GI Pharmacology Flashcards
Which part of the brain is responsible for vomiting?
Which three centres in this part of the brain are involved in vomiting?
Medulla
Vomiting centre
Chemoreceptor trigger zone (CTZ)
Vestibular nuclei
What does the CTZ do?
It contains receptors which detect emetic agents in the blood - signals to the vomiting centre to induce vomiting.
Which parts of the body can signal to the vomiting centre?
CTZ
GI tract (enterochromaffin cells)
Vestibular nuclei
Higher cortical structures
How does the GI tract signal the vomiting centre?
Enterochromaffin cells detect things like toxic agents, microorganisms, mechanical distension - they then release neurotransmitters which trigger the vomiting centre.
Which are the main neurotransmitters that directly trigger the vomiting centre?
ACh, Histaminę, 5-HT, Dopamine and Substance P
Which substances directly stimulate the CTZ?
Opioids, ketoacids and urea
What conditions can cause mainly morning vomiting?
Pregnancy
Uraemia
Alcoholic gastritis
What is feculent emesis a sign of?
Distal intestinal obstruction
What is projectile vomiting a sign of?
Raised ICP
What can cause vomiting during or shortly after a meal?
Psychogenic causes
Peptic ulcer disease
What is the treatment aim of anti-emetics?
To correct the specific cause of the vomiting
What is the MOA of Cyclizine?
Blocks histamine receptors in CNS - reducing stimulation of sickness neurons
Which drugs can be given for sickness caused by motion / narcotics / anaesthetics and radiotherapy?
Cyclizine
Promethazine
What are the CIs of Cyclizine and Promethazine?
- Don’t use if P has hypersensitivity to the drug
- May increase toxicity of alcohol so don’t use if P inebriated.
What are the SEs of Cyclazine and Promethazine?
Drowsiness
Confusion
Constipation
Urinary retention
What is the MOA of Promethazine?
Blocks cholinergic and histamine receptors in the CNS.
Give two examples of H1 receptor antagonists used as anti-emetics?
Cyclizine
Promethazine
How do muscarinic receptor antagonists work as anti-emetics?
Block the M1, M3 and M5 receptors in the central vomiting circuits and vestibular system.
Which anti-emetic is a 5HT-3 Receptor Antagonist?
Ondansetron
How does Ondansetron work?
It blocks the 5HT3 receptors involved in the vomiting reflex.
Which anti-emetic can be given for vomiting due to cytotoxic drugs, radiation or post-op sickness?
Ondansetron
What are the adverse effects of Ondanestron?
Headache, dizziness, constipation and QT prolongation
What are the CIs to Ondansetron?
Arrhythmia with QT prolongation
Hypersensitivity with any excipient
Name three dopamine receptor antagonists used as anti-emetics?
Chlorpromazine
Haloperidol
Metoclopramide
How do dopamine receptor antagonists work as anti-emetics?
They block the D2 receptors in the CTZ but also block histamine and muscarinic receptors.
Which anti-emetic drug has both a dopamine receptor antagonist effect and a peripheral effect on the GI tract itself inc its motility?
NB. This drug can also be used as a GERD treatment
Metoclopramide
Which drug can be used for delayed chemo induced N&V, and symptomatic treatment of N&V inc for migraine?
Metoclopramide
What are the adverse effects of metoclopramide?
Movement disorders
Fatigue
Motor restlessness
Spasmodic torticollis
Also - stimulates prolactin release = causes galactorrhea and menstruation disorders
What are the CIs of Metoclopramide?
Don’t use if hypersensitivity to this drug
GI haemorrhage
Mechanical obstruction
Neuroleptic or induced tardive dyskinesia
Parkinsons’s
DONT use if on levodopa or dopaminergic agonists
What is tardive dyskinesia?
Involuntary and abnormal movements of the jaw, lips and tongue
How does dopamine affect the gut?
It relaxes the gut - activates muscular D2 receptors in lower oesophageal sphincter and stomach AND inhibits the release of Ash from intrinsic myenteric cholinergic neurons.
How does metoclopramide promote gut motility?
Inhibits D2 receptors
Stops inhibition of muscarinic receptors
What is the primary ligand of NK1 receptors?
Substance P
Where are NK1 receptors found?
In vomiting areas of the brain
Throughout the GI tract.
What happens when Substance P is given IV?
Causes vomiting in the P.
How do cannaboids work as anti-emetics?
Are agonists of the endogenous cannabinoid receptors in the vomiting centre (CB1 and CB2).
Which glucocorticoid can be used as an anti-emetic?
Dexamethasone
What types of N&V is dexamethasone used for?
Chemotherapy and radiotherapy induced N&V
Post-op N&V
A patient is receiving highly emetogenic chemotherapy for metastatic carcinoma. To prevent chemotherapy-induced nausea and vomiting, she is likely to be treated with which of the following?
