Fitzaekerly: Antiemetics and Treatments for IBD Flashcards
What sensory inputs cause vomiting?
- Local irritation of GI tract → vagal & sympathetic afferents modulated by action on 5HT3 receptors → solitary tract nucleus (STN) and CTZ → vomiting center
- Inner ear (motion sickness, aminoglycoside abx) → cerebellum → vomiting center
- Glossopharyngeal & trigeminal afferents → STN → vomiting center (a.k.a. gag reflex)
What are blood borne emetics?
chemical agent irritates small intestine if oral or interacts w/ cells in the CNS outside the BBB>
stimulates vomiting center
What is anticipatory vomiting?
Learned response to chemo drugs that is controlled by higher centers that project into the vomiting center
What receptors are fundamental to the vomiting process? Where are they located?
5HT receptors
- Enteric system
- Chemoreceptive trigger zone
- Solitary tract nucleus
- Vomiting center
What are important anti-emetic drugs?
5HT antagonists
What receptors are OUTside the BBB in the GI tract?
5HT3 in the GI tract
What receptors act OUTside the BBB in the CTZ?
D2
Opiods
What receptors are located inside the BBB?
M1
H1
NK1
Cannabinonid
What receptors do emetics like L-dopa and apomorphine act on?
D2
What receptors do emetics like opiates act on?
opioid receptors
What drug acts on 5HT3 receptors and is used for chemotherapy?
“setrons”
What drugs are antiemetics that act on D2 receptors?
DROPERIDOL, METOCLOPRAMIDE
PROCHLORPERAZINE, PROMETHAZINE
THIETHYLPERAZINE
What drugs are antiemetics used for motion sickness that act on M1?
scopolamine
What drugs are antiemetics used for motion sickness that act on H1?
DIMENHYDRINATE, DIPHENHYDRAMINE, MECLIZINE
What antiemetics act on NK1 and are used for chemotherapy?
APREPITANT, FOSAPREPITANT
What drugs are antiemetics that act on corticosteroid receptors?
DEXAMETHASONE, METHYLPREDNISOLONE
What drugs are antiemetics that act on cannabinoid receptors?
DRONABINOL, NABILONE
What is used for GI contamination?
- Toxin binding (activated charcoal)
- cathartics (polyethylene glycol-electrolyte solution)
- emetic agents *(ipecac)
When would you use toxin binding activated charcoal and how does it work?
Used for upper GI Absorbs (binds to) many drugs and poisons d/t large surface area
Must be given in ratio of at least 10:1 (charcoal:toxin) by weight
What is toxin binding activated charcoal NOT good for?
Does not bind Fe, Li, or K
Binds alcohols and cyanide poorly
Not useful in cases of poisoning d/t corrosive mineral acids or bases
What are polyethelene glycol-electrolyte solutions used for? How does it work?
Lower GI problems or before endoscopic procedures
Removes toxins and reduces absorption, • May hasten removal of toxins and reduce absorption
*Whole bowel irrigation can enhance decontamination following ingestion of Fe tablets, enteric coated medicines, illicit drug-filled packets and FBs
How does ipecac work?
Local irritant effects and acts on CTZ (15-30 mins)> vomit if drug hasn’t effected the stomach (emesis may not occur if stomach is empty)
What is ipecac not good for?
dangerous is poison is corrosive, a petroleum distillate or a rapidly acting convulsant
What is the key mechanism for many antiemetics?
sedation
*more effective at PREVENTING vomiting than stopping it
What are the 7 types of antiemetic drugs?
5HT3 antagonists NK antagonists antimuscarinics Antihistamines D2 antagonists Cannabinoids Corticosteroids
Dolasteron, Granisteron, Ondansetron and palonsetron are…
5HT3 Antagonists (end in “etron”)
What are the best antiemetics available that are commonly used to treat N/V from chemo?
Dolasteron, Granisteron, Ondansetron and palonsetron
What is the MOA of 5HT3 Antagonists?
BLOCK:
peripheral 5HT3 receptors in GI tract on 1o afferents
receptors in CTZ & VC
What is the TU for 5HT3 Antagonists?
Prevent and treat chemo induced vomiting
*esp ACUTE phase if given 30 mins before chemo (not good for motion sickness or delayed phase)
What are SE of 5HT3 Antagonists?
well tolerated w/ good safety profile
Aprepitant and fosaprepitant are…
NK1 Receptor Antagonists
Is arepitatant or fosaprepitant oral or IV?
arepitant- oral
fosaprepitant- IV
What is MOA of aprepitant and fosaprepitant?
substance P receptor antag of HIGHER ORDER NK1 receptors
What is the TU of NK1 Antagonists? What is it often given with?
chemotherapy induced N/V
given in combo w/ 5HT3 antagonist and Dexamethasone
What are the SE of NK1 Antagonists?
generally well tolerated, usually fatigue, dizziness, and diarrhea
What are NK1 Antagonists metabolized by? what SE can this worsen?
