Health and Pills » Disorders and Conditions http://healthandpills.com Guide To Good Health and Drugs: Tablets, Gels, Capsules Tue, 07 Feb 2012 09:49:47 +0000 en hourly 1 http://wordpress.org/?v=3.3.1 Review of Patients Who Seek Assistance With Weight Control http://healthandpills.com/disorders-and-conditions/obesity/review-of-patients-who-seek-assistance-with-weight-control http://healthandpills.com/disorders-and-conditions/obesity/review-of-patients-who-seek-assistance-with-weight-control#comments Wed, 21 Dec 2011 13:19:02 +0000 admin http://healthandpills.com/?p=1254 Information Gathering 1. Gather essential information about the patient’s symptoms, including: a. description of symptom(s) (i.e., nature, onset, duration, severity, associated symptoms) Patient is concerned about her weight and overall appearance. She has never been obese, but she is slightly overweight and wants to lose approximately 15 pounds over the next month or two. b. description of any factors that seem to precipitate, exacerbate, and/or relieve the patient’s symptom(s) Patient tends to snack on sweets, particularly in the afternoon and when she studies at night. c. description of the patient’s efforts to relieve the symptoms Patient has tried several diets over the past 6 months, but she has not been successful in losing weight. 2. Gather essential patient history information: a. patient’s identity Heidi McMaster b. patient’s age, sex, height, and weight 15-year-old female, 5 ft 5 in, 165 lb c. patient’s occupation High-school sophomore d. patient’s dietary habits She typically skips breakfast because she “doesn’t have time.” Usually eats lunch at the salad bar at school. Often gets candy bar from snack machine in the afternoon. She has a big dinner every night with her family, often including dessert. e. patient’s sleep habits Averages about 7-8 hours per night f. concurrent medical conditions, prescription and nonprescription medications, and dietary supplements Ortho Tri-Cyclen 1 tablet once daily beginning on day 1 of menstrual cycle g. allergies NKA h. history of other adverse reactions to medications None i. other (describe) Patient participates in physical education classes at school twice a week. She has no other regular exercise activity. Both of her parents are also overweight. Assessment and Triage 3. Differentiate the patient’s signs/symptoms and correctly identify the patient’s primary problem(s). Patient’s body mass index is 27.5, placing her in the overweight category. This places her at increased risk for type 2 diabetes mellitus, high cholesterol, hypertension, sleep apnea, and orthopedic problems during both adolescence and adulthood if her weight is not normalized. Her skipping breakfast, regularly consuming sweets, and eating heavy dinners, together with minimal physical activity, are contributing to her weight problem. 4. Identify exclusions for self-treatment. Age less than 18 years is an exclusion for self-treatment. 5. Formulate a comprehensive list of therapeutic alternatives for the primary problem to determine if triage to a medical practitioner is required, and share this information with the patient. Options include: (1)  Refer Heidi to a primary care provider for a health screen. (2)  Refer to dietitian and/or personal trainer for diet and exercise advice, respectively. (3)  Recommend nonprescription orlistat. (4)  Recommend a dietary supplement weight-loss product. (5) Take no action. Plan 6. Select an optimal therapeutic alternative to address the patient’s problem, taking into account patient preferences. Refer the patient to a primary care provider for a health screen. 7. Describe the recommended therapeutic approach to the patient. N/A 8. Explain to the patient the rationale for selecting the recommended therapeutic approach from the considered therapeutic alternatives. You need to see a primary care provider to determine if a diet and exercise program is appropriate. Healthy eating habits and exercise are the mainstays of successful weight loss, and these should be a lifelong goal. Patient Education 9. When recommending self-care with non-prescription medications and/or nondrug therapy, convey accurate information to the patient. Criterion does not apply in this case. 10. Solicit follow-up questions from patient. Is there an OTC medication that might work? 11. Answer patient’s questions. No OTC medications are approved and/or appropriate to recommend without referral from a primary care provider. ]]> http://healthandpills.com/disorders-and-conditions/obesity/review-of-patients-who-seek-assistance-with-weight-control/feed 0 Assessment of Patients Who Seek Assistance With Weight Control http://healthandpills.com/disorders-and-conditions/obesity/assessment-of-patients-who-seek-assistance-with-weight-control http://healthandpills.com/disorders-and-conditions/obesity/assessment-of-patients-who-seek-assistance-with-weight-control#comments Wed, 21 Dec 2011 13:15:33 +0000 admin http://healthandpills.com/?p=1252 Relevant Evaluation Criteria Scenario/Model Outcome Information Gathering 1. Gather essential information about the patient’s symptoms, including: a. description of symptom(s) (i.e., nature, onset, duration, severity, associated symptoms) Patient has battled overweight and obesity his entire adult life. He has never been severely obese but tends to gain 10 to 15 pounds per decade. His obesity does not affect his ability to perform activities of daily living. b. description of any factors that seem to precipitate, exacerbate, and/or relieve the patient’s symptom(s) Patient is a stress eater: he tends to snack on unhealthy foods at work and late at night. c. description of the patient’s efforts to relieve the symptoms Various diets and exercise programs have been tried over the past 2 decades. Patient is usually able to lose a few pounds but gains it back when stresses of life contribute to declining compliance with diet and exercise regimens. 2. Gather essential patient history information: a. patient’s identity John Coughlin b. patient’s age, sex, height, and weight 45-year-old male, 5 ft 10 in, 220 lb c. patient’s occupation Computer software engineer d. patient’s dietary habits Typically skips breakfast and eats a sweet roll with his coffee mid-morning on workdays. Eats healthy lunch in workplace cafeteria. Wife fixes large dinner in evenings. He often gets pretzels and chips from snack machine at work and likes to eat candy and popcorn when working on home computer late at night. e. patient’s sleep habits Goes to bed late, gets up early in morning: averages about 6 hours of sleep per night f. concurrent medical conditions, prescription and nonprescription medications, and dietary supplements Simvastatin 20 mg daily forhyperlipidemia: lisinopril 10 mg daily for hypertension g. allergies NKA h. history of other adverse reactions to medications None i. other (describe) N/A Assessment and Triage 3. Differentiate the patient’s signs/symptoms and correctly identify the patient’s primary problem(s). Patient’s body mass index is 32, placing him in the obese category. Lack of exercise and poor dietary habits are probably contributory. 4. Identify exclusions for self-treatment. On the basis of the patient’s age and weight, he should see a primary care provider for medical clearance before beginning an exercise program. 5. Formulate a comprehensive list of therapeutic alternatives for the primary problem to determine if triage to a medical practitioner

is required, and share this information with the patient. Options include: (1) Refer John to a dietitian and/or personal trainer for diet and exercise advice, respectively. (2)  Refer John to a primary care provider for prescription medication for obesity. (3) Counsel John on diet and exercise. (4)  Recommend nonprescription orlistat. (5) Recommend a dietary supplement for weight loss. (6)  Take no action. Plan 6. Select an optimal therapeutic alternative to address the patient’s problem, taking into account patient preferences. Because of previous failures with diet and exercise alone, the patient chooses to try orlistat while again trying to diet. 7. Describe the recommended therapeutic approach to the patient. Take orlistat up to 3 times a day before meals that contain fat, as described in the text. 8. Explain to the patient the rationale for selecting the recommended therapeutic approach from the considered therapeutic alternatives. You can anticipate that weight loss may be slightly easier to achieve when combining orlistat with diet and exercise, compared with diet and exercise alone. Patient Education 9. When recommending self-care with non-prescription medications and/or nondrug therapy, convey accurate information to the patient: a. appropriate dose and frequency of administration 60 mg up to 3 times a day b. maximum number of days the therapy should be employed Greatest benefit is usually seen within first 6 months of therapy. c.product administration procedures Take before meals containing fat. Minimizing dietary fat and spreading it out between all meals should help to minimize the gastrointestinal side effects such as flatus and oily discharge associated with orlistat. Taking a multivitamin supplement at bedtime is wise in case fat-soluble vitamin malabsorption occurs with orlistat. d. expected time to onset of relief Weight loss should be detected with the first 2 weeks of initiating orlistat therapy along with diet and exercise regimen. e. degree of relief that can be reasonably expected Many patients lose 5 to 10 pounds during the first 6 months of therapy. f. most common side effects Flatulence, oily spotting, loose and frequent stools, fatty stools, fecal urgency, fecal incontinence g. side effects that warrant medical intervention should they occur None h. patient options in the event that condition worsens or persists Consult a dietitian or personal trainer for diet and exercise advice, respectively, or see a primary care provider for prescription medication for weight loss. i. product storage requirements No special requirements j. specific nondrug measures Continue diet and exercise measures. Find exercise that is enjoyable and thus sustainable. Attempt to reduce stress and thus stress eating. Too little sleep has been associated with increased body weight, so sleep hygiene measures may be helpful. 10. Solicit follow-up questions from patient. Can I double the dose of medication if weight loss slows? 11. Answer patient’s questions. Dosage above 60 mg up to 3 times a day should be attempted only under the supervision of a primary care provider.

