New drugs in your respiratory patients – are you up to date? Professor Emma Baker Professor of Clinical Pharmacology St George's, University of London

Learning outcomes Update on new medicines likely to be taken by patients with respiratory disease –Efficacy mechanism of action place in therapy –Safety main side effects respiratory side effects –Acceptability route of administration –Cost new drugs are more expensive than old ones so use them wisely!!

Question 1 1.Aliskiren 2.Dabigatran 3.Donepezil 4.Exenatide 5.Fondaparinux 6.Indacaterol 7.Ivabradine 8.Memantidine 9.Rivaroxaban 10.Sitagliptin A.Acetyl cholinesterase inhibitor B.Beta adrenoceptor agonist C.Dipeptidyl peptidase 4 inhibitor D.Direct thrombin inhibitor E.Factor Xa inhibitor F.If channel blocker G.Incretin mimetic H.Muscarinic receptor inhibitor I.N-methyl-d-aspartate (NMDA) receptor antagonist J.Phosphodiesterase 4 inhibitor K.Potassium channel opener L.Renin inhibitor AnswerLDAGEBFIEC

Question 2 1.Aliskiren 2.Dabigatran 3.Donepezil 4.Exenatide 5.Fondaparinux 6.Indacaterol 7.Ivabradine 8.Memantidine 9.Rivaroxaban 10.Sitagliptin A.Intramuscular B.Intravenous C.Oral D.Subcutaneous E.Topical

Question 2 1.Aliskiren 2.Dabigatran 3.Donepezil 4.Exenatide 5.Fondaparinux 6.Indacaterol 7.Ivabradine 8.Memantidine 9.Rivaroxaban 10.Sitagliptin A.Intramuscular B.Intravenous C.Oral D.Subcutaneous E.Topical

Question 2 1.Aliskiren 2.Dabigatran 3.Donepezil 4.Exenatide 5.Fondaparinux 6.Indacaterol 7.Ivabradine 8.Memantidine 9.Rivaroxaban 10.Sitagliptin A.Intramuscular B.Intravenous C.Oral D.Subcutaneous E.Topical

Question 2 1.Aliskiren 2.Dabigatran 3.Donepezil 4.Exenatide 5.Fondaparinux 6.Indacaterol 7.Ivabradine 8.Memantidine 9.Rivaroxaban 10.Sitagliptin A.Intramuscular B.Intravenous C.Oral D.Subcutaneous E.Topical AnswerCCCDD/BECCCC

Anticoagulants

Warfarin Proteins C and S

Anticoagulants Warfarin Proteins C and S Unfractionated heparin

Anticoagulants Low molecular weight heparin ?

Anticoagulants Fondaparinux Rivaroxaban Dabigatran

Which anticoagulant? EfficacySafetyAcceptabilityCost Unfractionated heparin Generally similar Newer drugs less proven benefit, less licensed indications – more and more trials being published Short half life, reversible with protamine SC/IV Monitoring £1.94 daily LMW heparinSC£2.82 daily WarfarinNotoriously dangerous! Oral Monitoring £0.03 daily 28 days ~92p FondaparinuxLess bleeding in ACS and more post surgery than LMWH SC£6.28 daily DabigatranLower risk of intracranial bleeding than warfarin Oral£4.20 daily 28 days £126 RivaroxabanOral£4.40 daily 28 days £132.44

Which anticoagulant? Unfractiona ted Heparin LMWHWarfarinFondapar inux DabigatranRivaroxaban VTE prevention Renal impairment NICE alternativ e Hip (28-35 days) or knee (10-14 days) replacement VTE treatment Renal impairment Acute, Cancer NICE alternativ e Not licensed AFPrevious stroke Heart failure >75 (>65 with risk factors) Previous stroke Heart failure >75 (>65 with risk factors) ACSRenal impairment Immine nt angiogr aphy Reduced risk of major bleeding

New drugs for type 2 diabetes sitagliptin (saxa/vilda) (liraglutide)

Treatment pathway First choiceAlternative(s) First lineMetforminSulphonylurea/ acarbose Second line Add sulphonylureaGlitazones DPP4 inhibitors GLP1 agonist Third line Add 3 rd oral agentInsulin Fourth line InsulinIntensify insulin regimen, add pioglitazone

Ivabradine

Ivabradine - NICE Stable angina –beta blocker/calcium channel blocker –3rd line options include nitrates/ nicorandil/ ivabradine Role in heart failure under appraisal Potential benefits in patients where beta blockers are contraindicated/ poorly tolerated

Ivabradine in airways disease Heart rate IvabradinePlacebo Asthma (n=20) 67 ± 883 ± 11* COPD (n=20) 70 ±981 ±19* No effect on peak flow, symptoms, use of rescue medicines Main side effect visual symptoms ~5% patients Majewski et al. Am J Cardiovasc Drugs ;12: Am J Cardiovasc Drugs.

Drugs for alzheimer's disease Less active in AD x x Disruption of signal transmission NMDA receptor antagonist

Aliskiren

1. A 66 year old man with COPD exenatide, aliskiren

2. 77 year old woman with ILD indacaterol (fondaparinux)

3. A 55 year old man with COPD indacaterol, ivabradine, donepezil

4. A 73 year old man with sleep apnoea exenatide, sitagliptin (memantidine)

5. 48 year old woman with asthma exenatide (dabigatrin)

GIAllergyCardiovascularRespiratoryCNSOther FondaparinuxRash/ pruritisAF reporteddyspnoea/ coughLess commonBleeding Dabigatranoesphagitis/ GORD/ PUD Bleeding RivaroxabanYesRash/ pruritisTachycardia/ edema, Hypotension Less commonBleeding ExenatideUpper GI/ GORD Anaphylactoid reactions Headache, dizziness, agitation Pancreatitis Pancreatic/thyroi d cancer SitagliptinGI upsetRash Stephens Johnson OedemaURTI Nasopharyngitis Less commonPancreatitis, pancreatic cancer? IvabradineLess common EosinophiliaBradycardia, 1st degree heart block VEs DyspnoeaVisual disturbance Hyperuricaemia Cramp IndacaterolPossibleAtrial fibrillationCough, nasopharyngitis, sinusitis, rhinorrhoea Cramp DonepezilCommonRash, pruritisBradycardia, heart block v rare CommonCramp MemantidineCommonDyspnoeaCommonPancreatitis rarely AliskirenDiarrhoeaRash Angiooedema Renal failure, hyperkalaemia