Met’d by CYP 3A4 (esp. some chemotherapeutic agents) → think about drug interactions and possibility of making other SEs worse (particularly BONE MARROW SUPPRESSION)
Dexamethasone and mehtylprednisone are both…
corticosteroids
What are corticosteroids used for?
reduce N/V
- don’t know MOA
- used in combo w/ 5HT3 antag and aprepitant
What is an anticholinergic used to treat motion sickness?
scopalmine
*distributes widely to CNS
What is the MOA of scopalmine?
Muscarinic & dopaminergic receptor antagonist, especially impt effects in cerebellum
What form of scopalmine has the fewest SE?
Given as transdermal patch to ↓ SEs compared to oral or parenterally
What are antihistamines that cause SUPER SEDATION?
Dimenhydrinate, Diphenhydramine, Meclizine
Which antihistamines cause the MOST sedation?
older H1
What are SE of antihistamines? When should they NOT be used?
anticholingergic SEs:
confusion
dry mouth
urinary retention
*Not to be used if PREGO
What are D2 receptor Antagonists?
Droperidol Metoclopramine Prochlorperazine Promethazine Thiethylperazine
Where do D2 receptor antagonists act?
at D2 receptors in the CTZ and possibly muscarinic receptors
What are D2 receptors antags “thought” to do?
reset GI motility
cause sedation
What are dronabiniol and nabilone?
Cannabinoids
Where do cannabinoids act?
central cannabinoid receptors> sedation
What are SE of cannabinoids?
hallucinations, euphoria, sedation, dry mouth, ↑ appetite (which can be good for cancer patients!)
What is IBD?
Chronic, progressive, disease d/t inflammation in the GI tract
*give drugs that work in the LOWER part of the GI tract
What are tx options for IBD?
- Anti-inflammatory agents (aminosalicylates) – based on 5-ASA (mesalamine- not absorbed in stomach and passes through to lg intestine)
- Immunosuppressive agents (corticosteroids and antimetabolites)
- Anti-TNFα therapy
What are Anti-Inflammatory Agents (Aminosalicylates):
Balsalazide
mesalamine
osalazine
sulfasalazine
What is the MOA of anti-inflammatory agents?
gut bacteria break bond and release ASA → can work extremely LOCALLY in GI only
*Also inhibits COX → ↓ PG synthesis
Where do anti-inflammatory agents act?
NO effects in the stomach, different drugs affect varying parts of GI tract (e.g. SI → rectum, or only distal colon→ rectum)
What are anti-inflammatory agents used for?
mild to mod. ulcerative colitis
Not effective for Crohn’s disease b/c can’t get high enough dose at site of disease
What are SE of anti-inflammatory agents?
no systemic absorption → minimal SEs (only one exception)
What are hte SE of sulfasalazine?
hypersensitivity rxns and ↓ in folate absorption, GI upset, nausea, HA, arthralgia, and BM suppression
Budesonide, Prednisone, and Prednisolone
are all….
Corticosteroids
What is the TU of Budesonide? Where does it act? How is it metabolized?
TU: mild to mod. Crohn’s disease involving the ileum and prox. colon
Local in lung and GI trat
Subject to extensive, rapid 1st pass met. → local rather than systemic effects
What are: Azathiorpine, 6-Mercaptopurine, Methotrexate
Antimetabolites
How are antimetabolites given?
Given in low doses for the induction and maintenance of remission of ulcerative colitis and Crohn’s disease
Allow dose reduction or elimination of steroids (?)
What is the MOA of Anti-TNFa therapy (infliximab)?
Ab against TNFα
What is TNFa?
a cell signaling protein that has been increased d/t dysregulation of TH1 responses d/t IBD; TNFα usually activates complement
Why does infliximab not work for all pts?
1/3 of pts become refractory b/c develop Abs against the Abs
What is infliximab used for?
symptomatic improvement (60%) and remission in pts w/ severe Crohn’s disease
What are hte SE of infliximab?
infections (more common w/ Infliximab vs. other Abs) – especially think of reactivation of TB → so any pt receiving this drug must screen for TB 1st
o Infusion rxns
o Hepatic probs
o Unique to these Abs → ↑ risk of lymphoma (although IBD pts more likely to get lymphoma or are drugs making it worse?)
