Gastrointestinal Flashcards
What immediate therapy would you initiate in a GI bleed?
IV fluid - 500mL IV crystalloid
containing up to 130-154mmol/L Na+
What is important to note about the amount of IV fluid administered?
Max 2L should be given in 1hr - don’t want to cause K+ overload.
What is the definitive investigation/ intervention for an upper GI bleed?
Endoscopy
What is the difference between the Blatchford and Rockall score?
Blatchford - Using clinical and lab data, distinguishes between high-risk and low risk-bleeds (can be used to decide who is eligible for endoscopy)
Rockall - predicts mortality for bleed following endoscopy
What agents can be used in a GI bleed?
Silver nitrate - cauterises
Adrenaline - causes vasoconstriction of vessels
Banding - blocks off bleed
What is pantoprazole?
Acid suppressive therapy with H2 receptor antagonist
Why are oral and IV PPIs used in GI bleeds?
Decreases:
- Length of hospital stay
- Re-bleed rate
- Need for transfusion
What would you do with antihypertensives in a patient who has had a GI bleed?
Withhold them - they’d promote hypotension which doesn’t help their hypovolemia.
How would you manage long-term prescriptions in an acute situation?
Can withhold them for a few days because they won’t have the same long-term effect if the patient isn’t physiologically stable
What are the risk factors in the formation of GI ulcers?
H.pylori infection
NSAIDs
Stress
Excess gastric acid
How do aspirin and NSAIDs contribute to the development of peptic ulceration?
COX-1 acts as housekeeping for the mucosa in the upper GI tract; inhibiting it encourages mucosal damage
What factors influence development of ulcers by NSAIDs?
- Duration
- Dose
- Increasing age
- Past history of gastroduodenal toxicity from NSAIDs
- Using steroids, anticoagulants, antiplatelets, bisphosphonates and SSRIs at the same time as NSAIDs
What investigations would you perform if you suspected H.pylori infection?
Biopsy urease testing = CLOtest
What is the rationale behind triple eradication therapy?
PPI suppressing acid
Dual antibiotic therapy to clear the infection
What interaction would you be wary of before prescribing clarithromycin in a patient with H.pylori infection?
Clarithromycin inhibits CYP3AP which would usually metabolise SIMVASTATIN -> accumulation of simvastatin
What advice/ warnings would you give a patient with H.pylori infection during their course of eradication therapy?
Avoid alcohol - has a disulfram type reaction with metronidazole
What is an investigative option for patients who cannot tolerate flexi sig?
Virtual colonoscopy
What are the drug therapies for ulcerative colitis following IV fluid treatment?
- Budesonide (oral glucocorticoid in severe UC patients)
- Sulfasalazine (5-ASA)
- IV steroids in hospital
- Fulminant disease - broad-spectrum antibiotics
- VTE prophylaxis
When converting a patient from IV steroid to an oral steroid, which would you use?
Prednisolone (when swapping from hydrocortisone; they both exert gluco- /mineralocorticoid effects
What other pharmacological option should you consider if a patient continues with high dose oral steroids?
Topical 5-ASAs are first in line for those who are willing to use rectal therapy
Rectal suppositories/ enemas induce remission in 90% of patients with mild-moderate proctitis.
Besides steroids, what oral therapy should you commence in UC patients with the aim of reducing oral steroids?
Azathioprine
Why are corticosteroids better weaned off gradually?
Addisonian crisis
What is azathioprine’s mechanism of action?
Prodrug
Converted to 6-mercaptopurine via nucleophilic attack by sulfahydryl compounds in RBCs
Accumulates in tissues, inhibits purine (and therefore DNA/ RNA) synthesis
Inhibits T and B cells
Immunosuppression
What is infliximab?
Chimeric monoclonal antibody
TNFa blocker
What is infliximab’s mechanism of action?
Binds to TNFa
Interferes with inflammatory activity
What are the mechanisms of pain in a thoracotomy?
Damage to normal anatomical structures -> inflammation -> release of inflammatory & pain mediators -> spinothalamic stimulation -> projection to limbic system -> pain perception
Direct nerve injury
How might an anaesthetic traditionally/ classically reduce pain peri-operatively?
Opioids to target central mechanisms involved in pain perception
What are the side-effects of opioids?
- Somnolence
- Respiratory depression
- Hypotension
- Urinary retention
- Nausea & vomiting (via CTZ)
- Histamine release can cause prophylactic symptoms
If a patient were to develop opioid toxicity and experience a drop in respiratory rate, what would the treatment be?
Naloxone
What is naloxone’s mechanism of action?
Opioid competitive antagonist
What does the term ‘competitive antagonist’ mean?
Drugs bind to receptor in a reversible way without activating the system
How might pharmacology help in treating opioid induced constipation in palliative care patients on long term opioids?
Methylnaltrexone
It doesn’t cross the BBB so it maintains central analgesic effects without mediating peripheral ones (like constipation)
Why do anaesthetics control pain peri-operatively using several agents?
Each agent can act at different sites of the pain pathway
Lessens dependence on a single medication and mechanism
What is Bupivacaine’s mechanism of action?
Local anaesthetic
Disrupts ion channel function within the neurone cell membrane -> prevented transmission of action potential
What is the mechanism of action for epidural opiates?
Directly binds to opioid receptors
Acts on the presynaptic nerve terminal to inhibit release of neurotransmitter.
Postsynaptic action (usually inhibitory)
What is morphine’s mechanism of action?
