Thursday, May 28, 2015

Management of Chronic Gout in Chronic Kidney Disease (CKD)

Chronic Gout: Pharmacologic strategies

First line: Xanthine Oxidase Inhibitors (XOI)
Allopurinol or Febuxostat

Starting dose: not greater than 100 mg/d and in CKD stage 4 or worse, no greater than 50 mg/d.
Doses can be increased up to 300 mg/d in CKD patients for as long appropriate parameters are closely monitored. The ACR does not recommend the traditional dosing methods for CKD patients but rather to start therapy with lower dose and gradually titrate upward every 2-5 weeks from the maintenance dose to the maximum dose needed to achieve serum rate target. This regimen may reduce occurrences of Allopurinol-induced hypersensitivity reactions (AHS).

AHS may lead to Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) as well as systemic abnormalities like vasculitis, rash, end organ disease and eoisonophilia.
A combination of CKD and Thiazide diuretics can increase risk if AHS.

Creatinine Clearance (ml/min)
Dose
10- 20
200 mg daily
3- 10
Maximum of 100 mg daily
< 3
100 mg at intervals of > 24 h may be necessary
Table 1: Dose of Allopurinol in CKD.

Because oxypurinol is excreted primarily by the kidneys, accumulation may occur in patients with renal failure. Patients receiving dialysis may require therapeutic doses of Allopurinol. For patients not receiving dialysis, creatinine clearance as above [Table 1] may be used as guide but is limited by the unreliability of creatinine of this low order.

First line: Uricosuric Agent
Probenecid 
It is not recommended for patients with creatine clearance (CrCL) < 50 ml/min.

Alternatives: Uricosuric Agents
Fenofibrate or Losartan
Consider urine alkalisation, urine pH monitoring and increased fluid intake to reduce risk of urolithiasis.

*If disease is refractory to monotherapy with either XOI options, then a uricosuric agent can be as a second line approach.

Prophylaxis for Gout Flares When Initiating Urate Lowering Therapy (ULT): 
Rapid drop in serum rate levels can trigger gout flares.

First line: Low dose Colchicine 0.6 mg OD-BD, with lower doses for moderate to severe CKD [eGFR: 15-59 mL/ min/ 1.73 m2) and potential drug-drug interaction.
Although low dose NSAIDS is recommended by ACR, they should generally be avoided in CKD. Additionally, a stronger level of evidence exists for using Colchicine over NSAIDS.

For patients with severe CKD (CrCL <30 ml/ min): Recommended starting dose of Colchicine is 0.3 mg/d.
For patients on dialysis, the starting dose is 0.3 mg twice a week. In CKD, even a lower dose of Colchicine may result in neuromyopathy and bone marrow suppression.

CAUTIONS: 
Colchicine + Macrolides: Toxicity in CKD.
Colchicine + Clarithromycin: Fatal Interactions in CKD.
Colchicine + elderly: Creatinine clearance may appear normal despite renal impairment.

AVOIDED NSAIDS IN:
PATIENTS WITH GFR < 30 ml/ min/ 1.73 m2.
GFR < 60 ml/ min/ 1.73 m2 when using it as a prolonged therapy.
Patients on Lithium and RAAS blocking agents.

*Second line agent when first line is contraindicated or ineffective: Low dose Prednisolone (<10 mg daily). 

Monitoring parameters:
Allopurinol:
-CBC, Serum uric acid levels every 2-5 weeks during dose titration until desired level is achieved; every 6 months thereafter, fluid input-output, hepatic and renal function, signs and symptoms of hypersensitivity.

Colchicine:
-CBC, Renal and hepatic function tests. Obtain baseline CBC and monitor while on long term therapy to observe for blood dyscrasias. Monitor for GI side effects.


Reference:
1. https://www.kidney.org/sites/default/files/02-10-6446_ABE_Gout_Bulletin_SINGLE_PAGES.pdf
2. Lexicomp


Wednesday, May 27, 2015

ARB Dose Conversions

Available Products in Hospital Keningau
SINGLE AGENT
Losartan 50mg and 100mg
Cozaar
Valsartan 80mg and 160mg
Diovan
Irbersartan 150mg and 300mg
Aprovel
Telmisartan 40mg and 80mg
Micardis
COMBINATION
Losartan 50mg + HCT 12.5mg
Hyzaar
Valsartan 80mg + HCT 12.5mg
Co Diovan
Valsartan 80mg + Amlodipine 10mg
Exforge
Irbersartan 300mg + HCT 12.5mg
Co Aprovel
Telmisartan 80mg + Amlodipine 5mg
Twynsta

Effect on Diastolic Pressure

Dose Equivalence:
ADR reported:
References:
  1. Angiotensin II receptor blockers. Proc (Bayl Univ Med Cent). 2003 Jan; 16(1): 123–126 
  2. Comparative ARB pharmacology. http://bjcardio.co.uk/2010/05/comparative-arb-pharmacology/
  3. Medicines Management Programme: Preferred Drugs.  http://www.hse.ie/eng/about/Who/clinical/natclinprog/medicinemanagementprogramme/yourmedicines/Evaluation_Reports/arb


Treatment of Otomycoses with Acetic Acid

Acetic acid can be prepared to be used in fungal infection of the ear.


