Ep.41 –Midazolam For The FRCA Primary

© GasGasGas – The FRCA Primary Anaesthetic Sciences Podcast 2025

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Quick Reference Tables

Parameter	Value
Classification	Imidazobenzodiazepine
Molecular Weight	325.8 g/mol
Preparations	1, 2, 5 mg/mL (clear, colourless)
pKa	6.2 (exhibits tautomerism)
Protein Binding	96%
Bioavailability (PO)	44%
Half-life	1.5-3.5 hours (↑5.4h in critically ill)
Metabolism	Hepatic CYP3A4
Elimination	Renal (as hydroxylated derivatives)

Dosing Reference Guide (70kg Adult)

Indication	Dose Range	70kg Example	Notes
Sedation / pre med	0.07-0.1 mg/kg	5-7 mg	Endpoint: drowsy, slurred speech, responds to commands – 20-30mins pre op..
Premedication (Paediatric)	0.5-1 mg/kg PO	N/A	Maximum 20mg, 20min onset
Co-induction	Variable	0.5-5 mg	Combined with primary induction agent
ICU Sedation	Higher doses acceptable	1-5mg/hour	Challenges with BP / Sedation
Poorly Patient going on a transfer not being woken up soon	10mg	one ampoule.	Keeps a patient neatly sedated alongside fentanyl boluses and propofol TCI.
Crisis Midazolam	10-20mg	Carotid blow out awfulness	Palliative care.

Cardiovascular Effects Profile

Parameter	Change	Clinical Significance
Systolic BP	↓5%	Minimal clinical impact
Diastolic BP	↓10%	Slight reduction
SVR	↓15-33%	Moderate vasodilation
Heart Rate	↑18%	Compensatory tachycardia
Overall	Haemodynamically stable	Preferred for unstable patients

Seems excessively detailed from Oxford Handbook broadly, it’s a stable drug.

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Midazolam in Detail

Classification & Basic Properties

Chemical Structure: Midazolam belongs to the imidazobenzodiazepine subclass, note its tautomeric behaviour (sort of an isomer thing). This molecular property allows pH-dependent solubility changes. Water-soluble at acidic pH (<4) in the ampoule, transitioning to lipophilic at physiological pH (7.4) for enhanced CNS penetration.

Physical Characteristics: Presented as a clear, colourless solution in standardized concentrations. The molecular weight of 325.8 g/mol.

Historical Context: While benzodiazepines emerged in the 1950s, diazepam achieving clinical utility in the 1960s.

Pharmacodynamics Of Midazolam

Mechanism of Action: Midazolam exerts its effects through potentiation of GABAergic neurotransmission. It binds to specific benzodiazepine binding sites on GABA-A receptors, distinct from GABA’s binding location, creating allosteric modulation that enhances channel opening probability and duration, lets more chloride in.

GABA-A Receptor Structure: These pentameric transmembrane proteins consist of five subunits surrounding a central chloride channel/pore. Multiple receptor subtypes exist throughout the CNS, with benzodiazepines, general anaesthetics, and ethanol all capable of binding and modulating activity through different sites.

Cellular Effects: Enhanced GABA-A receptor activation increases chloride influx, hyperpolarizing neurons and raising the threshold for action potential generation. This particularly affects postsynaptic membranes, requiring supranormal neurotransmitter release to achieve downstream signal transmission.

Clinical Actions:

• Primary: Sedation, hypnosis, anxiolysis, anterograde amnesia (cant form new memories, but anything in that memory bank waiting for filing will make it (check out millers anaesthesia for more memory formation theory)
• Secondary: Centrally-mediated muscle relaxation, anticonvulsant properties
• Novel: Potential kappa-opioid receptor agonism (observed in vitro) may explain intrathecal analgesic effects

Respiratory Effects: Creates a complex pattern of tidal volume reduction with compensatory respiratory rate increase, maintaining minute ventilation in healthy patients. However, it shifts the CO2 response curve rightward, reducing ventilatory drive to hypercarbia – particularly concerning in patients with sleep apnea or co2 retaining COPD types.

