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

Day 6: #naproxen (cont). Omega-3 ethyl esters taken with #naproxen also increase bleeding risk – this is denoted in BNF as a ‘severe’ drug-drug interaction

Day 6: DDIs:multiple ‘severe’ warnings!All drugs affecting haemostasis ↑ bleeding risk eg DOACs, corticosteroids. Lots diuretics either ↑risk renal failure eg indapamide or ↑risk hyponatraemia eg furosemide.↑risk nephrotox eg ACEIs. NOTE toxicity risk with lithium & methotrexate (NOT exhaustive)

Day 5: Adverse drug effects. These arise from blocking the ‘house-keeping’ cox-1 enzyme & include GI disorders, renal impairment & fluid retention (heart failure ‘common’). Uncommon include menstrual disorder, haemorrhage, sleep disorders. Rare: SCARs, myalgia, alopecia (NOT exhaustive)

Day 4: #naproxen is a non-selective non-steroidal anti-inflammatory drug (NSAID). This means it blocks cyclooxygenase forms 1 &2 resulting in decreased prostaglandin synthesis. The therapeutic action arises from blocking cox-2 leading to anti-pyretic, anti-inflammatory & analgesic properties

Day 3: #naproxen has high oral absorption, cmax 2-4 hrs. High plasma protein binding. Phase 2 metabolism. Excretion in urine as conjugated naproxen with some unchanged drug. Avoid severe hepatic impairment & caution/avoid with any renal impairment. Elimination t½ 12-17 hrs

Day 2 (cont). #naproxen is unlicensed use in juvenile idiopathic arthritis for < 5yrs. Unlicensed for <16 yrs for pain/inflammation from MSK disorders/dysmenorrhoea. If used, doses are weight based & maximum per dose is 500mg

Day 2: #naproxen is licensed for age 16+ in various oral formulations for pain & inflammation from rheumatic disease, MSK disorders, dysmenorrhoea & gout. Dose range 250-1000mg/day in 1-2 divided doses or 250mg x3-4/day. Unlicensed use acute migraine.

Day 1: The search for safer NSAID-type drugs compared to aspirin led to derivatives of arylproprionic acid (AA) discoveries, incl ibuprofen being discovered. In the late 1960s, addition of 2 fused benzene rings to the AA structure increased anti-inflammatory potency & longer half-life > #naproxen

New drug series 7 days of #naproxen starting today 😁

Day 7: #ticagrelor is usually stopped after 12 months. The ‘dual anti-platelet therapy (DAPT)’ is justified when thrombosis risk is high in the post event period, but once risk drops, the bleeding risk outweighs the anti-thrombotic value. There are exceptions to this & individual assessment needed

Day 6: Drug-drug interactions: synergistic effect with all antiplatelets, anti-coagulants & NSAIDs. Strong CYP3A4 inhibitors eg clarithromycin, keto/itraconazole, ritonavir can increase effects. CYP3A4 inducers e.g carbamazepine can lower (NOT exhaustive)

Day 5 (cont): Reversal of #ticragelor in emergency is possible via new monoclonal antibody drug Bentracimab. This has been designed to reverse #ticagrelor bleeding and is currently awaiting NICE/NHS approval, as well as FDA review.

Day 5: ADEs: Common include bleeding, constipation, hyperuricaemia/gout, dizziness/syncope, hypotension, rash. Uncommon/rare: haemorrhage eg eye, intra-cranial, muscular, angioedema (NOT exhaustive). Avoid in pregnancy

Day 4: Mechanism of action #ticagrelor. It is a potent reversible platelet P2Y12 receptor antagonist. This receptor normally promotes platelet aggregation via ADP binding as part of haemostasis. Blocking this pathway inhibits platelet activation/aggregation, exerting an anti-thrombotic effect

Day 3 (cont) #ticagrelor is a CYP3A4 & P-gp substrate & can itself cause inhibition of aforementioned processes. Some ethnic variation in response, for example, Asian populations may have higher bleeding risks

Day 3: Rapid oral absorption/low bioavailability/fast onset of action. High Vd & plasma protein binding. Hepatic metabolism via CYP450 enzymes;active metabolite ~ 40% activity of parent compound. Excretion hepatic/biliary. Caution in hepatic impairment. T½ 7hrs parent compound & 8.5 hrs metabolite

Day 2: Licensed for adults in combination with aspirin for prevention of events in acute coronary syndrome/post MI. Standard duration 12 mths; can continue for longer if nec. Unlicensed use for TIA/minor stroke when low bleeding risk. Dose dependent on indication, with loading dose for ACS

Day 1: The limitations of prodrug clopidogrel drove development of alternative orally active P2Y12 inhibitors for anti-platelet therapy. In 2003, a structure was discovered based on ATP, an endogenous P2Y12 inhibitor. #ticagrelor was licensed EMA 2011

New drug information series starting today '7 days of #ticagrelor'. Enjoy!

Day 7: In higher doses Pgp action can be saturated, allowing CNS entry of #loperamide with potential for euphoric effects/opioid issues. Abuse of loperamide linked to cardiovascular reactions eg syncope, rhythm disorders & rarely cardiac arrest. Abuse includes self-use to assist opioid withdrawal

Day 6: DDIs. Enzyme inhibition can lead to increased exposure to #loperamide & this can have a ‘severe’ warning & ‘caution advised’ eg dronedarone. Also, synergistic effect with other drugs which can produce constipation eg clozapine (NOT exhaustive)

Day 5(cont): SPC states #loperamide can have a ‘moderate’ impact on driving ability. Although not a controlled drug, if relevant impairment is present, a drug driving offense may be committed

Day 5: GI disorders are common ADEs for #loperamide & extension of MOA is constipation. However, abdo pain or vomiting are uncommon & paralytic ileus or megacolon are rare. Opioid-type issues are uncommon e.g dry mouth, or rare e.g impaired coordination, miosis, urinary retention(NOT exhaustive)

Day 4: #loperamide is a lipophilic synthetic opioid agonist which has a direct action on intestinal mu receptors. This slows peristalsis, retains water & electrolytes & increases rectal tone

Day 3 (cont) If hepatic impairment, there is reduced 1st pass/overall metabolism of #loperamide. Use with caution as may produce overdose effects. Also use with caution if history of opioid abuse. Avoid in pregnancy

Day 3: #loperamide is absorbed/acts in the gut:onset action ~1hr. ↑ 1st pass metabolism minimises systemic bioavailability, as does being a PgP substrate. ↑plasma protein binding & Vd. Extensive hepatic metabolism via CY450 pathways > biliary then faecal excretion (no active metabolites). T½ ~11hrs

Day 2 (cont): #loperamide also comes as combined with simeticone to calm colic & flatulence. As well as a POM, #loperamide can also be accessed over the counter in the UK

Day 2: Oral use (tabs,caps,melts)licensed for acute & chronic diarrhoea in adults (4-16mg/day divided) & for acute diarrhoea for those >4 (tabs:dose age dependent). Licensed for faecal incontinence & for palliative bowel colic pain & chemo-related diarrhoea; also symptoms of irritable bowel syndrome

Day 1: Invented in 1969, #loperamide was designed to be an active opioid compound in the peripheral nervous system, with low CNS effects. This allows slowed gut transition time, without psychoactive & addiction effects