GI pharm: antemetics, diarrhea, constipation Flashcards
List of antiemetics?
- anticholinergics
- antihistamines
- dopamine receptor antagonists:
phenothiazines
benzamides - serotonin antagonists
What are the neurotransmitter receptor sites involved in the vomiting reflex?
- M1: muscarinic
- D2: dopamine
- H1: histamine
- 5-hydroxytryptamine (HT)-3: serotonin
- neurokinin 1 (NK1) receptor: substance P
Main anticholinergic agent used as an antiemetic? Receptor targeted? SEs?
- M1: muscarinic receptor
- scopolamine is main drug of this category
- predominantly used as prophylaxis against motion sickness
- delivered transdermally, 1.5 mg q 72 hrs
- SEs: dry mouth, drowsiness, vision disturbance
Antihistamines used as antiemetics? SE?
- H1 blockers
- primary use is for motion sickness:
diphenhydramine (benadryl)
cylizine (cyclivert)
dimenhydrinate (dramamine)
meclizine (dramamine-les drowsy)
SE: sedation most common along with anticholinergic effects
3 subclasses of dopamine receptor antagonists?
- phenothiazines: prochlorperazine (compazine) promethazine (phenergan) - butyrophenones (antipyschotics) - benzamides: metachlopramide (reglan) trimethobenzamide (tigan)
Properties of phenothiazines? When are they used?
- have antagonistic properties at D2, H1, and M1 sites
- used as first line agents as antiemetics
- oral, rectal, or IV
- prochlorperazine (compazine): first line agent
- promethazine (phenergan): also acts as antihistmaine
Main adverse effects of phenothiazines?
-extrapyramidal rxns such as dystonia: compazine has higher incidence than phenergan
- tardive dyskinesia with prolonged use
- acute dystonia can be tx with diphenhydramine 25-50 mg IV or IM
- hypotension can also occur, particularly in elderly or with IV infusion
- other side effects:
sedation, drowsiness, anticholinergic effects (dry mouth, urinary retention, blurred vision)
Precautions with phenothiazines?
- use with caution with other CNS depressants, poorly controlled seizures, severe liver dysfxn
Mechanism of benzamides - reglan?
- central and peripheral dopamine D2 antagonism at low doses
- weak 5-HT3 blockade at higher doses
- stimulates cholinergic receptors on gastric smooth muscle cells and enhances acetylcholine release at neuromuscular jxn
mechanism of benzamides - tigan?
- MOA is unclear but works centrally in area of medulla oblongata
- is generally considered most potent antiemetic that doesn’t have effects on serotonergic, dopaminergic, or histaminergic systems, so it has lower likelihood of causing undesired side effects
MOA of serotonin 5-HT3 antagonists?
- potent antiemetic properties mediated mainly through central 5-HT3-receptor blockade in vomiting center and chemoreceptor trigger zone blockade of 5-HT3 receptors
Clinical uses for serotonin 5-HT3 antagonists?
- great for post op and chemo induced nausea and vomiting
- can be used for most cases of nausea and vomiting except not great for nausea secondary to vestibular system etiology (vertigo)
- usually effective as single agents
How are 5-HT3 receptor antagonists usually tolerated? Examples?
- generally well tolerated
- most common adverse effects: HA, dizziness, constipation
- examples:
ondansetron (zofran): most popular
granisetron (kytril)
dolasetron (anzemet)
palonosetron (aloxil)
Characteristics of Zofran? Drug interactions? Downside of it?
- approved for use in kids and adults
- preg:B/C
- drug interactions: caution for serotonin syndrome, QT prolongation, monitor LFTs if prolonged use, serotonin syndrome (rare, but can be deadly if not recognized)
- Super expensive - tablets - 30 4 mg tablets: $735
DDx of nausea/vomiting?
- meds, toxicities
- infections (GI, ear)
- Gut disorders
- CNS causes
- endocrine
- misc: post op, cardiac, radiation
What is impt to remember about antemetic therapy?
- always seek the cause and tx underlying disorder
- caution with anticholinergic side effects in the elderly
- don’t forget supportive therapy with fluids and correction of lytes
- N/V assoc with chemo is tx differently (with steroids)
- antiemetic drug selection should be based on underlying disorder
Tx for migraine HA with nausea?
- reglan or compazine
Tx of vetibular nausea?
- antihistamines and anticholinergics
Tx of preg induced nausea?
- nausea: ginger, vitamin B6
- phenergan first line for hyperemesis
- serotonin antagonists and corticosteroids 2nd line
Abx for tx of infectious diarrhea?
- empiric abx therapy:
first line: fluoroquinolone - cipro, or norfloxacin or levo
2nd line: oral macrolides - azithro, or erythro
When can pharm therapy for sx tx of diarrhea be initiated?
IF……
- no fever
- no blood in stool
- then you can use antimotility agent to decrease the number of stools/day
What can bismuth subsalicylate (pepto-bismol) be used for? MOA?
- can be used to reduce sxs and tx of travelers diarrhea (can be used prophylactically as well)
- considered an absorbant (bulks up stool)
- MOA: may exert its antidiarrheal action not only by stimulating absorption of fluid and electrolytes across intestinal wall but also when hydrolyzed to salicylic acid, by inhibiting synthesis of prostaglandin responsible for intestinal inflammation and hypermobility
SEs of bismuth subsalicylate?
- dark stools, black tongue
- cautions: don’t take with other ASA components, can potentiate anticoagulants
- CIs:
ASA allergy
infants and kids
Sx tx of diarrhea?
- loperamide (imodium)
- diphenoxylate/atropine (lomotil)
- cholestyramine: chronic diarrhea