Clinical Picture and Treatment of Guillain Barre Syndrome

A cute infective polyneuritis

"Landry Guillain Barre Syndrome"

 

Aetiology:

• It is due to an allergic or auto-immune reaction secondary to a previous non-specific virus infection.

Clinical picture:

Febrile stage:

• it starts with an influenza-like attack with fever, headache, malaise, pains all over the body with no nervous symptoms.

Latent stage:

• the above symptoms disappear and the patient is free for 1-4 weeks.

Paralytic stage:

• There is acute severe weakness or paralysis starting in the loewr limbs and ascending to involve the trunk and respiratory muscles, followed by the upper limbs muscles.
• Contrary to other types of polyneuropathy, the weakness is proximal more than distal.
• In spite of severe degree of paralysis, wasting is not present early in the disease.
• Sensory impairment may occur resulting in stock and glove hypothesia and deep sensory loss.

• Early in the disease there is tenderness of the calves.
• The cranial nerves are usually involved specially cranial nerves 7,10 resulting in bilateral facial paralysis and bulbar symptoms.
• C.S.F. show cytoalbuminous dissociation.
• Prognosis is good in 85% of the cases where recovery occurs in 3-4 weeks.

Treatment:

1)Absolute rest in bed till the heart rate reaches below 100/min.(i.e. return of the vagal tone).
2)Care of the bulbar muscles by:

• Frequent suction of secretions feom the pharynx.
• Neostigmine 1 mg hourly I.M.
• Tube feeding in case of phayngeal paralysis.

3)Care of the respiratory muscles by:

• Frequent suction to keep a patient airway.
• Tracheostomy may be needed.

4)Corticisteriods(Prednosone or Prednisolone 60 mg/day).
5)Gamma-globulins and plasmapheresis:

•  the most recent and effective treatment.

6)Vitamins B1,B6,B12(Trivarol,Tri-B),I.M. daily.
7)A.T.P. 25 mg daily I.M.(Adenoplex).
8)Antibiotics e.g. tetracycline to guard against 2ry infection.
9)Physiotherapy:

• Massage.
• Passive and active exercises.
• Proper positioning and electrical stimulation.

vitamin B complex deficiency"Pellagra"

Pellagra

 

Definition and Aetiology:

This is a multiple deficiency disease due to vitamin B complex deficiency specially niacin;
this may result from:

• Deficient intake of vitamin B or of proteins of high biological value (containing nicotinic acid or its precursor tryptophan).
• Deficient absorption as in gastro-enteritis.
• Parasitic infestation.

Clinical picture:

1)Cutaneous manifestations:

• They start as a bilateral and symmetrical dermatitis followed by hyperkeratosis(rough, scaly and desquamated skin) and pigmentation.

• The lesions involve the exposed areas(face, neck, dorsum of the hands and feet) and over bony prominences(trochanters, elbows, knees, heels)

 

2)Gastro-intestinal manifestations:

• Mouth: stomatitis, glossitis with atrophy of the papillae(glazed tongue).

• Stomach: dyspepsia, nausia, vomiting, epigastric pain.
• Intestines: colic, diarrhoea.
• Hepato-splenomegaly may be present.

3)Neuropsychiatric manifestations:

• Peripheral neuropathy mainly sensory due to peripheral nerves degeneration.
• Paraplegia or quadriplegia(systemic paraplegia) due to pyramidal tract degeneration(pellagral lateral sclerosis).
• Mentality changes as anterograde amnesia, depression, dementia and suicidal tendencies due to cerebral cortex degeneration.

Treatment:

1. Treatment of the cause e.g. parasitic infestation or gastro-enteritis.
2. Good diet, rich in animal proteins and vitamins.
3. Vitamin B complex(the cheapest source is yeast) iron supplement(to correct anaemia).
4. Nicotinamide 500 mg I.V. daily in severe cases, followed after improvement by 200 mg daily I.V. for 2 weeks; maintenance dose 100 mg t.d.s. orally.