]]> http://healthandpills.com/disorders-and-conditions/obesity/assessment-of-patients-who-seek-assistance-with-weight-control/feed 0 Claudication http://healthandpills.com/disorders-and-conditions/cardiovascular-diseases/claudication http://healthandpills.com/disorders-and-conditions/cardiovascular-diseases/claudication#comments Tue, 08 Nov 2011 12:17:45 +0000 admin http://healthandpills.com/?p=1232
Contents

      Description of Medical Condition

      A sensation of functionally impairing muscle fatigue, cramps and/or pain of the lower extremities brought on by exertion and relieved with rest. Less than 10% of patients with known lower extremity atherosclerosis develop claudication. Approximately 90% of all patients with claudication are cigarette smokers.

      System(s) affected: Cardiovascular, Musculoskeletal

      Genetics: Geni loci unidentified

      Incidence/Prevalence in USA:

      • Biennial incidence (Framingham study): 0.07% in men aged 35-44 years and 1.4% in men older than 65 years; diabetic patients 4-6 times that of nondiabetics

      • Prevalence: approximately 1.7-2.2% among older patients

      Predominant age: Common in males > 55, females > 60

      Predominant sex: Male > Female (by a less than 2:1 ratio)

      Medical Symptoms and Signs of Disease

      • Cold feet are an early warning symptom

      • Sudden or gradual onset

      • Restricted walking distance due to symptom onset

      • Symptom continuum from calf muscle fatigue to severe cramps/pain

      • Dependent rubor

      • Hairless lower extremities

      • Leg color may be normal when horizontal, but may appear dusky crimson hue when in lowered position

      • Marked blanching on evaluation

      • Poorly palpable or absent lower extremity pulses (may not be true for patients with blood vessel calcifications i.e. diabetic patients)

      • Paresthesias or numbness are later symptoms

      • Symptoms of pain may not be detected in a diabetic patient

      • Nonhealing ulcer associated with poor circulation

      What Causes Disease?

      • Sites affected depends on involved vasculature:

      • Aortoiliac disease — pain may extend from buttocks to thigh

      • Femoropoliteal disease — pain may extend from calves to feet

      • Superficial femoral artery occlusion accounts for most cases of lower extremity claudication symptoms.

      • Subclavian, axillary and/or brachial artery blockages may lead to upper extremity claudication symptoms.

      • Other causes of arterial occlusion to consider: emboli. popliteal entrapment, adventitious cystic disease of the popliteal arteries, and thromboangiitis obliterans (Buerger disease)

      Risk Factors

      (Cigarette smoking and hypertension are most closely linked with worsening claudication symptoms)

      • Smoking

      • Diabetes mellitus

      • Hypertension

      • Hypercholesterolemia

      • Family history

      • Obesity

      • Preexisting heart disease

      Diagnosis of Disease

      Differential Diagnosis

      [Neither pseudoclaudication nor osteoarthritis affects ankle brachial indices (see below)]

      • Pseudoclaudication: attributed to spinal cord impingement or spinal stenosis. Sitting or squatting helps relieve symptoms.

      • Osteoarthritis: pain made worse by weight bearing

      Drugs that may alter lab results: None

      Disorders that may alter lab results: Calcified, non-compressible vessels would affect ankle brachial indices (see below).

      Pathological Findings

      N/A

      Special Tests

      • The ankle brachial index (ABI) = systolic blood pressure at the ankle -f systolic blood pressure of the brachial artery. Normal indices are minimally greater than or equal to 1. The ABI provides information on proximal arterial disease extent and a general idea concerning functional compromise. For example, an ABI greater than 0.5 suggests stenosis of a single arterial segment An ABI less than 0.5 suggests multisegmental arterial stenoses. Claudicants tend to have ABIs ranging from 0.5 to 0.8. Probable tissue death and or rest pain is usually found at ABIs less than 0.3.

      • Since calcified vasculature impairs compressibility and ABIs cannot be conventionally measured, photoplethys-mography is another option to evaluate toe pressures. Normal toe pressures are 80-90% of brachial artery systolic blood pressures.

      • Two claudication screening tools are the Rose and Edinburgh questionnaires.

      – The Rose queries if calf pain while walking is relieved by 10 minutes of rest or if pain exacerbated by an increased pace (or walking uphill) is relieved by tapering or stopping the activity. Other items include persistent pain if walking continues and absence of calf pain while sedentary. If physicians’ diagnosis ot claudication is the gold standard, the Rose questionnaire has a specificity of approximately 99% and a sensitivity of 66%.

      – The Edinburgh is a modified Rose questionnaire taking into account that some patients might continue to walk through calf pain. This questionnaire has a sensitivity of approximately 91 % for the detection ot claudicants.

      Imaging

      • Duplex ultrasound

      • Angiography

      • Role of computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) in comparison to conventional angiography remains to be determined.

      Diagnostic Procedures

      • Arteriography — when surgical correction is anticipated

      • Noninvasive vascular tests

      Treatment (Medical Therapy)

      Appropriate Health Care

      Outpatient. An exception is those patients with severe disease who may require inpatient evaluation

      General Measures

      • Medical treatment

      • Elimination of risk factors whenever possible

      • Smoking cessation

      • Dietary optimization (low fat and low cholesterol diet)

      • Exercise (however, approximately 70% of claudicants will require medication for symptom control)

      Surgical Measures

      (Note: Most patients do not require surgical management.)

      • Angioplasty

      • Arterial bypass surgery

      Activity

      Ambulatory

      Diet

      Low fat, low cholesterol diet for avoidance and control of hyperlipidemia

      Patient Education

      • Primary prevention: Encourage an exercise program, no smoking, healthy dietary choices, management of blood glucose in diabetic patients, hypertension control

      • Secondary prevention: As above. Emphasize smoking cessation and hypertension control.

      Medications (Drugs, Medicines)

      Drug(s) of Choice

      • Aspirin — 80 mg qd to reduce platelet aggregation

      • Pentoxifylline (Trental) — to decrease internal configuration of red cells — 400-800 mg bid-tid. Administer for at least 6-8 weeks to determine if therapy is effective.

      • Cilostazol (Pletal) 50-100 mg bid

      Contraindications:

      • Cilostazol is contraindicated in patients with congestive heart failure

      • Pentoxifylline is contraindicated in patients with recent cerebral and/or retinal hemorrhage

      Precautions:

      • Headache occurs frequently (>30%) in patients taking cilostazol

      Significant possible interactions:

      • Cilostazol: Metabolized via the cytochrome P-450 isoenzymes. Use caution during coadministration of other inhibitors of CYP3A4 (e.g., grapefruit juice, ketoconazole, itraconazole, erythromycin and diltiazem), and during coadministration of inhibitors of CYP2C19 (e.g. omeprazole).

      • Pentoxifylline: theophylline levels may rise

      • Concurrent use of beta blockers in patients with coexisting cardiovascular disease does not appear to worsen claudication symptoms in affected patients

      Alternative Drugs

      • Ticlopidine (Ticlid)

      • Vasodilators

      • Calcium channel blockers

      • Anticoagulants

      • Role of PGE1 and PGI2 analogues and stimulants (i.e. AS-103, iloprost, beraprost, defibrotide) continues to be investigated

      Patient Monitoring

      Peripheral non invasive vascular studies every 6 months. If worsening, would be indication for surgery.

