VivaCast 12, Anti-Emetics, Propofol (again) and Anti-Microbials.

Tom’s exam inches ever closer to reality, here he gets caught out on Droperidol, nails the Journey a Propofol Bolus Takes and handles Anti-Microbial Surgical Prophylaxis.

This pharmacology viva covers three essential topics that could appear in the FRCA Primary exam: antiemetic mechanisms, propofol pharmacokinetics, and antimicrobial prophylaxis principles. Understanding receptor targets for antiemetics, the journey of a propofol bolus through distribution and redistribution phases, and the mechanisms by which antibiotics mangle bacteria forms core knowledge for safe anaesthetic practice. The session highlights common exam pitfalls, particularly around receptor locations, drug timing with tourniquets, and the importance of structured, classified or categorised responses when under pressure.

How does Droperidol function as an anti-emetic?

Droperidol acts as a dopamine D2 receptor antagonist in the chemoreceptor trigger zone, reducing nausea and vomiting. It also has sedative properties and can prolong the QT interval, it is incompatible with patients who suffer with Parkinson’s disease (Domperidone IS safe)

Why have you droperidoled me, James?” – Tom experiences a Viva curveball! @ 1min 13s

Anti-Emetics

• Discussion on the mechanisms of action of common antiemetics, including ondansetron (5-HT3 antagonist), droperidol (D2 antagonist), and cyclizine (H1 antagonist).
• The use of dexamethasone as an antiemetic and its unclear mechanism of action.
• Consideration of newer antiemetics like neurokinin receptor antagonists.

Ondansetron

5ht3 receptor antagonist – typically 4mg doses, up to 24mg in 24 hours – but bear in mind some may get excited about QT prolongation, 

Other side effects are headache and constipation – there is a mild possibility that it treats the shivering experienced peri-partum, but that’s on thin ice.

Droperidol

An anti-psychotic like haloperidol, D2 receptor antagonism. quite sedating in some ways and can be used IM or IV in rapid sedation of psychotic/challenging people in emergency departments.

Cyclizine

H1 Receptor antagonism, 50mg three times a day by IV/IM/PO routes, makes people drowsy, causes a bit of a tachycardia which can be useful sometimes. IV in awake patients, some get a buzz which means they start coming back for more, solved by putting it in 100ml of saline over half an hour. 

Dexamethasone

Steroid of exceeding potency, generally a ~3-6mg dose, given at the start of a case. Unclear as to why it has anti-emetic effects. But still has all the worrying, and bothersome side effects of steroids, partciularly in multiple doses.

In the context of operative intervention – it looks like it also has a role in reducing post operative pain – there is a meta analsysis from the european obstetric association that outlines this for LSCS which I would believe translates into other areas. https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.16034#:~:text=Intravenous%20dexamethasone%20was%20associated%20with,wound%20infiltration%20were%20also%20reinforced. 

Dont give to awake people as sometimes they get stark peri-anal burning, I once gave it whilst waiting for the fentanyl to work on a LMA flavoured anaesthetic and a young patient started screaming their bum was on fire. The propofol came quickly after that, this was not ideal anaesthesia.

Other Agents in the wings

Aprepitant – NK-1 Receptor Antagonist – Approved in the US by the FDA as a pre-med.

Used in the uk for chemotherapy emesis prevention, where a patient starts taking it a day or so before they begin chemo to try and stop the vomiting if they had an awful time first time around. 

Nabilone – a CB-1 and CB-2 receptor agonists (cannabinoid receptors)

Propofol Pharmacokinetics:

• The journey of an intravenous bolus of propofol, including its distribution, metabolism, and elimination.
• The influence of lipid solubility, protein binding, and redistribution on its onset and duration of action.
• Explanation of concepts like context-sensitive half-time and the exponential nature of drug elimination.

Check out the Propofol episode and show notes for the full dance through propofol!

Factors that increase the dose requirement of propofol

• Heightened states
  • Anxiety
  • Sympathetic activation
• Alcoholics
• Acute alcohol or drug withdrawal leading to agitated states (ie SNS activation)
• High BMI
• The Young
• Those who frequent ilicit depressant substances, but have not currently got any in their system

Factors that decrease the dose requirement

• Elderly
• The critically unwell
• Low BMI
• Those who are currently obtunded ie drunk / stoned / half anaesthetised with their drug overdose.
• Malnourished / thoser with lower plasma protein levels

Antimicrobial Prophylaxis in Surgery:

• Covering the principles of using antibiotics to prevent surgical site infections.
• Importance of timing in administration, especially in orthopaedic surgery with tourniquet use.
• When to give another dose (long surgery, or when there has been an unexpected exsanguination)
• Overview of the mechanisms of different antibiotic classes (penicillins, aminoglycosides, macrolides, etc.).