Non-pharmacological management of Orthostatic Hypotension

Orthostatic Hypotension

Definition:

• A systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg  within three minutes of standing.

Causes:

1. Nervous system diseases, such as a neuropathy.
2. Prolonged bed rest.
3. Dehydration.
4. Irregular heart beat(heart arrhythmia).

Symptoms:

1. Dizziness.
2. Weakness.
3. Blurred vision.
4. Fatigue.
5. Fainting.

Treatment options:

   Treatment for hypotension depends on the cause. For example, the dosage of existing medications may need to be altered, or a bleeding stomach ulcers surgically repaired.If no particular cause can be found, drugs may be used to raise blood pressure . In extreme cases, a lower body pressure suit may be required.

Management:

Non-pharmacologic management:

• Slow changes in position.
• Stockings: to increase venous return / decrease lower extremity pooling.
• Temperature: avoid extremes.
• Activities:

                              1.Dorsiflexion several times before standing.
                              2.Before rather than after a meal.
                              3.Afternoon rather than morning.
                              4.Swimming pool.
                              5. Avoid heavy lifting.

• Night time: slight elevation of head of bed.
• Meals normalize salt and water intake.

Pharmacologic management:

Fludrocortisone:

Mechanism: sodium retention.
Midodrine:
Mechanism:  alpha-l-adernoreceptor against increase peripheral vascular resistance.

Degenerative Disorders(Lumbar Disc Prolapse)

Degenerative Disorders

"Lumbar Disc Prolapse"

 

Definition:

• It is herniation of nucleus puposus of the intervertebral disc through a tear in the annulus fibrosus.

Incidence:

• Age:- mostly middle age.
• Commonest level L4/L5 followed by L5/S1.
• Lumbar disc prolapse:- cervical disc prolapse 4:1.

Aetiology:

1. Trauma:- lifting heavy objects.
2. Degeneration:-causing weakness of annulus fibrosis.
3. Both of the above.

Pathophysiology:

1)Stages of lumbar disc herniation:

• Tearing of the ring of annulus fibrosis.

• Protrusion of the disc against neural structures.

• Extrusion of nucleus pulposis in the neural canal.

 

2)Direction of the cervical disc prolapse:

• Posterolateral>>>root compression>>> sciatica(most common).
• Posterior>>> thecal compression>>> cauda equina(in the cervical region posterior protrusion>>> spinal cord compression i.e. myelopathy.

Clinical Picture:

1)Related to stretching of annulus fibrosis:

a)back pain for several weeks or years before leg pain.
Pain increase with straining, coughing, sitting or standing for a long time and leaning forward.
Improves by bed rest.

b)Spasm of paravertebral muscle limits spinal mobility to reduce pain.

2)Related to neural compression:

a)In posterolateral disc herniation:
1)Sharp lancinating leg pain occurs along one of the dermatomal supply of the lower limbs. It is increased and decrease by the same factors mentioned with back pain.
Pain is called sciatica when it occurs along the distribution of the sciatic nerve.
Pain is called femoralgia if a long the distribution of the femoral nerve.
2)Numbness and parethesia may occur.
3)Motor weakness.
4)Straight leg raising test(Lesegue's sign). w hile the patient in the supine position, raising the leg less than 60 degrees>>> elicits the pain, Dorsiflexion of the foot while the leg is elevated aggravates the pain.

b)In posterior herniation(Cauda equina syndrome):
1)Sensory
a. Saddle anaesthesia.
b. Sciatica and low back pain.
2)Motor:

 weakness e.g. foot drop.
3)Autonomic:
a. Sphincteric disturbance.
b. Sexual dysfunction.

Differential Diagnosis:

1)Osteoarthiritis of the hip joint:

• This can be differentiated by faber test which is Flexion, Abducion, External rotation of the hip.This usually increases pain originating from hip joint.

2)Sacroiliitis:

• There is tenderness on the sacroiliac joint and pain does not extend below the knee.