Therapy
Regimen
Notes
Acetic acid 2% w/v in spirit drops
3- 5 drops of the solution every 4-6 hourly. Continue to instill 5 drops of acetic acid solution for 3-4 times daily thereafter for 5 days.
Clean ear canal and remove cerumen and debris before instillation.
Store away from light and should be discarded after a week.
Preparation
Ingredients
Quantity required
Acetic acid 33%
2 ml
Methylated spirit
50 ml
Distilled water
100 ml q.s.
Procedure:
  1. Prepare acetic acid 33 % from glacial acetic acid by mixing 1 ml of the latter with 2 ml of water.
  2. Mix the prepared acetic acid 33 % with methylated spirit in a measuring cylinder.
  3. Add distilled water to make up the volume of the preparation to 100 ml.
  4. Pack it and label accordingly. Expiry date should be no longer than 1 week after preparation.



Tuesday, May 26, 2015

Antiretroviral and Liver Injury

  • Antiretroviral drug-related liver injury is a common cause of morbidity, mortality and treatment discontinuation in HIV-infected patients,
  • Antiretroviral drug-related liver injury is defined by elevations in liver enzymes in serum, with ALT characteristically greater than AST.
  • After initiating HAART, the reported incidence of severe liver toxicity ranges from 2 to 18%.
  • Antiretroviral drug-related liver injury, especially severe toxicity, is clearly more frequent in HIV-infected patients with underlying chronic HBV and/or HCV infection.
  • Other predisposing factors are alcohol, consumption of ecstasy and cocaine; risk of liver injury is increased in those patients with transaminases elevations prior to initiating HAART

Potential and common Biochemical features


Drug related Liver Injury




References:
  1. Liver Disease and Cirrhosis PRIMARY CARE OF VETERANS WITH HIV Organ Systems and Metabolic. April 2009; Last reviewed/updated: October 28, 2011
  2. Soriano V. et al. Antiretroviral drugs and liver injury. AIDS. 2008 Jan 2;22(1):1-13.
  3. Antiretroviral Drugs and Liver Injury. http://www.medscape.com/viewarticle/568415_2

Monitoring Parameters for Zinc Phosphide Poisoning



1.     VITAL SIGNS
Hypotension, shock, and tachycardia occur commonly. 

2.     CARDIOVASCULAR
Cardiac dysrhythmias and ECG abnormalities have ben reported following zinc phosphide ingestions. Hypotension, shock, toxic myocarditis, myocardial failure, and massive focal myocardial injury with elevated cardiac enzymes may occur. 

3.     RESPIRATORY
Cough, dyspnea, cyanosis, chest tightness, and tachypnea may occur. Pulmonary edema has been reported following zinc phosphide ingestion. Zinc phosphide releases toxic and irritating fumes of oxides of phosphorus and zinc oxide when heated to decomposition. Inhalation exposure to such fumes would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema. 

4.     NEUROLOGIC
Acute exposure may result in headache, dizziness, fatigue, and CNS depression leading to coma, and chronic exposure may lead to neuropsychiatric manifestations. Seizures are not uncommon after acute exposure. Restlessness and anxiety may be noted following acute zinc phosphide ingestion. 

5.     GASTROINTESTINAL
Nausea, vomiting, and abdominal pain may occur. Pancreatitis has been rarely reported.

6.     HEPATIC
Acute exposure may produce jaundice with hepatomegaly. Elevations of serum transaminases may be noted. 

7.     ACID-BASE
Metabolic acidosis may be seen in acute poisonings. 

8.     FLUID-ELECTROLYTE
 Hypokalemia may occur secondary to profuse vomiting following zinc phosphide ingestion.

9.     ENDOCRINE
Severe hypoglycemia has been reported. 

10.  REPRODUCTIVE
At the time of this review, no data were available to assess the teratogenic potential of this agent. 

Monitoring parameters:
1.     Monitor vital signs & mental status.
2.     Monitor continuous pulse oximetry.
3.     Institute continuous cardiac monitoring & obtain an EEG.
4.     Monitor serum electrolytes, blood glucose, renal function, and liver enzymes.
5.     Obtain a chest radiograph in patients with respiratory symptoms.

References:
  1. UpToDate. Available from: http://www.uptodate.com.ezp.imu.edu.my/contents/overview-of-rodenticide-poisoning?source=machineLearning&search=zinc+phosphide&selectedTitle=1%7E1&sectionRank=1&anchor=H352512775#H352516540
  2. CDC. Available from: http://www.atsdr.cdc.gov/mmg/mmg.asp?id=1013&tid=214
  3. http://www.ncbi.nlm.nih.gov/pubmed/19280425