In episode 113, Mike and James interact in a mainly positive way about what to do with the 1000s of drug interactions that are out there. They talk about the concepts of pharmacokinetic and pharmacodynamic interactions and outline which ones appear to be clinically important. At the end they realise that all of their interactions over the last 113 podcasts episodes have been clinically irrelevant and vow to interact much more usefully in the future.

Show notes

1) Hospitalizations due to interactions

BMJ 2004;329:15–19

2) Plasma-protein binding interactions – they are not clinically important

Br J Clin Pharmacol 1994;37:125-8

3) Key Players in Metabolism Drug Interactions

Inhibitors

fluvoxamine

gemfibrozil

fluconazole

omeprazole

paroxetine

fluoxetine

clarithromycin

Inducers

Rifampin

carbamazepine

4) What drug interactions are clinically important?

J Am Pharm Assoc 2004;44:142–151

THE MAIN ONES (DRUG affected – DRUG interacting)

Warfarin – Thyroid, NSAIDs, cimetidine, fibric acid, barbiturates, sulfinpyrazone

Benzodiazepines – Azoles

Carbamazepine – Propoxyphene, macrolides

Cyclosporine  – Rifampin

Dextromethorphan – MAOIs

Digoxin – Clarithromycin

Ergots  – Macrolides

Ganciclovir – Zidovudine

MAOIs – Sympathomimetics

Meperidine – MAOIs

Methotrexate – Trimethoprim

Nitrates – Sildenafil

Pimozide – Macrolides, azoles

SSRIs  – MAOIs

Theophylline – Quinolones, fluvoxamine

5) Oral contraceptives and antibiotic interactions – a myth?

J Am Acad Dermatol 2002;46:917-23

6) Drug interaction websites/tools

http://www.drugs.com/drug_interactions.php

http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-herbal-di.pdf

iPhone apps – Medscape, Epocrates

In episode 112, Mike and James discuss the who, what, why, where and when of dabigatran in atrial fibrillation. We look at the data, and then discuss what we as individuals would do when making a decision between dabigatran and warfarin. At the end we both agree to disagree with the fact that we agree to disagree.

Show notes

1) Dabigatran versus Warfarin in Patients with Atrial Fibrillation

N Engl J Med 2009;361:1139-51

N Engl J Med 2010;363:1875-76 – update

N Engl J Med 2009;361:1200-02 – editorial

2) Keeping INR in the range – does it make a difference when comparing warfarin to dabigatran

Lancet 2010;376:975–83

3) Tools For Practice – Dabigatran versus Warfarin in Atrial Fibrillation

James and Mike briefly outline the new PREMIUM TEC podcast model.

In episode 111, Mike and James bring you the premier edition of the new PREMIUM TEC podcast episodes. We discuss high dose versus low dose statins, we possibly put the final nail in the rosiglitazone coffin and finally report that single high annual doses of Vitamin D didn’t do what they were supposed to do. At the end we discuss whether or not the PREMIUM label really should have been given to this podcast and decide to let the listeners make that decision.

Show notes

1) SEARCH – low dose (20 mg) vs high dose (80 mg) simvastatin in patients after an MI

Lancet 2010;376:1658-69

2) Rosiglitazone – are we really done with it?

N Engl J Med 2007;356:2457-71

ACP Journal Club 2007Nov-Dec;147:66

Arch Intern Med 2010;170(14):1191-1201

Food and Drug Administration. Briefing document:July13-14,2010 meeting of the

Endocrinologic and Metabolic Drugs Advisory Committee

JAMA 2010;304:411-418

BMJ 2010;340:c1344.doi:10.1136/bmj.c1344

Diabetes Care 2009;32:193-203

3) Annual high-dose (500,000 IU) oral Vitamin D and falls and fractures in older women

JAMA 2010;303:1815-22

In episode 110, in this final episode of the year James and Mike attempt to answer even more questions. They discuss the benefits and harms of using atypical antipsychotics in the elderly and decide that ‘microdoses’ is the correct answer. They get into a heated debate on the issue of the interaction with PPIs and clopidogrel and at the end both agree on the answer which is “Yes, but only on a Tuesday”. We finish off with a rousing discussion on the grapefruit/felodipine interaction and realise that neither of us like grapefruit so who cares. We both wish you and your family a Happy Holidays.

Show notes

1) Data on benefit

Psychother Psychosom 2007;76:213-8

Cochrane Library 2006:CD003476

2) Data on harm

Atypical meta-analysis (of trials not designed to assess harm)

JAMA 2005;294:1934-43

Cohort of conventional vs atypical

NEJM 2005;353:2335-41

CMAJ 2007;176:627-32

3) Actual RCT to assess risk benefit of withdrawal of antipsychotics

Lancet Neurol 2009;8:151–57

PLoS Med 5(4): e76.doi:10.1371/journal.pmed.0050076

4) One page summary of risks/benefits of anti-psychotics:

See Tools for Practice Website: http://www.acfp.ca/tfp_original.php

Specific reference: http://www.acfp.ca/docs10/Antipsychotics%20in%20Elderly%20_2_.pdf

In episode 109, Mike and James continue on with listener questions and start off trying to reduce the risk of using risk assessment tools and risk reduction information. They then delve into questions about tapering steroids, antidepressants, side effects from thiazides and sitagliptin and the amazing clarity of their answers is only outdone by the vagueness of their conclusions.

