, benzamines, benzodiazepines, butrophenones, cannabinoids, glucocorticoids, 5-HT3 antagonists, NK1 antagonists, phenothiazines
What anti-emetics are anticholinergics?
atropine, hyoscine, scopolamine
What antiemetics are benzamines?
metoclopramide
What antiemetics are benzodiapezines?
midazolam
What antiemetics are butrophenones?
droperidol, haloperidol
What antiemetics are cannabinoids?
dronabinol, nabilone
What antiemetics are glucocorticoids?
dexamethasone
What antiemetics are 5-HT3 antagonists?
dolasetron, granisetron, ondansetron, palonosetron, ramosetron, tropisetron
What antiemetics are NK-1 antagonists?
Aprepitant, Fosprepitant
What antiemetics are phenothiazines?
prochlorperazine, promethazine, chlorpromazine
What is the MOA of Scopolamine?
block transmission of impulses from vestibular apparatus to the medulla. can cross BBB.
What is the dose of scopolamine?
5mcg/hr for 72 hours (best 4 hours before stimulus) transdermal provides sustained effect and avoids anticholinergic side effects. If given IV can cause anticholinergic syndrome
What are the uses for scopolamine?
motion sickness, middle ear surgery, N/V with PCA or epidural morphine
True/False: Narcotics increase the sensitivity of vestibular apparatus to motion.
True
What are the side effects of scopolamine?
possible visual disturbances.
What is the MOA of metoclopramide?
stimulate GI tract via cholinergic mechanism and an anti-dopaminergic effect: contraction of lower esoph sphincter and gastric fundus, increased gastric and SI motility, decreased muscle activity in pylorus and duodenum with stomach contraction
Who should you use caution in with metoclopramide?
parkinsons and RLS in high doses due to antidopamine effects
What is the MOA of midazolam?
thought to decrease the synthesis and release of dopamine within the CTZ. give at END OF CASE
What is the MOA of droperidol?
competitive dopamine antagonist, receptor is D2 and ligands are dopamine and GABA
What is the dose of prophylactic droperidol?
(prophylactic)0.625-1.25mg(rescue)
When should you use caution with droperidol?
parkinsons, RLS, high doses black box warning for prolonged QTc
What is the MOA of dexamethasone?
centrally inhibits prostaglandin synthesis and controls endorphin release
What is the dose of dexamethasone?
4mg
When should you use caution with dexamethasone?
obese patients, patients with DM
Describe 5-HT3 serotonin receptor.
ligand-gated Na and K cation channel. depolarizes plasma membrane, excitatory. stimulated by serotonin..
Where is serotonin found?
intestines: regulates intestinal movement, raphe nucleus in the brainstem projecting to other regions of brain to affect mood, cognition, and sleep.
What does stimulation of the 5-HT3 serotonin receptor cause?
nausea
What are other effects of serotonin?
addiction, aggression, vasoconstriction, increased intestinal motility, learning and memory consolidation
When are 5-HT3 antagonists used?
N/V related to chemo/PONV. NOT useful for motion sickness and vestibular stimulation related nausea–there’s no 5-HT3 receptors in the vestibular apparatus.
Does ondansetron cross the BBB?
No, little CNS side effects
What is the dose and onset of ondansetron?
4mg, 30-60 min
What are the side effects of ondansetron?
headache, diarrhea, QTc prolongation
What is tropisetron used for?
treat symptoms with carcinoid syndrome
What is the dose and DOA of granisetron?
dose 0.1mg, lasts 24h
What is the only 5-HT3 antagonist that has an active metabolite?
dolasetron
What is substance P’s claim to fame?
primary NT produced by pain/temperature afferent peripheral neurons
What are the receptors for substance p?
neurokinin receptors (NK1, NK2, NK3)
Where are substance P and its receptors located?
gut and N/V pathways
What is the MOA of Aprepitant/Fosaprepitant?
competitive antagonist at the NK1 receptors, inhibiting substance P from binding to this protein coupled receptor.
What is Aprepitant/fosaprepitant used for?
chemo induced N/V.
What is an important side effect of aprepitant/fosaprepitant?
can inhibit steroidal contraceptives for 7-10 days.
What is the MOA of phenothiazines?
antagonizes H1 (stimulated by histamine) and M1 (stimulated by ACh) receptors
What is histamine synthesized from?
histadine
Where is histamine?