3)Spondylolithesis:

• Is anterior subluxation of a vertebra on another.Most commonly at L4/L5 and is due to degeneration of the facet joints.
• Back pain is significant. Sciatica, if present, is usually bilateral. X-ray is diagnostic.

4)T.B of the hip joint(rare).

Investigation:

1)MRI:

• Is the modality of choice.
• Demonstrates the prolapsed disc and any canal stenosis.

 

2)X-ray(A-P and Lateral)

• Has a limited value in diagnosis of lumbar disc. It shows a reduced disc height& osteophytes.
• On the contrary it is very useful in

                                                           Spondylolisthesis
                                                            Detects spina bifida
                                                           Detects secondary tumros

3)CT scan is useful but to a less degree than MRI.

 

4)Myelography is invasive and no longer used.

Treatment:

Conservative(succeeds in 90% of cases):

1. Bed rest for 2-4 weeks. Boards are placed under mettress.
2. Analgesics.
3. Muscle relaxants.
4. Weight reduction is advisable.

2)Surgical

Indications of surgery:

1. Failure of conservative treatment.
2. Intolerable pain in spite of initiation of conservative treatment.
3. Progressive motor weakness.
4. Cauda equina syndrome.

Type of surgery:
1)Discectomy: different approaches are used:

• After laminectomy or hemi laminectomy.
• Interlaminar.
• Microscopic.
• Endoscopic.
• Laser.

2)Chemonucleolysis in some cases.

N.B.

• In surgery we remove L4 lamina to gain access to L4/L5 disc which causes compression on L5 root.

Degenerative Disorders (Cervial Disc Prolapse)

Cervical Disc Prolapse

 

Back ground:

• The cevical spine is very mobile and is liable to osteoarthiritic changes(cervical spondylosis). This affects more than 50% of people above 50 years.
• 20% of those affected develop symptoms.

Definition:

• It is herniation of nucleus puposis of the intervertebral disc through a tear in the annulus fibrosis.

Aetiology:

• Degenerative is the most important(spondylosis).
• Traumatic is less important.
• Both.

Pathophysiology:

• Two clinical types of cervical disc prolapse are known: soft disc& hard disc(spondylosis)
• The stages are

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       Soft Disc                                                         Hard Disc
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Laceration of annulus fibrosis                     Instability(degeneration)
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Protrusion of nucleus pulposis           Osteophytes formation+_compression

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Extrusion of nucleus pulposis                             Stabilization
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• Directions of the cervical disc prolapse:

Posterolateral>>> root compression>>>Radiculopasy.
Posterior>>> spinal cord compression>>> Myelopathy.

Clinical Picture:

1)Related to annulus tearing or spine degeneration and instability:

• Neck and interscapular pain of referred type.
• Spasm of muscles>>> straight cervical spine.

2)Related to neural compression:

A)IN posterolateral disc herniation:
1)Sensory:

• Radicular pain(Brachialgia):which is asharp lancinating pain radiating along one of the dermatomes of upper limbs.
• Numbness and paresthesia.

2)Motor(lower motor neuron lesion)

• Motor weakness and muscle wasting and fasciculation.

3)Autonomic:

• Negligible.

B)IN posterior disc herniation(Myelopathy):
Sensory

• Numbness and paresthesia below the level of lesion.
• Lhermitte sign:Electric like pain radiating down the spine provoked by neck flexion.

Motor(upper motor neuron lesion):

• Hpertonia.
• Hyperreflexia.
• Weakness of lower limbs.
• Babiniski sign.

Autonomic

• Precipitancy of urine.

Differential Diagnosis:

• Amyotrophic lateral sclerosis(mixure of upper and lower motor neuron lesions).

Investigation:

1)MRI:

• Is the modality of choice.
• Demonstrates the prolapsed disc and any canal stenosis.

2)X-ray(A-P and Lateral)

• Has a limited value in diagnosis of lumbar disc. It shows a reduced disc height& osteophytes.
  
