PPT Flashcards
What are examples of classes of drugs used as antiemetics?
Antihistamines
Antimuscarinics
Cannabinoids
Dopamine antagonists
Glucocorticoids
5HT3 antagonists
Neurokinin-1 antagonists
What are examples of antihistamines used as antiemetics?
Cinnarizine
Cyclizine
Promethazine hydrochloride
Promethazine theoclate
What are examples of antimuscarinics used as antiemetics?
Hyoscine
What are examples of cannabinoids used as antiemetics?
Nabilone
What are examples of dopamine antagonists used as antiemetics?
Phenothiazines - prochlorphenazine, perphenazine, trifluorphenazine, chlorpromazine
Droperidol and haloperidol
Metoclopramide
Domperidone
What are examples of glucocorticoids used as antiemetics?
Dexamethasone
What are examples of 5-HT3 antagonists used as antiemetics?
Granisteron
Ondansetron
Palonosetron
What are examples of neurokinin-1 antagonists used as antiemetics?
Aprepitant
Fosaprepitant
Where do 5-HT3 receptor antagonists antiemetics act?
Central serotonin receptors in the vomiting centre as well as peripheral serotonin receptors in vagus nerve (GIT)
What are the main uses of 5-HT3 receptor antagonists as antiemetics?
Vomiting caused by acute gastroenteritis
Postoperative nausea and vomiting
Cytotoxic drug-induced vomiting
Where do phenothiazines act as antiemetics?
D2 receptors in the CTZ
Where do droperidol and haloperidol act as antiemetics?
D2 receptors in CTZ
Where does metoclopramide act as antiemetics?
D2 antagonist at CTZ and gastric smooth muscle stimulating gastric emptying
Where does domperidone act as antiemetics?
D2 receptors in CTZ
What are the indications for phenothiazines as antiemetics?
Cytotoxic drug-induced N+V
Postoperative N+V
Radiation sickness
What are the indications for haloperidol as antiemetics?
Cytotoxic drug-induced N+V
Postoperative N+V
Radiation sickness
What are the indications for metoclopramide as antiemetics?
Postoperative NV
Cytotoxic drug-induced NV
What are the indications for domperidone as antiemetics?
Cytotoxic drug-induced NV
which antiemetics are best for motion sickness?
Hyoscine hydrobromide
Antihistamine drugs
Which group of antiemetics are typically used in the management of NV in to recieving cytotoxics?
5HT3 receptor antagonists
What are the neurogenic 1-receptor antagonists usually given for?
prevent nausea and vomiting associated with chemotherapy.
What are the indications for nabilone?
It can be considered as an add-on treatment for chemotherapy-induced nausea and vomiting unresponsive to optimised conventional antiemetics.
Which antiemetic is typically given for morning sickness?
chlorpromazine hydrochloride
cyclizine
doxylamine with pyridoxine
metoclopramide hydrochloride
prochlorperazine
promethazine hydrochloride/promethazine teoclate
ondansetron
Which antiemetics are best for managing Ménière’s disease?
Antihistamines
Phenothiazines
Which antiemetic share typically given for vomiting induced by vestibular disturbances e.g. vertigo or motion?
H1 antihistamines
Antimuscarinics
Whats the issue with serotonin receptor antagonist use for post operative nausea and vomiting?
Dose-dependant but can cause QT prolongation
Why are neurokinin receptor antagonists not used more frequently?
They are really expensive
Whats the moa of metoclopramide
Antiemetic action- antagonist activity at D2 receptors in the CTZ
Gastroprokinetic activity - mediated by muscarinic activity, D2 receptor antagonist activity, and 5-HT4 receptor agonist activity. The gastroprokinetic effect itself may also contribute to the antiemetic effect
Metoclopramide also increases the tone of the lower esophageal sphincter
What is the main issue with using metoclopramide as an antiemetic?
It can cause extrapyramidal sympotms thta generally manifest as acute dystonia - particularly in people <30 ans females (should not give to anyone under 20)
How do you treat acute dystonia acutely?
Procyclidine hydrochloride
Whats the moa of procyclidine?
The mechanism of action is unknown. It is thought that Procyclidine acts by blocking central cholinergic receptors, and thus balancing cholinergic and dopaminergic activity in the basal ganglia. Many of its effects are due to its pharmacologic similarities with atropine.
