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.

First choice to treat Parkinsonism

First choice to treat Parkinsonism

L-Dopa

 

Definition:

Levo-Dopa is the precursor of dopamine that bass blood brain barrier(BBB) to be converted into dopamine and increase its activity in basal ganglia to correct all syptoms of parkinsonism especially bradykinesia.

Kinetics:

L-dopa is administered orally to be absorbed by an active process in intestine(decrease by some amino acids in food), peak concentration in 1-2 hours,t1/2=1-3 hours.

*Most(more than 95%)of ingested l-dopa is metabolized in peripheral tissues by:

• DD(dopa decarboxylase) to dopamine, which cannot pass the BBB (pyridoxine"vitamin B6" activate peripheral DD,so decrease the efficacy & increase toxicity of L-dopa).
• COMT to 3-O-methyl dopa(3OMD) that complete with L-dopa for active uptake to CNS.

*Only 1-3% of ingested dose reaches CNS to be metabolized by central DD into dopamine to produce the therapeutic effect ,then metabolized br MAO-B enzyme.

Efficacy& brain level of L-Dopa is increased by adding:

• Peripheral dopa decarboxylase inhibitor(not pass BBB)as carbidopa or benserazide:-

               * Carbidopa(10 or 25 mg)+L-dopa(100 or 250 mg)=Sinemet.
               * Benserazide925mg)+ L-dopa(100 mg)=Madopar.

• COMT inhibitor as tolcapone (hepatotoxic) or entacapone.
• MAO-B inhibitor as selegiline(deprenyl) (slow disease progression).

Side effects of L-Dopa:

1. Fluctuation of response (on-off phenomenon);may be reduced by use of drug holidays& reserve l-dopa for late severe disease.
2. CNS effects: dyskinesia, psychological disturbances, hallucination, insomnia, anxiety, agitation& mood changes.
3. CVS effects: tachycardia, arrhythmia, postural hypotention.
4. GIT effects: anorexia, nusia, vomiting, peptic ulceration.
5. Other effects:mydriasis, increaso IOP, hemolysis, brown secretion.

Contraindication:

1. Psychosis.
2. Glaucoma.
3. Peptic ulcer.
4. Cardiac disease.
5. Melanoma.
6. With MAO-A inhibitor.

Neurological manifestations of Diabetes

 Neurological Manifestations of Diabetes

"Diabetic Polyneuropathy"

 

Pathogenesis:

1. Diabetic microangiopathy of the vasa nervosa.
2. Ischaemia of the nerves, 2ry to atherosclerosis of vasa nervosa.
3. Nutritional 2ry to hypovitaminosis (vit. B1, B6 and B12).
4. Metabolic due to production of toxic ketonic bodies, leading to nerve damage.

Clinical Picture:

1. In early diabetes  or in the pre-diabetic stage, the neuropathy is of mononeuritic type which may affect the sciatic. femoral, lateral popliteal, ulnar or median nerves or cranial 3,6,7 nerves.
2. In the frank diabetes, the neuropathy is of the poly neuritic type.
3. The polyneuropathy is mainly sensory with pain and parathesia specially in the lower limbs followed by superficial sensory loss of stock and glove type. the deep sensations are also lost early in the disease,resulting in loss of deep reflexes and sensory ataxia.
4. The muscle sense is increased at first resuting in tender calf followed later on by lost muscle sense.
5. Motor weakness may occur late in the disease.
6. Autonomic manifestations:

• Impotence.
• Sensory, motor or autonomic bladder.
• Postural hypotention.
• Silent myocardial infarction.
• Gastroparesis diabeticorum: indigestion and delayed gastric emptying.
• Hyperhydrosis.
• Trophic skin changes: Ulcers, loss of hair, brittle nails, charcot's neuropathic joint.

Treatment:

1. Proper management of diabetes: diet, oral hypoglycemic drugs or insulin.
2. Vasodilator as Piribedil(Trivastal) 50 mg daily.
3. Capillary modulators: Ca Dobesilate(Doxium).
4. Vitamins B1 100 mg daily, B6 200 mg daily, B12 1000 micro gram  dailyand A.T.P.(Adnoplex).
5. Carbamazepine(Tegretol) 200 mg twice daily or Gabapentine(Neurontine) 400 mg twice daily for neuropathic pain.
6. Physiotherapy if motor weakness is present.

Thiamine deficiency disorder

Thiamin deficiency disorder
"Beri-beri"

 

Aetiology:

A disease 2ry to thiamine(vitamin B1) deficiency affecting the nervous system(dry beri-beri) or the cardiovascular system(wet beri-beri).