  • On the contrary it is very useful in

1. Spondylolisthesis
2. Detects spina bifida
3. Detects secondary tumros

3)CT scan is useful but to a less degree than MRI.

4)Myelography is invasive and no longer used.

Treatment:

1)Conservative:

1. Neck collar and traction.
2. Analgesics
3. Muscle relaxant.

2)Surgical:

Indications of surgery:

1. Failure of conservative treatment.
2. Intolerable pain in spite of initiation of conservative treatment.
3. Progressive motor weakness.
4. Cauda equina syndrome.

Surgical procesures

1)Soft disc:

• Discectomy by anterior approach via incision.

2)Hard disc:

• Discectomy by anterior approach via neck incision+removal of the osteophytes+fusion of vertebrae by a bone graft.

Milk and Medications For Treatment of Hypertension

Hypertension
"A Silent Killer"

 

Definition:

Persistance elevation of arterial blood pressure above normal limit under normal basal condition.

Symptoms:

• Hypertension is called silent killer because it rarely causes symptoms.when blood pressure is very very high, these symptoms may occur:-

1. Headache.
2. Nosebleeds.
3. Palpitations.
4. Dizziness.
5. Numbness or tingling in the hands or feet.
6. Confusion.
7. Blurred vision.
8. Vomiting.

Management:

 STEP 1

The four main choices for initiating therapy of essential hypertension(HTN):
A)Diuretics.
B)Beta adrenergic blockers.
C)Calcium channels blockers.
D)Angiotention converting enzyme.

A)Diuretics:

• Effective alone or adjunct to other antihypertensives.
• Considered as(prefferd) starting agent for most patients, and an impotant part of multidrug HTN therapy.

>>>>The  diuretic chioces for HTN:
Thiazides(oral diuretics)used most _prototype is hydrochlorothiazide:

ACTION:-

1. Modest renal Na+ loss seems ti decrease vascular responsiveness to vasoconstrictors such as norepinephrine, peripheral vascular resistance falls.
2. Reduction of circulating fluid volume(diuresis) probably contributes to initial antihypertensive action in some patients, however the diuretic effect is usually short-lived but blood pressure control usually persists.
3. Flat dose-response curve : markedly insrease antihpertensive effect(but often does increase number, severity, of side effects).

Main side effects:-

1. Hypokalemia (Thiazides are potassium-wasting).
2. Risk of hyper uricemia, gout(Thiazides elevate serum urate).
3. Hyperlipidemias, hyperglycemia:
4. thiazides increase blood lipids and glucose, yet these drugs shouldn't  be absolutely avoided in patients with hyperlipidemias and/or frank diabetes mellitus.
5. Risk of hypovolemia(a particular concern in pregnancy: maternal volume depletion may>>> hyoperfusion of placenta)
6. Loop agents(e.g. furosemide__LASIX); NOT often a chioce for HTN , rarely chosen goal is to use diuretic for uncomplicated HTN.

B)Beta-blockers (e.g. propranolol; INDERAL)

• All orally effective B_blockers are approved for HTN.

Action:-

1. Reduce cardiac contractility.
2. Reduce renin release.

Uses:-

1. Effective alone or as adjunct(mainly to inhibit reflex tachycardia caused by some other antihypertensives).
2. May be preffered for patients who also have angina (not vasospastic),tachycardia, myocardial infarction,hyperthyroidism, migraines.
3. Reduction exercise tolerance may take these less than ideal chioce for some patients who are very physically active.

Contraindication:-

1. Asthma, emphysema.
2. Insulin-dependant diabetes mellitus.
3. Atrio-ventricular block or bradycardia.
4. Vasospastic angina.
5. Severe congestive heart failure.
6. Peripheral arterial disease.

N.B.

• B_blockers raise serum triglyceride levels and lower HDL.
• Discontinuing B_blockers Tx:

        never stop abruptly(to avoid risk of rebound increase heart rate).

