Dr Sharon Rees @reesprescribe
Day 1: The Tetracycline drug class was derived from soil bacteria ‘actinomycetes’. Tetracycline represents an early example of a broad-spectrum and semi-synthetic antibiotic. Modification to oxytetracycline to increase potency, oral absorption and t½ led to #doxycycline, approved by the in FDA 1967.
Dr Sharon Rees @reesprescribe
Day 2: #doxycycline is active against multiple infections, Gram positive and negative organisms, anaerobes, mycoplasmas, intra-cell chlamydiae, rickettsiae, as well as protozoan parasites. Can be used (where suitable) as oral single agent for methicillin-resistant Staphylococcus aureus.
Dr Sharon Rees @reesprescribe
Day 3: Mode of action. Bacteria have transport systems that admit tetracyclines (TCs), but human cells mostly do not uptake. #doxycycline binds to bacterial ribosome, prevents tRNA binding mRNA, inhibits protein synthesis, cell functions and replication. Predominantly bacteriostatic.
Dr Sharon Rees @reesprescribe
Day 3 (cont): TCs have anti-inflammatory/anti-oxidant properties that may be helpful for inflammatory conditions such as rosacea and periodontitis (low dose). Mechanism possibly via reduced cytokine production, such as TNF-decreased, IL-6, 8 and alpha decreased matrix metalloproteinases so decreased tissue remodel/destruction. Also impaired enzyme production such as phospholipase, so there's decreased prostaglandin synthesis.
Dr Sharon Rees @reesprescribe
Day 4: Widespread use for over 60 years and low-level use for livestock/crop protection has caused high levels of tetracycline resistance; semi-synthetic modifications such as #doxycycline and newer tetracyclines like tigecycline have helped to overcome resistance issues. Some bacteria can sense a repressor gene prod by TCs prompting up-regulation of an efflux pump, which pushes the antibiotic out of the cell. Some bacteria have ribosomal protection tools, which dislodge the TC. Enzyme inactivation pathway also discovered, predominantly in vitro.
Dr Sharon Rees @reesprescribe
Day 5: #doxycycline kinetics; well-absorbed from GI tract unless Ca, Mg, Al, Fe present as can form insoluble complexes with tetracyclines. Interaction with Ca can lead to teeth staining and reduced bone growth in children/newborns, or if taken after fourth month of pregnancy.
Dr Sharon Rees @reesprescribe
Day 5 (cont): Summary of product characteristics states OK to take with milk (despite Ca levels), as #doxycycline has low Ca binding, hence no label 7 (no milk two hours before/after taking). NHS sites state avoid dairy without clariflcation re milk, which could cause confusion. #doxycycline has high bioavailability, high Vd and good tissue penetration (low in CSF) + high intra-cellular penetration. Low hepatic/GI metabolism (CYP pathways unknown) with excretion mainly unchanged (despite lipophilic drug?) in urine and faeces, t½ 16–22 hours.
Dr Sharon Rees @reesprescribe
Day 6: #doxycycline common adverse drug reactions include; rash, headache dyspnoea, tachycardia, peripheral oedema, photosensitivity; rare/serious, antibiotic-associated colitis, raised intracranial pressure, severe cutaneous adverse reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome.
Dr Sharon Rees @reesprescribe
Day 6 (cont): Drug-drug interactions; severe include lithium (increase risk toxicity) and systemic/topical retinoic acid derivatives; multiple ‘moderate’ drug interactions such as an increased effect of warfarin (monitor) and in combination eg #doxycycline and rosuvastatin both increase risk hepatotoxicity (not exhaustive)
Dr Sharon Rees @reesprescribe
Day 7: #doxycycline #coronavirus possible roles
- Some anti-viral action, such as lower cytokines when used for dengue virus
- Treatment of COVID-19-associated pneumonia (NOT first line unless penicillin allergy)
- Possibly helps reduce lung injury in acute respiratory distress syndrome
- May remove ‘aged/damaged’ cells vulnerable to COVID-19 attack.
NOTE: points 1,3,4 based on mostly animal/in vitro research.