Comparison : Amisulpride vs Sulpiride

Suggested Antipsychotic Treatment

Based on up to date evidence, first line recommended antipsychotic options are:

• Amisulpride (greater comparative cost may outweigh first line choice).
• Aripiprazole
• Olanzapine (significant risk of metabolic adverse effects may outweigh first line choice).
• Quetiapine
• Risperidone
• Sulpiride (greater comparative cost may outweigh first line choice).

Licensed ages (BNF for Children)

• Amisulpiride : > 15 years
• Sulpiride: > 14 years

Cost

Side effects

QT prolongation

Effect on Prolactin Levels

Breast feeding

Elderly

Conclusion

• Amisulpride and Sulpiride are listed as the first line recommended antipsychotic.
• There is not much different in the side effects of both drugs.
• In terms of cost, sulpiride is cheaper than amisulpride.

References

1. BNF, March –September 2016
2. BNF for Children, September 2015-2016
3. http://www.sussexpartnership.nhs.uk/
4. http://www.malaysianpharma.com/index.php/articles22/

Celebrex : Renal Dose Adjustment

Renal Effect

• Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
• Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation.
• Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE-inhibitors, angiotensin II receptor antagonists, and the elderly.
• Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Clinical trials with Celebrex have shown renal effects similar to those observed with comparator NSAIDs.

Studies & Evidences

• 40 patients on a low-salt diet were randomized to receive celecoxib (200 mg twice daily or 400 mg twice daily), naproxen (500 mg twice daily), or placebo. A single 400-mg dose of celecoxib significantly decreased GFR and renal plasma flow, demonstrating that COX-2 inhibition with this agent can affect renal function under conditions of increased renal dependence on PGs. As in the other studies, both celecoxib and naproxen produced transient reductions in urinary sodium excretion over the first 3 days of treatment.
• In another study, 71 patients with stable chronic renal insufficiency were randomized to receive celecoxib (200 mg twice daily, naproxen (500 mg twice daily), or placebo for 7 days.^[65] After 7 days of treatment, statistically significant decreases in GFR were observed in patients receiving celecoxib and those receiving naproxen. Sodium excretion was transiently reduced with both active treatments

Renal Dose Adjustment

• Contraindicated in severe renal impairment (creatinine clearance <30 mL/min or 0.5 mL/sec) or deteriorating renal disease (individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored)
• In elderly volunteers with age-related reductions in glomerular filtration rate (GFR) (mean GFR >65 mL/min/1.73 m2) and in patients with chronic stable renal insufficiency (GFR 35-60 mL/min/1.73 m2) celecoxib pharmacokinetics was comparable to those seen in patients with normal renal function.
• No significant relationship was found between serum creatinine (or creatinine clearance) and celecoxib clearance.
• Severe renal insufficiency would not be expected to alter clearance of celecoxib since the main route of elimination is via hepatic metabolism to inactive metabolites.
• No information is available from controlled clinical studies regarding the use of Celebrex in patients with advanced renal disease. Therefore, treatment with Celebrex is not recommended in these patients
• If Celebrex therapy must be initiated, close monitoring of the patient's renal function is advisable.
• In a cross-study comparison, celecoxib AUC was approximately 40% lower in patients with chronic renal insufficiency (GFR 35-60 mL/min) than that seen in subjects with normal renal function.

References:

1. Celebrex Drug Monograph
2. Celebrex Data Sheet 2015
3. https://www.medicines.org.uk/emc/medicine/14534
4. www.drugs.com
5. http://www.medscape.org/viewarticle/422939_3

CPD Offline Sept 2016

Sila Klik Pautan(link/bergaris) di bawah untuk mendapatkan artikel dan soalan:

September

01 Proton Pump Inhibitors

02 Needle Stick Injury

01 & 02 Questions

 

Mata CPD: 1 mata / Artikel

Sila hantar jawapan anda ke Unit DIS dalam masa 2 minggu

 

Vitamin K & Liver Disease

Liver : Normal Physiology

• Liver has a crucial role in hemostasis in which it synthesize all the coagulation factos with the exception of von Willebrand factor.
• It also synthesize inhibitors of coagulation 9antithrombin, protein C, and protein S and proteins of the fibrinolytic system 9plaminogen and α-antiplasmin).
• It is also involved in the clearance of activated clotting factors from circulation.

