Opioid Dose Conversions

• The guidelines are applicable to chronic pain for palliative care patients
• Calculate the equianalgesic starting dose of the new opioid using the guidelines
• Apply a dose reduction of 25% to 50% to the equianalgesic starting dose to allow for cross-tolerance
• A dose reduction closer to 50% is appropriate if the patient is elderly or medically frail
• Also consider
•  dose and duration of previous opioid treatment
• current pain severity
• renal and hepatic function
• occurrence of adverse effects
• direction of switch of opioid
• Provide supplemental opioid analgesia (breakthrough medication) during the titration process of 1/10th to 1/6th of the total daily opioid dose
• Frequently monitor for patient response and individual dose titration

References:

1. Opioid Conversion Ratios - Guide to Practice 2013. Eastern Metropolitan Region Palliative Care Consortium
2. http://www.gpnotebook.co.uk/simplepage.cfm?ID=x20041106080808159860
3. Opioid Conversion Guidelines February 2011 Gippsland Region Palliative Care Consortium Clinical Practice Group

Analgesia in Breastfeeding

Agent	·         Recommendation	·         Monitoring
Non Opiod Analgesics (preffered)
Paracetamol	·         Good Choice ·         Amounts in milk are much less than doses usually given to infants	·         Generally ADRs are rare ·         Case report of maculopapular rash ·         Safe and effective for analgesia in postpartum mothers
Ibuprofen	·         Preferred choice ·         extremely low levels in breastmilk, short half-life and safe use in infants	·         no adverse effects reported ·         safe and effective for analgesia in postpartum mothers
Diclofenac	·         consider diclofenac to be acceptable during breastfeeding ·         Other agents may be preferred	·         Data are limited  ·         Case report of Urticaria
Indomethacin	·         Acceptable/ other agents preffered ·         low levels of in breastmilk	·        No adverse events ·        Should be avoided if possible as there is one report of convulsions in a neonate exposed to this drug through breastmilk
Celecoxib	·         amount of celecoxib passing through breastmilk is too small to be harmful	·        must be balanced with higher cost and possible cardiovascular risks, which should be minimal with short-term use in healthy young women
Opioid Analgesics
Tramadol	·         excretion of tramadol into milk is low	·         unlikely to adversely affect nursing infant ·         monitor infants for increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties or limpness, and contact a physician immediately if any of these occu
Morphine	·         considered an ideal due to its limited transport to milk and its poor oral bioavailability ·         Epidural morphine – small amounts of morphine in milk. ·         IV or oral - higher milk levels than with epidural morphine.	·         Newborn infants seem to be particularly sensitive even to small doses ·         Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of morphine to a few days at a low dosage ·         close infant monitoring- increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness,
Fentanyl	·         amounts of fentanyl ingested by the neonate are small in epidural and IV ·         No waiting period or discarding of milk is required

References:

 1.                  www.drugs.com

2.                  Analgesia and anesthesia for the breastfeeding mother, revised 2012.

3.                  http://www.australianprescriber.com/magazine/34/1/8/10

4.                  Analgesics (Pain killers) and Breastfeeding. The Breastfeeding Network

Platelet Dysfunction in Uremia

• Clinical bleeding in uremia may involve the skin, resulting in easy bruising, or the oral and nasal mucosa, gingiva, gastrointestinal and urinary tracts, and respiratory system. 
• Excessive bleeding may also occur in response to injury or invasive procedures
• Uremic patients may display increased bleeding sensitivity to aspirin as there is a transient, cyclooxygenase-independent prolongation of the bleeding time

Cause

• Causes of platelet impairment include intrinsic platelet defects, abnormal platelet-endothelial interaction, uremic toxins, and anemia

Treatment

• Either hemodialysis or peritoneal dialysis can partially correct the bleeding time and other in vitro tests of platelet function in approximately two-thirds of uremic patients
• most rapidly acting, and probably least toxic acute treatment for platelet dysfunction in the uremic patient is the administration ofdesmopressin, an analog of antidiuretic hormone with little vasopressor activity
•  Raising the hemoglobin to approximately 10 g/dL or higher will reduce the bleeding time in many patients, occasionally to a normal level, but, as with desmopressin, there has not been demonstration that bleeding or risk of bleeding is ameliorated with correction of anemia
• The infusion of cryoprecipitate (10 units intravenously every 12 to 24 hours) can shorten the bleeding time in many uremic patients