C)Calcium channels blockers:

• Block slow voltage gated (L-type) Ca channels >>> decrease calcium influx to heart, blood vessels.

Types:-

1)Nondihydropyridines:Prototype verapamil(ISOPTIN):

Action:-

1. Reduce contractility.
2. Reduce vasoconstriction(i.e. cause vasodilatation).

Uses:-

• Mainly as alternative to B-blocker, antoanginal& antiarrhythmics as well.

Side effects:-

• Contipation is most common side effect.

Contraindication:-

• any situation in which depression of cardiac contractility, rate, automaticity, impulse conduction, would be dangerous(never combine with B-blocker).

 2)Dihydropyridines: prototype nifedipine(ADALAT):

• Selective vasodilator.
• No verapamil-like cardiac depression, thus...
• Might be chosen when cardiac depression from anondihydropyridine is to be avoided, or when the mild cardiac "stimulation" from dihydropyridine might be beneficial(e.g. concomitant bradycardia).
• Produces ankle edema.

D)ACE inhibitors (and other angiotensin"modifiers"):

• Propotype ACE inhibitor is captopril(CAPOTEN).

Actions:-

1. Inhibit Angiotension 2 synthesis(hence consequent vasoconstriction and aldosterone release).
2. Inhibit breakdown of bradykinin, avasodilator(ACE = bradykininase).

Uses:-

• Hypertention:

often cosidered suitable for hypertensive patient who also has congestive heart failure|(CHF) and/or diabetes mellitus w/o evidence of severe kidney diseases, and/or hyperlipidemia.

• Tx of CHF.
• Help delay progression of renal disease in patients with diabetic neuropathy.

Side effects:-

1. Most common : cough esp. with captopril(due to bradykinin)
2. Taste loss; allergic skin rash; drug fever.
3. Rare but serious: angioedema(to bradykinin).
4. May lead to excessive hypotention when used with diuretics(synergistic effects).
5. Aldosterone levels may indirectly>>> hyperkalemia, so K-sparing diuretics or oral K supplements cautiously.
6. Acute renal failure (in patients with bilateral renal artery stenosis).
7. Proteinuria with captopril.

Contraindications:-

• Bilateral renal artery stenosis >>>  acute renal failure.

• Angiotensin 2 receptors blockers (ARBs):

>>>prototype Losartan(COZAAR):

• Alternative to ACE inhibitor, fewer/no typical ACE inhibitor side efeeccts (e.g. cough&angiodema)
• Action:-
• only block A-11 receptors(>>>decrease mediated vasoconstriction and decrease aldosterone release.
• Lack effects on bradykinin metabolism.
• Share same pregnancy contraindication as ACE inhibitors.

STEP 2

• Alternative initial agents(sympathetic inhibitors)

A)selective peripheral alpha-blockers:

 Prazosin:

Actions:-

1. Block sympathomimetic-induced vasoconstriction in periphery via postsynaptic(alpha-1)blockade, with no effect on presynaptic alpha-receptors(alpha-2)
2. Usually 2nd line, but may be turned to as first choice in some cases e.g. patients with:
3. Hyperlipidemias.
4. Benign prostatic hypertrophy, as smooth muscle relaxing effect in GU tract(also due to alpha-blckade).

Side effects&Contraindication:-

1. Most important:Orthostatic hypotention(first dose faint effect)
2. Long term hypotention may trigger                     

• Reflex tachycardia(may need to add B-blocker to control it)
• Compensatory renal Na retention(may need diuretics).

• B)Centrally acting Alpha-Agonist: Clonidine(Catapress)

Actions:

• Central alpha-2 agonist reduces "sympathetic outflow" to periphery (e.g. to blood vessels& heart).