Clinical Picture:

1)Dry beri-beri: peripheral sensory neuropathy:

• Subjectively there is pain and paraesthesia in the limbs,espcially distally
• Objectively there is:

*Superficial sensory impairment of the stock and glove nature.

*Deep sensory loss specially distally with absence of deep reflexes.

2)Wet beri-beri: congestive heart failure.

3)Cerebral type(werni cke's encephalopathy): amnesia,ophthalmoplegia,nystagmus&ataxia.

Treatment:

1)thiamine 100 mg daily snd vitamin B complex.
2)Diet rich in vitamins and low in salt.
3)Digitalisation and diuretics in in case of heart failure.

Bell's Palsy Prognosis and management

Bell's Palsy

 

Definition:

It is an acute paralysis of the face due to non suppurative inflammation of the facial nerve near the stylomastoid foramen . usually unilateral,may be recurrent&sometimes run in families.

Atiology:

1)exposure to air drafts usually preceed the onset:this may lead to ischaemia,oedama&compression of the nerve at the stylomastoid foramen.
2)It may 2ry to a neurotropic virus e.g. Herps Zoster.
3)It may be autoimmune,as evidenced by high levels of immunoglobulins in the patient.

Clinical Picture:

1)the onset is usually acute with pain behind the ear.
2)one or two days later,there is complete paralysis of the facial muscles on the affected side of lower motor neuron lesion nature which are:
*obliteration of naso-labial fold.
*Dropping of the angle of the mouth with dripping of saliva.
*accumulatin of food behind cheek.
*inability to blow the cheek.
*inability to show the teeth properly.
*inability to raise eyebrows with absence of wrinkles of the forehead.
*inability to close the eye: when the patient attempt to close his eye, the eye ball rolls upward(Bell's Phenomena).
3)there may be impairment of taste on the anterior 2/3  of the tongue on the same side.

Treatment:

A)Medical:

1)Prednisolone tablets 30 mg/day or Synacten amp. I.M. for 2-3 weeks.
2)Vasodilators, vitamens B complex & Neostigmine.
3)Protection of the exposed cornea:eye ointment during sleep, sunglasses during day time.

B)Physiotherapy:

1)Massage of the facial muscles.
2)Infrared irradiaton on the face.
3)Galvanic stimulation to the facial muscles.

C)Surgical:

1)Decompression of the facial nerve.
2)facial nerve grafting.
3)Plastic surgery for residual facial asymmetry.

Prognosis:

*most patients(80%)recover in 4-6 weeks; the remaining 20% need surgical intervention.
*occasionally aberrant reinnervatin occur where the regenerating facial fibers anastomose with trigeminal fibers. thus when the patient move his jaw while eating or speaking there may be:
_Winking( jaw winking)

_Lacrimaton(crocodile tears)

The Epilepsy, Treatments and its side effects

Treatment of Epilepsy

A)General Treatment
1.    moderation of the patient's physical activities specially swimming , driving or working near machines or at heights for fear of drowning or injury during a fit
2.    precipitating factors are avioded as photic stimulation(e.g. watching T.V. in thedark) or hyperventilation(e.g. running along distance)
3.    Alcohol intake is forbidden
4.     ketogenic diet,inducing acidosis,used to be given.Acidosis raises threshold of stimulation of brain cells,while alkalosis lowers it


B)Specific Treatment
1.    treatment of the cause in symptomatic epilepsy
2.    Anti-epileptic drugs


Anti-epileptic drugs
for at least 2 to 3 years
1)barbitarates:
•    Luminal(phenobarbitone)
Dose
•    100-600 mg daily
Best indicated
•    broad spectrum anticonvulsant
•     NOT for petit mal seizure

2)Hydontion:
•    Epanutin
Dose
•    200-600 mg daily
Best indicated
•    simple partial motor seizure
•    Grand mal seizure

3)Carbamazepine
•    tegretol
Dose
•    400-800 mg daily
Best indicated
•    Simple partial motor seizure
•    Complex partial motor seizure
•    Grand mal seizure
•    NOT for petit mal seizure


4)Clonazepam
Rivotril
Dose
•    2-6 mg daily
Best indicated
•    myoclonic seizure
•    Grand mal seizure


5)Valproate:
Depakin
Dose
600-1500 mg daily
Best indicated
•    Simple partial motor seizure
•    Complex partial motor seizure
•    Grand mal seizure
•    Myoclonic seizure

6)Succinimide
•    Zarontin
Dose
•    500-1000 mg daily
Best indicated
•    Petit mal seizure

7) New antiepileptics
1.    Gabapentin(Neurontin)
2.    Vigabation(Sbril)
3.    Topiramate(Topamax)
4.    Lamotrigine(Lamictal)
5.    Tiagabine(Gabitril)