      Prevention / Avoidance

      • Walking program

      • Avoid smoking

      Possible Complications

      • Tissue/ limb loss- predominantly affects diabetic patients as disease progresses

      • Complications of reperfusion

      – Compartmental syndrome

      – Venous thrombosis induced by low flow state which may flush to right side of heart to pulmonary circulation

      Expected Course / Prognosis

      • Gradual improvement with use of medical therapy/walking program and diminution/elimination of risk factors. Some patients may require revascularization. Disease progression may include rest pain, tissue loss and gangrene.

      • Chronic intermittent ischemia may cause lasting defects in muscle function resulting in weakness which could be an early sign of peripheral arterial disease

      Miscellaneous

      Associated Conditions

      – Other mani festations of arteriosclerotic vascular disease — myocardial infarction(s), carotid artery occlusive disease, renovascular occlusive disease, and hypertension

      Age-Related Factors

      Pediatric: N/A

      Geriatric: More common with advancing age

      Pregnancy

      N/A

      International Classification of Diseases

      443.9 Peripheral vascular disease, unspecified

      See Also

      Thromboangiitis obliterans (Buerger disease)

      ]]> http://healthandpills.com/disorders-and-conditions/cardiovascular-diseases/claudication/feed 0 Carpal Tunnel Syndrome http://healthandpills.com/disorders-and-conditions/neurology/carpal-tunnel-syndrome http://healthandpills.com/disorders-and-conditions/neurology/carpal-tunnel-syndrome#comments Tue, 08 Nov 2011 08:25:30 +0000 admin http://healthandpills.com/?p=1226
      Contents

          Description of Medical Condition

          This is the most common cause of peripheral nerve compression. The median nerve is compressed as it traverses the carpal tunnel in the wrist and hand. The tunnel is composed of the carpal bones dorsally and the transverse carpal ligament ventrally. It contains flexor tendons and the median nerve. Symptoms tend to affect the dominant hand but over half the patients experience bilateral symptoms.

          System(s) affected: Musculoskeletal, Nervous

          Genetics: Unknown, however a familial type has been reported

          Incidence/Prevalence in USA: Most common entrapment neuropathy. Most recent estimates of prevalence indicate that the disorder occurs in 346/100,000 population.

          Predominant age: 40 to 60

          Predominant sex: Female > Male (3-10:1)

          Medical Symptoms and Signs of Disease

          The symptoms characteristically are relieved by shaking or rubbing the hands. During waking hours symptoms occur when driving the car, reading the newspaper and occasionally when using the hands for repetitive maneuvers. The altered sensation is characteristically confined to the thumb, index and middle finger but many patients do not distinguish this localization and feel the entire hand is affected

          • Tingling or prickling sensations in the fingers

          • Burning pain in the fingers particularly at night (acropar-esthesias)

          • Arm pain

          • Finger sensory loss

          • Positive Tinel’s sign

          • Positive Phalen’s sign

          • Wasting of the thenar and hypothenar muscles is a late sign

          • Weakness of the hand, however, for such tasks as opening jars is often noted by the patient early in the disorder

          What Causes Disease?

          • Disorders affecting the musculoskeletal system in the region of the wrist including trauma or Colles’ fracture, degenerative joint disease, rheumatoid arthritis, ganglion cyst, scleroderma

          • Hypothyroidism and diabetes are frequently associated with this condition which also occurs with increased frequency during pregnancy

          • Other miscellaneous causes include acromegaly. lupus etythematosus, leukemia, pyogenic infections, sarcoidosis, primary amyloidosis and Paget disease

          • Hyperparathyroidism, hypocalcemia

          Risk Factors

          Repetitive flexion and extension of the wrist may influence the development of carpal tunnel syndrome. Occupation as a seamstress or computer operator may aggravate carpal tunnel syndrome. There is, however, no universal agreement that carpal tunnel syndrome is job related.

          Diagnosis of Disease

          Differential Diagnosis

          • Cervical spondylosis

          • Generalized peripheral neuropathy

          • Brachial plexus lesion

          Laboratory

          • No one laboratory test is diagnostic

          • Normal thyroid function studies and normal glucose metabolism studies may be helpful in excluding these conditions which may be associated with CTS

          Drugs that may alter lab results: N/A

          Disorders that may alter lab results: N/A

          Pathological Findings

          N/A

          Special Tests

          • Electromyography

          – Wll be abnormal in more than 85% of cases

          – Prolonged distal latency of the median motor nerves may be seen

          – The most sensitive indicator is the median sensory distal latency which is prolonged. Furthermore the sensory nerve action potential may be reduced or unobtainable.

          • Stimulation of the ulnar nerve should be done as well to exclude generalized polyneuropathy

          Imaging

          • Special x-ray views of the carpal tunnel may be obtained. These are of limited usefulness unless heterotopic calcification can be identified.

          • Magnetic resonance (MR) neurography may be used to confirm compression of the median nerve in the carpal tunnel and to assess the success of surgical decompression

          Diagnostic Procedures

          • Tinel’s sign — tapping of the wrist proximal to the carpal tunnel may produce electric sensation perceived by the patient, a sign of nerve compression

          • Phalen’s sign — holding the wrist flexed for 60 seconds may precipitate the paresthesias experienced by the patient

          • A blood pressure tourniquet to cut off circulation to the arm may precipitate symptoms promptly

          Treatment (Medical Therapy)

          Appropriate Health Care

          • Outpatient

          • Outpatient surgery

          General Measures

          • Splinting of the wrist in extension may provide significant relief of symptoms. Prolonged use of splinting if possible may allow some symptoms to resolve.

          • Injection of the carpal tunnel with hydrocortisone (Medrol 40 mg/mL). 1 mL + 1% lidocaine (1 mL) may provide significant temporary relief. This is particularly useful during pregnancy.

          Surgical Measures

          • Surgical decompression of the carpal tunnel by dividing the transverse carpal ligament completely provides almost complete relief of symptoms in over 95% of patients

          • Surgical decompression is usually done as an outpatient under local anesthesia

          • Healing of the incision generally takes two weeks; an additional two weeks of recuperation may be required before the hand can be fully utilized for tasks requiring strength

          • Recent randomized, controlled studies indicate that surgery is more effective than splinting at 18 months

          Activity

          As tolerated

          Diet

          No special diet

          Patient Education

          Carpal Tunnel Syndrome Foundation. For patient education materials favorably reviewed on this topic, contact: American Academy of Family Physicians Foundation, P.O. Box 8418, Kansas City, MO 64114, (800)274-2237, ext.4400

          Medications (Drugs, Medicines)

          Drug(s) of Choice

          Nonsteroidal anti-inflammatory agents such as ibuprofen 400 mg three or four times a day or naproxen sodium 500 mg twice a day will provide significant relief of symptoms in many patients

          Contraindications: Gastrointestinal intolerance

          Precautions: Gastrointestinal side effects of NSAIDs may preclude their use in selected patients

          Significant possible interactions: Refer to manufacturer’s literature

          Alternative Drugs

          – Other NSAIDs

          Patient Monitoring

          • Patients treated with wrist splints or other palliative measures such as cortisone injections will require followup in the ensuing 4 to 12 weeks to assess the success of treatment modalities

          • Patients treated surgically rarely experience recurrence of the disorder. Routine followup once healing of the incision has occurred is not necessary.

