Flashcards in GI pharm: antemetics, diarrhea, constipation Deck (53)
List of antiemetics?
- dopamine receptor antagonists:
- 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:
meclizine (dramamine-les drowsy)
SE: sedation most common along with anticholinergic effects
3 subclasses of dopamine receptor antagonists?
- butyrophenones (antipyschotics)
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
ondansetron (zofran): most popular
Characteristics of Zofran? Drug interactions? Downside of it?
- approved for use in kids and adults
- 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
- 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?
- 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
infants and kids
Sx tx of diarrhea?
- loperamide (imodium)
- diphenoxylate/atropine (lomotil)
- cholestyramine: chronic diarrhea
MOA of loperamide (imodium)?
- acts directly on circular and longitudinal intestinal muscles, through opioid receptor
- inhibits peristalsis and prologs transit time
- reduces fecal volume, increases viscosity
- diminishes fluid and lyte loss
- demonstrates antisecretory activity
- increases tone on anal sphincter
Preg, dosing and usage of imodium?
- preg: C
- 4 mg initially then 2 mg after each stool
- don't use longer than few days, if needed longer: reevaulate pt
- avoid if enteroinvasive organism is suspected
SEs of imodium?
- abdominal pain
- abdomnal distension
- dry mouth
- dizziness, drowsiness
MOA of dipenoxylate/atropine (lomotil)?
opioid antagonist and anticholinergic:
- inhibits peristalsis and slows intestinal motility
- inhibits GI propulsion
- prolongs the movement of fluid and lytes through the bowel
Preg, dosing, usage of lomotil?
- preg C
- 2 tabs QID until diarrhea controlled
- maintenance 2 tabs/day
- avoid if enteroinvasive organism is suspected
(not for chronic diarrhea unless rx by GI)
SEs of lomotil?
- paralytic ileus, toxic megacolon
- drowsiness, dizziness
- pruritus, urticaria
- respiratory depression
- anticholinergic effects
use of cholestyramine (Questran)?
- preg C
- bile acid binding agent used for hyperlipidemia
- useful in tx of chronic diarrhea post cholecystectomy
- 1 pack or scoop mixed with fluids or food BID
SEs of cholestyramine?
- abdominal pain and bloating
- excessive flatulence, diarrhea
- wt loss
- decreases absorption of warfarin, thyroid hormones, digoxin, and thiazide diuretics. These drugs should be admin 1 hr b/f or 4-6 hrs after admin of cholestyramine
Classes of laxatives?
- bulk forming
- lubricants and surfactants
- saline agents
- hyperosmotic agents
Step therapy - laxatives?
- 1st line: bulk forming or surfactant agents
- 2nd: saline or hyperosmotic laxatives
- 3rd: stimulant laxatives (shouldn't be used long term)
First line therapy for tx of constipation?
- bulk forming agents: psyllium (metamucil)
- ducosate derivatives: ducosate sodium (colace): stool softener
- glycerin: supp (most often used in infants)
OTC bulk forming laxatives agents?
- metamucil (pysllium): preferred agent as it is most physiologic
- fibercon (polycarbophil)
- citrucel (methylcellulose)
- benefiber (wheat dextrin): powder and chewables, not for pts with celiac
MOA of bulk forming laxatives? Onset of action?
- not systemically absorbed
- bind to fecal contents and pull water into stool
- softens and lubricates stool
- increased water in stool makes it swell and increase in size - stimulates movement of the intestines
- onset of action: 12-24 hrs but may take up to 3 days for full effect, take with at least 8 oz of water (super impt esp in elderly - need to stay hydrated)
SEs of bulk forming laxatives?
- most common: flatulence
- abdominal cramping
- excessive use can cause N/V
CI to bulk forming laxatives? Interactions?
- esophageal strictures
- GI ulcerations
- strictures anywhere along GI tract
- bowel obstruction
- celiac pts need specific gluten free formulation
- Caution in DM: some contain up to 20 g carbs/serving - metamucil does have a sugar free formula]
- interactions: fibercon can decrease absorption of tetracycline and quinolones
ducosate derivatives - MOA, meds?
- first line still for constipation
- surfactant laxatives
- reduces surface tension of liquid contents of the bowel
- commonly referred to as stool softeners
- ducosate sodium (colace): 50-500 mg/day
- ducosate calcium (surfak)
What pts are surfactant laxatives used in?
- for pts who shouldn't strain with BMs and for those on narcotics (opioids)
- only prevent constipation: doesn't tx!!!
- no systemic absorption
- combining with fiber based laxatives help promote defecation
SEs of surfactant laxatives?
- overally: very well tolerated
- most common SE: stomach upset
- mild abdominal cramping
2nd line therapy for constipation?
- milk of magnesia
- magnesium sulfate (epsom salt)
MOA of magnesium hydroxide (milk of mag)?
- saline laxative: draws water into bowel through osmosis
- increases intraluminal pressure and motility
- used for more rapid onset of action
- dehydration is concern if excessive use (be careful with renal dysfxn - avoid if renal dysfxn and elderly)
- SE: GI upset, diarrhea
Lactulose (kristalose) or sorbitol use?
- use if failed bulk forming agents, and failure of MOM
- hyperosmotic laxatives
- use with caution in diabetics: soln contains galactose and lactose
lactulose (kristalose) and sorbitol MOA, SEs?
- metabolized to solutes and increase osmotic pressure by drawing in fluid from less concentrated areas
- increased pressure stimulates intestinal motility
- can be given PO or as an enema
- SE: GI upset, diarrhea, flatulence
3rd line therapy for constipation?
- stimulant laxatives
- mineral oil
- sodium biphosphates
- magnesium citrate
- castor oil
- senna (senokot)
- bisacodyl (dulcolax)
Use of stimulant laxatives? onset of action?
SE- not for long term use
- increase peristalsis through direct effects on smooth muscle of the intestines
- promote fluid accum in colon and small intestine
- onset of action:
15 min- 2 hrs PR
6-10 hrs PO
SEs of stimulant laxatives? CIs?
- N/V, abdominal cramping
- rectal fissures and hemorrhoids can be exacerbated
- CIs: surgical abdomen, fecal impaction
Use of sodium phosphate?
- fleet enema
- fleet phospho-soda: oral (BB warning for nephrotoxicity)
- can cause lyte disturbances
- can be used as bowel prep for endoscopy procedures
- osmotic effect in small intestine by drawing water into lumen of gut, producing distension and promoting peristalsis and evacuation of the bowel
USe of magnesium citrate (citroma)?
- rapid onset of action
- can be used for bowel prep for endoscopy procedures