Reference:

1. www.uptodate.com

Antiplatelet in CKD

Aspirin

• Long-term aspirin therapy reduces the risk of subsequent myocardial infarction (MI), stroke, and vascular death among patients without CKD
• There are fewer data related to the effectiveness and safety of antiplatelet therapy in patients with CKD
• The best data come from a meta-analysis of 27,139 patients with CKD who participated in 50 randomized trials that tested the efficacy of antiplatelet agents (mostly aspirin) for prevention of CVD
• Antiplatelet therapy significantly reduced the incidence of fatal or nonfatal myocardial infarction as compared with either placebo or no therapy (6.7 versus 7.0 percent, or 3 myocardial infarctions prevented for every 1000 patients treated).
• However, antiplatelet therapy also significantly increased the rate of major bleeding (4.4 versus 2.9 percent, or 15 additional major bleeding events for every 1000 patients treated).
• Antiplatelets had no effect on stroke or mortality.
• The results were similar in patients of all CKD stages.
• Based upon these data, we suggest that decisions about antiplatelet therapy to prevent cardiovascular disease in patients with CKD be individualized depending upon the patient's overall risk for CHD (for example, a prior history of myocardial infarction) and for bleeding, and also upon their preferences.
• This suggestion is broadly consistent with guidelines made by the Kidney Disease Improving Global Outcomes (KDIGO) report on the management of CKD
• The prescription of low-dose aspirin is probably safe in most patients with CKD

Clopidogrel

• The current ACC/AHA guidelines recommend the use of clopidogrel in patients with ACS.
• No specific recommendations exist for the adjustment of clopidogrel dosage in renal insufficiency.
• A post-hoc analysis from the CREDO (Clopidogrel for Reduction in Events During Observation) trial, patients with mild and moderate CKD did not have any significant difference in outcomes (mild 10.3 % vs. 12.8%, p = 0.30; moderate 17.8% vs. 13.1%, p = 0.24) with increased risk of bleeding with clopidogrel
• A post-hoc analysis of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial showed no interaction between clopidogrel and renal function (p value for homogeneity 0.11). 
• However, there was no significant benefit from using clopidogrel for patients in the lowest tertile (relative risk: 0.89 [95% confidence interval [CI]: 0.76 to 1.05]), and patients in this group had a significant increase in minor bleeding (hazard ratio: 1.5, 95% CI: 1.21 to 1.86) and blood transfusion (3.5%).

References:

1. www.uptodate.com
2. Safety and Efficacy of Anticoagulants in Kidney Disease
3. http://www.medscape.com/viewarticle/753721_2

Otomycosis

• also known as fungal otitis externa 
• fungal infection of the external auditory canal and its associated complications, sometimes involving the middle ear
• extensive and sometimes unnecessary use of antibiotic ear drops for the treatment of otitis media and otitis externa has been linked to the important increase in the prevalence of otomycosis.

Treatment

•  mainstay of therapy for otomycosis is meticulous cleaning of the ear canal and topical antifungal therapy
• Clotrimazole has the greatest zone of inhibition for common fungi
• appears to be one of the most effective agents for the management of otomycosis, with a reported rate of effectiveness that varies from 95% to 100% in most studies
• clotrimazole 1% solution, applied twice daily for 10 to 14 days, and then reassess the ear canal. If fungal elements are identified, the ear canal should again be meticulously cleaned and undergo a further 10 to 14 day course of topical antifungal with reassessment thereafter
• Oral antifungals may be used in refractory cases. Intravenous antifungals are reserved for patients suspected of having invasive otomycosis

References:

1. www.uptodate.com
2. https://www.academia.edu/730001/Ototopical_antifungals_and_otomycosis_a_review
3. http://www.aafp.org/afp/2012/1201/p1055.html

Suppression of Lactation

• Women may not breastfeed their newborn babies for a variety of reasons, ranging from personal choice, HIV-infection to stillbirth
• Galactorrhea is nonlactational milk production, which is usually defined as milk production one year after pregnancy and cessation of breastfeeding. It can also occur in nulliparous and postmenopausal women, and even in men

Management Algorithm:

Medication Associated Galactorrhea

• Antipsychotics
• Gastrointestinal motility drugs: Metoclopramide / Domperidone
• Antidepressant: Rare
• Antihypertensive Medications: Verapamil, Methyldopa, Reserpine
• Others: Opioids, Cocaine