          Prevention / Avoidance

          Take a break once an hour when doing repetitive work involving hands

          Possible Complications

          • Post-op infection (rare)

          • Injury to recurrent branch of the nerve

          Expected Course / Prognosis

          Untreated the condition can be expected to lead to numbness and weakness in the hand with atrophy of hand muscles and permanent loss of function of the extremity

          Miscellaneous

          Associated Conditions

          • Diabetes

          • Obesity

          • Pregnancy

          Age-Related Factors

          Pediatric: N/A

          Geriatric: N/A

          Pregnancy

          May occur in pregnancy

          International Classification of Diseases

          354.0 Carpal tunnel syndrome

          See Also

          Acromegaly

          Arthritis, rheumatoid (RA)

          Hypoparathyroidism

          Systemic lupus erythematosus (SLE)

          Scleroderma

          ]]> http://healthandpills.com/disorders-and-conditions/neurology/carpal-tunnel-syndrome/feed 0 Treatment Of The Epilepsy Patient With Concomitant Medical Conditions http://healthandpills.com/disorders-and-conditions/epilepsy/treatment-of-the-epilepsy-patient-with-concomitant-medical-conditions http://healthandpills.com/disorders-and-conditions/epilepsy/treatment-of-the-epilepsy-patient-with-concomitant-medical-conditions#comments Tue, 16 Aug 2011 11:57:19 +0000 admin http://healthandpills.com/?p=1204
          Contents

              Epilepsy is common, affecting up to 2% of the population. Thus, it is inevitable that most doctors, whether neurologists, surgeons, general practitioners or hospital physicians, will at some stage have to manage a patient with epilepsy. People with epilepsy may have an exacerbation in their seizures due to a concomitant medical condition or its treatment, a person without epilepsy may have an acute symptomatic seizure during an acute illness, or a patient may develop epilepsy associated with a medical condition.

              Even though a patient’s seizures may be well controlled at baseline, an untimely seizure during a systemic disturbance may impact adversely on outcome, predispose the patient to infections and cause metabolic or cerebral dysfunction. Additionally, the situation may be further complicated by the presence of anti-epileptic drugs, as pharmacodynamics and pharmacokinetics may be altered during a systemic illness.

              Unfortunately, patients with epilepsy who have comorbid diseases are often excluded from anti-epileptic drug trials, which means there are few data about this group of patients. This chapter addresses the difficult topic of managing the patient with epilepsy and a co-morbid medical condition.

              Cerebrovascular disease

              Stroke may cause acute symptomatic seizures in the initial post-stroke period, as well as epilepsy in the long term. In fact, stroke is the most common cause of epilepsy in older patients. Stroke treatments, such as thrombolysis and revascularization procedures, may also result in seizures. The risk of seizures is highest after intracerebral haemorrhage, but they may also occur after ischaemic stroke and in the setting of transient ischaemic attack due to focal neuronal dysfunction. Animal studies suggest that the risk of seizures is proportional to the volume of damaged tissue.

              Anti-epileptic drug prophylaxis is not recommended after stroke or intracerebral haemorrhage, unless the patient has had a seizure. The risk of seizures is greatest at presentation, and in patients with lobar haemorrhage. However, seizure occurrence does not appear to affect mortality and the risk of developing epilepsy in patients who have not had a seizure at intracerebral haemorrhage onset is low, suggesting that anti-epileptic drug prophylaxis is unnecessary. In the setting of an acute symptomatic seizure following a stroke or intracerebral haemorrhage, some would advocate the use of an anti-epileptic drug for the initial few weeks, followed by gradual weaning if the patient remains seizure free. If, however, a patient has a remote unprovoked seizure in the setting of an underlying structural lesion such as a focal infarct, most epileptologists would commence long-term anti-epileptic drug treatment, as the risk of recurrent seizures is high. The choice of anti-epileptic drug is important, as many of the older anti-epileptic drugs are sedating, affect coordination and may impact on rehabilitation. Phenytoin was found to impact adversely on functional outcome post subarachnoid haemorrhage (SAH) and phenytoin, phenobarbital and benzodiazepines were all found to be associated with less independence in activities of daily living (ADL) in patients following focal brain injury. In addition, many stroke patients also have cardiac disease, therefore phenytoin may not be ideal.

              Fortunately, epilepsy occurring as a result of stroke is usually relatively easily treated, most patients becoming seizure free on monotherapy and most anti-epileptic drugs being effective. Anti-epileptic drug choice depends on other factors, such as co-morbidities, medications and side-effect profiles. However, gabapentin and lamotrigine have been found to be useful because of lack of interactions, side-effect profile and efficacy. Although there is a lack of specific data on the other newer anti-epileptic drugs, levetiracetam and topiramate would also be expected to be useful in this patient population, although both may have cognitive and behavioural adverse effects.

              Cardiac disease

              Atrial fibrillation occurs in 9% of patients over the age of 80 years, and prevalence is increasing as the population ages. All patients with Atrial fibrillation should be anti-coagulated with warfarin for stroke prevention unless there is a clear contraindication. It is therefore particularly important in this patient group that seizures are well controlled, as a minor injury may cause devastating haemorrhage. Epilepsy, however, is not a contraindication to anti-coagulation. One study found that warfarin remained the drug of choice in elderly patients with Atrial fibrillation despite a risk of falls. Several anti-epileptic drugs may interact with warfarin, in particular the enzyme inducers (phenytoin, phenobarbital and carbamazepine), which may enhance its metabolism, requiring an increase in warfarin dose to maintain therapeutic anti-coagulation. Importantly, there is a significant risk of over-anticoagulation if the enzyme-inducing anti-epileptic drug is withdrawn. Thus, if an anti-epileptic drug is added or withdrawn, the international normalized ratio should be monitored particularly closely. Phenytoin has an unpredictable effect on the international normalized ratio as it affects both protein binding and enzyme induction.

              Cardiac arrhythmias have been reported frequently during and after seizures. The most common rhythm seen periictally is a sinus tachycardia, which is a normal physiological response to the seizure. However, symptomatic sinus bradycardias, including asystole, may occur.

              Table Effects of anti-epileptic drugs on the international normalized ratio

              anti-epileptic drugs which may reduce international normalized ratio anti-epileptic drugs which may increase international normalized ratio
              Carbamazepine Phenytoin
              Phenobarbital Valproate
              Phenytoin
              Primidone

              Such patients should be considered for pacemaker insertion. S-T-segment abnormalities have also been reported in association with seizures. Patients with epilepsy who have a history of ischaemic heart disease may therefore be at increased risk of cardiac ischaemic events during a seizure.

              It is important to consider that not every patient with recurrent unprovoked episodes of loss of consciousness has epilepsy. It is not uncommon for a patient with syncope to have brief convulsive jerks, which may be misinterpreted as seizure activity. Cardiac conditions, such as arrhythmias, are another common cause of recurrent collapses. Confusingly, some anti-epileptic drugs may even help prevent attacks which are not seizures. For example, patients with long Q-T syndrome may have recurrent episodes of loss of consciousness due to a brief asystole. In this situation, phenytoin, which shortens the Q-T interval, may actually prevent the arrhythmia, thereby giving a false impression of ‘seizure’ control.

              Cardiac medications, particularly the class I anti-arrhythmics (lidocaine, flecainide, propafenone), which block sodium channels, may lower the seizure threshold even at therapeutic doses. Some cardiac medications, in particular quinidine and flecainide, are also metabolized by the cytochrome P450 system and may interact with certain anti-epileptic drugs. Some anti-epileptic drugs have cardiovascular side-effects, particularly when administered by intravenous infusion; this may make acute seizure management difficult in patients with cardiac conditions. Phenytoin infusion causes significant hypotension in approximately 5% of patients, and maybe pro-arrhythmogenic when administered rapidly. For patients with heart disease, the rate of phenytoin infusion should be <25mg/min. Fosphenytoin, a pro-drug of phenytoin, was initially thought to be free of cardiac adverse effects; however, recent literature suggests that cardiac adverse events are not uncommon.

              Carbamazepine has also been associated with adverse cardiac events. With acute overdose, acute cardiac failure and tachyarrhythmias have been reported; with chronic use and therapeutic drug levels, bradyarrhythmias and refractory hypertension have been reported. It has been suggested that sudden unexpected death in epilepsy (SUDEP) may in some cases be attributable to anti-epileptic drug-induced cardiac dysfunction ; this remains controversial.

              For acute seizure treatment in a patient with cardiac disease, intravenous valproate may be preferred to phenytoin or fosphenytoin, while the second-generation anti-epileptic drugs, such as topiramate and lamotrigine, may have fewer cardiac adverse events for patients requiring long-term seizure prophylaxis.

              Renal Disease

              Hepatic Disease

              Metabolic Disorders

              The acutely unwell or periprocedural patient

              People with epilepsy are often considered to be at higher risk when undergoing procedures. This is mainly due to the possibility of seizures occurring periprocedurally or due to the potential for interactions between drugs used during the procedure and the patient’s anti-epileptic drugs.