Liver Disease & Hemostasis

• The complex nature of haemostasis in patients with liver disease can result in bleeding and/or thrombosis.
• Patients with end-stage-liver disease (ESLD) do not suffer only from procoagulant deficiency; there is also a lack of natural anticoagulants (i.e. proteins C and S) and profibrinolytics.

Bleeding Risk Assessment in ESLD

• Bleeding risk assessment is imperative in ESLD patients before any intervention is considered.
• However, conventional coagulation tests such as for the international normalized ratio (INR) or the activated partial thromboplastin time (aPTT) only poorly reflect the pathophysiological changes in advanced liver cirrhosis. 
• Patients in advanced stages of liver disease develop thrombosis despite pathological procoagulation profiles.
• Still, INR and aPTT are predictive for procoagulation factor deficiency, but they are not sensitive for decreased protein C and S activity.

When to give Vitamin K?

• In most patients, intervention is not in the setting of asymptomatic laboratory changes.
• An exception is that, vitamin K is given to patients with suspected deficiency, including any patients with suspected poor nutrition and cirrhosis, as well as those with cholestatic disease, diarrheal illness, or antibiotic use.
• There is little evidence regarding the efficacy of administering vitamin K; however, toxicities are also negligible.
• A typical dose of vitamin K in this setting is 10 mg orally per day for three days, or 10 mg intravenously as a single dose for individuals who cannot take vitamin K orally or who may not adequately absorb vitamin K (eg, ascites, gut edema).  

Vitamin K in ESLD Adults

• A study quoted that the replacement of vitamin K-dependent coagulation factors in patients with ESLD differs from the reversal of oral vitamin K antagonists. 
• Patients with vitamin K antagonists require 1 IU/kg PCC to increase the prothrombin time (PT) time by 1%, while patients with ESLD require 1.6 IU/kg to achieve the same increase.

Vitamin K in Acute Liver Failure Adults

• Vitamin K (5-10 mg subcutaneously) should be administered routinely, since vitamin K deficiency has been reported in patients with ALF.
• In another study, in acute liver patient for control of coagulopathy is recommended with the adminstration of intravenous vitamin K (2–10 mg). 

Vitamin K in Liver Failure Peadiatric

• Oral vitamin K supplementation is usually adequate to prevent severe vitamin K deficiency-associated coagulopathy.
• Children are given 2.5 - 5 mg/day although supplementation three times per week is often adequate to prevent coagulopathy.

Reference: 

1. Uptodate 
2. E. D. Nel and A. J. Terblanche, “Nutritional support of children with chronic liver disease,” vol. 105, no. 7, 2015.
3. W. M. Lee, A. M. Larson, and R. Todd Stravitz, “The Management of Acute Liver Failure,” 2011.
4. D. A. Kelly, “Managing liver failure,” Postgrad. Med. J., vol. 78, no. 925, pp. 660–667, Nov. 2002.
5. F. H. Saner, R. K. Gieseler, H. Akiz, A. Canbay, and K. Görlinger, “Delicate Balance of Bleeding and Thrombosis in End-Stage Liver Disease and Liver Transplantation,” Digestion, vol. 88, no. 3, pp. 135–144, 2013.

