TB treatment and common side effects

Initial phase (2 months):
- Isoniazid (INH)
Can cause hepatotoxicity and peripheral neuropathy (give with Vitamin B6, especially in patients at risk for neuropathy - diabetics, alcoholics, HIV, pregnant)
- Rifampin (RIF)
Excreted as a red-orange compound in urine, tears, sweat, and stool
Can cause hepatotoxicity (less common than with INH)
Induces hepatic microsomal enzymes and may increase hepatic clearance of other drugs
- Pyrazinamide
Commonly causes GI upset
Can cause hepatotoxicity and hyperuricemia (can induce gout flares in patient's at risk)
- Ethambutol
Can cause hepatotoxicity and optic neuritis (screen monthly for visual disturbances)


Continuation phase (4 or 7 months):
- INH
- RIF


Follow-up:
- Repeat sputum smear and culture two months after initiation of therapy
- Liver panel

Pulsus Paradoxus

Definition: Exaggerated drop in systemic blood pressure during inspiration that can cause weakening of peripheral pulses

Causes:
1) Cardiac: tamponade, shock, pericardial effusion
2) Pulmonary: PE, tension pneumothorax, asthma, COPD
3) Misc: anaphylactic shock, SVC obstruction

Measurement:
1) Inflate a sphygmomanometer cuff as if measuring BP. As the cuff is deflating, measure the systolic pressure at which Korotkoff sounds become audible during expiration and inspiration. The difference between these 2 pressures is the pulsus paradoxus.
2) Decrease in the pulse wave amplitude during inspiration seen on an arterial tracing or pulse oximeter waveform
3) Severe pulsus paradoxus can be palpated in the radial, brachial, or femoral pulses as a weakening or disappearance of the pulse during inspiration

HIDA scan

HIDA (hepatobiliary iminodiacetic acid) nuclear medicine scan

- IV iminodiacetic acid derivative is taken up by hepatocytes and excreted into bile with concentration in the gallbladder. A series of images are taken visualizing the pathway of bile excretion.
- Used to diagnose obstruction (secondary to cholecystitis or cystic duct obstruction), gall bladder perforation, or congenital abnormalities in the bile ducts
- Normal study: gallbladder visualization within an hour
Abnormal: failure to visualize the gallbladder within 4 hours or leakage into the pericholecystic space
- False positives: severe liver disease causing abnormal HIDA uptake, TPN patients with an already distended gallbladder, biliary sphincterotomy causing decreased filling of the gallbladder

Skeletal Survey vs Bone Scan

Skeletal Survey:
- X-rays of the major bones of the body, including chest, spine, skull, pelvis, femora, and humeri
- Used to diagnose fractures, bone metastasis, osteomyelitis, assessment after a trauma, degenerative conditions of the bone, child abuse


Bone Scan - nuclear medicine scan:
- Uses a radionuclide tracer (technetium 99m MDP) that accumulates in areas of bone turnover and increased osteoblast activity
- Used to diagnose fractures hard to diagnose on xrays, bone metastases, osteomyelitis, metabolic disorders of the bone (ie: Paget disease of the bone, hyperPTH, renal osteodystrophy), primary bone tumors


Dual energy X-ray absorptiometry (DXA or DEXA scan):
- Measure bone mineral density
- Used to diagnose and follow osteoporosis

Peaks + Troughs

Peak and trough levels are methods used to establish the effectiveness of a drug.

Peak:
- Highest drug level after distribution
- Drawn after the last dose of drug, usually one hour.
- Commonly obtained with use of aminoglycosides
- Used to change dose

Trough:
- Lowest drug level that is needed to reach therapeutic range
- Drawn before the next dose of drug is given.
- Commonly obtained with use of vancomycin
- Used to change frequency

IRIS

IRIS - Immune reconstitution inflammatory syndrome

Definition:
Worsening of preexisting infectious processes (ie: herpes zoster, TB, MAC, CMV, Cryptococcus) after initiation of HAART treatment secondary to re-activation of the immune system

Management:
- Treat underlying opportunistic infection
- Continue ART treatment unless patient is experiencing life-threatening IRIS requiring hospitalization, intubation, etc
- Consider prednisone (1 mg/kg/day with a 10-14 day taper) to decrease inflammatory response

