Anti-emetics and Antidiarrhoeals and GI pathology Flashcards
Name two classes of drugs that can target the vestibular nuclei to prevent stimulation of the CTZ
- Muscarinic receptor antagonists
- H1 receptor antagonists
Describe the mechanism of action of hyoscine hydrobromide.
- Competitive block of mAChR
- Acts on the vestibular nuclei and the CTZ
Why are side effects of muscarinic receptor antagonists experienced all over the body and what are these side effects?
- mAChR are found all over the body and the drug suppresses the PNS
- Side effects of sedation, memory problems, dry mouth, constipation, glaucoma
Explain why this drug can be exploited?
- Due to its side effects that can be beneficial in treating patients with diarrhoea and anxiety/agitation.
What is hyoscine hydrobromide used for?
- Travel sickness
- Bowel obstruction as it switches off the PNS so decreases gut motility via the vagus nerve
- For people who cannot take tablets as they come in patches.
What is the first line drug for motion sickness and when is it taken?
- Hyoscine hydrobromide is the first line drug for motion sickness.
- Taken before the journey.
Name the drugs in the H1 receptor antagonist class.
- Cyclizine
- Levomepromazine
- Promethazine
Mechanism of action of H1 receptor antagonists.
- Inhibits histaminergic signals from the vestibular system to the CTZ in the medulla.
- Acts on the vestibular nuclei.
Side effects of H1 receptor antagonists:
- Sedation
- Excitation
- Anti-muscarinic effects: dry mouth, constipation, urinary retention.
- Cardiac toxicity: long QT interval (proarrhythmic).
In which patients should you avoid cyclizine? Why?
- Avoid in little old ladies and young children as it causes excitation side effect to be more pronounced. Gives a high.
What are H1 receptor antagonists good for use for?
- Motion sickness especially long plane journeys
What H1 receptor antagonist is used in pregnancy?
- Promethazine is used for morning sickness
Name the two classes of drugs that acts on the visceral afferents in the gut.
- 5HT3 receptor antagonists
- D2 receptor antagonists
Name the drugs in the class of 5HT3 receptor antagonists.
- Ondansetron
- Granesetron
- Palonosetron
What is the mechanism of action of 5HT3 receptor antagonists?
- Acts on visceral afferents in the gut to reduce gut motility - reducing retrograde peristalsis.
- Also reduces gastric secretions - less gastric liquid in the stomach
- Inhibits CTZ.
- Used to prevent post-op vomiting.
What are the side effects of 5HT3 receptor antagonists?
- Uncommon side effects
- Constipation
- Headache
- Elevated liver enzymes
- Long QT syndrome
- Extra pyramidal effects: dystonia, parkinsonism
Which drug is offered as first line treatment for those with gut problems causing vomiting?
- Ondansetron (5HT3 receptor antagonists)
Name the drugs in the D2 receptor antagonist class.
- Metoclopramide
- Domperidone
Mechanism of action of D2 receptor antagonist.
- Increases ACh at mAChR in gut.
- Acts on the visceral gut afferents promoting gastric emptying by increasing tone at LOS so it closes, increasing tone and amplitude of gastric contractions, decreasing tone of pylorus so it opens.
- Increases peristalsis
Side effects of metoclopramide
- Galactorrhoea via prolactin release
- Extra pyramidal effects: dystopia, Parkinsonism - worse in children and young people.
Metoclopramide is best used in:
- GORD as it closes the LOS
- Ileus
Avoid usage of D2 receptor antagonists in patients with:
- Bowel obstruction as it can cause ischaemic gut and increased peristalsis will result in perforation.
What are the side effects of domperidone?
- Sudden cardiac death (long QT and VT)
- Galactorrhoea
What is the main usage of domperidone?
- Improves lactation in breastfeeding mothers as the increase in prolactin will stimulate increased milk production.
Name the drugs in D2 receptor antagonist class that act directly on the CTZ.
- The zine’s
- Prochlorperazine
- Chlorpromazine
- Levomepromazine
- Haloperidol
These drugs are also antipsychotics.
What is the main action of the zine’s?
- Acts on the CTZ
- Also blocks H1 and muscarinic receptors too.
Side effects of the zine’s and haloperidol
- Extra pyramidal effects: dystonia and Parkinsonism.
- Sedation
- Hyotension
What is prochlorperazine used in?
- Pregnancy
What are the zine’s useful for?
- Good for motion sickness, vertigo as it has H1 receptor antagonist and muscarinic antagonist effects.
What is haloperidol used for?
- Chemotherapy and palliation.
What drugs are found in the corticosteroid class?
- Dexamethasone
- Methylprednisolone
Mechanism of corticosteroids
- Acts on CTZ
- Had properties of D2 receptor antagonist
Side effects of corticosteroids that act on CTZ
- Insomnia
- Increased appetite
- Increased blood sugar
- Cushing syndrome is a long term side effect
What are the uses of corticosteroids?
- Good for perioperative nausea and vomiting
- Chemotherapy
- Palliation
Name a drug in the class of Cannabinoids
- Nabilone
Where do cannabinoids act?
- Acts on CTZ
Side effects of cannabinoids:
- Dizziness
- Drowsy
What are cannabinoids used for?
- Last line for chemotherapy.
What are the drugs in the neurokinin 1 receptor antagonists?
- Aprepitant
- Fosaprepitant
- Netupitant
What is mechanism of action of neurokinin 1 receptor antagonists?
- Prevents the action of substance P (neurotransmitter that causes excitation) at CTZ and in peripheral nerves (can be used as pain relief)
- Boosts the effect of 5HT3 receptor antagonists.
What are the side effects of neurokinin 1 receptor antagonists?