CNS Effects: Beyond sedation, midazolam produces dose-dependent reductions in cerebral blood flow and cerebral metabolic oxygen consumption while maintaining their normal coupling relationship. It attenuates the adrenergic stress response to surgical stimuli it doesn’t significantly affect cortisol.

Pharmacokinetics of Midazolam

Absorption: Oral bioavailability of 44% fair first-pass hepatic metabolism, making intravenous administration preferred for predictable onset and dosing precision.

Distribution: The high protein binding (96%) creates clinical concern in hypoalbuminemic states. Small changes in protein concentration can alter free drug levels, explaining enhanced sensitivity in liver disease, malnutrition, or sepsis / prolonged critical illness. Volume of distribution ranges from 0.8-1.5 L/kg in healthy adults but can expand to 3.1 L/kg in critically ill patients due to increased capillary permeability and fluid shifts.

Metabolism: Near-complete hepatic metabolism via CYP3A4 produces two primary metabolites: α-hydroxymidazolam (equipotent to parent compound) and 4-hydroxymidazolam (minimal activity). Rapid subsequent glucuronidation renders metabolites inactive, explaining the drug’s predictable recovery profile despite ‘active’ metabolite formation.

Age and Gender Considerations: Pharmacokinetic studies reveal interesting demographic variations. Elderly men demonstrate slower clearance compared to younger males, while this age-related difference doesn’t appear in women. This may relate to body composition changes, protein binding alterations, or hepatic enzyme activity variations. (or be dodgy science)

Elimination: Primarily renal as glucuronidated metabolites are nicely water soluble. Clearance averages 5.8-9 mL/kg/min with an elimination half-life of 1.5-3.5 hours in healthy adults, extending to 5.4 hours in critically ill patients due to altered pharmacokinetics rather than impaired elimination.

Special Clinical Applications

Never Events: Inadvertent administration of incorrect midazolam concentrations for sedation procedures constitutes a Never Event in UK healthcare, emphasising the importance of careful dose verification and concentration awareness.

MAC Reduction: Midazolam premedication reduces minimum alveolar concentration requirements by ~15%, though this effect is time-limited to the drug’s active period rather than providing prolonged anaesthetic-sparing effects throughout lengthy procedures.

Challenging Scenarios: The drug finds particular utility in:

• Hemodynamically unstable patients requiring sedation without significant cardiovascular depression
• Co-induction protocols, especially when combined with ketamine to counteract emergence phenomena
• Intensive care sedation when prolonged unconsciousness is planned, allowing larger doses without concern for rapid awakening

Cardiac Arrest Considerations: In witnessed VF arrests where patients regain consciousness during CPR cycles, midazolam use raises ethical and clinical questions about memory formation, PTSD prevention, and maintaining appropriate CPR endpoints. The primary resuscitation goal remains achieving sustainable circulation and in prolonged arrests the odds of a patient having a gcs of 15 on ROSC is unlikely, with current UK practice all these patient require periods of neuroprognostication on critical care.

Safety Considerations

Contraindications:

• Severe respiratory compromise without airway protection…
• Acute narrow-angle glaucoma
• Known hypersensitivity to benzodiazepines
• Severe hepatic impairment (relative contraindication)

Drug Interactions:

• CYP3A4 inhibitors (erythromycin, ketoconazole, grapefruit juice) significantly prolong effects
• CNS depressants create synergistic respiratory depression risk
• Ethanol potentiates sedative effects through GABA-A receptor modulation

Reversal Agents:

• Flumazenil: Specific benzodiazepine receptor antagonist, rapid onset
• Physostigmine: Anticholinesterase with central effects, less commonly used
• Important: Avoid flumazenil in polydrug overdoses where benzodiazepines may be preventing seizures from other substances

Emergency Management: Respiratory depression requires immediate airway management, ventilatory support, and consideration of flumazenil if isolated benzodiazepine overdose is confirmed. Always consult Toxbase for comprehensive poisoning management.

