Day 7: In view of the sedative effect, studies are ongoing to assess the abuse potential for #daridorexant. At clinical doses, the risk appears low for abuse or dependence. Unknown at higher doses, or for those with history of addiction. Schedule IV Controlled Drug in USA
Day 6: Lower dose 25mg for CYP3A4 inhibitors (↓drug metabolised) eg diltiazem, clarithromycin,ciclosporin. Minor effect grapefruit/avoid in evening. Avoid strong CYP3A4 inhibitors eg fluconazole. No recommendation for inducers re loss of efficacy. Will ↑ CNS depressants eg alcohol (NOT exhaustive)
Day 5: Common adverse drug effects for #daridorexant include headache, sleepiness, dizziness, GI disorders. Hypersensitivity, hallucinations & abnormal dreams are all uncommon (NOT exhaustive)
Day 4: #daridorexant selectively antagonises orexin 1 & 2 receptors. Neuropeptides orexin A/B normally act on these receptors to increase wakefulness; preventing docking promotes sleep onset & maintenance
Day 3: #daridorexant has ↑absorption, bioavailability, Vd, protein binding. Extensive hepatic metabolism by CYP3A4/no active metabolites. Minor inhibition OAT & P-gp transporters. Main excr faeces, 28% renal. Terminal t½ 8hrs. Dose adjust moderate+ hepatic impairment. No renal function adjustments.
Day 2: #daridorexant tablet is licensed for insomnia in adults if symptoms present for > 3mnths & other interventions have been ineffective. 25 or 50mg oral tablet once daily taken 30 minutes before bedtime. Duration of treatment ‘as short as possible’ with efficacy data up to 1 year
Day 1: In the late 1990s, investigations into brain feeding systems led to discovery of orexin peptides/receptors, a system stimulating arousal, hunger & food seeking behaviour. As a drug target, blockade was found to promote sleepiness. #daridorexant licensed c. 2022
New series '7 days of #daridorexant' starting today - hope you enjoy
Day 7: Poor evidence re neuropsychiatric effects of #varenicline. Outlined in a post-marketing observational cohort study were:mood swings, depression, hallucinations, changed libido as uncommon events & psychosis noted ‘rare’ (not exhaustive). Risk ↑ if history of psych illness; warn accordingly
Day 6: #varenicline has no known clinically signif drug-drug interactions. A putative interaction with alcohol, namely ↑ intoxication effects is not established. Can use with nicotine replacement products, but advice needed pre use with other cessation meds as can ↑ risk of ADEs eg psych disorders
Day 5: Common ADEs for #varenicline include GI disorders, muscle/joint disorders, headache, skin reactions, sleep disorders. Mood change, sexual dysfunction & seizure are all 'uncommon'. Angioedema & SCARs are rare (NOT exhaustive)
Day 4: #varenicline is a partial nicotine receptor agonist which has its greatest effect in the CNS. Binding leads to controlled dopamine release, alleviating craving & withdrawal. By preventing nicotine itself binding, #varenicline reduces the reinforcing effects of nicotine/lessens addiction
Day 3: #varenicline (cont). Severe renal impairment may require dose adjustment & consideration should be given to the effect of smoking cessation on kinetics of other drugs eg olanzapine, clozapine, theophylline
Day 3: Cmax 3-4 hrs, high bioavailability & high Vd. Low plasma protein binding. Minor metabolism, majority not transformed/no active metabolites. Renal excretion mostly unchanged drug. No impact CYP450 system. Elimination t½ ~24 hrs
Day 2(cont) #varenicline can be continued to support abstinence @ same dose for further 12 weeks
Day 2: #varenicline is a tablet licensed as smoking cessation aid for 18+. Started when person is still smoking & once therapy established, they stop smoking after 1-2 weeks. Titration up to 1mg twice daily; Days 1-3, 500 micrograms o.d, Days 4-7, 500 micrograms b.d. Treatment course 12 weeks
Day 1: An alkaloid extract from the Laburnum tree, cytisine was used in E.Europe/known for mild impact on smoking cessation. Exploration of structural analogues with better efficacy led to #varenicline discovery. FDA/EMA approved as a stop smoking aid in 2006
New drug series '7 days of #varenicline' starting today
Day 7: Resistance to #teicoplanin is rarer than for vancomycin but growing concern in UK re acquired resistance eg MRSA, E.faecium, S haemolyticus & coagulase neg staphylococci. Multiple mechanisms include increased cell wall thickness & changed cell wall structure reducing drug affinity
Day 6: There are no specified drug-drug interactions for #teicoplanin in the BNF. Caution for all drugs which can cause nephrotoxicity e.g ciclosporin, furosemide (NOT exhaustive)
Day 5: #teicoplanin ADEs: Common include: fever, pain, rash. Uncommon include:hypersensitivity, ototoxicity, diarrhoea, N&V. Frequency not known include:nephrotoxicity, SCARs, seizure. Prolonged use can cause superinfection. (NOT exhaustive)
Day 4: #teicoplanin is 1 of 2 ‘glycopeptide’ antibiotics; other is vancomycin. The mechanism of action is inhibition of bacterial cell wall synthesis by binding to peptidoglycan (PG) precursors. This is distinct from penicillins; these target the enzymes which cross link PG chains in cell wall
Day 3(cont) #teicoplanin has a relatively narrow therapeutic index. Therapeutic drug monitoring of trough concentrations required. Renal impairment warrants dose/interval adjustment
Day 3: Parenteral delivery of #teicoplanin yields high bioavailability. High protein binding & good Vd. Penetration to bone/synovium, soft tissues, lungs, heart, kidney. Poor reach to CNS. Minimal metabolism, renal excretion as unchanged drug. Long t½ up to 100hrs @steady state >needs loading dose
Day 2 (cont) #teicoplanin taken by mouth only for C.difficile 100-200mg twice daily for 7-14 days;#teicoplanin is not absorbed from gut, so high concentration in gut to manage C.difficile
Day 2: #teicoplanin is used i.m/i.v for serious gram-positive infections: complicated soft tissue /urinary tract/lung infections, diabetic foot infections, bone & joint infections. Unlicensed use surgical prophylaxis. Dosing regimens by weight & varied re infection/site
Day 1: Isolated in 1970s from an Indian soil sample #teicoplanin is derived from the bacterium Actinoplanes teichomyceticus. The structure was revealed in 1980s & the drug licensed in Europe 1988. Remains unlicensed by FDA
New series '7 days of #teicoplanin' starting today
Day 7: #naproxen is categorised as having a better cardiovascular side-effect profile compared to other NSAIDs. Believed to be because of low COX-2 selectivity; this means that the anti-thrombotic effects of local prostaglandins continue to work & protect atherosclerotic plaques from thrombosis