Side effect & Contraindications:-

1. Sedation, dry mouth and impotence(in men)common.
2. Little or no reflex tachycardia.
3. Danger: rebound increase blood pressure and heart rate with abrupt discontinuation; never stop abruptly

Related drugs:

• Methyldopa(ALDOMET)
• Preferred drug for managing HTN during pregnancy.
• Risk of hepatotoxicity.

C)Catecholamine Dopletor: Reserpine(Serpasil)

Actions:-

• Depletes peripheral neuronal norepinephrine>.>decrease vasoconstriction and heart rate.

Uses;-

• mainly when any of above drugs are ineffective (even in combination) or high cost is factor, otherwise this drug is seldom used.

Side effects&Contraindication:-

1. Bradycardia,possible CHF.
2. Peripheral autonomic: parasympathetic predominance,not used in peptic ulcer.
3. CNS: fatigue,drowsiness, suicidal depression,parkinsonism.

STEP3

Hydralazine:oral administration

Actions:

1. Direct acting vasodilator(dilate arteries& not veins)
2. Relatively rapid response.

Uses:-

1. For HTN when Step 1/2 drugs  ineffective
2. After load reduction for severe  CHF .

Side effects,need for adjuncts:

1. Reflex tachycardia(may necessitate B-blocker).
2. Renal Na retention(might have to add diuretic).
3. Lopus like syndrome(facial "rash"; joint pain, fever, characteristic blood tests)
4. Peripheral neuritis(hydralazine interferes with vitamin B6 metabolism).

Related drugs:

Minoxidil:-

• Seldom used because of side effects (only in life threatening severe hypertention),used topically in Tx of hair fall.

Side effects of Minoxidil:-

• Hirsutism
• Tachycardia
• Fluid&salt retention
• SO used with B-blocker and diuretic.

STEP4

Other oral antihypertensives:(RARLY USED)

• Mao inhibitors
• Guanethidine(acts like reseprine that also>>> mor complete NE depletion than reseprine).

Importance of MILK in Treatment of Hypertension:

• recent studies at the "American Heart Association's" and confirmed that addition of milk a few calories to the diet reduces the risk of developing high blood pressure, and proved that drinking milk for long periods of time decreases their systolic blood pressure, so decreasing the likelihood of hypertension in the future. In previous studies were detected multiple health benefits of eating yogurt repeated with regard to maintaining the body mass index (BMI) and body weight.

• Milk consists of a high concentration of calcium and other essential nutrients easily be affixed to the daily diet, is also a source of protein and imparts a feeling of fullness for a longer period of time.

• Underwent the study of nearly 2,000 volunteers proven safety diagnosed with high blood pressure at the beginning of the study, which lasted for 15 years during which fill a questionnaire to three times to check their consumption of milk, and the results confirmed the decreased likelihood of developing " high blood pressure" for approximately 31% of the volunteers were a daily consumption of milk for at least 2% of daily calories equivalent to 4.53 g of low-fat yogurt every three days as the rate of high systolic blood pressure decreases compared to those who did not rely milk part of their daily diet.

• Contribute to a diet with few calories and physical activity in reducing the incidence of chronic diseases such as high blood pressure, which causes delay in treatment in the damaged arteries and torn and works as a network picks up cholesterol and moves through the bloodstream to accumulate on the vascular wall.

Prophylaxis and Treatment of Gout

Gout

" Kings disease"

Definition:

Gout is a metabolic disease charactrized by recurrent episodes of acute arthiritis due to depositis of ureate crystals in joints and cartilage. it is usually associated with high serum levels of uric acid.

Smptoms

• Gout causes sudden severe pain, and is usually at the base of the big toe, but it may affect another joint, especially joints damaged by other conditions such as osteoarthritis inflammation.

• It can affect lobe of ears and skin surrounding the joint, especially the joints of the fingers or the back of the heel 

• The symptoms begin with sharp pain in the affected joints with swelling and redness around it,and these symptoms may be associated with high temperature (fever)and in most cases these crises occur in the evening, but the symptoms go away permanently  within a week or more to re-appear again at intervals over several weeks or months or years.

