Tailoring Anti-retroviral Therapy to Weight

EFAVIRENZ

• Adult : 600mg OD (similar as peads above 40kg)
• Dosage adjustment for concomitant rifampin (only if patient weighs ≥50 kg): Increase efavirenz dose to 800 mg once daily.
• Dosage adjustment for concomitant voriconazole: Reduce efavirenz dose to 300 mg once daily and increase voriconazole to 400 mg every 12 hours.

TENOFOVIR

1. Adult: 300mg OD (similar as peads above 35kg)

EMTRICITABINE

• Adult: 200mg OD (similar as peads above 33kg)

Effect of Weight on Dosing

• Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range
• A standard-dose efavirenz-based regimen is appropriate for HIV patients with tuberculosis who are receiving rifampin and have body weights of <60 kg

References:

1. www.lexi.comp
2. Body Weight Cutoff for Daily Dosage of Efavirenz and 60-Week Efficacy of Efavirenz-Based Regimen in Human Immunodeficiency Virus and Tuberculosis Coinfected Patients Receiving Rifampin http://aac.asm.org/content/53/10/4545.full
3. Standard Efavirenz Dose Appropriate for Overweight Patients http://www.thebodypro.com/content/75476/standard-efavirenz-dose-appropriate-for-overweight.html

Salbutamol Infusion Protocol

Available Product: 

• Injection Salbutamol 0.5mg/ml (1ml ampoules)

Diluents recommended: 

• Sodium Chloride and Dextrose Injection, Water for Injections, Sodium Chloride Injection or Dextrose Injection

This recommendation is based on available product information leaflets

For administration via peripheral line

• The maximum concentration for infusion differs according to products
• Most products recommend 10mg Salbutamol in 50ml diluents (0.2mg/ml)
• No information is stated on the product leaflet (generic) used in Hospital Keningau. According to the company representative, the recommendations are based on the original product Ventolin®, which also states the maximum concentration is 0.2mg/ml
• Some also recommends to use lower concentration- 0.01mg/ml to 0.02mg/ml

Need for Dilution

• Recommendation from Injection Ventolin 1mg/ml – the injections has to be diluted at least by 50% before administration. Extrapolating from the recommendation, the max concentration has to be at least 0.5mg/ml

Central line

• Based on the PICU guidelines, a maximum concentration of 0.5mg/ml can be given via the central line.
• Common Practices (not supported by evidence)
• 1mg/kg injection Salbutamol in 50ml diluents (up to 50ml)
• This would provide an equivalence of 1ml/hr= 20mcg/kg/hour=0.33mcg/kg/min

Based on the dosing guide:

5-10mcg/kg/min for 1 hour followed by 1-2mcg/kh/min (Drug Doses)

1-2mcg/kg/min and adjust according to response and heart rate up to 5mcg/kg/min

(doses above 2mcg/kg/min are given at intensice care unit) (BNF 2013)

0.33mcg/kg/min (20mcg/kg/hour) and Up to a max of 2mcg/kg/min (60mcg/kg/hour)

References:

1. BNF for Children 2013
2. www.lexi.comp
3. Drug Doses, Frank Shann
4. http://www.drugs.com/uk/pdf/leaflet/474844.pdf
5. PICU, Nottingham Childrens' Hospital https://www.nuh.nhs.uk/media/1216339/salbutamol_v2.pdf
6. http://www.medsafe.govt.nz/profs/datasheet/v/VentolininjIV.pdf

Vitamin D requirement for BreastFeed infants

Concerns:

• Vitamin D requirements cannot ordinarily be met by human milk alone which provides <25 IU/L to 78 IU/Lwhich provides <25 IU/L to 78 IU/L
• breast milk alone does not provide infants with an adequate intake of vitamin D
• The vitamin D content of human milk is related to the mother's vitamin D status, so mothers who supplement with high doses of vitamin D may have correspondingly high levels of this nutrient in their milk
• Most breastfed infants are able to synthesize additional vitamin D through routine sunlight exposure
• While the sun is a potential source of vitamin D, the AAP advises keeping infants out of direct sunlight and having them wear protective clothing and sunscreen

High Risk Groups:

• Babies of mothers with darker skin types, particularly when living in high latitude areas such as the UK where the winter sun provides little or no access to vitamin D;
• Babies and mothers who wear concealing clothing, preventing skin exposure to sunlight;
• Babies and mothers who spend a lot of time indoors or use sun creams critically reducing exposure to sunlight;
• Babies of obese mothers (BMI >30).
• Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism and behavioral differences that lead to less sun exposure

Need for Vitamin D Supplementation

• It is essential that vitamin D deficiency is prevented and / or corrected during pregnancy in order to prevent babies being born with depleted stores. A baby born deficient in vitamin D will not restore their levels from breastmilk alone.
• Healthy breastfed babies born to mothers (who have been taking 400mcg Vit D daily) should receive a vitamin D supplement from six months of age (as part of a multivitamin supplement)
• if the mother’s vitamin D status in pregnancy is uncertain, or if she falls into one of the risk groups, vitamin D supplements for mother and baby should be started soon after birth
• AAP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of vitamin D per day [23], the RDA for this nutrient during infancy

Available Products

Adequate amounts of vitamin D can be achieved by currently available multivitamin products (Appeton, syrup multivitamins etc) containing 400 IU of vitamin D per mL

Prescription preparations of vitamin D have very high vitamin D concentration and are not for routine home use.

If an infant is weaned to vitamin-D fortified infant formula (consuming at least 1000 mL per day) or a child one year of age or older is weaned to vitamin-D fortified milk, then further supplementation is not necessary

References:

1. www.uptodate.com
2. http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
3. http://www.cdc.gov/breastfeeding/recommendations/vitamin_d.htm
4. http://www.unicef.org.uk/BabyFriendly/News-and-Research/News/UNICEF-UK-Baby-Friendly-Initiative-Statement-on-vitamin-D-supplementation-for-breastfed-babies/

Interaction: Cough and Cold Medications and Remedies

Effect from the Disease

• Hypermetabolic states produced by fever (or hyperthyroidism) increase warfarin responsiveness
• This might be probably by increasing the catabolism of vitamin K–dependent coagulation factors
• Patients taking warfarin who contract the flu are at increased risk of bleeding due to the combination of reduced appetite, fluid loss, and general stress to the body
• presence of a respiratory infection untreated by an antibiotic, as well as exposure to an antibiotic, were both associated with more than twice the likelihood of having an INR reading of 5.0 or higher

Effect from the Medications used

TRADITIONAL
PRODUCTS	INR/severity	NOTE
GARLIC	↑ / possible	decreased platelet aggregation
GINGER	↑/ probable	antiinflammatory antispasmodic, and antiplatelet activities
TUMERIC	↑/ probable	antiinflammatory
CHAMOMILE	↑/ possible
OTC
PARACETAMOL/ ACETOMINOPHEN	↑ / moderate	Not > 2g/day and for not more than a few days
SALICYLATES drugs	↑ / moderate
ASPIRIN	↑ / major	Avoid/ stop/ adjust dose
DIPHENHYDRAMINE / BENADRYL	No interactions
BROMHEXINE
CHLORPHENIRAMINE
LORATIDINE
PSEUDOEPHEDRINE

Effects from Antibiotics

Need for Adjustments

• most patients with previously stable warfarin therapy will not experience clinically relevant increases in INR following antibiotic exposure or acute upper respiratory tract infection
• BUT as the levels will fluctuate, it is necessary for more stringent monitoring of INR

References:

1. lexicomp
2. www.uptodate.com
3. Systematic Overview of Warfarin and Its Drug and Food Interactions
4. Coumadin Interactions. http://www.bjchealth.org/warfarin
5. Foundation Guide to Warfarin Therapy. http://circ.ahajournals.org/content/107/12/1692.full
6. Interactions wit Warfarin. http://www.coumadin.com/pdf/Interactions_With_COUMADIN.pdf

Differential signs between nephrotic syndrome and nephritis

	Nephrotic Syndrome	Nephritis
Edema	Yes	Yes
Proteinuria	>3.5 g in 24 hours	<3.5 g in 24 hours
Hypoalbuminemia	Always	Rare
Hyperlipidemia	Yes	No
Hematuria:		Hallmark
·         Microscopic	Sometimes	Yes
·         Gross	No	Usually
Hypetension	Sometimes	Always (Mild)
Decreased GFR	Sometimes	Usually
Congested State	No	Yes

References:

1. Clinical Renal Syndromes. https://www.studyblue.com/notes/note/n/clinical-renal-syndromes/deck/10632588

Amlodipine-induced petechial rash

• Reported to be only occurring in 1 – 2% of individuals taking amlodipine
• The likely mechanism is an increase in capillary hydrostatic pressure with dihydropyridines, which selectively relax the precapillary sphincter. The increased hydrostatic pressure causes a few red blood cells to migrate to extravascular space giving the appearance of petechial rash.
• Amlodipine is also a common drug that causes fixed drug eruption, where the eruption can appear within a day to a few weeks of ingesting the causative drug and can occur on any part of the skin or mucous membranes (frequently hands, feet, tongue, penis or perianal areas)
• The site of eruption is fixed, occurring within hours of ingesting the causative drug at exactly the same site.
• Oral challenge is accepted and safe practice to confirm the diagnosis of amlodipine-induced fixed drug eruption.
• Management option would be to withdraw the offending drug, thus facilitating absorption of exuded red cells and resolution to be expeceted over a few weeks time.
• Topical corticosteroids may help reduce the intensity of the reaction.

References:

1. UpToDate. Amlodipine: Drug Information. http://www.uptodate.com.ezp.imu.edu.my/contents/amlodipine-drug-information?source=search_result&search=amlodipine&selectedTitle=1~109
2. ADR Report. Amlodipine-induced petechial rash. http://www.jpgmonline.com/article.asp?issn=0022-3859;year=2011;volume=57;issue=4;spage=341;epage=342;aulast=Murthy
3. Anne Lee and JoDrug-induced skin reactions. http://www.pharmpress.com/files/docs/ADRe2Ch05.pdf

Antibiotic Treatment for Recurrent AGN

ü Although the exact mechanism leading to recurrence of APSGN has not yet been determined, three possible explanations have been postulated:

o the suppression of immune response against nephritogenic streptococcal strains due to early antibiotic therapy

o an absence of natural immune responses against nephritogenic streptococcal components without antibiotic therapy

o a failure to exclude microbial agents through the digestive and respiratory tract due to IgA deficiency

ü Since only 10-20% of patients presented with sore throat have a positive culture for group A streptococci, the following clinical scoring is used to increase the accuracy of diagnosis for the prescription of antibiotics:

o Temperature higher than 38 ^º C and no cough = 1 point

o Tender anterior cervical adenopathy = 1 point

o Tonsillar swelling or exudates = 1 point

o Age between 3 and 14 years = 1 point

o Age ≥44 years = –1 point

Points	Recommendations
0 – 1	Antibiotic treatment is not necessary and culture is unneccesary
2 – 3	Obtain culture and give antibiotic treatment only when result is positive
4	Administer antibiotic treatment

ü  Choose an agent with greater beta-lactamase stability than the previous agent used:

o If a full course of penicillin was completed as initial therapy, a first-generation cephalosporin may be used

o If a first-generation cephalosporin was used for initial therapy, a second- or third-generation cephalosporin may be used

o Alternative agents include amoxicillin-clavulanate or clindamycin. 

References:

1. Medscape. Acute Poststreptococcal Glomerulonephritis Treatment & Management. http://emedicine.medscape.com/article/980685-treatment#a1156
2.  Atypical Clinical Manifestations of Acute Poststreptococcal Glomerulonephritis. http://cdn.intechopen.com/pdfs-wm/22828.pdf
3. UpToDate. http://www.uptodate.com.ezp.imu.edu.my/contents/treatment-and-prevention-of-streptococcal-tonsillopharyngitis?source=see_link#H16

Jaundice in Newborn

• Jaundice is a yellow discoloration of the skin and/or whites of the eyes that is often seen in newborn infants.
• The discoloration is caused by a yellow substance called bilirubin.
• Jaundice is not a disease, but is a symptom of an elevated blood bilirubin level
• Jaundice is not painful, but serious complications can occur if elevated bilirubin levels are not treated in a timely manner.
• Jaundice is a marker used to identify those infants who may be at risk for developing severe hyperbilirubinemia.
• Severe hyperbilirubinemia can be toxic to the nervous system of infants, potentially causing brain damage.