Pharmacological Management

DOPAMINE AGONIST	COMMON DOSAGES	COMMON ADVERSE EFFECTS	COMMENTS
Bromocriptine	2.5 to 15 mg daily	·  Both medications have similar adverse effects, ·   including gastrointestinal (nausea, vomiting), cardiovascular (postural hypotension, dizziness), and neurologic (drowsiness, headache); cardiac valvulopathy reported with high dose of cabergoline (more than 4 mg daily)	·       Compared with bromocriptine, the adverse effects of cabergoline are usually less frequent, of shorter duration, and less severe ·       Bromocriptine is preferred by some women who are trying to conceive because of the larger safety database; it typically should be discontinued once pregnancy is confirmed
Cabergoline	0.25 to 1 mg twice weekly Or 0.5 to 2 mg once weekly

• 11 trials using oestrogen preparations (diethylstilbestrol, quinestrol, chlorotrianisene, hexestrol) also showed suppression of lactation.
•  A combination of testosterone and oestrogen preparations was of some benefit in reducing symptoms in three trials (436 women)
• Other pharmacologic agents (clomiphene, tamoxifen, prostaglandins, pyridoxine, oxytocin, L‐dopa and homeopathic preparation) were tested in single small trials. 
• Generally, side effects were poorly reported and no case of thromboembolism was recorded among trials that included it as an adverse treatment outcome

Non-Pharmacological Management

• insufficient evidence to recommend the widespread use of any particular treatment
• Binding the breasts or wearing a tight brassiere, applying an infra‐red lamp, fluid and diet 
• restrictions, external application of jasmine flower and ice packs are tried non‐drug approaches
• Washed cabbage leaves have been documented as a treatment for engorgement. 
• The application of cold therapy may be soothing, is unlikely to cause harm, and cabbage leaves are readily available. 
• Cochrane 2003, cabbage leaves and other vegetable substances on the breast did not show greater comfort than the placebos
• A study by a group of nurses in Sweden (1998) did find that for women who had lost a baby, breast binding served as a concrete reality of the loss and aided in the grieving process.
• More recent study (2003) found the women with bound breasts had more leakage, more pain, and needed more pain medication than the non-bound group.
• Removing just enough milk to reduce the pressure in the breasts, but not enough to empty them, will gradually diminish milk production without excessive discomfort for the mother
• Warm showers will help induce milk leakage and reduce pressure
• With regards to pharmacological analgesia, evidence for engorgement suggests NSAIDs are effective if not contraindicated

References:

1. http://www.medscape.com/viewarticle/464568
2. http://www.aafp.org/afp/2012/0601/p1073.html
3. Treatments for suppression of lactation (Review). Cochrane 2003
4. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0013616/
5. Suppression of Lactation or Weaning. Royal Hospital for Women

Effectiveness of Pharmacological Interventions in Smoking Cessation

DRUG	Effectiveness
NRT and bupropion	·         helped about 80% more people to quit than placebo ·         (for every 10 people who quit with placebo about 18 could be expected to quit with NRT or with bupropion)
Varenicline	·         doubled the chances of quitting compared with placebo, ·         (for every 10 who quit with placebo about 28 could be expected to quit with varenicline)
Varenicline vs NRT	·         Varenicline helped about 50% more people to quit than nicotine patch and 'other' NRT (tablets, sprays, lozenges and inhalers), and about 70% more people than nicotine gum
Varenicline vs combination of NRT	·         was as effective as using varenicline, and helped more people to quit than single types of NRT. ·         There was little to choose between different types of NRT, apart from 'other' NRT, which helped slightly more people than nicotine gum
NRT combined with nortriptyline or with bupropion	·         not more effective than NRT alone
cytisine and nortriptyline	·         improved the chances of quitting, with minimal risk of harms
	Adverse reaction
Bupropion	·         carries a known risk of seizures (about 1 per 1000 users) ·         did not find increased risks of neuropsychiatric or heart and circulatory problems
Varenicline	·         still under investigation; we found no evidence from the trials that it is linked to an increase in neuropsychiatric problems, or with increased heart and circulatory problems
Clonidine	·         helped people to quit, but caused side effects

Reference:
Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database of Systematic Reviews 2013, Issue 5. Art