GABA System Pathophysiology

GABA Synthesis: Gamma-aminobutyric acid synthesis depends on pyridoxine (vitamin B6) as a cofactor. Deficiency states can precipitate seizures treatable with pyridoxine supplementation rather than traditional anticonvulsants.

Disease States:

• Huntington’s Disease: Associated with reduced GABA in striatal-pallidal projections
• Alcohol Use Disorder: Chronic consumption creates tolerance requiring neuronal adaptation; withdrawal produces relative GABA (like agent) deficiency explaining why benzodiazepines effectively treat alcohol withdrawal syndrome

Clinical Pearl: The shared GABA-A receptor pathway explains why benzodiazepines and alcohol demonstrate cross-tolerance and why each can theoretically treat withdrawal from the other, though benzodiazepines remain the safer clinical choice.

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Support Materials Referenced

Primary References

• Oxford Handbook of Drugs Used in Anaesthesia and Intensive Care
• Textbook of Experimental Pharmacology
• British Journal of Anaesthesia Education: “The molecular mechanisms of general anaesthesia: dissecting the GABAA receptor” (2017)
• NCBI Bookshelf: StatPearls Midazolam Chapter

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“Thanks for listening guys… Every day you are getting better at this. Take it day by day, don’t overcook yourself, don’t freak out, and keep studying!”

Podcast Information

Transcript

00:00-00:32 Hello and welcome to Gas, Gas, Gas. This is the best podcast for the FRCA primary exam. Our goal is to fill your brain with all this highly useful information. You might be in the gym right now, commuting or ironing your scrubs. Regardless, the revision is eventually going to end, but for now, expect facts, concepts, model answers, and the odd tangent. Make sure to check out gasgasgas.uk. There’s show notes there, there’s loads more detail. Make sure to like and subscribe. Anyway, buckle up, get ready for your mind to be bent into a new shade and let’s get on with the show.

Introduction and Episode Format Updates

00:37-01:36 Before we get into the bulk of this episode on midazolam, I just want to say I’ve had a look at some old episodes and realise that the “classify and cry” and “define or die” elements have kind of dropped to the wayside a little bit. And I think they’re quite fun and it’s also quite important from just answering questions in the exam perspective. So I’m going to make some slightly ridiculous voiceovers so that when we come to a different define or die or classify and cry moment, it gets marked in the episode. We know a little bit of drama is good, but interestingly, if anyone has any other adages, figures of speech, or idioms like this that are relevant to anaesthetic practice overall. I’m just thinking of something like: is there one that says that you should probably get really prepared other than the seven P’s and “proper and prior preparation prevents piss poor performance” that might come from other parts of the world? Is there a Norwegian define or die or an Australian classify and cry? So if there is one, email me. And you know, it’ll probably make it into the show. Anyway, that’s all tickety boo and great.

Benzodiazepines Overview and Midazolam Introduction

01:36-02:06 What about benzodiazepines? We are going to focus chiefly on midazolam today. There are a bunch of other benzodiazepines: diazepam, temazepam, lorazepam, alprazolam, ad infinitum-ish, but midaz is the one that we tend to see in the cupboards and is the one we use from a general anaesthetic and sedation perioperative perspective. So midazolam, what is it? It’s an imidazole benzodiazepine. Benzos were first synthesised in the 1950s and diazepam actually saw clinical use first in the 1960s.

02:06-02:28 Midazolam is a clear colourless solution in one, two or five milligram per mil preparations. Midazolam hydrochloride. Importantly folks, inadvertent use of the wrong concentration of midazolam for sedation is a never event in the UK. That sometimes comes up in exams. Molecular weight 325.8 grams per mole. I’m sure you’re writing that down.

Mechanism of Action

02:28-03:02 Mechanism of action of midazolam. It potentiates neural inhibition by mediating the effects of GABA. It acts via a specific binding point, or GABA-A transmembrane proteins in cortex, midbrain, spinal cord, etc. We’re going to talk about in reasonable detail how GABA-A receptors behave. In vitro, midazolam also seems to have some opioid receptor agonism at the kappa opioid receptor. Might fit with how it has a degree of analgesic effect if you give it intrathecally. But this is niche stuff.

