Dr Sharon Rees @reesprescribe
Day 1: After large-scale production of cortisone was enabled in the 1950s, more cortisol derivatives were discovered, such as #dexamethasone in 1957. Long acting and more potent, #dexamethasone has primarily glucocorticoid effects, an advantage for a minimal effect on fluid retention.
Dr Sharon Rees @reesprescribe
Day 2: Indications for #dexamethasone in adults and children include suppression of inflammatory and allergic conditions, cerebral oedema, croup, palliative care (anorexia, dysphagia, nausea and vomiting, pain), malignant bowel obstruction, soft tissue injections. Recently found to lower COVID-19 deaths in ventilated patients.
Dr Sharon Rees @reesprescribe
Day 2 (cont). #dexamethasone dose range oral adult 0.5 – 10 mg, usually starting high, then tapering down, although higher doses needed for some palliative care conditions. Children variable mg/kg.
Dr Sharon Rees @reesprescribe
Day 3: #dexamethasone kinetics. Well absorbed via all routes with a high volume of distribution and moderate protein binding. Liver & renal metabolism via CYP3A4. Mainly urinary excretion. Biological half-life 35-54 hrs.
Dr Sharon Rees @reesprescribe
Day 4: mechanism of action: increases anti-inflammatory compounds and in higher doses, lowers production of pro-inflammatory/immune agents eg cytokines, which causes immunosuppression. Changes via glucocorticoid receptor/altered genes can take hours-days, but some non-genomic effects can be faster e.g reduced vaso-dilation and capillary permeability.
Dr Sharon Rees @reesprescribe
Day 4 (cont): Action of #dexamethasone in specific conditions is poorly understood; may reduce tumour-induced fluid by lowering permeability of tumour capillaries. Used alone, or in combination, the anti-emetic action may activate brain NTS pathways (rich in glucocorticoid receptors) and/or antagonise 5HT3A receptors.
Dr Sharon Rees @reesprescribe
Day 5: Adverse drug events #dexamethasone (can be dose dependent): Common include insomnia, mood changes, fatigue, hypertension, nausea, skin reactions, high-risk infection, osteoporosis, GI bleeding Uncommon incl; psychosis (lower risk compared to other CCS), eye disorders, venous thromboembolism (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 5 (cont): ADEs can be more serious in elderly. See resources eg CKS for how to minimise ADEs: https://cks.nice.org.uk/topics/corticosteroids-oral/management/corticosteroids/#minimizing-adverse-effectsk. Careful withdrawal if more than 1 mg/day for more than 3 weeks (also for other scenarios eg taking doses in evening).
Dr Sharon Rees @reesprescribe
Day 6: Drug-drug-interactions #dexamethasone. CYP3A4 enzyme inducers eg rifampicin reduce effects, while inhibitors eg clarithromycin increase effects. All drugs which can cause hypokalaemia elevate arrhythmia risk. NSAIDs increase GI bleed risk; #dexamethasone can also increase warfarin effects (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 7: The mechanism for COVID-19 effects is unclear, while corticosteroid harm in severe infection remains a threat; possibly helps because the differential between COVID-induced impaired immunity (less impact from CCS low immunity) and benefit from anti-inflammatory actions and help with lung regeneration is exploited by #dexamethasone.
EARN YOUR CPD CERTIFICATE
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
Complete the additional reading suggested below and then answer the ten questions. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A, B, C, D option. If you achieve 8 or more out of ten on the questions, a CPD certificate will be emailed to you.
Further reading on #dexamethasone
- Corticosteroids, general use : https://bnf.nice.org.uk/treatment-summary/corticosteroids-general-use.html
- Corticosteroids, inflammatory disorders : https://bnf.nice.org.uk/treatment-summary/corticosteroids-inflammatory-disorders.html
- DEXAMETHASONE : https://bnf.nice.org.uk/drug/dexamethasone.html
- Dexamethasone 2mg Tablets : https://www.medicines.org.uk/emc/product/5411/smpc#gref
Dexamethasone is a derivative of epinephrine
TRUE or FALSE?
Dexamethasone is a medium potency corticosteroid
TRUE or FALSE?
Which of the following does NOT benefit from dexamethasone in end-of-life care?
- Nausea and vomiting
- Constipation
- Reduced appetite
- Pain
Which of the following is TRUE?
- All the actions of dexamethasone take days to begin
- Dexamethasone has a short half-life
- Dexamethasone is broken down in the kidney by phase 2 metabolism
- High doses may be needed for some palliative care conditions
Many of the side-effects of dexamethasone are dose-related
TRUE or FALSE?
Which of the following is NOT thought to be an anti-emetic action for dexamethasone?
- Preventing dopamine from docking into the chemoreceptor trigger zone
- An anti-inflammatory effect in the central nervous system
- Opposing the emetic effect of serotonin (5HT)
- Acting on the nucleus tractus solitarius (NTS) to interfere with vomiting pathway
Tendon rupture is a common side-effect for dexamethasone?
TRUE or FALSE?
The drug-drug interaction between dexamethasone and phenytoin is because phenytoin is an inducer of liver enzymes and this will reduce the efficacy of dexamethasone
TRUE or FALSE?
Taking dexamethasone will always mean a programme of careful withdrawal
TRUE or FALSE?
Dexamethasone can reduce mortality in severe COVID-19 cases?
TRUE or FALSE?