Signs and Symptoms:

• Jaundice initially causes the skin to become yellowed. Later, the whites of the eyes may have a yellowish tinge. These changes may be hard to recognize in children with a dark skin color or if a baby is unable to open eyelids. The color change:
• Is noticeable in the face first, and may progress down the chest, abdomen, arms, and then finally the legs.
• Can be checked by pressing one finger on your baby's forehead or nose. If the skin is jaundiced, it will appear yellow when you release pressure from the skin.
• Can be tracked in some babies by pressing over the bony prominences of the chest, hips, and knees to check if the jaundice is progressing.
• Should be checked before your baby leaves the hospital. If your baby goes home sooner than 72 hours after birth, you will need to monitor the baby's skin color at home every day. In addition, your infant should see a doctor or nurse within one to three days after going home.

Worsening of Jaundice

• If the yellow coloring is at the knee or lower, or if the yellow color is more intense, lemon yellow to orange yellow
• If the baby has any difficulty in feeding
• If it is hard to wake up your infant
• If your infant is irritable and is difficult to console
• If your infant arches his/her neck or body backwards

Causes

‘Too early’ (< 24 hours of age)

• always pathological
• usually due to haemolysis, with excessive production of bilirubin
• babies can be born jaundiced due to:

hepatitis (unusual)

severe haemolysis

• causes of severe haemolysis (decreasing order of probability):

ABO incompatibility

Rh iso-immunisation

sepsis

• rarer causes:

other blood group incompatibilities

red cell enzyme defects eg G6PD deficiency

red cell membrane defects, eg, hereditary spherocytosis

‘Too high’ (24 hours -10 days of age)

• If the SBR concentration exceeds 200-250 micromol/L, over this time, various causes include:
• mild dehydration/insufficient milk supply (breastfeeding jaundice)
• breast milk jaundice
• haemolysis - continuing causes as discussed under ‘too early’
• breakdown of extravasated blood (eg cephalhaematoma, bruising, CNS haemorrhage, swallowed blood)
• polycythaemia (increased RBC mass)
• infection - a more likely cause during this time
• increased enterohepatic circulation (e.g. bowel obstruction)

‘Too Long’ (> 10 days of age, especially > 2 weeks)

• The major clue to diagnosis is whether the elevated bilirubin is mostly unconjugated (>85%) or whether the conjugated fraction is substantially increased (>15% of the total).
• breast milk jaundice (diagnosis of exclusion, cessation not necessary)
• continued poor milk intake
• haemolysis
• infection (especially urinary tract infection)
• hypothyroidism

References:

1. http://www.uptodate.com/contents/jaundice-in-newborn-infants-beyond-the-basics
2. http://www.health.vic.gov.au/neonatalhandbook/conditions/jaundice-in-neonates.htm

Disinfectants: Alcohols and Chlorhexidine solutions

• Alcohol refers to Ethanol
• Methylated spirits is also known as denatured alcohols. It includes specific additives (Methanol) that make it non-drinkable. This form of ethanol has a bad taste, smells foul, and is poisonous if ingested
• Isopropyl alcohol (also isopropanol, rubbing alcohol, or the abbreviation IPA) is a common name for propan-2-ol.  It is a very useful solvent for things like nail polish, rubbing alcohol, sterile gauze pads, handiwipes. It evaporates very quickly and kills bacteria so it is used to sterilize the skin before injections.
• Chlorhexidine is a  bisbiguanide antiseptic and disinfectant. Combinations (cetrimide or in alcoholic soln): enhance efficacy

USE

• Alcohol compounds with strengths of 70-95% are used as disinfectants. For disinfectant properties, the contact time needs to be at least 10 minutes (up to 30 minutes)
• Selections between agents usually are dependent on the site of disinfection:

PRODUCTS	USE
Chlorhexidine Gluconate 0.2% Mouthwash	·       Mouth disorders e.g. gingivitis
Chlorhexidine Gluconate 0.05% Lotion	·       Swabbing in obstetrics, wounds and burns.
Chlorhexidine Gluconate 0.5%in spirit 70%	·       Cleaning of the birth canal ·       To be used undiluted for pre-operative skin preparation and instruments disinfection
Chlorhexidine Gluconate 4% Scrub	·       To be used instead of soap for pre-operative hand and skin preparation and for general hand and skin disinfection
Alcohol 70 % (ethanol)	·       Disinfecting the outside surface of small containers
Methylated Spirit 70%	·       Decontamination of equipment which might be damaged by aqueous disinfectants

References:

1. Antiseptics & Chemical Disinfectants Authorised for Use Within WUTH
2. Selection and Use of Disinfectant. University of Nebraska.