Clinical Uses

03:02-03:38 What do we use midazolam for? We use it induction of anaesthesia. We use it for sedation. We can use it as a pre-med to get someone down to the anaesthetic room, quite classically used in kids in the UK. 0.5 milligrams per kilo in some orange juice, up to fifteen milligrams. We sometimes reach for it to induce amnesia. Patients sometimes benefit from benzos if they have muscle spasm, and it is an anticonvulsant in a pinch, although lorazepam is the one that’s more studied for that. Comparing it to lorazepam and diazepam, midazolam has the shortest recovery profile as well, and that’s perhaps why we end up using it more.

Dosing Strategies

03:38-04:14 Delightful dosing strategies. So I think everyone kind of just operates in 0.5-10 milligram per patient doses. If you’re being particular, 0.07 to 0.1 milligrams per kilo. So in a 75 kilo patient, you could give them 5.25 to 7.5 milligrams. I don’t think anyone bothers with that. We’ve noted the pre-med PO dose, 0.5 milligram per kilo. You can give up to 1 milligram per kilo, up to 20 milligrams, but I think there might be other better options like dexmedetomidine. Which is going to be another episode later. Up the nose, dexmed, up the nose. Great.

Pharmacodynamics – Side Effects

04:14-04:43 Side effects. Again, remember we’re on the pharmacodynamic side of our conversation, which is what it does to the person, not what the person does to the drug. Side effect profile, midazolam. Cardiovascularly. Just sneaks your blood pressure down a tad, is what the argument would be. Systolic down by 5%, diastolic down by 10%. So really barely a whiff. It might reduce your systemic vascular resistance by 15 to 33%, but it speeds your heart rate up by about 18%. So it sounds very accurate. Someone’s done a very particular study here.

04:44-05:16 Respiratory effects. So it does drop your tidal volume. However, it also causes a compensatory increase in respiratory rate. So your minute ventilation remains about the same, but it also causes apnoea. So if you give too much, then obviously your respiratory system is in a pickle. Midazolam has a negative effect on the dose response curve for carbon dioxide though. So in a patient with sleep apnoea, CO2 retaining COPD, then it’s probably not the drug to reach for unless you’re intubating and sedating a patient and taking them to ITU, knowing that you’re not going to wake them up today, then you might use it as a co-induction agent.

CNS Effects and Memory Formation

05:19-06:24 CNS effects of midazolam. Now, you guys can guess this. Hypnosis, sedation, and antegrade amnesia, i.e., you can’t form new memories, but memories that have already been formed are going to stick around. One of my colleagues at work had mentioned that when they had an anaesthetic for a joint, they asked their colleague, “just make sure I don’t remember anything,” and just gave me some midaz to kick off with, had a midazolam + general anaesthetic approach, and his first new memory following his joint procedure was when he was sat on the ward with a cheese sandwich in his hand. That’s the first memory he formed. Obviously his brain was working enough to request a cheese sandwich and to begin eating cheese sandwich. I don’t know how many bites were out of that sandwich. I don’t think he looked specifically. But it just demonstrates that, you know, a patient can be walking around quite functionally, but not yet be forming memories. It’s crazy, really, isn’t it?

06:21-06:26 It drops cerebral blood flow and also cerebral metabolic consumption of oxygen in a dose-related manner, and it dampens the adrenergic response to stress, but it doesn’t do anything about cortisol secretion, etcetera.

Pharmacokinetics Overview

06:26-06:36 Righto, kinetics, pharmacokinetics. This breaks down, guys, remember, into absorption, distribution, metabolism and elimination: if ever you get a question that says, talk about the pharmacokinetics of, break it down into that, and then you’re going to probably bag some points.

Absorption and Distribution

06:36-07:02 Absorption of midazolam. Oral bioavailability 44%. Distribution. So it’s 96% protein bound in the plasma. So you can imagine then that small changes in protein binding leads to large free fraction agent availability. So in someone with low albumin, your liver cirrhotic patient, as we all know, benzos seem to work really well and last a really long time. This is why. Steady state volume of distribution 0.8 to 1.5 litres per kilo.