Show notes

1) Prediction with Framingham versus the real risk primary care patients

Heart 2009;95:125–9

2) Relative risk reduction with statins in primary prevention

BMJ 2009;338:b2376

ACP J Club 2009;151:14

Lancet 2005;366:1267–78

Diabetes – Lancet 2008;371:117–25

3) Issues with Framingham/UKPDS risk assessments

4) Tapering corticosteroids

Am J Med 2009;1222:977-91

5) Incomplete publication of antidepressant studies leading to bias (publication bias)

NEJM 2008;358:252-60

BMJ 2003;326:1171-3

6) Meta-analysis of antidepressants

Ann Intern Med 2005;143:415-26

Ann Intern Med 2008;149:734-50

Lancet 2009;373:746–58

Tools for Practice Website

http://www.acfp.ca/docs09/SecondGenerationAntidepressantsToolsforPracticefinal.pdf

In episode 108, Mike and James get back to listener questions and discuss drugs in the same class and different classes, get nowhere on a discussion about how to extrapolate 5-year data to infinity and beyond, get a little smelly with fish oil data, and find out that the new low dose colchicine is also high price which also stinks. Finally we sort out a steroid and sore throat issue and at the end both James and Mike find all their answers difficult to swallow.

Show notes

1) Fish oil

Arch Intern Med 2005;165:725-30

Can Fam Phys 2006;52:734-40

BMJ 2006;332:752-760

2) Colchicine – exclusive rights and high costs

N Engl J Med 2010;362:2045-7

3) Sore throat and steroids

www.emergency-medicine.jwatch.org/cgi/content/full/2009/828/1

In episode 107, Mike, James and Bruce Arroll once again team-up and this time bring you a cornucopia of dermatolgical evidence and advice. By the end of the podcast, both Mike and James develop psychogenic itch and Bruce successfully treats them with Kenacomb.

Show notes

1) DermNet NZ – pictures of more rashes than you could possibly imagine

http://dermnet.org.nz

2) Erythromycin for Pityriasis rosea

J Am Acad Dermatol 2000;42:241-4

3) Community-acquired pneumonia – covering for the atypicals – is it really needed?

BMJ 2005;330:456 doi:10.1136/bmj.38334.591586.82

4) Chronic erythromcin for COPD

Am J Respir Crit Care Med 2008;178:1139-47

5) TMP/SMX for head lice

Pediatrics 2001;107:e30

6) Send in pictures of your rashes and find out what it is

http://www.telederm.org/

7) Recurrent eczema – liquid bleach

Pediatrics 2009;123:e 808-14

In episode 106, James and Mike welcome back our good friend and colleague from New Zealand, Bruce Arroll. Out of respect, we made sure there were no earthquakes during his visit because earthquakes, as we found out, can be somewhat depressing. On that note, Bruce brings us some very useful information about non-drug treatments for depression and towards the end Mike and James breath deeply, meditate, problem solve and then write about it in their gratitude diaries and lo-and-behold we finish the podcast feeling much better than when we started – always a good thing.

Show notes

Seeing patients weekly

BMJ 2001;323:1011

Exercise

Cochrane Library

Practice nurse phone call

Arch Fam Med 2000;9:700-8

Gratitude diaries

Am Psychologist 2005;60:5:410–421

Breathing

Int J Nurs Stud 2010;47:1346–1353

Meditation

www.calm.auckland.ac.nz

J Consult Clin Psychol 2008;76:966-78

Light therapy

Cochrane Library

Problem solving

BMJ 1995;310:441-5

Cognitive behavioural therapy

10 Minute Consultation By Lee David

J Affect Disord 1998;49:59-72

In episode 105, James and Mike continue on with breathless abandon their discussion about the use of drugs in asthma. With chronic asthma the whole concept of low dose and shared-informed decision making comes right back into focus (thank goodness) and so both of us rest easy that the last 104 podcasts, at least from that perspective, have not been a waste of time.

Show notes

1) PRN versus chronic use of inhaled salbutamol

Lancet 2000;355:1675-9

2) Inhaled corticosteroids in patients with new-onset asthma

NEJM 1991;325:388-92

“all patients with mild persistent asthma deserve the opportunity to decide whether the benefit from their use is worth the effort of taking a very safe medication,  usually once daily”

Am J Res Crit Care Med 2005;172:410-2

3) Choice of inhaled corticosteroid – no difference

Ann Allergy Asthma Immunol 2003;91:326-34

Ann Pharmaco 2009;43:519-27

4) Doses of inhaled corticosteroid – low doses

“published data provide little support for dose titration above 400 mcg/d in patients with mild to moderate asthma”

Cochrane Library

5) Equipotent daily doses of inhaled corticosteroids in adults – the doses listed below are considered ‘low” doses, “moderate doses = doubling these doses; “high” doses = quadrupling these doses. In children the corresponding doses are usually about 2/3 of the adult doses

Triamcinolone/Flunisolide 400/500-1000 mcg

Beclomethasone 200-500 mcg

Budesonide /Mometasone 200-400 mcg

Fluticasone 100-250 mcg

Ciclesonide 80-160 mcg

Eur Respir J 2008;31:143–78

6) Doubling the dose of inhaled CS when symptoms get worse provides no benefit

Lancet 2004;363:271-5

Thorax 2004;59:550–6

Cochrane Library

7) Maybe quadrupling the dose will work????

Am J Respir Crit Care Med 2009;180:598–602

8) High dose inhaled corticosteroids can often be reduced without any change  in symptom control

NEJM 1994;331:700-5

9) After inhaled steroids what’s next – tiotropium or salmeterol?

NEJM 2010;Sept 19

10) LABA vs LTRA

“In asthmatic adults inadequately controlled on low doses of inhaled steroids, the addition of LABA is superior to LTRA for preventing exacerbations requiring systemic steroids, and for improving lung function, symptoms, and use of rescue ß2-agonists”

Cochrane Library

11) Peak flow measurements

Am J Respir Crit Care Med 2006;174:1077–87