Saturday, January 22, 2011

Effectiveness of the Different Treatments in Smoking Cessation

Cochrane reviews:

Nicotine Replacement Therapy (NRT): 132 RCTs.

-Overall risk ratio (RR) and 95% confidence interval (CI) of abstinence: 1.58 (1.50 to 1.66); similar for gum, patch, inhaler, and lozenge.

-Adverse events (AEs): local irritation related to product type; no evidence of increased myocardial infarction.

Varenicline: 9 RCTs.

-The RR (95% CI) for cessation at 6 to 12 months over placebo was 2.33 (1.95 to 2.80).

-Varenicline AEs: primarily nausea, insomnia, and abnormal dreams; 10% AE drop-out rate; neuropsychiatric AEs (eg, depression, agitation, suicidal thoughts or behaviour) are infrequent butrequire monitoring.

-Reported benefit of varenicline might be influenced by industry funding and lack of a pragmatic design.

Antidepressants: 49 bupropion and 9 nortriptyline RCTs.

-The RR (95% CI) for cessation over placebo at 6 to 12 months: bupropion 1.69 (1.53 to 1.85); nortriptyline 2.03 (1.48 to 2.78).

-Bupropion AEs: primarily insomnia and dry mouth; 7% to 12% AE drop-out rate; rarely seizure (about 1/1000) and suicidal thoughts or behaviour (association unclear).

-Nortriptyline AEs: primarily dry mouth, drowsiness, light-headedness, and constipation (less at lower doses); 4% to 12% drop-out rate from AEs.

Assuming 10% placebo cessation rates (mean across studies), approximate numbers needed to treat (at 6 to 12 months) are as follows: varenicline 8, nortriptyline 10, bupropion 10, and NRT 16.


Smoking cessation is the most effective preventive manoeuver for high-risk patients: an RCT of aggressive intervention for 209 patients after critical care admission achieved a 2-year quit rate of 39% (9% for placebo) and mortality of 3% (vs 12%); number needed to treat was 11.


-Bupropion: 150 mg is equivalent to 300 mg.

-Varenicline: 0.5 mg twice daily is as effective (or almost as effective),as 1 mg twice daily, but with fewer AEs.

-Nortriptyline: start with 25 mg at bedtime and increase by 25 mg every 3 to 4 days, if the desire to smoke persists, to a maximum of 75 to 100 mg; encourage a quit date 10 days in (or so) and continuefor 10 to 12 weeks.

Bottom line

Nicotine replacement, bupropion, nortriptyline (off label), and varenicline are all effective in smoking cessation; AEs vary (and might relate to quitting smoking), but they are important and require monitoring.


In Malaysia, the recommended (and available) pharmacotherapy for smoking cessation are NRT (gum, lozenges, patch, inhaler) and varenicline.

Nicotine 16hour-patch and varenicline are listed in the Ministry of Health Drug Formulary as A/KK (Category of prescribers: Consultants/ Specialists/Family Physician Specialists).


Allan,GM, Ivers N and Els C. Can Fam Physician, 57 (1), January 2011: 47.

Sunday, January 9, 2011

Chapter for Pharmacist-To-be : Pharmaceutical Care Plan for Asthma Patients

Recently, final year pharmacy student or/also known as the pharmacist-to-be, asked me about some questions regarding management of an asthmatic patient.

So to summarise the discussion, When comes to asthmatic patients, there are few things you ned to make it clear before you jump into recommendation:

1) Patient's compliance on inhaler techniques. If non-compliance, there is a bigger issue for u to address before you add in an extra med.

2)How to step up and to step down in asthma management? What parameters you look at ?
If to step up, which agent will you choose ? What monitoring parameters are you interested to look at?
- after corticosteroid, what is next in the list?
- can long acting beta-agonist be given alone?
- what are the up-coming innovation in management of asthma patients, that could improve compliance, improve efficacy and reduce side effect?

3) think about what is the pathophysiology of asthma?
- why we will step up to inhale corticosteroid instead of other agent?

4) How different is the management of asthma vs COPD? why is it so?

5) How the difference of management of acute exacerbation of asthma vs chronic asthma?

6) What is the differences in inhaler corticosteroid and oral corticosteroid?
- why do we have an invention of inhaler?
- When do we oral (systemic) corticosteroid in management of asthma patient?

7) Check the differences in each corticosteroid inhaler (Budesonide, beclomethasone, ciclesonide, fluticasone, betamethasone) By finding the differences, You will then understand why in the market, there is so many different corticosteroid inhalers, and why some inhale corticosteroid were phased out from the market already.