Chemical Properties and Tautomerism

07:02-07:46 Now you might say, “hey, what’s the pKa of midazolam?” Well, we know that midazolam behaves a bit strangely because it’s another one of these tautomers, although in previous episode we pointed out that midazolam is not quite really one hundred percent a tautomer. If you’re in an exam and it says what sort of isomerism does midazolam have? And the option is tautomerism or geometric isomerism, blah blah blah. It’s just tautomerism. It’s just being finickity. So it’s tautomer. We’re going to say it. In its water soluble form in that ampoule where its pH is less than four, it’s nice and happily water soluble, and that’s because there’s a ring that is open in the molecule. Chuck it into someone’s plasma, pH now is 7.4. That ring closes, it makes it very lipid-soluble, and it piles across the blood-brain barrier. Great.

Metabolism

07:46-08:53 Now, how is midazolam metabolised? I took four goes to say that. So it’s near complete metabolism in liver. It is CYP3A4 metabolised into two metabolites, alpha hydroxy midazolam and 4-oxymidazolam. Now the alpha hydroxymidazolam is potent, however they are promptly glucoronidated into inactive metabolite. So you could say, well, it has active metabolites, but then you could also say, yeah, but then they just get glucoronidated. So it’s really just academic. Someone called Greenblatt in the late 1970s and early 1980s was doing some experiments, and actually, it’s quite interesting. Who knows if it was because there was an issue with the experiment or not, but old blokes and young lads. Old blokes cleared midazolam more slowly than the young lads. Whereas elderly ladies and young lassies showed no difference in their clearance of midazolam. I do know that we are taught that old folks don’t clear benzos as well. Now, perhaps this is actually based on old folks with low albumin, so they’ve got a greater free fraction and therefore they have higher potency of effect. Who knows? I think I would still be giving only a smidge to an old person and perhaps be a bit more liberal in a younger person.

Elimination and Clearance

08:58-09:30 How is it eliminated? Well, as you can imagine, using your powers of imagination, you can know that if something has been beautifully glucoronidated, it is delightfully water-soluble. And how do we get rid of water-soluble molecules? Kidneys cleared through the kidneys. Clearance is 5.89 mils per kilo per minute. Renal impairment has minimal effect on the clearance of this. Elimination half-life, 1.5 to 3.5 hours. In critically ill folk, the elimination half-life goes up, but that would suggest to me that it’s actually perfusion of kidney-related clearance as opposed to active excretion.

MAC Reduction and Clinical Timing

09:30-10:00 So other points of note, a midazolam premedication reduces your MAC requirements by 15%, but remember guys, it’s only going to reduce those MAC requirements by 15% whilst the drug works, it’s not just like, “ah, my whole operation, my 18 hour laparotomy. It’s okay, folks, we can go with the Mac of point 6. I gave them the midazolam at the start,” so you know… Probably just means it’s quicker to get them asleep at the start, and you have a lower chance of having accidental awareness under general anaesthesia in that trip to theatre from the anaesthetic room phase.

Clinical Applications

10:00-10:23 When do I use midazolam? For slightly hairy intubations where you don’t want to mess with blood pressure too much, I’ll give midazolam. I give midazolam if I’m giving someone ketamine, and I’ll give them a really big dose of midazolam if it’s the post-cardiac arrest, or “we’re not going to wake them up today” sort of patient, whereby you really want to chill them out as best you can, but you don’t want to be smashing them with buckets of propofol, so they get midazolam and fentanyl, etc.