              Factors which may exacerbate seizures, such as sleep deprivation and alcohol, should be avoided prior to a procedure, and patients undergoing surgery should be advised to take their usual anti-epileptic drugs on the morning of surgery, even if fasting, and should continue their usual doses as soon as it is safe to do so.

              Seizures are common after neurosurgical procedures, and are also common following cardiac operations, possibly due to complex alterations in metabolism, haemodynamic changes, alteration in blood/clotting factors and cerebral perfusion which may occur during cardiopulmonary bypass.

              Although most of the local and general anaesthetic agents may have pro- as well as anti-convulsant effects, the actual risk of inducing a seizure is small. Enflurane appears to be associated with the highest risk of seizure.

              Benzodiazepines are often used perioperatively and may prevent acute seizures, but care must be taken when weaning off these agents to avoid withdrawal seizures. Some analgesics such as the opiates – pethidine (meperidine) in particular – are associated with seizures, and should be avoided, where possible, post-operatively.

              Anti-epileptic drug levels may be altered significantly post-operatively due to changes in hydration, volume of distribution, pharmacokinetics, pharmacodynamics, altered protein binding and blood loss. It is useful to have a baseline anti-epileptic drug level at which the patient is seizure free to allow comparison and dose alterations post-operatively.

              Patients with epilepsy in the intensive care unit are at high risk of seizures. Seizures are often precipitated by this environment, even in patients without any history of epilepsy. Organ failure, metabolic changes, electrolyte and fluid imbalance, cerebral oedema, hypoxia, hypotension and hypoglycaemia are all common occurrences, as is the presence of many drugs which may lower the seizure threshold. Most patients in the intensive care unit are also sleep deprived. Pre-existing anti-epileptic drug regimens are often disturbed due to altered absorption, metabolism, dosing schedules and because the patient is unable to take drugs orally. In addition, because of the frequent use of sedation and neuromuscular blocking drugs, it may be difficult to know if a patient is actually seizing.

              Oral dosing may be limited in patients who are fasting, post-ictal, have a reduced level of consciousness or who are intubated. Most anti-epileptic drugs can be given via an alternative route if the patient cannot swallow tablets:

              •   Phenytoin may be given intravenously, in suspension form via enteric tubes, or

              rectally If given enterally, it should be given separately from feeds as these may reduce absorption.

              •   Fosphenytoin, a pro-drug of phenytoin, may be substituted. It can be given intramuscularly which is useful when access is difficult, or intravenously.

              •   Phenobarbital may be given intravenously intramuscularly or rectally It is also available in liquid form which may be given via enteric tubes.

              •   Valproate may be given intravenously as a syrup which may be given via enteric tubes, or by rectal suppositories which give good bioavailability

              •   Carbamazepine can be given by suppository using the same dose as orally, and is also available in suspension form which can be given via enteric tubes.

              •   Benzodiazepines are usually used for acute seizure management rather than for chronic epilepsy treatment, but are available in many different forms which may be useful for patients who are acutely unwell. Lorazepam may be given intravenously or sublingually Rectal diazepam is well absorbed, and is also available intravenously. Midazolam can be given into the buccal cavity or intranasally

              Most of the newer anti-epileptic drugs are still not available in intravenous form. However, most can be given via enteric tubes in the following preparations:

              •   Oxcarbazepine suspension

              •   Lamotrigine (tablets may be crushed)

              •   Topiramate (sprinkles may be injected using water)

              •   Levetiracetam liquid (intravenous levetiracetam is at an advanced phase of development and is expected to be commercially available in the near future)

              •   Gabapentin liquid.

              Elderly Patients

              Drugs And Drug Interactions

              Other Conditions Which May Benefit From Anti-epileptic Drug Treatment

              Conclusion

              Epilepsy frequently occurs in association with another medical condition. In such patients, introduction of a new anti-epileptic drug should be accompanied by close monitoring for potential adverse effects. Careful selection of an appropriate anti-epileptic drug should allow for seizure control in the majority of patients, bearing in mind potential drug interactions and alterations in pharmacodynamics and pharmacokinetics which may occur due to the underlying disease.


              ]]> http://healthandpills.com/disorders-and-conditions/epilepsy/treatment-of-the-epilepsy-patient-with-concomitant-medical-conditions/feed 0 Renal Disease http://healthandpills.com/disorders-and-conditions/epilepsy/renal-disease http://healthandpills.com/disorders-and-conditions/epilepsy/renal-disease#comments Tue, 16 Aug 2011 11:56:10 +0000 admin http://healthandpills.com/?p=1215 Seizures may occur in uraemic encephalopathy, dialysis disequilibrium syndrome and dialysis encephalopathy. In addition, renal insufficiency and dialysis may both have effects on anti-epileptic drug pharmacokinetics. Renal impairment can alter the fraction of anti-epileptic drug absorbed, volume of distribution, protein binding and renal drug clearance.

              Renal impairment may alter the gastric pH, cause small intestinal bacterial overgrowth, gastrointestimal tract oedema and impaired gastrointestinal motility. These factors may cause reduced ionization of some drugs and reduce drug absorption.

              The volume of distribution of drugs may be increased in patients with end-stage renal failure, resulting in lower total plasma levels. However, protein binding of acidic drugs may be significantly reduced in renal impairment; total plasma levels of anti-epileptic drugs may therefore be misleading. A total drug level may appear within the therapeutic range, despite a toxic-free level. For anti-epileptic drugs metabolized by the liver, changes in protein binding will affect the steady-state plasma concentration, but the free concentration will remain unchanged. For these reasons, it is often more useful to measure free concentrations of anti-epileptic drugs which are highly protein bound, such as phenytoin and valproate.

              Renal impairment may affect drug clearance depending on the extent of renal clearance, drug filtration and tubular secretion and resorption. Gabapentin, topiramate, pregabalin and levetiracetam are almost exclusively cleared by the kidneys. These drugs have reduced elimination and prolonged half-lives in patients with renal impairment and dosages should be adjusted accordingly. For other anti-epileptic drugs such as phenytoin, carbamazepine and tiagabine, renal excretion is minimal, and unless creatinine clearance is below 25ml/min there is no need to adjust the dose.

              Table Effect of renal disease on specific anti-epileptic drugs

              anti-epileptic drug Protein binding (%) Half-life (h) Effect of renal disease
              Carbamazepine 80 36; 16-24 with repeated doses; 9-10 with enzyme inducers Anti-diuretic effect, may increase fluid retention
              Felbamate 25 Reduced clearance; prolonged half-life
              Gabapentin 0 5-9 Reduced clearance; significantly removed by Haemodialysis; company advises 200-300 mg bolus post Haemodialysis
              Lamotrigine 50 24-34; doubled with valproate; 15 with enzyme inducers Prolonged half-life; reduce dose; 20%removed by Haemodialysis
              Levetiracetam <10 6-8 Reduced clearance; 50%removed by Haemodialysis; company advise giving 250-500 mg bolus post Haemodialysis
              Oxcarbazepine 40 of active metabolite Parent drug, 2; active metabolite, 9 Reduced clearance; reduce dose
              Phenobarbital 40-50 55-118 Removed by Haemodialysis; reduce dose
              Phenytoin >90 22-36 Reduced total concentration but increased free fraction; only 2-4% removed by Haemodialysis; monitor free levels
              Pregabalin 0 6 Reduced clearance, prolonged half-life; reduce dose; significantly removed by Haemodialysis; supplement dose post Haemodialysis
              Tiagabine 96 5-8 Minimal effect
              Topiramate <20 21 Reduced clearance; reduce dose; significantly removed by Haemodialysis; company advise loading before Haemodialysis to avoid sub-therapeutic levels. Note: risk of renal stones
              Valproate 85-95 12-16 Reduced protein binding; reduced total concentration but increased free fraction; 20%removed by Haemodialysis
              Vigabatrin 0 5-8 Reduced clearance; reduce dose
              Zonisamide 40 50-70; 30 with Reduced clearance; some is removed by
              enzyme inducers Haemodialysis

              Several methods have been proposed to calculate anti-epileptic drug dose based on creatinine clearance, volume of distribution and other variables. However, these are complex and the actual drug concentration may vary considerably from that calculated. In patients with renal impairment, anti-epileptic drugs should be slowly initiated at low doses and clinical assessment and drug level monitoring are necessary.