Aim of treatment:

1. To relieve acute gouty attacks.
2. To prevent recurrent gouty episodes and urate lithiasis.

Treatment of acute gout:

1)Non-steriodal anti-inflammatory drugs(NSAIDs):

• All NSAIDs except aspirin, salicylates, and tolmetin can successfully treat acute gouty episodes.
• Oxaprozin lowers serum uric acid, it should not be given to patients with uric acid stones because it increase uric acid excretion in the urine.
• Indomethacin is commonly used.

>>>N.B.

• SAIDs may be given to patients unable to take NSAIDs.

2)Colchicine:

• Colchicine relieve the pain and inflammation of gouty arthiritis in 12-24 hours without altering the metabolism or excretion of urates and without other analgesic effects.
• It acts by inhibition of leukocyte migration and phagocytosis.

Indications:

1. Treatment of acute gout(largely replaced by NSAIDs).
2. Colchicine is now used for the prophylaxis episodes of gouty arthiritis.
3. Has a mild beneficial effect in sarcoid arthiritis and in hepatic cirrhosis.
4. Although it can be given intravenously, this route should be used cautiously because of increased bone marrow toxicity.

Adverse effects:

• Diarrhea.

• Nausia, Vomiting and abdominal pain.

• Rarely: hair loss and bone marrow depression as well as peripheral neuritis and myopathy.

• A cute intoxication after overdoses is characterized by burning throat pain, blood diarrhea, shock, hematuria, and oliguri. fetal ascending CNS depression has been reported. Treatment is supportive(Colchicine has a small fatal dose).

Prophylaxis:

1)Uricosuric Agents:

Probenecid and sulfinpyrazone are uricosuric drugs(increase urine secretion of uric acid).
In a patient who excretes large amounts of uric acid, uricosuric should't be used.

Advese effects:

1. Gastrointestinal irritation(should be given with food to reduce irritation).
2. Rash.
3. Rarely:aplastic anemia.
4. Nephrotoxicity may occur with Probenecid.

Contraindications&Cautions:

• It is essential to maintain a large urine volume to minimize the possibility of urinary stone formation. Also alkalinization of urine  decreases incidence of stone formation.

• N.B.

• Because aspirin in doses less than 2,6 g daily causes net retention of uric acid, it shouldn't be used for analgesia in patients with gout.

2)Allopuinol:

Mechanism of action:

• inhibit synthesis of uric acid (by inhibition of xanthine oxidase enzyme).

Indications:

1. Prophylaxis of gout: when starting allopurinol, colchicine should also be used untill serum uric acid is decreased to less than 6 mg/dl. Therefore colchicine can be stopped, while allopurinol is continued.
2. Antiprotozoal agent.

Advese Effects:

1. Acute attack of gout during initiation of trearment(add colchicines or NSAID prophylactically).
2. Nusia, vomiting and diarrhea.
3. Preipheral neuritis and necrotizing vasculitis.
4. Bone marrow depression and, rarely, aplastic anemia may also occur.
5. Hepatic toxicity and interstitial nephritis have been reported.
6. Allergic skin reaction.

Interactions&Cautions:

1. When azathioprine is given concomitantly with allopurinol, its dosage must be reduced by about 75%.
2. Allopurinol may increase the effect of cyclophosphhamide.
3. Allopurinol inhibits the metabolism of probenecid and oral anticoagulants.

3)Febuxostat:

• Inhibitor of xanthine oxidase therefore reduces the formation of uric acid.

Adverse Effects:

• As with allopurinol, prophylactic treatment with colchicine or NSAIDs should start at the begining of treatment to avoid gout flares.

• The most frequent adverse events are liver function abnormalities, diarrhea, headache,and nusia. Febuxostat appear to be well tolerated in patients with a history of allopurinol intolerance.

N.B.

• Febuxostat is awaiting FDA approval for the treatment of chronic gout.It is the first new drug for the treatment of gout in over 40 years.