A. Levodopa
B. Methotrexate
C. Misoprostol
D. Ondansetron
E. Omeprazole
The 5-HT3 receptor antagonists are highly effective at preventing chemotherapy-induced nausea and vomiting, which can be a dose-limiting toxicity of anticancer drugs. The answer is D
Spasmodic torticollis is side effect of which antiemetic drug?
A. Aprepitant
B. Cyclizine
C. Metoclopramide
D. Nabilone
E. Ondansetron
C
A patient is recently diagnosed as having Parkinson disease. Which antiemetic drug is contraindicated in this patient?
A. Aprepitant
B. Cyclizine
C. Metoclopramide
D. Ondansetron
E. Scopolamine
Metoclopramide.
Its a D2 receptor antagonist
In Parkinson there is degeneration of dopamine neurons.
Giving metoclopramide will block D2 receptors leading to decrease availability of D2 receptors on which dopamine require to act.
Following drugs act on various receptors in chemoreceptor trigger zone. Identify receptors on which these drugs act?
A. Aprepitant
B. Cyclizine
C. Metoclopramide
D. Ondansetron
E. Scopolamine
A. Aprepitant Neurokinin1
B. Cyclizine Histamine1
C. Metoclopramide Dopamine2
D. Ondansetron Serotonin (5HT3)
E. Scopolamine Muscarinic
Name a drug that is a bulk-forming laxative.
Ispaghula Husk - Fybogel
What is a first line osmotic laxative?
What is a second line osmotic laxative?
First line - macrogol
Second line - lactulose
What stimulant laxatives can you name?
Senna (1st line)
Bisacodyl (2nd line) - avoid in IBD
Docusate sodium (3rd line)
How long do you need symptoms to be diagnosed for chronic constipation?
At least 12w in the preceding 6m.
How do we treat acute / chronic constipation?
Step 1 = bulk forming laxative
Step 2 = + or switch to osmotic laxative (esp if stools are hard)
Step 3 = + in stimulant laxative
How do we treat opioid induced constipation differently?
Offer osmotic and stimulant laxatives - do not offer bulk forming!
If no response - consider naloxegol
How do you stop laxatives?
Don’t stop suddenly
Reduce gradually based on frequency & consistency
If on combo - reduce and stop one at a time (Stimulant laxatives first)
What suppositories / enemas can you name?
Glycerol suppository
Bisacodyl suppository
Citrate (Micralax) enema
Phosphate enema
What actions does a glycerol suppository have?
Is a softener, stimulant and lubricant
How do PPIs work?
Inhibit the H+/K+ ATPase pump on parietal cells
What are the side effects of PPIs?
Diarrhoea
Inc risk of C Diff
How does ranitidine work?
H2 receptor blocker - blocks the receptor on parietal cells for histamine - therefore stopping stimulation of the H+/K+ ATPase pump
How do NSAIDs work?
Inhibit COX enzymes - COX 1 (GI tract) and COX 2 (pain and inflammation generally)
What is a potential complication of Ferrous Sulphate?
Constipation - current guidance = repeat iron studies and review if medication absolutely necessary and review dose when needed.
What medications can be given for IBS diarrhoea?
Loperamide
Antispasmodics - hyoscine butylbromide (buscopan)
How does loperamide work?
What are its side effects?
Is an agonist for opioid receptors in the bowel wall - reduces intestinal motility and secretion. (specific to gut mu receptors)
Commonest = constipation
Can cause cardiac arrhythmias in higher doses
Which laxative should be avoided in IBS?
Lactulose - as it can cause excessive bloating
What unusual medical Tx can be given to help with IBS symptoms?
Tricyclic antidepressants (amitriptyline ) - low dose. >90% respond to some extent.
What is the brand name of loperamide?
Immodium
Name one pro-kinetic agent used in management of chronic constipation that is a 5HT4 receptor agonist?
Prucalopride
How do bulk forming laxatives work?
Retain fluid in the stool - which increases faecal mass, causing distension and triggering peristalsis.
Softens stool as well.
How do osmotic laxatives work?
How do stimulant laxatives work?
How do stool softeners work?
What are the potential side effects of laxatives?
What is the ladder of treatment for chronic IBD
Which corticosteroids can be used for IBD in
(a) IV
(b) oral formulation?
a = Hydrocortisone
b = Prednisolone
What is first line treatment for
(a) UC
(b) CD?
(a). mesalazines
(b) thiopurines
What is the MOA of biguanides?
Overall reduction in insulin resistance
Name a biguanide drug?
Metformin
What are the SEs of biguanides / metformin?
NB. Diabetic population are at risk of neuropathy and B12 deficiency can present in the same way (i.e. peripheral neuropathy)
When is metformin contraindicated?
Acute metabolic acidosis - inc lactic acidosis & DKA
eGFR <30
Liver problems
What are the SEs of sulphonylureas?
Name a sulphonylurea drug.
Gliclazide
What is the MOA of sulphonylureas?