              Haemodialysis may clear anti-epileptic drugs from the circulation depending on their molecular size, water solubility, protein binding, volume of distribution and dialysis conditions. Drugs such as ethosuximide, gabapentin, levetiracetam, phenobarbital, pregabalin and topiramate which are highly water soluble, not protein bound and with a small volume of distribution are readily removed by Haemodialysis. Carbamazepine, clonazepam, phenytoin, tiagibine and valproate have a low risk of removal, although even these will have some removal during Haemodialysis.

              If an anti-epileptic drug has been partially removed by Haemodialysis, the following equation can be used to calculate the loading dose required to restore the desired plasma concentration:

              LD = С ь X VD change

              where LD = loading dose; CAan = desired change in plasma concentration; VD = volume of distribution.

              The kidney is the most commonly transplanted organ, usually as a result of hypertensive disease, diabetes or glomerulonephritis, all of which cause uraemia and may be associated with seizures. The immunosuppressant agents most often used in renal transplantation are cyclosporine, tacrolimus, azathioprine and mycophenolate; most patients are also on steroids. Cyclosporine and tacrolimus are well known to be associated with posterior leukoencephalopathy and seizures. Cyclosporine has also been shown to reduce seizure threshold. These immunosuppressants are mainly metabolized by the liver. Enzyme-inducing anti-epileptic drugs such as phenytoin, carbamazepine and phenobarbital may reduce the plasma concentration of cyclosporine; it is therefore particularly important to monitor cyclosporine levels in such patients. It has been reported that phenytoin and phenobarbital reduce renal allograft survival, possibly due to increased metabolism of immunosuppressive agents. Owing to fewer effects on the cytochrome P450 system and fewer drug interactions, some of the second-generation anti-epileptic drugs are preferred in renal transplant patients with epilepsy; however, gabapentin has been reported in association with acute renal dysfunction in an allograft.

              If transplant patients with epilepsy have breakthrough seizures, it is important to consider aetiologies other than their epilepsy as the cause. In particular, uraemic encephalopathy, metabolic derangement, opportunistic infection or leukoencephalopathy should be considered.

              In summary, gabapentin and levetiracetam may accumulate in patients with renal failure. Valproate, carbamazepine, oxcarbazepine and tiagabine are less likely to cause toxicity, although their protein binding will be affected.

              ]]>               http://healthandpills.com/disorders-and-conditions/epilepsy/renal-disease/feed 0               Hepatic Disease http://healthandpills.com/disorders-and-conditions/epilepsy/hepatic-disease http://healthandpills.com/disorders-and-conditions/epilepsy/hepatic-disease#comments Tue, 16 Aug 2011 11:55:18 +0000 admin http://healthandpills.com/?p=1213 The liver is the principal organ of drug metabolism. Some drugs are absorbed from the gut, delivered to the liver and undergo first-pass metabolism prior to reaching the systemic circulation. Metabolism of these drugs is significantly affected by hepatic vascular supply; if hepatic blood flow is reduced, first-pass metabolism is decreased and more drug reaches the systemic circulation. Other drugs reach the systemic circulation before being delivered to the liver for metabolism; hepatocyte function is more important than the blood supply for their metabolism.

              Cytochrome P450 enzymes are involved in Phase I metabolism (non-synthetic metabolism which includes oxidation, reduction and hydrolysis). There is substantial genetic polymorphism within these enzymes, and people may be slow or fast metabolizers. These enzymes are also frequently induced or inhibited by drugs, including anti-epileptic drugs. Phenytoin, phenobarbital and carbamazepine are well-known enzyme inducers.

              The liver is also involved in protein production; impaired protein production reduces the amount of drug that is protein bound, increasing the free fraction. This is relevant for phenytoin, valproate, tiagabine and carbamazepine, which are highly protein bound. The true plasma concentration of phenytoin in a patient with low albumin can be calculated by Equation 2.

              Table Effects of liver disease on specific anti-epileptic drugs

              anti-epileptic drug Protein

              bound (%)

              		 Half-life (h) Liver disease
              Carbamazepine 80 36; 16-24 with repeated doses; 9-10 with enzyme inducers Reduced protein binding; reduced metabolism
              Felbamate 25 Potentially hepatotoxic; inadvisable to use in liver disease
              Gabapentin 0 5-9 Not affected
              Lamotrigine 50 24-34; doubled with valproate; 15 with enzyme inducers Slight reduction in clearance and prolonged half-life but considered clinically insignificant in trials
              Levetiracetam <10 6-8 Not affected
              Oxcarbazepine 40 of active metabolite Parent drug, 2; active metabolite, 9 No need to alter dose
              Phenobarbital 40-50 55-118 Prolonged half-life; reduced metabolism; reduce dose and increase time between doses
              Phenytoin >90 22-36 Reduced metabolism, therefore accumulates and may become toxic quickly; reduced protein binding; increase in free fraction; monitor free levels
              Pregabalin 0 6 Not affected
              Tiagabine 96 5-8 Prolonged half-life; increased free fraction; reduce dose; increase time between doses
              Topi ram ate <20 18-23 Reduced clearance; prolonged half-life; felt to be clinically insignificant
              Valproate 85-95 12-16 Reduced protein binding; rarely hepatotoxic
              Vigabatrin 0 5-8 Not affected; however, some reports of liver damage
              Zonisamide 40 50-70; 30 with enzyme inducers Reduced metabolism; prolonged half-life; increase interval between dose adjustments

              All anti-epileptic drugs except levetiracetam, gabapentin, pregabalin and vigabatrin have some hepatic metabolism, therefore hepatic disease may affect pharmacokinetics of most of the anti-epileptic drugs. Additionally, patients with liver disease may be encephalopathic and have altered pharmacodynamics, having a lower seizure threshold as well as being more vulnerable to the central nervous system adverse reactions of anti-epileptic drugs.

              Seizures occur frequently after liver transplantation. Immunosuppressants are mainly metabolized by the liver, as are most anti-epileptic drugs. In addition, many anti-epileptic drugs may induce or inhibit hepatic metabolism. These factors make management of epilepsy difficult in patients with a liver transplant. Levetiracetam may be a good choice of anti-epileptic drug in such patients because of its predominantly renal metabolism and excretion, low protein binding, lack of enzyme induction, lack of drug interactions and broad-spectrum use in different seizure types.

              A number of anti-epileptic drugs may rarely be hepatotoxic; the most common culprit is valproate, which is contraindicated in patients with hepatic failure. However, other anti-epileptic drugs, including phenytoin, may cause an acute drug-induced hepatitis. These reactions are idiosyncratic and usually occur soon after commencing the drug. Hepatic toxicity should prompt immediate discontinuation of the offending drug and substitution of an alternative anti-epileptic drug.

              As gabapentin, pregabalin and levetiracetam are not significantly protein bound or metabolized by the liver, these are good choices for long-term anti-epileptic drug in patients with hepatic disease. If a patient with liver disease has an acute seizure, benzodiazepines may be used, although there is an increased risk of respiratory depression.

              Table Drugs that induce or inhibit hepatic enzymes

              Enzyme inducers Enzyme inhibitors
              Anti-epileptic drugs Anti-epileptic drugs Antifungals
              Phenytoin Valproate Ketaconazole
              Carbamazepine Antibiotics Itraconazole
              Phenobarbital Erythromycin Fluconazole
              Topi ram ate Clarithromycin Anti-arrhythmics
              Felbamate Metronidazole Amiodarone
              Tiagabine Cotrimoxazole Quinidine
              Zonisamide Isoniazid Verapamil
              Antibiotics Ciprofloxacin Proton pump inhibitors
              Rifampicin Protease inhibitors Omeprazole
              Rifabutin Ritonavir Antidepressants
              Indinavir Fluoxetine
              Nelfinavir Fluvoxamine
              Saquinavir Nefazodone
              Histamine 2 blockers Monoamine oxidase inhibitors
              Cimetidine Lithium
              ]]>               http://healthandpills.com/disorders-and-conditions/epilepsy/hepatic-disease/feed 0               Metabolic Disorders http://healthandpills.com/disorders-and-conditions/epilepsy/metabolic-disorders http://healthandpills.com/disorders-and-conditions/epilepsy/metabolic-disorders#comments Tue, 16 Aug 2011 11:54:33 +0000 admin http://healthandpills.com/?p=1211 Metabolic disturbances are a common cause of seizures, even in patients without epilepsy. In most cases, acute metabolic derangements causing seizures are potentially reversible. Seizures due to metabolic derangements are often refractory to anti-convulsant medications; correction of the underlying abnormality is required.