Tom found himself listing drugs and their functions here, and its definitely examinable content!

VS Cell Wall – (bactericidal) 

BETA LACTAMS

• Penicillins – Block transpeptidase / carboxypeptidase (so called penicillin binding proteins)
  • Chief = amoxicillin / Tazobactam (G+ve and anaerobes  / benzylpenicillin (streptococci and neisseria are v sensitive) Flucloxacillin good vs Staphlycocci which have Beta-lactamASE as its resistant to this bacterial resistance enzyme
• Cephalosporins – many generations, the more modenr the more G-ve cover exists – Ceftriaxone is good at getting into brain – and has a fairly long half life
• Carbapenems – Block penicillin binding protiens for peptidoglycan synthesis – very broad -ve and +ve and anaerobes Fail vs psuedomonas and enterococccus faecalis Chief – Meropenem
• Monobactams – Block penicillin binding protiens for peptidoglycan synthesis – Gram -Ve only!  Safe in penicillin anaphylaxis, good vs enterobacter/psuedomonas

NOT a beta lactam

• Glycopeptides – Inhibit glucopeptide synthetase – blocking peptidoglycan formation- Chief = Teic / Vanc, Teic lasts longer, = fewer dose/day

Vs Protein Synthesis

• Tetracycines
• Aminoglycosides – 30s Ribosome – Gentamicin / Streptomycin / Tobramycin Vs gram -ve enterococcie and staphs, no anaerobic cover
• Macrolides – 50s ribosome (the M has 5 points in its shape) Claritho/Erythromycin Vs Gram +ves and legionella
• Lincosamides – 50s ribosome, Chief = Clindamycin Great vs Gram+VE & Anaerobes + Plasmodium Falciparum and Toxoplasma!
• Chloramphenicol – vs 50s ribosome – bone marrow toxic, excellent in the middle of a helmand foxhole as its very stable and very broad, not so useful in a DGH

VS DNA synthesis

• Quinolones – Vs DNA Gyrase, cant coil up dna = dead bug – Ciprofloxacin
• Sulphonlyureas
• folatey boys
• Rifamycins -Beta subunit of DNA-Depend RNA polymerase  Cheif = rifampicin – Good Vs Staph / Strep

Vs ‘Other’

• Nitroimidazoles – Chief one = Metronidazole – unclear mechanism, good vs anaerobes
• Bacteriophages! 😛

Exam Strategy and Learning Approach:

• We discussed structuring answers effectively in a pharmacology Viva.
• The importance of categorising information (e.g., patient factors, drug mechanisms, and clinical considerations).
• Strategies to handle unexpected questions and maintain composure under pressure.

Summary

Antiemetics target different receptors to prevent nausea: ondansetron blocks 5-HT3 receptors, droperidol antagonises D2 receptors in the chemoreceptor trigger zone, cyclizine blocks H1 receptors (useful for vestibular causes), while dexamethasone’s mechanism remains unclear despite proven efficacy. Droperidol, an antipsychotic, contraindicates use in Parkinson’s disease (unlike domperidone which doesn’t cross the blood-brain barrier). Dexamethasone (3-6mg) reduces postoperative pain and swelling but causes neuropsychiatric effects, immunosuppression, and perineal burning if given awake.

Propofol’s pharmacokinetic journey follows: IV administration → rapid CNS distribution (highly lipid-soluble, unionised at pH 7.4) → therapeutic effect → redistribution to peripheral tissues → offset of action. Context-sensitive half-time reflects accumulation in adipose tissue during infusions. Onset time increases with high cardiac output (dilution effect) and normal protein binding, but decreases in elderly/malnourished patients. Chronic alcohol use and anxiety states increase dose requirements through GABA receptor downregulation and heightened CNS activity.

Antimicrobials prevent surgical infections by targeting bacterial structures: beta-lactams (penicillins, cephalosporins, carbapenems) inhibit cell wall synthesis via penicillin-binding proteins; aminoglycosides and tetracyclines block 30S ribosomes; macrolides and lincosamides target 50S ribosomes; quinolones inhibit DNA gyrase; sulphonamides disrupt folate synthesis. Timing is very important, antibiotics must be given before tourniquet inflation in orthopaedics to achieve therapeutic tissue levels. Redosing is required during prolonged surgery or significant blood loss.

Key point: Structure pharmacology answers systematically for exampl, with antibiotics, group by mechanism (cell wall, protein synthesis, DNA synthesis) to avoid rambling lists under exam pressure.

Resources

• Guidelines on antimicrobial prophylaxis
• Antimicrobial Prophylaxis NICE Guidelines