- Headache
- Diarrhoea/ constipation
- Steven-Johnson syndrome
What are the uses of neurokinin 1 receptor antagonists?
- Anxiolytics and antidepressant properties.
- Good for chemotherapy - particularly delayed emesis.
- Works better in conjunction with 5HT3 receptor antagonists - Ondansetron.
What are the drugs prescribed of a patient had gut problems?
1) Ondansetron (5HT3 receptor antagonist)
2) and/or Cyclizine (H1 receptor antagonist)
3) Then add dexamethasone (corticosteroid)
What are the drugs prescribed to treat vomiting in a pregnancy lady?
1) Promethazine (H1 receptor antagonist) or prochlorperazine (D2 receptor antagonist)
2) Then add Metoclopramide (D2 receptor antagonist)
3) Then add ondansetron (5HT3 receptor antagonist)
What are the main classes of drugs used as anti-diarrhoeals?
- Opioid receptor agonist
- Loperamide
- Codeine
- Morphine
Describe the mechanism of action of loperamide?
- Specific u receptor agonist in the gut in the myenteric plexus
- Decreases the tone of longitudinal and circular smooth muscle.
- Reduces peristalsis but increases segmental contraction of gut.
- Decreases colonic mass movement by suppressing gastrocolic reflex - urge to defecate.
What are the side effects of opioid receptor agonist?
- Paralytic ileus
- Nausea and vomiting
- Sedation
- Addiction (codeine and morphine)
What is the difference between loperamide and codeine and morphine?
- Codeine and morphine also act at u and delta receptors and are not specific to the gut.
- More often used in patients who also have pain
What is the mechanism of action of osmotic laxatives?
- Increase the amount of water in the lumen by drawing in fluid or retaining the fluid they came with. (macragol is sachet based so water is retained). Can take 12 sachets a day.
Name the three osmotic laxatives
- Movicol
- Cosmocol
- Lactulose
Name some stimulant laxatives
- Senna
- Bisacodyl
- Docusate sodium
- Glycerin (suppositories)
Mechanism of action of the stimulant laxatives
- Increases intestinal motility.
- May be given orally or per rectum.
What does docusate sodium do?
- Stool softener and is a stimulant
What do glycerin suppositories do?
- Rectal irritation and lubrication
What is the mechanism of action of bulk forming laxatives - methylcellulose, ispaghula husk?
- Medicinal fibre which increases the water in the stool and makes it bulkier and soft.
What is the action of stool softeners?
- Docusate sodium
- Glycerin suppositories
- Liquid paraffin
- Arachis oil
- Decreased surface tension of stool allowing fluid into faeces to break it down.
- Rectal route
Name some proton pump inhibitors?
- Omeprazole
- Esomeprazole
- Rabeprazole
- Pantoprazole
- Lansoprazole
What is mechanism of action of proton pump inhibitors?
- Pro-drug metabolised by CYP2C19 and CYP3A4
- Drawn to the most acidic areas; they are weak bases and accumulate in acidic space of secretory canaliculus.
- Suppression of acid secretion by binding to gastric H+ covalently and K+ ATPase irreversibly and blocks function.
Side effects of proton pump inhibitors:
- Decreases effectiveness of clopidogrel (antiplatelet drug) as both use CYP2C19 for metabolism.
- Reduces innate barrier to ingested bacteria so increased risk of enteric infections.
- Headache
- Nausea
- Abdominal pain
- Metronidazole has increased size effects - diarrhoea and nausea
What is the treatment for H pylori?
- PPIs + amoxicillin + clarithromycin + metronidazole.
- PPIs + bismuth + 2x antibiotics - if allergic to clarithryomycin.
Why do you get risk of carcinoid tumours when using proton pump inhibitors?
- Acid production being suppressed leads to parietal cell and ECL hyperplasia so increased levels of gastrin.
When should you use a H2 receptor antagonist?
- If incomplete response to PPI
- Cimetidine is an example of a drug in this class
What is the mechanism of action of H2 receptor antagonist?
- Competitively and irreversibly inhibits binding of histamine to H2 receptors.
- Blocks effects of gastrin and Ach on parietal cells so lack of cAMP production, PKA activation and decreased conformational change of parietal cell. Less H+ pumped out.
What are the side effects of H2 receptor antagonist?
- Diarrhoea
- Constipation
- Muscle ache
- Fatigue
- Reduces antifungal - ketoconazole - absorption (required an acidic environment).
What are contraindications of cimetidine?
- Inhibits CYP450 enzymes decreasing metabolism of lidocaine, phenytoin, theophylline, warfarin.
What is mechanism of action of prostaglandin analogue - misoprotol?
- Inhibits adenylate cyclase so, decreased cAMP and therefore, proton pump activity.
- Acts on PGE2 inhibiting cAMP production and therefore, PKA production = less H+ secreted due to lack of conformational change of parietal cell.
Why are prostaglandin analogues not used as first line treatment?
- They cause diarrhoea
What can prostaglandin analogues be used for?
- Treatment for NSAIDs induced ulcers.
- In pregnant women, it can cause uterine contractions - abortion.
- Used in PPH to clamp down uterus and terminate pregnancies.
What is the mechanism of antacids?
- Aluminium hydroxide, Mg hydroxide, Sodium bicarbonate, Calcium carbonate
- Neutralises HCL and therefore acts a symptom relief for dyspepsia.
Features of aluminium hydroxide:
- Constipation
- Nephrotoxicty in renal failure patients
Features of magnesium hydroxide
- Diarrhoea
- Avoid in renal failure
Sodium bicarbonate antacid should be avoided in:
- Hypertension and fluid overload