Challenging Clinical Scenarios – Cardiac Arrest

10:23-12:15 Where have I seen it reached for? So I’ve seen it reached for during that awful cardiac arrest CPR situation when you’re doing CPR on often a fittish person. And they start going “ow ow no oh who’s that there” and you stop CPR thinking they’re conscious and that maybe they’ve got output and then they just go “brrr” and lose consciousness again. It’s very unpleasant for all involved, and it’s challenging to figure out if they’re ROSC’d or you’re just doing excellent CPR. And if you’re in the excellent CPR and they’ve got VF and it’s just a bugger and it won’t zap back to something more sufficient and they need, you know, your three hundred of amiodarone, your hundred and fifty of amiodarone, your four grams of magnesium, and then you think “let’s give another two grams of magnesium”…

Them not returning to consciousness after that is not the end point of your CPR. Your end point of your CPR is either they’ve got a pulse again, “oh, look, they’re not waking up” – well, you know, they’ve just had loads of CPR, that doesn’t really mean anything at that point, or they’re so metabolically deranged they’ve got no hope. So, the next step in that thought process is: Are they forming memories? Are they going to get PTSD from those formed memories? Or is this just scant perfusion of their brain? And we might be hearing a no, but we might not. It’s hard to really tell.

12:15-12:45 I haven’t decided if in that situation I would or would not give the patient midazolam. It’s not in ALS, but then ALS, remember folks, is not the be all and the end all of resuscitation. It’s a guideline. It misses the load of nuance because it has to be simple enough to teach people in either two days or one day. a load of e-learning. That’s not the same as a clinician with donkeys’ years of experience. But it’s a great place to start to get people skilled up in the technical procedural aspects of CPR instead of the wider doctorate aspects of resuscitation.

12:45-12:47 I think it’s a crying shame that anaesthetists are coming off of the cardiac arrest bleeps in hospital because whilst a lot of those cardiac arrest bleeps are in old folk who should have had DNARs, there’ll be a subgroup of those people who actually might survive if they had blisteringly effective CPR and peri-arrest care that your experience might deliver, whereas a ward junior medical registrar, some foundation doctors following the ALS algorithm, which is deemed to be this, you know, gold standard thing, is perhaps not the best thing for the patient. It’s a pity. It really is. Anyway, getting carried away here.

Antidotes and Reversal

12:47-13:50 Antidotes for midazolam. Say someone’s accidentally done the never event and they’ve given a bucket of midazolam instead of a thimble. Then flumazenil, our benzodiazepine receptor binding molecule that antagonises the receptor, is a great choice. Interestingly physostigmine, which is an anticholinesterase, can also alter the sedating effects of benzodiazepines and wake people up. Cool. Not something I knew about before, but people are going to use flumazenil. But why don’t we just use flumazenil on anyone who’s come to A&E, you know, Tammy or Tommy? So Friday night they’ve taken a load of alprazolam, that’s Xanax, and you think, “well, we could just give them some flumazenil, wake them up, send them on their way,” because they might have been taking other things beyond the Xanax alprazolam. That Xanax in their system might be stopping them from actually seizing like it’s the 31st of December 1999. So it’s better just to let those drugs cook off, clear out, keep them hydrated, warm, safe, breathing, oxygenated, etc. Always look at Toxbase.

GABA and GABA-A Receptors

13:50-14:28 So moving on from the section on midazolam and midazolam kinetics and pharmacodynamics. We mentioned GABA receptors here, GABA, etc., etc. We just probably need to make sure we remember what the heck that is. So GABA, GABA, we’ve said GABA a lot – GABA gamma aminobutyric acid. It’s an endogenous neurotransmitter that is incredibly important when it comes to CNS activity. The receptor we’re interested is the GABA-A receptor. This is a five unit i.e. pentameric membrane bound group of proteins which have a central chloride channel. There are a bunch of subtypes of GABA-A receptors – not doing that.

GABA-A Receptor Function

14:28-15:28 What happens when GABA binds to a GABA-A receptor? Well, it alters the shape of that receptor, opening that chloride pore, and lets chloride ions into the cell. Chloride ions, as we all remember folks, are negatively charged. They are anions, an anion, a negative ion. That’s how I remember it. If you make the cell more negative, it’s harder for it to depolarise when an action potential comes along and prods it. Therefore, you inhibit transmission. Now, more specifically, you find clusters of these GABA-A receptors on the postsynaptic membranes of neurons. That means that when you modulate that, increase the chloride influx, you end up with a postsynaptic negative environment. So those neurotransmitters that are crossing the synaptic cleft have a higher threshold before they’re going to communicate downstream. So you’d need a supranormal amount of neurotransmitter being ejected from that nerve to trigger downstream ongoing communication of that potential.