8) can asthma patient be given aspirin?
if can, what would be your concern?
if cant, what would you recommend to your doctor?

If you could find out all the answers, you will have a better understanding of how to manage an asthma patient! But dont forget about his/her other co-morbidity(ies).

Wednesday, January 5, 2011



Stephen R. Hammes
Division of Endocrinology & Metabolism, Department of Medicine, University of Rochester School of Medicine & Dentistry
Laurence L. Brunton
Professor of Pharmacology and Medicine, Department of Pharmacology, University of California San Diego School of Medicine

Related To: Chapter 57. Estrogens and Progestins

View in chapter

The FDA has recently approved ulipristal for post-coital contraception. Ulipristal could be considered “Plan C”, similar in overall effect to the current “Plan B”, mifepristone. Ulipristal can inhibit follicular rupture when administered prior to ovulation (Brache et al, 2010) and is effective post-coitally in preventing pregnancy (Fine et al, 2010; Glasier et al, 2010). The clinical studies with ulipristal have raised some questions about the drug’s equivalence to existing medications (Page and Verhaeghe, 2010) and prompted an interesting discussion of the ethics of including a placebo-control in a study of efficacy of a drug such as this one (Glasier and Gainer, 2010). As may be expected, ulipristal has also provoked an adverse reaction in the United States by opponents of the termination of pregnancy. Ulipristal is included in the recently published 12th edition ofGoodman & Gilman's The Pharmacological Basis of Therapeutics. (Chapter 40, Estrogens and Progestins)

Chemistry. Ulipristal (PubChem CID: 130904) is another derivative of 19-norprogesterone (PubChem CID: 95585) that functions as a selective progesterone receptor modulator (SPRM) with both agonistic and antagonistic effects on the progesterone receptor. Ulipristal has the same dimethyl-aminophenol group at the 11b position as seen in mifepristone (PubChem CID: 55245) with an additional acetoxy group at position 17. Unlike mifepristone, ulipristal appears to be a relatively weak glucocorticoid antagonist.

Pharmacological Actions. Ulipristal is known to have anti-proliferative effects in the uterus at high doses; however, its most relevant actions to date are its ability to inhibit ovulation. While still not clear, ulipristal’s anti-ovulatory actions likely occur due to progesterone regulation at many levels, including inhibition of LH release through the hypothalamus and pituitary, as well as inhibition of LH-induced follicular rupture within the ovary.

Dosing. A 30 mg dose of ulipristral can inhibit ovulation when taken up to five days after intercourse. In fact, ulipristal can block ovarian rupture at or even just after the time of the LH surge, confirming that at least part of its effects are directly in the ovary. Ulipristal may also block endometrial implantation of the fertilized egg, although whether this contributes to its ability to function as an emergency contraceptive (see below) is not clear.

Therapeutic Uses. Ulipristal acetate, which is sold as ella and ellaOne, has recently been licensed in Europe and the United States as an emergency contraceptive. Studies comparing ulipristal to levonorgestrel (progesterone-only emergency contraception, or POEC) have found that ulipristal is at least as effective when taken up to 72 hours after unprotected sexual intercourse. Most importantly, while levonorgestrel does not work well beyond 72 hours after unprotected intercourse, ulipristal remains effective up to 120 hours (5 days) after intercourse, making ulipristal a more versatile emergency contraceptive. The most severe side effect in clinical trials using ulipristal has been a self-limited headache and some abdominal pain. The drug should not be taken by women who are breastfeeding or who are pregnant and wish to remain so.


Brache V, Cochon L, Jesam C, et al. Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod 2010;25:2256-63. [PMID: 20634186]

Fine P, Mathé H, Ginde S, et al. Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception. Obstet Gynecol 2010;115:257-63. [PMID: 20093897]

Glasier A, Gainer E. Correspondence: Ulipristal acetate for emergency contraception? Authors’ reply. Lancet 2010;375:1608. [PMID: 20452518]

Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 2010;375: 555-562. [PMID: 20116841]

Page GH, Verhaeghe V. Correspondence: Ulipristal acetate for emergency contraception? Lancet 2010;375:1608. [PMID: 20452519]

Hammes Stephen R, Brunton Laurence L, "ella: a Newly-Approved Selective Progesterone Receptor Modulator" (Update). Laurence L. Brunton, John S. Lazo, Keith L. Parker: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e: