Therapeutics: Anti-Emetics

Take Aurally · Nausea & Vomiting

In this episode recorded in March 2020 Kunal Gohil joined the podcast to take us through anti-emetics. Featuring a whistle-stop tour of the vomiting reflex, the mechanisms of anti-emetics and a discussion on how they sound like Transformers!

Here is our Take Visually going through the vomiting reflex:

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The vomiting centre (VC) sits in the medulla oblongata of the brain. In the vomiting reflex the diaphragm contracts, abdominal muscles tense, the gastric sphincter relaxes, the epiglottis closes to prevent aspiration and the stomach contracts. Outside of the blood-brain barrier (BBB) sits the chemoreceptor trigger zone (CTZ) whose job is to detect blood borne insults and send signals to the VC which sits within the BBB.

There are 5 key mechanisms which trigger the vomiting reflex

Blood-borne agent

Typically poisoning such as electrolyte disturbance, medication side effect or a noxious substance. Detected by the CTZ which signals to the VC.

Direct insult to gastrointestinal tract

Something within the GI tract such as medication or rotten food. Detected by lumen cells which signal to the VC via serotonin along the vagus nerve.

Vestibular system

‘Motion Sickness’. The labyrinth within the inner ear signals to the vestibular nuclei close to the VC via the vestibulocochlear nerve.

Higher centres

Fear, anxiety, disgust, noxious stimuli. Mediated by higher cortical centres and self-perpetuated in a vicious cycle.

Direct insult to brain

Head injury, space occupying lesion, inflammation/swelling. Increased intracranial pressure.

All of these mechanisms use different neurotransmitters and can be targeted with different agents.

The VC uses mostly muscarinic (M1) receptors and so can be blocked by antimuscarinic agents but as it sits within the BBB it is hard to reach. The CTZ mostly uses dopamine (D2) receptors and serotonin (5-HT). The vagus nerve also uses 5-HT. The vestibular nuclei use histamine (H1) receptors. Higher centres (sensory input) can be targeted with anxiolytics (especially benzodiazepines). Direct insult by inflammation can be treated with steroids, especially dexamethasone.

Here is our Take Visually going through the different anti-emetic mechanisms:

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Therapeutics: Anti-Epileptics

Our favourite pharmacist Kunal Gohil rejoins the podcast to take us through anti-epileptic medications!

Epilepsy is a neurological condition where abnormal electrical brain activity causes uncontrolled movements, behaviour and sometimes loss of awareness. It affects around 600,000 people in the UK. This means that almost 1 in 100 people in the UK have epilepsy. Around 87 people are diagnosed with epilepsy in the UK every day.

In the UK every year about 1000 people die due to epilepsy. One cause is status epilepticus. Status epilepticus describes a seizure which lasts longer than 5 minutes or recurrent seizures without recovery between them. Sometimes there is no clear cause and this is called sudden unexplained death in epilepsy (SUDEP).

Epilepsy causes unprovoked seizures. Provoked seizures are caused by space occupying lesions, infections or electrolyte abnormalities.

Pharmacology

Excitatory neurones (the accelerator) cause a positive charge in the post-synaptic neurone through sodium influx while inhibitory neurones (the brake) cause a negative charge through chloride influx.

The basis of epilepsy treatment is therefore either to reduce the accelerator or increase the brake.

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The three mechanisms of treatment

Modulate Ion Influx

These drugs block the action of ion channels either on the pre-synaptic or post-synaptic neurone.

Sodium valproate, lamotrigine, carbamazepine and phenytoin block pre-synaptic sodium channels.

Lamotrigine, Pregabalin and Gabapentin block calcium channels on the pre-synaptic neurone.

Type 2 calcium channels are on the post-synaptic membrane; these are blocked by sodium valproate.

GABA Propagation

This is all about increasing inhibition by reducing membrane positivity and reducing the propagation of action potentials. Chloride channels have a benzodiazepine and barbiturate receptor so these drugs can be used. This is the basis of treatment for status epilepticus.

Novel Mechanism

Levetiracetam doesn’t work on ion channels or affect GABA. It works by stopping the release of glutamate from vesicles and so reduces NDMA action and so reduces transmission.

Sodium Valproate (Epilim)

Works on sodium and calcium channels and does have some action on GABA receptors. First line in generalised, partial and absence seizures. Also used in status epilepticus refractory to benzodiazepines.

Teratogenic; can cause spina bifia. In female patients of childbearing potential need to be on pregnancy prevention.

Can cause acute pancreatitis, hepatitis, blood dyscrasia and hyperammonemia.

Phenytoin (Epanutin)

One of oldest anti-epileptics. Non-specific for cardiac sodium channels and so can cause arrhythmia and so needs monitoring.

Very narrow therapeutic index with saturation kinetics. Enzyme inhibitor. Albumin bound. Causes gingival hyperplasia.

Doses differ depending on administration.

Carbamazepine (Tegratol)

Useful in partial seizures but poor for absence seizures. Powerful enzyme inducer. Associated with Stevens-Johnson Syndrome especially in Korean/Japanese populations.

Levetiracetam (Keppra)

Good for partial seizures and second line in generalised. Now being used in status epilepticus. Was the focus of the EcLiPSE trial which we have previous podcasted about. Can also be given IV.

Lamotrigine (Lamictal)

Also associated with Stevens-Johnsons Syndrome but has a lower rate of adverse drug reactions if dose started low and gradually increased. Can only be given orally.

Clobazam/Clonazepam

Lorazepam, Midazolam and Diazepam are reserved for rescue use in status. Clobazam and Clonazepam are safer for longer term temporary use.

Kunal also emphasised how important the brand of Anti-Epileptic is. In January 2014, the Medicines and Healthcare products Regulatory Authority (MHRA) issued guidance on the safe prescription of anti-epileptics and which brands can and can’t be substituted:

Category 1  Phenytoin, carbamazepine, phenobarbital and primidone. Specific measures are necessary to ensure consistent supply of a particular product. This means that individuals should not be switched between versions of these AEDs, but should always kept on the same version.                                                    

Category 2  Sodium valproate, lamotrigine, perampanel, retigabine, rufinamide, clobazam, clonazepam, oxcarbazepine, eslicarbazepine acetate, topiramate and zonisamide. The need for continued supply of a particular product should be based on ‘clinical judgement’ (the doctors judgement of the risk of problems) and in consultation with the individual.This means that a doctor should decide, with the individual, whether it is important to always stay on the same version or whether it is ok to switch between different versions.

Category 3  Levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide and vigabatrin. No specific measures are normally required and these AEDs can be prescribed generically.This means that individuals can be switched between different versions of their AEDs.

Kunal recommended the Epilepsy Society website

You can find our episode on Seizures here

The NICE Guidelines for Epilepsy diagnosis and management can be found here

Here is the Take Visually for this episode:

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Therapeutics: Adverse Drug Reactions Part Two

In the second part of our Adverse drug reactions (ADR) series recorded in Annie’s Burger Shack Kunal takes us through:

• Type D (Delayed)

• Type E (End of Dose)

• Type F (Failure)

• An example of each one and what we can do about them

You can find Part One here

ADRs cost the NHS in England £380 million a year (Source: NICE)

Here is the #TakeVisually for this episode:

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1.6% of hospital inpatients will have an avoidable ADR during their stay (Source: NICE)

Therapeutics: Adverse Drug Reactions Part One

Kunal Gohil joins Jamie at Annie’s Burger Shack in Nottingham to discuss Adverse Drug Reactions.

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ADRs are responsible for 6-7% hospital admissions each year in the UK (from NICE)

Kunal defines adverse drug reactions before going through the first three types:

• Type A (Augmented)

• Type B (Bizarre)

• Type C (Chronic)

Giving examples of each and steps of how to avoid them!

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ADRs affect 10-20% of hospital inpatients each year in the UK (from NICE)

Here is the #TakeVisually for this episode:

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45% of ADRs are preventable (from NICE)

Therapeutics: Anti-Parkinson's

In our first podcast back from our Easter Holidays our favourite pharmacist Kunal Gohil joined us in the booth to tackle anti-Parkinson's medications.  Expect the usual blend of physiology, pathophysiology and pharmacology as well as Jamie showing off his rapid Googling skills. 

Here is the Take Visually for this episode:

If, like Jamie, you also struggle with the anticholinergic toxidrome here is a useful cartoon from Life in the Fast Lane:

Therapeutics: Anticoagulants

In this podcast Kunal Gohil joined us in the recording booth to take us through anticoagulants.  

Kunal talks about the clotting cascade (simplified) as well as:

• Heparins
• Coumarins
• DOACs
• Fundoparinux
• Thrombolytics

As ever Kunal shares his great knowledge including the reason why warfarin might actually increase your risk of clot!

This is the Take Visually for this episode:

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Therapeutics: Antiplatelets

Kunal Gohil made his way down to the pod to talk us through antiplatelet treatment in the first of two podcasts on Antithrombotics.

The focus is on Aspirin and Clopidogrel but we also cover Prasugrel and Ticagrelor.  

Here is the CHA2DS2VASc Score for Stroke Risk in Atrial Fibrillation as mentioned in this episode.  

Here is the HAS-BLED Score for assessing bleeding risk before starting anti-coagulation in atrial fibrillation.

Remember: antiplatelets have NO role in atrial fibrillation.

Here is the Take Visually for this episode:

Therapeutics: Asthma

In this episode our favourite Pharmacist Kunal Gohil joined us again to talk us through the treatment of Asthma.  

Here is the full British Thoracic Society Guidelines for Asthma (the guidelines this podcast is based on are on page 78).

Don't forget to check out our Take Aurally Asthma episode for more information on Asthma and its acute management.

And here is our Take Visually for treating Asthma:

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Therapeutics: COPD

For this episode ED pharmacist Kunal Gohil came down to talk us through the management of COPD.  

This is based on NICE Guidelines CG101.

Remember for the acute management of COPD to check out our podcast.

Here is the Take Visually for this podcast:

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Therapeutics: Hypertension

In our first Therapeutics special our NUH ED Pharmacist Kunal Gohil came down to discuss the treatment of Hypertension.  Kunal had previously joined us to discuss the role of the ED Pharmacist.

The guidelines discussed are NICE CG127.

ACE Inhibitors end in 'pril' - such as Ramipril

Angiotension II Receptor Blockers end in 'sartan' - such as Candesartan

Peripheral Calcium Channel Blockers end in 'pine' - such as Amlodipine

Central Non-Dihydropyridine - e.g. Verapamil and Diltiazem

Beta Blockers end in 'lol' - such as Bisoprolol

Here is the Take Visually for this podcast:

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