Blocks the K ATP channels within β cells of pancreas => stimulates insulin secretion
When are sulphonylureas contraindicated?
Name a DPP4 Inhibitor drug
Sitagliptin
Linagliptin
What is the mechanism of action of Gliptins (DPP4 inhibitors)?
Increases insulin levels and reduces insulin resistance
What are the side effects of gliptins?
When are gliptins contraindicated?
Ketoacidosis
Renal failure
Name an SGLT2 Inhibitor
Dapagliflozin
Canagliflozin
Empagliflozin
What are the side effects of SGLT2 Inhibitors?
Name a GLP1 Agonist
Dulaglutide
Exanatide
Liraglutide
Semaglutide
What is the mechanism of action of GLP1 Agonists?
Inc insulin resistance
Inc β cell replication in pancreas and prevents their death
Delayed gastric emptying
Decreased glucagon secretion
What are the benefits of GLP1 Agonists?
Improved BP and lipid profile
Improve HbA1c
Decreased weight
No hypoglycaemia
What are the SEs of GLP1 agonists?
When are GLP1 agonists contraindicated?
What are the side effects of insulin?
How long should Sx of constipation be present for to qualify as chronic constipation?
At least 12w in the preceding 6m
In acute/chronic constipation - what are the 3 steps of pharmacological management?
Step 1 - Offer a bulk-forming laxative (Fybogel - Ispaghula Husk)
Step 2 - Add in / switch to osmotic laxative (esp if stools hard) (Macrogrol 1st line, Lactulose 2nd line)
Step 3 - Add in a stimulant laxative gel) (Senna 1st, Bisacodyl 2nd, Docusate Sodium 3rd)
In opioid induced constipation, what is the pharmacological management?
Step 1 - offer an osmotic and stimulant laxative
Step 2 - if inadequate response, consider naloxegol (high cost!)
In faecal loading / impaction - what is the pharmacological management?
1). High dose macrogol
2) Consider bisacodyl / glycerol suppository or citrate enema
3). Phosphate enema
How do you stop laxatives?
Reduced gradually based on frequency / consistency - dont stop suddenly.
If on a combo - reduce and stop 1 at a time.
What is the interaction between Adcal-D3 and Ferrous Sulphate?
Adcal (oral CaCO3) decreases the absorption of oral iron.
Therefore take Adcal 1 hour before or 2 hours after iron is taken.
What side effect can ferrous sulphate cause?
Constipation
Which is more likely to have rectal involvement - UC or Crohn’s?
UC
What Sx are different between UC and Crohn’s?
How does Rx of UC and CD differ?
CD is less likely to respond to 5ASAs (Mesalazine) - therefore not recommended due to limited benefit.
Specialists may prescribe to see if there is a response.
UC much better response to Mesalzaine
When should steroids be used for an IBD flare?
When it has been severe as an inpatient (IV then switch to oral)
or moderate Sx as an outpatient (oral)
Why do we have different dosing regimes for 5ASAs in UC?
Maintenance dosing regime
Flare management dosing regime (usually double the maintenance dose)
What SEs do you need to beware of when prescribing steroids?
Osteoporosis – Adcal D3 (or other calcium & vit D supp)
Peptic ulceration and perforation – with/after food. Could use PPI but then have risk of fractures
Diabetes – monitoring and then std treatment if needed
Muscle wasting – appropriate exercise/movement
Psychiatric – switch of steroid
Long-term steroid can be associated with extreme side effects including mood changes such as irritability and depression, osteoporosis, cataracts, and risk of steroid dependency and withdrawal
Which laxatives are bulk forming?
Fybogel
Which laxatives are osmotic?
1st line = Macrogol
2nd line = Lactulose
Which laxatives are stimulants?
1st line = Senna
2nd line = Bisacodyl
3rd line = Docusate Sodium
What should be offered for acute / chronic constipation that is non-opioid induced?
1). Bulk forming
2) +/- Osmotic laxative (esp if stools are hard)
3). + Stimulant laxative
What should be offered for opioid induced constipation?
1). Osmotic + Stimulant laxative
2). If inadequate response - consider naloxegol - HIGH COST
What should be offered for Ps with faecal impaction?
1). High dose macrogol
2) Consider bisacodyl/glycerol suppository or citrate enema
3). Consider phosphate enema
How should Ps stop taking laxatives?
Dont stop suddenly
Gradually reduced based on frequency and consistency of stools
If on a combo of laxatives - stop one at a time (starting with stimulants)
Which marker is very sensitive for inflammation in the GI Tract?
Faecal calprotectin
Which drug is used for UC but no longer used for Crohn’s?
Mesalazines
Which steroid should be used for UC and Crohn’s flares if symptoms are moderate?
Prednisolone PO - 40mg
Which steroid should be used for UC and Crohn’s if Sx are severe?
Hydrocortison IV 100mg QDS
typically 2-5 days
then switch to oral prednisolone 40mg on a reducing regime (5mg per week)