              Hyponatraemia is the most common electrolyte disturbance encountered in clinical practice. It is a common side-effect of many drugs, including carbamazepine and oxcarbazepine. Oxcarbazepine seems to be associated with a higher incidence of hyponatraemia than carbamazepine, 30% vs. 14% in one study. Risk factors for the development of hyponatraemia are age >40, female gender, use of drugs associated with hyponatraemia, psychiatric illness and surgery. It may also be due to the syndrome of inappropriate anti-diuretic hormone secretion (SIADH) which may occur in patients with cerebral pathology. Symptoms of hyponatraemia are lethargy, confusion, muscle twitching, seizures and coma. Chronic mild hyponatraemia may be asymptomatic, and may not need specific treatment. However, acute hyponatraemia associated with neurological symptoms may need urgent treatment, in some cases requiring careful administration of hypertonic saline. It is important not to increase the sodium by more than 12mmol/l/day as there is a risk of central pontine myelinolysis with a rapid change in sodium. In epilepsy patients with pre-existing hyponatraemia, carbamazepine and oxcarbazepine should not be used if possible. If a patient with epilepsy develops hyponatraemia because of their anti-epileptic drug, it may be sufficient to reduce the dose, as the severity of hyponatraemia appears to be dose related; if persistent, however, it may be necessary to use an alternative anti-epileptic drug.

              Hypernatraemia is much less common than hyponatraemia, but may occur transiently following a convulsion. Significant hypernatraemia may cause intracerebral haemorrhage, cerebral vein rupture, seizures, coma and death. Treatment is water replacement, although again it is important not to correct the sodium too quickly, as there is a risk of cerebral oedema.

              Symptomatic hypoglycaemia is a common cause of seizures. Hypoglycaemia is often medication related; other causes are sepsis and inborn errors of metabolism. Serum glucose usually needs to be less than 2.2mmol/l for seizures to occur. Refractory nocturnal seizures should raise the possibility of insulinoma. Patients with diabetes who suffer from recurrent episodes of symptomatic hypoglycaemia and seizures require modification of their hypoglycaemic medication rather than anti-convulsant treatment. Phenytoin has been shown to interfere with carbohydrate metabolism, the usual effect being hyperglycaemia; however, it has also been reported in association with hypoglycaemia. An alternative anti-epileptic drug should be used in patients with diabetes.

              Non-ketotic hyperglycaemia usually occurs in older patients with non-insulin-dependent diabetes. It is associated with significant morbidity and mortality and often causes seizures. It may be precipitated by infection, surgery or other physiological stress. In contrast, ketotic hyperglycaemia rarely causes seizures, as ketosis is thought to have an anti-convulsant effect. Patients with Non-ketotic hyperglycaemia are often also hyponatraemic and may develop areas of potentially reversible focal cerebral damage, both of which increase the risk of seizures. Treatment of Non-ketotic hyperglycaemia is with insulin, fluids and correction of the metabolic abnormalities.

              Seizures occur in up to one-quarter of patients admitted emergently with acute hypocalcaemia. Rarely, hypocalcaemia has caused seizures in patients on long-term anti-epileptic drugs such as phenytoin and phenobarbital due to their effects on vitamin D metabolism. Acute valproate overdose has also been associated with hypocalcaemia. Treatment of symptomatic hypocalcaemia is with intravenous calcium gluconate; replacement of magnesium may also be required if the patient has co-existing hypomagnesaemia.

              Porphyria is a group of disorders caused by inherited deficits of enzymes involved in haem synthesis. Seizures occur in the hepatic porphyrias: acute intermittent porphyria, hereditary co-poporphyria and variegate porphyria. Between 5% and 20% of patients with porphyria have seizures. Unfortunately, many drugs can precipitate an acute attack, including the enzyme-inducing anti-epileptic drugs. This makes treatment of epilepsy and of acute symptomatic seizures very difficult. Gabapentin and vigabatrin have both been used successfully and appear to have a low risk of precipitating a crisis. Lorazepam seems to have the lowest risk of the benzodiazepines, although all cause porphyrin accumulation. Less is known about the second-generation anti-epileptic drugs; tiagabine and topiramate appear to have the potential to cause an acute attack, while oxcarbazepine and levetiracetam have both been used safely in case reports. Pregabalin is expected to be safe, although to date there are no published data on its use in porphyria.

              ]]>               http://healthandpills.com/disorders-and-conditions/epilepsy/metabolic-disorders/feed 0               Elderly Patients http://healthandpills.com/disorders-and-conditions/epilepsy/elderly-patients http://healthandpills.com/disorders-and-conditions/epilepsy/elderly-patients#comments Tue, 16 Aug 2011 11:53:26 +0000 admin http://healthandpills.com/?p=1209 The incidence of epilepsy is highest in patients >75 years, with a point prevalence of 1.5%, and as the population ages doctors will treat increasing numbers of older patients with epilepsy. Treatment of epilepsy in older patients is complicated by alterations in pharmacodynamics and pharmacokinetics, metabolic derangements, presence of multiple co-morbid diseases, polypharmacy and psychosocial factors.

              The aetiology of epilepsy in older patients differs from that of young people; the most frequent cause being cerebrovascular disease. Seizures are usually partial in onset and may be mistaken for recurrent strokes or TIAs, which may lead to unnecessary investigations and inappropriate treatment. In addition, morbidity and mortality are higher in elderly patients with seizures. However, the literature suggests that if the elderly patient can tolerate the anti-epileptic drug, the prognosis is usually good, with seizure freedom rates of over 60% at 1 year.

              Physiological changes occur with increasing age, and these affect anti-epileptic drug absorption and metabolism. Gastric emptying, gastrointestinal blood flow and bowel motility are often reduced and gastric pH higher in elderly people. These affect drug solubility and ionization and may reduce the rate and amount of drug absorbed. In addition, the volume of distribution of a drug may be altered by muscle loss and an increase in fat which occurs with age.

              Protein binding is altered due to low levels of albumin, which occurs in normal elderly people as well as those with malnutrition, renal or hepatic disease. This affects anti-epileptic drugs which are highly protein bound such as phenytoin, valproate and carbamazepine, meaning that the free drug level may be more useful in these patients.

              Hepatic phase I reactions and renal clearance both decrease with advancing age; elderly patients are therefore at higher risk of anti-epileptic drug toxicity at lower doses. While there are no specific recommendations with regard to anti-epileptic drug dosing in the elderly, they may develop toxic effects at lower levels and may only tolerate lower doses.

              Depression is common in the elderly, as it is in epilepsy. Johnson found that interictal psychiatric features impacted more on quality of life in people with epilepsy than did seizure frequency. Depression is frequently under-diagnosed and inadequately treated, and may impact negatively on long-term outcome. Unfortunately, most anti-depressant medications can lower the seizure threshold. Selective serotonin re-uptake inhibitors have a lower risk of seizures than the tricyclic anti-depressants. The risk of seizures associated with most anti-depressants is <0.4% overall with a dose-dependent relationship; however, the risk is probably higher in patients with epilepsy and in the elderly. If a patient at higher risk of seizures requires an anti-depressant, using a low dose and slower dose escalation may reduce the seizure risk.

              Many of the anti-epileptic drugs have cognitive adverse effects, which should be considered prior to prescribing them for elderly people who may be more sensitive to these side-effects. Some of the newer anti-epileptic drugs, such as lamotrigine and zonisamide, may have less cognitive adverse effects than some of the first-generation anti-epileptic drugs.