Acts on muscarinic receptors, inhibits noradrenaline, acetylcholine and substance P (neuropeptide)
Why are local anaesthetic and opioid administered by IV via epidural catheter for post operative pain?
Reduces the required dose
Reduces possible side effects
What medication could you add during the operation if you had a concern about break through pain?
IV opiate
Why do patients develop post operative nausea and vomiting?
Drugs & ingested toxins
Efferent impulses from medullary centres influence brainstem nuclei to initiate vomiting reflex
What are the drug classes available for prophylaxis or rescue therapy for post operative nausea & vomiting?
Serotonin-R antagonists
Corticosteroids
Anticholinergic agents
Neurokinin-R antagonists
What is ondansetron’s mechanism of action?
Suppresses initiation of nausea and vomiting by blocking 5HT peripherally at vagal afferents and centrally in the chemoreceptor trigger zone.
What drug class does ondansetron belong to?
Selective serotonin-R (5HT3) antagonist
Why is ondansetron most commonly used for post operative nausea and vomiting?
IV preparations are available
No sedative side effects
Besides ondansetron, what other drugs can be used for post operative nausea and vomiting?
Hyoscine - Anti-ACh
Cyclizine - Anti-H1
Dexamethasone - steroid
Despite being an antihistamine, why does terfenadine not have anti-emetic properties?
It does not cross the blood brain barrier.
When is the antipsychotic prochlorperazine indicated as an anti-emetic?
Acute nausea and vomiting, e.g. acute gastroenteritis
What is metoclopramide’s drug class?
Dopamine receptor antagonist
Why is metoclopramide contraindicated in Parkinson’s patients?
Can cause Parkinsonian like symptoms, would exacerbate symptoms
How do you manage a patient’s severe dystonic reaction after taking metoclopramide?
Procyclidine = first-line
Diazepam is an alternative treatment
Once metoclopramide has left the system, dystonia should resolve.
What agents could you give to counteract opioid accumulation in the CTZ?
Ondansetron Metoclopramide Domperidone Paliperidone Scopolamine Aprepitant
What is a common cause of hyponatraemia combined with hypokalaemia?
Vomiting
Which anti-emetics are known to cause constipation?
Ondansetron
Prochlorperazine
Dexamethasone
How do you add an opiate for breakthrough pain?
Rescue dose should be a sixth of the total 24 hour dose; adjusts based on how much was taken in the previous 24 hours
What is apparent volume of distribution (Vd)?
Theoretical volume necessary to contain total amount of an administered drug at the same concentration as whatever’s in the plasma; reflection of distribution
How would you calculate apparent volume of distribution?
Amount of drug in body
DIVIDED BY
Plasma concentration of drug
What physicochemical properties affect apparent volume of distribution?
Solubility
Charge
Size
What is a two compartment model?
A model which divides the body into a central compartment (1) and peripheral compartment (2).
What is the role of the central compartment in the two compartment model?
Consists of plasma and tissues; drugs are administered to and distributed from this compartment. Usually linked to all the other compartments.
What is the role of the peripheral compartment in the two compartment model?
The peripheral compartment consists of tissues and drug distribution is slower.
Compared to a two compartment model, how does drug distribution differ in a single compartment model?
Drug distribution is considered instantaneous within a single compartment.
What is the distribution phase?
The decrease in drug plasma corresponding with transfer of drug from the central to the peripheral compartment.
What is the elimination phase?
Removal of drug from the central compartment
In pharmacokinetics, why is the elimination phase longer than the distribution phase?
The drug must diffuse back from the peripheral compartment to the central one to be eliminated.
If a drug’s volume of distribution approaches that of body water, what does this suggest about the drug’s distribition?
The drug must be predominantly distributed in body water
How long do drugs typically take to reach steady state?
Approx 5 half-lives
What action can you take to ensure that lithium (with a very narrow therapeutic index) doesn’t become toxic?
Measure blood levels 12 hours after a dose
How do standard and modified release formulations affect bioavailability of the drug?
Modified release may increase bioavailability, therefore you’d need less of the drug for it do exert its therapeutic (and toxic) effects
What is a loading dose?
Higher dose of drug is administered when the treatment starts.
Allows the drug to reach steady state concentration faster
Why should dosing of digoxin be based on estimated lean body mass?
Digoxin has a large volume of distribution and has a high affinity for skeletal and cardiac muscles. Adipose tissue is NOT a reservoir for it.
Tubular secretion of digoxin is mediated by p-glycoprotein (p-gp). What drugs are known to inhibit p-gp?
Spironolcatone
Quinidine
Verapamil
Amiodarone
What factors affect the bioavailability of drugs taken orally?
- Physicochemical drug properties
- Decomposition of the drug in the gut lumen
- pH and perfusion of the small intestine
- Surface and time available for absorption
- Competing reactions in the gut lumen (e.g. drug vs. food)
- Hepatic first-pass effect
When re-dosing drugs based on bioavailability, what do you do?
[Year 5 calculation]
- Multiply current dose if old drug by the percentage change in bioavailability = dose of old drug with new drug’s bioavailability
- Result divided by new bioavailability’s dose = concentration of drug to prescribe.
How would you manage a patient with a GI bleed?
IV fluids - resuscitation
Transfusion of two units of cross-matched packed red cells
Endoscopy once haemo-dynamically stable
Give an example of an opioid antagonist that does not cross the blood-brain barrier
Methylnaltrexone