What are side efefcts of antihistamines?
Drowsiness, reduces coordination reaction times and judgement
Dry mouth, blurred vision, difficulty peeing
Headache
Why is prochlorperazine such a useful antiemetic for those with persistent vomiting ?
It is available as a buccal tablet
Whats the advanatage of domperidone over metoclopramide and the phenothiazine’s?
Less likely to cause central effects e.g. sedation and dystonia reactions because it does not readily cross the bloo brain barrier
What are examples of the less sedating antihistamines?
Cinnarizine and cyclizine
What are examples of the more sedating antihistamines?
Promethazine
What are examples of bulk forming laxatives?
Bran
Ispaghula husk (fybogel)
Methyl cellulose
Sterculia
Whats the indication for bulk-forming laxatives?
adults with small hard stools if fibre cannot be increased in the diet
Whats the onset of action of bulk-forming laxatives?
Up to 72 hours
What should you inform a pt about to take bulk forming laxatives?
Side effects include nausea, vomiting, flatulance, bloating and diarrhoea
Adequate fluid intake must be maintained to avoid intestinal obstruction.
How do bulk forming laxatives work?
They draw water in the stool to form a soft, bulky mass which stimulates intestinal peristalsis
What are examples of stimulant laxatives?
Bisacodyl
Sodium picosulfate
Senna
Co-danthramer and co-danthrusate
What are contraindications of all laxatives?
Intestinal obstruction
Severe abdominal pain
Symptoms of appendicitis, diverticulitis or UC
What are side efefcts of stimulant laxatives?
Abdominal cramp
Nausea, vomiting
Diarrhoea
Weakness
Fluid and electrolyte imbalance
(Senna also causes reddish/brown urine and Melanosis coli)
Why is the use of co-danthramer and co-danthrusate is limited to constipation in terminally ill patients?
because of potential carcinogenicity (based on animal studies) and evidence of genotoxicity.
Whats the moa of docusate sodium?
Acts as both a stimulant laxatives and as a faecal softener
It acts as a surfactant (lowers surface tension) that allows water to penetrate the stool and make it softer
Whats the moa of stimulant laxatives?
They irritate nerve endings in intestinal walls, stimulating smooth muscle contraction and intestinal peristalsis
What are contraindications for all laxatives?
Intestinal obstruction
Severe abdo pain
Symptoms of appendicitis, diverticulitis or UC
What are examples of faecal softeners?
Docusate sodium
Glycerol suppositories
Enter as containing arachis oil
Liquid paraffin
How do faecal softeners work?
It acts as a surfactant (lowers surface tension) that allows water to penetrate the stool and make it softer
What are side effects of faecal softeners?
Nausea, vomiting
Abdominal cramping
Diarrhoea
Why should liquid paraffin be used with caution as a faecal softener?
because of its adverse effects, which include anal seepage and the risks of granulomatous disease of the gastro-intestinal tract or of lipoid pneumonia on aspiration.
Whats the moa of osmotic laxatives?
increase the amount of water in the large bowel, either by drawing fluid from the body into the bowel or by retaining the fluid they were administered with.
What are examples of osmotic laxatives?
Lactulose
Macrogol (brand names include movicol, molative etc)
Polyethylene glycol
Why is lactulose also useful in the treatment of hepatic encephalopathy?
lactulose is thought to work by promoting the excretion of ammonia and increasing the metabolism of ammonia by gut bacteria
What are macrogols?
Inert polymers of ethylene glycol which sequester fluid in the bowel
What are the contraindications specific for osmotic saline laxatives?
Renal, hepatic impairment and cardiac conditions
What are the contraindications specific for lactulose?
Galactosaemia; gastro-intestinal obstruction; gastro-intestinal perforation; risk of gastro-intestinal perforation
Caution with lactose intolerance
What is linaclotide? Whats it used for treating? How does it work?
a guanylate cyclase-C receptor agonist
Licensed for the treatment of moderate-severe IBS associated with constipation.
It increases intestinal fluid secretion and transit, and decreases visceral pain.
What is prucalopride? Whats it used for treating?
a selective serotonin 5HT4-receptor agonist with prokinetic properties.
