Motility d/o Flashcards
What are prokinetics
Drugs that selectively stimulate gut motor function
Explain the enteric nervous system
Serotonin is released from EC cells in gut
Distention stimulates intrinsic primary and extrinsic primary afferent neurons
Submucosal IPAN activate enteric neurons responsible for peristalsis and secretory reflex
5HT4 receptors release ACh and promote reflex activity
What drugs stimulate GI motility (prokinetics)
Cholinomimetics
Metoclopramide, Domperidone
Macrolides
What are the cholinomimetic agents
Bethanecol: stimulates M3 receptors on muscle and myenteric plexus. Tx GERD and gastroparesis
Neostigmine:ACh inhibitor, enhances gastric, small intestine, and colonic emptying
What are ADE of cholinomimetics
excess salivation nausea vomiting diarrhea bradycardia (cholinergics; SLUDGE)
Cholinomimetics can be used for
GERD: used w/ anti-secretory agents if w/ regurg
Impaired gastric emptying: post-op, diabetic gastroparesis, promote advancement of NG tube
NUD: Sx improvement
Prevent vomiting: metoclopramide
What id Domperidone
Dopamine antagonist/cholinomimetic used in Canada (not FDA approved in US) to promote postpartum lactation
What is Metoclopramide
Dopamine antagonist with prokinetic mechanisms
Inhibit cholinergic smooth muscle stimulation
Increase esophageal peristaltic amplitude
Increase LES pressure
Enhance gastric emptying
-no effect on small or large intestine
How does metoclopramide help nausea and emesis
Blocks D2 receptor in the chemoreceptor trigger zone of the medulla
ADE of metoclopramide are
CNS: restless, drowsy, insomnia, anxiety, agitation
EPS: dystonia, akathisia, parkinsonian features
Tardive dyskinesia
Elevated PRL: galactorrhea, gynecomastia, impotence, menstrual disorders
How does erythromycin (macrolide) affect motility
Directly stimulate motilin receptors on GI smooth muscle
Benefits gastroparesis but tolerance develops fast
Can also be used for an upper GI bleed to empty stomach of blood prior to EGD
What meds have an ADE of constipation
Analgesics Antihistamines, antiparkinsons, phenothiazine, TCA Antacids w/ calcium carbonate or aluminum hydroxide Barium sulfate CCB Clonidine Diuretics NSAIDs
Intermittent constipation is best prevented with
high fiber diet
adequate fluid intake
regular exercise
going to the bathroom when you need to
If you do not have a specific Dx (and Tx) how do you treat constipation
Diet mod (increase fiber) Add osmotic laxative (PEG) 2-4 wks Add stimulant laxative Lubiprostone Linaclotide Opioid antagonists if opioid induced
What are some laxatives you can use
Bulk forming Stool surfactant agents (softeners) Osmotic laxative: PEG Stimulants: senna, cascara, bisacodyl Cl channel activator: Lubiprostone Guanylate cyclase C agonist: Linaclotide Serotonin agonist: Tegaserod
List agents that soften stool in 1-3 days
Osmotic laxatives: psyllium, polycarbophi, methylcellulose
Emollients: Docusate
PEG: Lactulose, sorbitol
List agents that cause soft semi-fluid stool evac in 6-12 hours
Bisacodyl
Senna
Mag sulfate
List agents that cause watery evacuation in 1-6 hours
Mag citrate
What are bulk forming laxatives
Indigestable hydrophilic colloids that absorb water and cause a bulky, emollient gel that distends the colon and promotes peristalsis
Natural: Psyllium, Methylcellulose (bloating and gas)
Synthetic: polycarbophil
What are stool surfactant agents
Soften stool material by mixing aqueous and fatty materials within intestine Docusate (oral or enema) Mineral oil (clear viscous oil that lubricates stool but retards water absorption)
What is mineral oil used for
to prevent fecal impaction in young kids and debilitated adults
CAUTION: aspiration can lead to lipid pneumonitis
If used long term, can impair A, D, E, K absorption
What are osmotic laxatives
Soluble but not absorbable compounds resulting in increased stool liquidity
Colon normally can’t concentrate or dilute fecal fluid bc fecal water is isotonic
What are non-absorbable sugars or salts
Mag hydroxide (milk of magnesia)-osmotic laxative to Tx acute constipation and prevent chronic Sorbitol, Lactulose: prevent or treat chronic constipation. sugars are metabolized by colon bacteria and produce flatus and cramps
Use Milk of magnesia cautiously long term in
pts with renal insufficiency, risk of hypermagnesemia
What are purgatives
Cause rapid water movement into distal small bowel and colon
Mag citrate and Sodium phosphate: empty bowel in 1-3 hours. Stay hydrated!
What are some ADE of sodium phosphate
Hyperphosphatemia, Hypernatremia
Hypokalemia, Hyocalcemia
-These can cause arrhythmias or acute renal failure (calcium phonphate deposits in the renal tubules
Who should you NOT use sodium phosphate in
Elderly
Renal insufficiency
Cardiac disease
Unable to maintain adequate hydration during bowel prep
What is PEG (polyethylene Glycol)
Balanced, isotonic sln made of non-absorbable sugar (PEG) with sodium sulfate/chloride/bicarb, or potassium chloride
Designed so NO significant intravascular fluid or electrolyte shifts occur= Safe for all patients! No cramps or gas!