Clonidine: Tourette Syndrome

Clonidine & Breath Holding Spells (BHS)
Treatment for cyanotic breathholders has been more difficult. Given our current understanding of the underlying pathophysiology, central sympathetic outflow modulators would be anticipated to provide potential benefit. In an uncontrolled study, the use of tetrabenazine (a centrally acting a-adrenergic antagonist) has been effective in preventing cyanotic BHSs in a group of 15 patients.  A dose of 1.0 mg/kg/d divided into 3 or 4 doses was used. The addition of clonidine to tetrabenazine was even more effective	(Dimario, 1999)
Multiple medications have been tried with variable success, including iron therapy for children with low hemoglobin levels, piracetam, and central sympathetic modulators such as tetrabenzamine and clonidine for cyanotic BHS .	(Legge, Kantoch, Seshia, & Soni, 2002)
Clonidine in Neurodevelopmental Disorder
α2-adrenoreceptor agonist; activates inhibitory neurons resulting in decreased sympathetic outflow and decreased vasomotor tone and heart rate Clinically, clonidine is often used in the setting of poor sleep in children with NDDs, particularly those who have associated behavioral symptoms. Indicated for neurodevelopmental disorder (autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, and Smith-Magenis syndrome)	(Blackmer & Feinstein, 2016)
Clonidine in Taurette Syndrome (Tics )
The alpha-2 adrenergic agonist clonidine inhibits the release of noradrenaline. Studies supporting the efficacy of this drug in ameliorating tics include a retrospective study which found clonidine was efficacious in 47% of patients treated and had few side effects Similar figures were reported by a single-blind, placebo-controlled trial conducted by Leckman and colleagues, where 46% of the patients treated responded well, exhibiting improved motor and phonic tics Treatment with clonidine was associated with a decrease in the mean total tics score from 25.2 to 21.8 and minor sedation-related side effects.	(Eddy, Rickards, & Cavanna, 2011)
Alpha-agonists include clonidine and guanfacine, and though they lessen CNS adrenergic outflow, their mechanism in reducing tic frequency is not clear at present  Clonidine is a central-acting, presynaptic, alpha2-adrenergic agonist prescribed two to four times a day with a daily dose range of 0.05–0.3 mg; sometimes it is given only at bedtime	(Patel, D.R., Greydanus, D.E., Omar, H.A., Merrick, 2011)
Clonidine in Taurette Syndrome (Sleep Paralysis )
Treatment approaches have not been evaluated. Some success treating isolated sleep paralysis with REM-suppressing agents such as low doses of tricyclic agents, clonidine, or clonazepam	Uptodate
Clonidine & Sleep Disturbance in Children with Neurodevelopmental Disabilities
Clonidine received notoriety for being prescribed as a sleep aid in children, but currently, there are no well-controlled studies that address the effects of clonidine in children with sleep problems. Administration of low doses of clonidine (range, 0.025–0.05 mg) has little effect on sleep and can either increase or decrease the duration of REM sleep. At medium-to-high doses (range, 0.1–0.3 mg), clonidine appears to have postsynaptic activity on the α2-adrenergic receptors, which results in decrease of acetylcholine, which increases REM latency, stage 2 sleep, and slow-wave sleep. Ingrassia Turk in a retrospective chart review found clonidine to be an effective therapeutic intervention for alleviating sleep disturbances in six children, whose ages ranged from 6 to 14 years. Dose titration began at 0.05 mg and was gradually titrated up to 0.1 mg at bedtime. No severe side effects were reported. In a recent open label retrospective review, 19 children with ASD were treated with oral clonidine (range, 0.1–0.2 mg) 30 minutes before bed-reduced sleep latency and lessened nocturnal awakenings; this is especially important in children with ASD who are overly aroused or mildly anxious at bedtime. Moreover, Hollway et al performed a vast literature search, and clonidine was reported to be effective in children who experienced sleep disturbances with comorbid ASD and other neurodevelopmental disorders with behavioral problems at doses ranging from 0.05 to 0.225 mg/d.	(Angriman, Caravale, Novelli, Ferri, & Bruni, 2015)

Reference:

1.       Angriman, M., Caravale, B., Novelli, L., Ferri, R., & Bruni, O. (2015). Sleep in Children with Neurodevelopmental Disabilities. Neuropediatrics, 46(03), 199–210. http://doi.org/10.1055/s-0035-1550151

2.       Blackmer, A. B., & Feinstein, J. A. (2016). Management of Sleep Disorders in Children With Neurodevelopmental Disorders: A Review.

3.       Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 36(1), 84–98. http://doi.org/10.1002/phar.1686

4.       Dimario, F. J. (1999). Breathholding Spells in Childhood.

5.       Eddy, C. M., Rickards, H. E., & Cavanna, A. E. (2011). Treatment strategies for tics in Tourette syndrome. Therapeutic Advances in Neurological Disorders, 4(1), 25–45. http://doi.org/10.1177/1756285610390261

6.       Legge, L. M., Kantoch, M. J., Seshia, S. S., & Soni, R. (2002). A pacemaker for asystole in breath-holding spells. Paediatrics & Child Health, 7(4), 251–4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20046299

7.       Patel, D.R., Greydanus, D.E., Omar, H.A., Merrick, J. (2011). Neurodevelopmental Disabilities. Neurodevelopmental Disabilities