CNS (wakefulness), immune cells (basophils/mast cells), GI tract (mast cells in stomach wall)
Where are H1 receptors and what do they do?
vascular smooth muscle (dilation), bronchial smooth muscle (contraction), and in CNS
What are the H1 receptor antagonists?
diphenhydramine, loratadine (treat allergic reactions); hydroxyzine, phenergan, meclizine, dimenhydrinate
Where are H2 receptors and what do they do?
stomach, increase acid secretion
What is an H2 antagonists?
famotidine
What do H3 receptors do?
presynaptic reduction in further histamine release
What is the dose, onset, duration of benadryl?
25-50mg IV, onset 3 min, DOA 1-7h
What does dimenhydrinate do?
antagonizes H1 and M1 receptors, used for motion sickness and sleep aid (crosses BBB)
What are the clinical uses for H1 receptor antagonists?
allergic reactions, motion sickness and vestibular disturbances, N/V of pregnancy.
What effects of H1 antagonists are NOT due to H1 blockade?
sedation, anti-nausea/anti-emetic actions (especially motion sickness), adrenoreceptor blocking actions (especially in phenothiazine group (phenergan) may cause orthostatic hypotension.
What is the incidence of aspiration in adults? kids?
1:8500 adults; 1:4400 in kids <16yo
How do you prevent aspiration?
antacids (increase pH of gastric contents); prokinetic drugs (decrease gastric fluid volume)
Who is at increased risk for aspiration?
pregnancy, DM (delayed gastric emptying), mask induction, emergency cases
What salts are oral antacids usually?
aluminum, magnesium, calcium
True/False: Oral antacids increase gastric volume.
True
True/False: Oral antacids do not change the metabolism of other drugs.
False, they can.
What is the main oral antacid used before surgery?
Bicitra, liquid, 15-30mL given right before induction, used in c-sections
What is the most frequently prescribed type of drug in USA?
H2 antagonists: Tagamet (cimetidine), zantac, pepcid, axid (nizatidine)
How do H2 antagonists work?
Selectively and reversibly compete with histamine at H2 sites.
What are the clinical uses of H2 receptor antagonists?
treatment/prevention of peptic duodenal ulcers, gastric ulcers, erosive esophagitis, hypersecretory conditions.
What are the toxicity effects of H2 antagonists?
CNS dysfunction–slurred speech, delirium, confused states in elderly (most often with tagamet); liver toxicity; pregnancy (DO cross placenta and into breastmilk
What are some common drug interactions with H2 antagonists–specifically Tagamet?
Dilantin, Propranolol, metoprolol, labetalol, diazepam, calcium channel blockers, also warfarin, quinidine, caffeine, lidocaine, theophylline, aprazolam, flurazepam, triazolam, carbamazepine, ethanol, TCAs
Why does Tagamet interact with many drugs?
reduces hepatic blood flow and inhibits P450 system so can have increased risk of toxicity if given with several drugs.
What are some proton pump inhibitors?
omeprazole, pantoprazole, esomerprazole, lansoprazole
What are gastrointestinal prokinetics?
dopamine blockers–metoclopramide, domperidone
What are prokinetic drugs used for?
treating esophagitis, treating GERD, prescribed less due to increased expense.
How do PPI’s work?
increase gastric pH, decrease gastric volume
Does omeprazole cross the BBB?
yes
What are side effects of omeprazole?
headache, agitation, confusion
What ailment is omeprazole used for?
zollinger-ellison syndrome
How do gastrointestinal prokinetic drugs work?
modulate motility by increasing lower esophageal sphincter tone, enhancing peristaltic contractions, and accelerating rate of gastric emptying.
What is the MOA of metoclopramide?
competitive dopamine antagonist, stimulates GI tract via cholinergic mechanisms; contraction of LES and gastric fundus; increase gastric and SI motility, decrease muscle activity in pylorus and duodenum
Does metoclopramide cross the BBB?
yes and affect CTZ
What is the dose of metoclopramide?
10-30mg IV over 3-5 min
What are some cautions with metoclopramide?
parkinsons, RLS, patients on MAOI, tricyclic antidepressants, GI surgery, patients taking phenothiazines or butrophenones
Does metoclopramide change gastric pH?
NO
What is metoclopramide used for?
diabetic gastroparesis, preop to decrease gastric fluid volume, antiemetic, GERD, assist with enteral feeding in chronically ill
What are some side effects of metoclopramide?
placental transfer, abdominal cramping if given fast, extrapyramidal reactions–related to antidopamine effects, prolonged Succs–inhibits plasma cholinesterase activity, c