Other GABA-A Receptor Ligands

15:28-16:07 What binds to a GABA-A receptor? Well, we’ve said GABA, gamma-aminobutyric acid, and there’s a specific home on that receptor for that ligand, but then a bunch of other stuff binds to it, but it doesn’t bind to the GABA site. So benzodiazepines bind to it, general anaesthetic agents seem to bind to it, and ethanol binds to it, and these all allosterically modulate this receptor. Those agents tend to make this receptor more likely to be open and therefore let chloride ions in and therefore make it harder for transmission to occur. Now, you’re probably thinking now: GABA-A, what does that mean? Well, it means that GABA-B must also unfortunately exist, otherwise, it would just be called a GABA receptor. GABA-B is a G protein coupled membrane bound protein that we’re not interested in and no one tends to be interested in for anaesthetic purposes.

GABA Deficiency and Clinical Relevance

16:15-16:54 So let’s just have a bit of a thought experiment here. Imagine if you took away someone’s ability to synthesise GABA. They’re going to be rattling, they’re going to be all disinhibited and really easily communicating signals down their neurons, and it’s all probably a bit of a mess. They’ll probably have a seizure. There are some rare diseases which can involve this, but interestingly, pyridoxine is critical in the synthesis of GABA-gamma aminobutyric acid. If you have a pyridoxine deficiency or a defect in one of the enzymes that’s involved in the pathway of converting pyridoxine to GABA, you’ll end up in a bad way. Now you can treat those seizures seemingly with anticonvulsants, but most of the time if you supplement the patient with pyridoxine or the relevant derivative, the problem goes away.

16:54-17:05 Huntington’s disease seems to be partially associated with a lack of GABA in the striatal projections that go to your globus pallidus. Remember, globus pallidus is part of your basal ganglia.

Alcohol Withdrawal and GABA

17:05-18:26 But now, we’ve all seen patients with a relative deficiency of GABA. Yes, that’s right. Our dear population of people who drink too much alcohol too frequently. The mechanism of this is: booze modulates GABA, means that your neurons are all suppressed. Over chronic alcohol consumption time frames your neurons upregulate themselves to try and contend with this suppression that the alcohol causes. That returns you to a modicum of functioning. You don’t seem drunk anymore, and that’s because your neurons are countering the booze. You remove the booze and then your neurons have the brakes taken off of them because they were fighting to be active and now you’ve taken away the thing that they were fighting against. So they’re really jazzed up. So you end up sweaty, agitated, delirious, hallucinating, confused, hypertensive, tachycardic, and ending up with seizures, delirium tremens, etc., being pinned down by all the on duty police officers in North Wales whilst getting a ketamine anaesthetic on the floor of AMU. And this is why benzodiazepines are an effective treatment for alcohol withdrawal, because they replace the role of the alcohol. But that makes me think that if a patient with acute benzodiazepine withdrawal was on your ward, well, you could treat them with alcohol. Arguably, you could also just treat them with benzodiazepines, but you know, you could have a twinkle in your eye as you suggest that to the consultant.

Closing Remarks

18:26-18:35 So, I hope you have enjoyed that episode, folks. I hope you have a nice weekend next week where we’re gonna probably do dexmedetomidine or clonidine, one of the two.

18:42-19:06 Thanks for listening, guys. I hope you found it useful, but if you found it awful, do let me know. Please like and subscribe, register with whichever podcast platform you find yourself using. Leave a comment if you think I need to square something away. I just want to make sure that you guys know that every day you are getting better at this. There is a bucket of content to try and consume, and it is like drinking from a fire hose. Take it day by day, don’t overcook yourself, don’t freak out, and keep studying.