              Osteoporosis is frequent in the elderly population, and fractures are a major cause of morbidity and mortality. Patients with epilepsy on anti-epileptic drugs have double the risk of fractures, probably due to a combination of increased risk of falls due to adverse effects of anti-epileptic drugs, seizure-related trauma and reduced bone health. A number of anti-epileptic drugs, predominantly phenytoin, valproate and phenobarbital have been associated with reduced bone mineral density, although more recent studies have also implicated carbamazepine and oxcarbazepine. Patients at risk should be offered dual energy X-ray absorptiometry (DEXA) scanning and may require treatment with bisphosphonates and calcium and vitamin D supplementation.

              One study found that the mean number of daily medications for elderly patients in the community was eight, with 40% prescribed more than nine medications daily. Polypharmacy increases the risk of medication non-compliance, which may in turn increase the risk of seizures. In addition, polypharmacy increases the potential for drug-drug interactions. Elderly patients are more likely to have memory problems and visual impairment and these factors make medication errors more likely. Because of the narrow therapeutic index, lower tolerability and higher adverse effect rate of anti-epileptic drugs in older patients, it is preferable to initiate anti-epileptic drugs at lower doses and titrate more slowly than is necessary in younger patients.

              Adverse effects of anti-epileptic drugs are one of the most important problems in epilepsy management in elderly people. Older patients are often excluded from drug trials due to co-morbid illnesses and presence of other medications; however, the literature suggests decreased tolerability of the first-generation anti-epileptic drugs with increasing age. In addition, the recent Veterans’ Affairs Cooperative Study found that retention rates in elderly people with epilepsy were better for lamotrigine and gabapentin than for carbamazepine, without any significant difference in rates of seizure freedom. Despite this, phenytoin, carbamazepine and valproate remain the most frequently prescribed anti-epileptic drugs in nursing home residents. Elderly patients are more likely to develop adverse effects of drugs at lower doses, as they tend to tolerate a narrower therapeutic range. Adverse effects such as tremor, ataxia, visual disturbances and sedation are common and occur at lower drug levels in elderly people. These adverse effects in turn increase the risk of falls and of non-compliance.

              When choosing an anti-epileptic drug for an elderly patient with epilepsy, one needs to consider co-morbid conditions and medications. Monotherapy is preferable as they are often on many other medications, and the recent literature would suggest that the second-generation anti-epileptic drugs are preferable as first-line treatment rather than the more established first-generation anti-epileptic drugs (phenytoin, carbamazepine, valproate). If a patient is on other sedating medications, it would be wise to avoid prescribing potentially sedating anti-epileptic drugs such as gabapentin. A patient with tremor or ataxia may be made worse by valproate, phenytoin and carbamazepine. However, even a carefully chosen medication may be less well tolerated and require lower dose and slower titration in this group of patients.

              ]]>               http://healthandpills.com/disorders-and-conditions/epilepsy/elderly-patients/feed 0               Drugs And Drug Interactions http://healthandpills.com/disorders-and-conditions/epilepsy/drugs-and-drug-interactions http://healthandpills.com/disorders-and-conditions/epilepsy/drugs-and-drug-interactions#comments Tue, 16 Aug 2011 11:52:25 +0000 admin http://healthandpills.com/?p=1207 The goal of epilepsy treatment is ‘no seizures, no side-effects’. Monotherapy is preferred if possible, because of greater patient compliance with medications, better quality of life, more favourable adverse effect profile, lack of drug interactions and cost issues. However, many patients with epilepsy will require more than one anti-epileptic drug, and many patients will also be on other medications for co-morbid conditions. This means that a large proportion of people with epilepsy are at risk of drug interactions.

              When new anti-epileptic drugs are undergoing trials, they are almost invariably tested as add-on therapy, meaning that they are initially licensed only as add-on treatment rather than as monotherapy.

              Drug interactions may be pharmacodynamic or pharmacokinetic. The clinical significance of a drug interaction depends on the drugs involved as well as patient factors such as age and co-morbid conditions. However, drug interactions are not necessarily harmful. There are several combinations of anti-epileptic drugs with synergistic effects on each other, such as lamotrigine and valproate, meaning that lower doses of both are required, which may reduce cost. The combination of phenytoin and valproate also appears to have some synergistic activity, so lower drug levels may confer the same anti-convulsant effect. Using an anti-epileptic drug which prolongs the half-life or reduces the metabolism of another may mean prolonging the time between doses, which may improve patient compliance.

              There are several ways in which anti-epileptic drug absorption may be altered. Activated charcoal, antacids and resins reduce drug absorption by adsorbing drugs onto their surface and preventing passage of drug across the stomach wall. As soon as this occurs, serum concentration of the drug begins to decrease, the rate of decrease depending on its half-life. Metoclopramide and other drugs that increase gastric motility may increase the absorption of drugs, while anticholinergics and other drugs that slow gastric emptying may delay absorption. An increase or decrease in the rate of absorption may not alter drug bioavailability, but may be important if a rapid effect is required. Drugs that alter gastric pH, such as histamine receptor blockers, proton pump inhibitors and antacids, may change ionization of acidic or basic drugs, thereby affecting absorption. All of these local factors may be reduced by the patient taking the interacting drugs several hours apart.

              Alterations in protein binding may be another mechanism for drug interactions. This is largely important for drugs which are highly protein bound and have a narrow therapeutic index, such as phenytoin. If one drug is commenced when a patient is stable on another, the new drug will displace some of the original drug from plasma proteins, causing an increase in the unbound fraction. However, when the unbound fraction of a drug increases, more is available for metabolism and clearance, so in fact the drug concentration may decrease. These interactions are unpredictable, so it is important to monitor free anti-epileptic drug levels as total levels are misleading.

              The most common cause of drug interaction, however, is induced alterations in hepatic metabolism. Phenytoin, phenobarbital, carbamazepine, topiramate, tiagabine, zonisamide and f elbamate are all metabolized by the cytochrome P450 enzyme system. Several drugs can induce or inhibit these enzymes in a dose-dependent fashion. Carbamazepine, for example, is an autoinducer as it induces the isoenzyme which is responsible for its own metabolism. Phenytoin, phenobarbital, carbamazepine and topiramate all induce cytochrome P450 enzymes, while valproate is an inhibitor. Interactions due to enzyme induction occur relatively slowly, as new proteins have to be synthesized. Those resulting from enzyme inhibition depend on the half-life of the affected drug as it takes approximately five half-lives for a drug to reach a steady-state concentration. Gabapentin, levetiracetam and vigabatrin are only minimally metabolized and so have less potential for these type of interactions.

              An important interaction occurs in young women who are using the oral contraceptive pill. Phenytoin, phenobarbital, carbamazepine, oxcarbazepine, felbamate and topiramate increase the metabolism of ethinyl estradiol and progestogens, reducing the effectiveness of the oral contraceptive pill. With these anti-epileptic drugs, the dose of oestrogen should be increased to at least 50µg, or an alternative form of contraception used.

              One should always remember that patients with chronic medical conditions such as epilepsy are more likely to use over-the-counter non-prescription medications. Several of these, in particular St John’s Wort and Ginkgo biloba, may have effects on enzyme activity and have the potential for altering anti-epileptic drug metabolism. In addition, some may have pharmacodynamic interactions, and may have a clinically significant effect without any effect on drug levels. Most patients using complementary medicine do not inform their doctor, so it is important to ask the patient directly, as self-medication with over-the-counter medications may be a reason for subtherapeutic or toxic drug levels.

              It is not an exhaustive list of interactions, as there are many other non-anti-epileptic drugs which are also inducers or inhibitors and may cause interactions. Consult the British National Formulary (BNF) for more information.

              In conclusion, although the potential for drug interactions is high with anti-epileptic drugs, the majority of patients prescribed potentially interacting drugs do not in fact develop any clinical consequences. Patient factors are probably the most important reason behind this. The physician may prevent serious consequences by being aware of the potential interaction, anticipating it, monitoring the patient clinically and using drug levels wisely. As a general rule, the second-generation anti-epileptic drugs have far fewer pharmacokinetic interactions as most do not have any appreciable effect on metabolizing enzymes. If the risk of a serious interaction is high, it may be preferable to use an alternative drug.

              ]]>               http://healthandpills.com/disorders-and-conditions/epilepsy/drugs-and-drug-interactions/feed 0