1)Gabapentin(Neurontin)
Dose
•    1200-2400 mg daily
Best indicated
•    Refractory partial and generalized seizure

2)Vigabation(Sbril)
Dose
•    2000-3000 mg daily
Best indicated
•    Refractory partial and generalized seizure

3)Topiramate(Topamax)
Dose
•    400-800 mg daily
Best indicated
•    Refractory partial and generalized seizure

4)Lamotrigine(Lamictal)
Dose
•    200-600 mg daily
Best indicated
•    Refractory partial and generalized seizure

5)Tiagabine(Gabitril)
Dose
•    30-60 mg daily
Best indicated
•    Refractory complex partial seizure

Side effects of antiepileptics
•    drowsiness,Ataxia,skin rash and blood dyscrasias; therefore blood pictures should be done
•    Depakin rarely cause hepatic insufficiency;thus frequent liver function tests are needed early in the treatment
•    Epanutin also produce gum hyperplasia and hirsutism
•    antiepileptics have teratogenic effect thus an epileptic woman should postpone pregnancy untill she is fit-free and off medication;however,if achild ia wanted,or she is already pregnant,she should continue her medication,as the fits are dangerous to her and to her foetus
Guidlines for drugs used
1)Always start with one drug to avoid iteracton between antiepileptics
2)If the patient doesn't respond to one drug another drug may be added. the new antiepileptic drugs are mainly used as add-on treatment in case of refractory epilepsy not responding to classical treatment
3)Antiepileptics are discontinued only when the patient has been free from fits foe at least 2 years and his E.E.G. is normal

The end

drug therapy in Diabetes Mellitus

treatment of diabetes mellitus

types of DM
•    type1>>>> insulin dependent diabetes mellitus(IDDM):
occer during childhood or puberty
beta cells are dertroyed

•    type2>>>non insulin dependent diabetes mellitus(NIDDM):
occur over age 35
beta cells are unable to produce sufficient insulin

Treatment
1.    Insulin
2.    Oral Hypoglyecemic Drugs>>for treatment of patient with type2 DM

1.    Insulin:
is apolypeptide hormone given by subcutaneous injection


Indication of insulin:
1.    IDDM
2.    Diabetic ketoacidosis
3.    NIDDM:with
•    permanent:failed oral hypoglycemic ttt in IDDM
•    temporarily:in some stress situation as infection,surgery,pregnancy

Adverse effects of insulin
1)Hypoglycemia:
most sreious&common in overdose
•    treatment of hypoglycemia
if conscious : sweets or juice
if unconscious : 20_50 ml glucose 50% intravenous or glucagon 1mg intramuscular
2)Lipodystrophy(less common)
3)Allergic Reaction(less common)
4)insulin resistance

2)Oral Hypoglycemic Drugs
for treatment of patient with type2 DM

Types of oral hypoglycemic drugs:
A.    insulin secretagogues as Sulfonylureas>>>increase insulin resistance
B.    insulin sensitizers as Biguanide(metformin) or glitazones>>>improve insulin action
C.    Modify intestinal absrption of carbohydrates as alpha glucosidase inhibitor


A)insulin secretagogues
Sulfonylureas
•    indication of Sulfonylureas
stimulate  insulin release from the beta cells of pancreas

•    Adverse effects of  Sulfonylureas
1.    Hypoglycemia
2.    weight gain
3.    Sulfonylureas transverse the Placenta(beplate insulin from fetal pancreas)

B)insulin sensitizers
1.    Biguanide(metformin)
2.    glitazones

1)Biguanide(metformin) :
•    Indication of Biguanide(metformin)
1.    increase glucose uptake  by target tissues,thereby decreaseing insulin risistance
2.    Euglycemia(no fear of hypoglycemia)
3.    loss of weight(loss of appetite)
N.B
these effects maynot be apparent untill 4-6 weeks of use

Adverse effects of Biguanide(metformin)
1.    Gastrointestinal(anorexia,nausia,vomiting,diarrhea)
2.    longterm use may iterfer with vitamin B12 absorption
3.    Potentially fetal lactic acidosis may occur

2)glitazones
•    Indication of glitazones
increase insulin sensitivity in adipose tissues,liver and skeletal muscles

•    Adverse effects of glitazones
1.    strongly recommended to measure liver enzyme levels of patients on these medications initially and periodically
2.    weight increase(increase subcutaneous fat or due to fluid retention)


C)alpha glucosidase inhibitor
Acarbose(glucobay):

•    Indication of Acarbose(glucobay)
Reversibly inhibiting membrane-bound-glucosidase in the intestinal brush border thereby decreasing glucose absorption

•    Adverse effects
flatulence,diarrhea and abdominal cramping