It is licensed for the treatment of chronic constipation in adults, when other laxatives have failed to provide an adequate response.
What are options for bowel cleansing preparations?
Macrogol 3350 with anhydrous sodium sulfate
Potassium chloride
Sodium bicarbonate and sodium chloride
Citric acid with magnesium carbonate
Magnesium citrate with sodium picosulphate
Sodium acid phosphate with sodium phosphate
How do you manage short-duration constipation?
If dietary measures are ineffective…
1. Bulk-forming laxative
If stools remain hard… Add or switch to osmotic laxative
If stools are soft but diffiuclt to pass or there is tenesmus -> add stimulant laxative
How should you manage opioid-induced constipation?
- Osmotic laxative and stimulant laxative
- If inadequate response use naloxegol
- If inadequate response use methylnaltrexone bromide
(avoid bulk-forming laxative altogether)
How should you manage faecal impaction of hard stools?
High dose of an oral macrogol
(If not response consider rectal glycerol or rectal glycerol and bisacodyl)
If still inadequate response -> May consider arachis oil overnight before giving an enema
How should you manage faecal impaction of soft stools?
Oral stimulant laxative
(Ir response is inadequate consider rectal bisacodyl)
If response is still inadequate an enema may be used
How should you manage chronic constipation?
- Bulk-forming laxative
- Add or change to osmotic laxative (if not effective use lactulose)
- Stimulant laxative can be added
Whats the priority aim of treating diarrhoea?
the prevention or reversal of fluid and electrolyte depletion and the management of dehydration when it is present. This is particularly important in infants, frail and elderly patients, when excessive water and electrolyte loss and dehydration can be life-threatening.
How can we prevent or correct diarrhoea dehydration?
Oral rehydration therapy
(If severe or unable to drink then urgent admission to hospital and urgent replacement therapy with IV rehydration fluid)
What are examples of oral rehydration therapy?
Disodium hydrogen citrate with glucose
Potassium chloride and sodium chloride
Potassium chloride with rice powder
Sodium chloride and sodium citrate
How can you treat diarrhoea?
- Loperamide hydrochloride
No other sufficient evidence for any drugs
Whats the moa of loperamide?
Loperamide acts on the mu-opioid receptor on the circular and longitudinal intestinal muscle -> inhibit enteric nerve activity -> inhibits the release of acetylcholine and prostaglandins -> reducing propulsive peristalsis and increasing intestinal transit time
Loperamide stimulates the intestinal absorption of water and electrolytes by inhibiting calmodulin.
Loperamide can bind to and hyperpolarize submucosal secretomotor neurons, promoting dry, hard stools
What ate the indications of loperamide?
Symptomatic treatment of acute diarrhoea
Chronic diarrhoea
Facial incontinence
Pain of bowel colic in palliative care
What are contraindications of loperamide?
Active ulcerative colitis; antibiotic-associated colitis; bacterial enterocolitis; conditions where abdominal distension develops; conditions where inhibition of peristalsis should be avoided
Children under 12
What are common side efefcts of loperamide?
GI disturbance
Headache
What are some antimotility drugs?
Loperamide (imodium)
Codeine phosphate
Co-phenotrope
Kaolin
Morphine mixture
Whats the moa of dicyclomine?
M1, M2 and M3 receptor antagonist as well as a non-competitive inhibitor ad histamine and bradykinin
What is dicyclomine used to treat?
Functional bowel disorder and IBS
Whats the moa of mebeverine?
Anticholinergic - works on smooth muscle in GIT
It’s an antispasmodic
Whats mebeverine used to treat?
IBS
Why should lactulose not be used in IBS?
As it can cause bloating
What can be used as a second-line option for abdominal pain in IBS in patients who have not responded to antispasmodics, anti-motility drugs, or laxatives?
Low dose TCA (or SSRI if they don’t respond)
How does peppermint oil help in IBS?
Peppermint oil has been shown to reduce gastric motility8 by directly acting on gut calcium channels to relax gastrointestinal smooth muscle
What are important side efefcts of mesalazine?
GI upset, headache, agranulocytosis, pancreatitis (7x more likely), interstitial nephritis
What are important side efefcts of sulphasalazine?
rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, lung fibrosis
As well as all other side effects common to 5ASA drugs
