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Gout and Hyperuricemia
Gout and Hyperuricemia
Rajeh H Munir
Gout and hyperuricemia
Definitions :
: Pathophysiology
The uric acid is the end product of the degradation of purines . the purines
: from which uric acid is produced originate from three sources
- Dietary purine .
- Conversion of tissue nucleic acid to purine nucleotides .
- De novo synthesis of purine bases .
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Pharmacotherapy
Rajeh H Munir
These two conversion require PRPP as the cosubstrate and are important
reutilization reaction involved in nucleic acid synthesis .
drugs that decrease renal clearance of uric acid include diuretics , nicotinic
acid , salicylates, ethanol , pyrazinamide , levodopa , ethambutol ,
cyclosporine , cytotoxic drugs .
treatment:
patients may be advised to reduce their intake of foods high in purines e.g
organ meats , avoid alcohol , increase fluid intake and lose weight if obese.
Joint rest for 1 to 2 days should be encouraged , and local application of ice
may be beneficial .
Indomethacin : 25-50 mg four times aday for 3 day , then taper twice daily
for 2-7 days ,
Naproxen : 500mg twice daily for 3 days , then 250-500 mg daily for 4-7
days .
3- Colchicine
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Pharmacotherapy
Rajeh H Munir
Colchicine is an anti mitotic drug that is highly effective in relieving acue
attacks . oral colchicine causes dose-dependent GI adverse effects e.g
nausea , vomiting , diarrhea . non-GI adverse effects include neutropenia
and axonal neuromyopathy which may be worsened in patients taking
other myopathic drugs e.g statins or in those with renal insufficiency .
The usual oral colchicine dose is 1mg initially followed by 0.5mg every 1
hour until the joint symptoms subside , the patient develops abdominal
discomfort or diarrhea or total dose of 8mg has been given.
After full IV course . patients should not receive colchicine by any route for
at least 7 days.
4-Corticosteroids :
the recommended dose is prednisone 30-60mg orally once daily for 3-5days
. because rebound attacks may occur upon steroid withdrawal , the dose
gradually tapered in 5mg increments over 10-14days and discontinued .
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Pharmacotherapy
Rajeh H Munir
single IM of long acting corticosteroid e.g methyl prednisone acetate can de
used as alternative to oral route .
the dose should be reduced in patients with renal insufficiency (200 mg/day
for CLcr 60ml/min or less and 100mg/day for CLcr 30ml/min or less).
6- Uricosuric drugs
Probenecid is given initially at dose of 250mg twice daily for1-2 weeks then
500mg twice daily for weeks .
Osteoporosis
Definition
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Pharmacotherapy
Rajeh H Munir
Osteoporosis is a skeletal disorder characterized by compromised bone
strength predisposing individuals to an increased fracture risk.
Pathophysiology
Men and women begin to lose small amount of bone mass strating in the
third or fourth decade as a consequence of reduced bone formation.
Treatment :
All individuals should have balanced diet with adequate intake of calcium
and vitamin D . if adequate dietary intake can not be achieved . calcium
supplements are necessary.
Smoking cessation can help to optimize peak bone mass , minimize bone
loss and ultimately reduce fracture risk.
Pharmacologic therapy
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Pharmacotherapy
Rajeh H Munir
Calcium should be combined with vitamin D .
Calcium carbonate is salt of choice because it contains the highest
concentration of elemental calcium (40%) >
Calcium citrate absorption is acid independent and not be taken with
meals . because the fraction of calcium absorbed decreases with
increase dose , maximum single doses of 600mg or less of elemental
calcium are recommended . constipation is the most common
adverse reaction .
Vitamin D supplementation maximizes intestinal calcium absorption .
Infants 6-12 months need of calcium about 270 mg .
Children 1-3 years need of calcium about 500 mg .
Children 4-8 years need of calcium about 800 mg .
When Children 1-8 years need of vitamin D about 200 i.u
Adult need of calcium about 1300 mg . and of vitamin D about 400-
600 i.u . therapeutic dose to vitamin D about 50.000iu once weekly
or once monthly .
Bisphosphonates are bind to hydroxyapatite in bone and decrease
resorption by inhibiting osteoclast adherence to bone surface . all
bisphosphonates become incorporated into bone giving them long
biologic half-lives of up to 10 years e.g alendro nate , risedronate ,
ibandronate are indicated only for treatment of postmenopausal
women . Risedronate and alendronate are also use for male .
Poorly absorbed ( bioavailability 1% to 5% ) each oral tablet should
be taken in the morning with at least 150ml tap water ( not coffee ,
juice , mineral water , milk ) at least 30 minutes and 60 minutes for
oral ibandronate before consuming any food . most patients prefer
once weekly or once-monthly .
alendro nate dose 5mg daily , 35mg weekly .
Risedronate dose 5mg daily , 35mg weekly . 150mg monthly .
ibandronate dose 2.5mg daily , 150mg monthly , 5mg I.V infusion
yearly.
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Pharmacotherapy
Rajeh H Munir
The most common bisphosphonate adverse effects are nausea ,
abdominal pain and dyspepsia , esophageal , gastric or duodenal
irritation , perforation , ulceration or bleeding .
Mixed estrogen agonist / antagonists
Raloxifene is estrogen agonist on bone but antagonists on breast and
uterus use treatment of postmenopausal osteoporosis . has dose
60mg daily.
Calcitonin is released from the thyroid gland when serum calcium is
elevated . salmon calcitonin is used clinically because more potent .
Calcitonin is indicated for osteoporosis treatment for women at least
5 years past menopause .
The intranasal dose is 200 i.u daily .
Anabolic therapy
Terparatide is recombinant product representing the first 34 amino
acids in human parathyroid hormone . Terparatide increase bone
formation . contraindication in patients at baseline increased risk for
osteosarcoma (e.g pagets bone disease , unexplained alkaline
phosphatase elevations , pediatric patients , young adults with open
epiphyses or patients with prior ration therapy involving the
skeleton). The dose 20mcg subcutaneously daily for up to 2 years.