What can PEG be used for
Bowel prep: ingest rapidly (2-4L over 2-4 hours)
Prevent chronic constipation: mix smaller doses w/ water or juice
What are cathartics
Stimulant laxatives that induce BM by directly stimulating enteric nervous system, colon electrolyte & fluid secretion
Who are cathartics good for
Long term treatment is neurologically impaired, and bed bound patients in long term care facilities
Can laxatives be used long term
Long term use is controversial; new studies say it’s ok because it is nerve damage that causes constipation, not using laxatives
BUT, if used long term, still need to monitor ADE
What are Anthraquinone derivatives
Aloe, Senna, Cascara (natral plants)
They are poorly absorbed, undergo hydrolysis in the colon and produce BM in 6-12 hours (PO) or in 2 hours (per rectum)
Chronic use of anthraquinones causes
brown pigmentation of the colon (melanosis coli)
They may be carcinogenic, but no studies prove relation to CRC
Senna is used frequently in those that
Have opioid induced constipation
What is Bisacodyl (ducolax)
Diphenylmethane derivative to treat chronic constipation
Used with PEG solutions as bowel prep prior to colonoscopy
Induces BM in 6-10 hours (PO) or 30-60 min (per rectum)
Safe for short and long term use bc of minimal systemic absorption
How do opioids cause constipation
They decrease intestinal motility leading to prolonged transit time and increased absorption of fecal water
What are the two selective agents of the mu-opioid receptor
Methylnaltrexone bromide
Alvimopan and Naloxegol
-They do not cross the BBB
-Inhibit peripheral mu receptors w/o impacting analgesic effects w/in the CNS
What are the agents used in opioid induced constipation
Methylnaltrexone: approved for those receiving palliative care for advanced illness.
Alvimopan: short term use in post-op ileus in hospitalized pts s/p bowel resection. 7 days max.
Naloxegol: any opioid induced constipation
ADE of mu receptor antagonists are
Methylnaltrecone: Adjust if CrCl <30
Alvimpoan: cardiovascular toxicity
Naloxegol: Adjust dose if CrCl <60. Avoid if w/ hepatic impairment. CI if w/ GI obstruction
Treatment goals when treating diarrhea
Manage diet Prevent excess whater, electrolyte, and acid base disturbances Provide Sx relief Treat curab;e causes Manage secondary disorders
Define fever levels
PO: 100.4
Axillary: 1 degree lower
Rectal: 1 degree higher
What are key points that spark clinical controversy in regards to diarrhea
Most recommend no solid food or dairy for 24 hours if w/ acute diarrhea
But withholding food is not appropriate in pts / no signs of severe dehydration
Osmotic diarrhea, food may control problem
If it is secretory, diarrhea will persist
If w/ N/V, eat low residue diet for 24 hours. if vomiting persists and not controlled w/ antiemetics, NPO
What is in oral rehydration solutions
Carbs
Calories
Na, K, Cl, citrate, bicarb
*Listen to slide 34?
What are some antidiarrheals
Antimotility: opioid agonists
Adsorbents: Kaolin pectin, polycrbophil, attapulgite
Antisecretory: colloidal bismuth, bile salt binding resins, octreotide
Bacterial replacement and enzymes
Who should NOT use antidiarrheals
Bloody diarrhea High fever Systemic toxicity -risk of worsening underlying condition -d/c in pts who's diarrhea is worsening despite therapy
How do opioid agonists act as antidiarrheals
Increase colonic phasic segmentation activity by inhibiting presynaptic cholinergic nerves in myenteric plexus= increased fecal colonic transit time and fecal water absorption
What are the opioid agonist antidiarrheals
Loperamide: does not cross BBB. Not an analgesic, no addiction potential. No tolerance reported (non-Rx)
Diphenopxylate: Rx. No analgesics in regular dose. High dose has CNS ADE. Prolonged use can lead to dependence. Some formulations have atropine in them to discourage overuse. (atropine also an anticholinergic)
What do adsorbent antidiarrheals do
Adsorb nutrients, toxins, drugs, and digestive juices. like sponges
Colloidal bismuth compounds are
Mucosally protective
Who are bile acid binding resins used for
They are normally absorbed in the terminal ileum
In those w/ terminal ileum d/o (crohn’s), they have malabsorption of bile salts= colonic secretory diarrhea
What are the bile acid binding resins
Cholestyramine, colestipol, colesevelam: decrease diarrhea 2/2 excess fecal bile acids
ADE of bile acid binding resins are
Bloating flatulence constipation fecal impaction Fat malabsorption if they already have low circulating bile acids
Do bile acid binding resins interact with other drugs
cholestyramine and colestipol bind a few drugs and reduce their absorption. Wait 2 hours to admin other drugs
colesevelam does not
What is octreotide
Somatostatin;
Inhibits secretion of hormones and transmitters (gastrin, CCK, glucagon, GH, insulin, secretin, 5HT)
Reduce intestinal and pancreatic fluid secretion
Slow GI motility and inhibit gallbladder contraction
Reduce portal and splanchnic blood flow
Inhibit secretion of other ant pit hormones
Octreotide’s usefulness is limited by
it’s short half life (3 minutes) when given IV
Octreotide is used clinically for
Inhibiting endocrine tumor effects (secretory diarrhea, flushing, and wheezing 2/2 carcinoid or VIPoma)
Other causes of diarrhea (low dose stimulates motility but high dose inhibits): Vagotomy, dumping syndrome, short bowel syndrome, AIDS
-also: inhibit pancreatic secretion value in patients w/ pancreatic fistula, Tx pit tumors and GI bleeding
ADE of octreotide are
Steatorrhea
Nausea, abdominal pain, flatulence, diarrhea
Altered fat absorption (inhibits gallbladder contractility)
Hyperglycemia (sometimes hypo-)
Hypothyroid w/ prolonged use Bradycardia