TIPS

Transjugular Intrahepatic Portosystemic Shunt

• Treatment for patients who bleed from portal hypertension
• Limited by high incidence of stent stenosis or thrombosis in first year
• Effective in reduction of refractory ascites, but associated with increased hepatic encephalopathy (vs serial paracentesis)

LVH EKG criteria

1: R aVL + SV3 >25 (men) or >20 (women)

2: SV1 + R V5 or 6 > 35, RV5 or 6 > 25

3: R aVL > 8

4: RV6 > 18

5: VAT > 0.05s

These criteria have high specificity (in the 90s) but low sensitivity (10-25%)

Cheyne-Stoke Respiration

Periodic respiration/cyclic respiration: hyperventilation and hypocapnea followed by recurrence of apnea

• common in advanced heart failure
• associated with low cardiac output
• decreased sensitivity of respiratory center to arterial CO2

Diuretics

Loop Diuretics (Furosemide)

• acts in thick ascending limb of loop of Henle to block the Na+/K+/2Cl- co-transporter, preventing reabsortion of Na, K, Cl
• increase fractional excretion of Ca++ up to 30%, increase fractional excretion of Mg++ up to 60%
• used to tx hypercalcemia, edematous states ie CHF

Thiazides and Thiazide-like Diuretics (chlorothiazide)

• acts in distal convoluted tubule to block coupled Na and Cl reabsorption
• increase excretion of Na, K, Cl but less potently than loop diuretics
• reduce Ca++ excretion
• used in uncomplicated hypertension, less useful in edematous states

Distal Potassium-Sparing Diuretics (spironolactone, amiloride)

• acts in cortical collecting duct prinicpal cells on aldosterone-sensitive Na+ channel
• reduced excretion of K+, Ca++, Mg++
• first line for cirrhotic ascites, also can be used in heart failure w/ systolic dysfunction, weak diuresis so commonly used in combination with a loop/thiazide diuretic to decrease K+ loss, increase diuresis in refractory edema

Carbonic Anhydrase Inhibitors (acetazolamide)

• act in proximal tubule to inhibit bicarbonate absorption
• transient, brisk alkaline diuresis
• useful in edema w/ metabolic alkalosis to help restore acid-base balance

Osmotic Diuretics (Mannitol)

• freely filtered but poorly reabsorbed
• acts in proximal nephron and thin loops of Henle to prevent urinary concentration

Adrenal Insufficiency

Primary Adrenal Insufficiency (Addison's)

• caused by autoimmune, infectious (TB, cryptococcus, CMV, pneumocystis), iatrogenic (bilateral adrenalectomy), or metastatic (lung, breast) etiologies
• clinical features related to lack of cortisol: GI symptoms (anorexia, nausea/vomitting, abdominal pain), hypoglycemia, hypotension, hyperpigmentation, intolerance to physiologic stress
• clinical features related to lack of aldosterone: hyponatremia and hypovolemia-->decreased cardiac output and renal perfusion, syncope, shock, hyperkalemia
• tx in acute crisis: several liters of IV fluids (D5NS), IV hydrocortisone, tx underlying condition
• chronic tx: daily oral glucocorticoid, daily mineralocorticoid

Secondary Adrenal Insufficiency

• Causes: long term steroid therapy + illness/trauma
• clinical features: same as above except that hyperpigmentation and hyperkalemia are not seen because ACTH is low, and aldosterone is normal
• tx: same as above except that only glucocorticoid supplementation is necessary

Heart sounds--gallops

Order of heart sounds: S4-->S1-->S2-->S3

S3

Occasionally heard in healthy children or adults, esp athletes

Occurs in dilated ventricles, for ex:

large VSD

CHF

volume overload

S4

Usually pathologic

Occurs with decreased ventricular compliance , for ex:

Normal (especially athletes)

Hypertensive

Coronary artery disease

Aortic stenosis

Restrictive cardiomyopathy

Chronic Pain Treatment

Chronic pain treatment optimally involves a combined pharmaceutical and non-pharmaceutical approach. Pharmaceutical options include a range of classes:

• Opioids, side effect: sedation, constipation, respiratory depression, abuse potential
• NSAIDS: GI ulcers, bleeding, renal impairment
• Serotonin agonists: MI, stroke, peripheral vascular occlusion
• Antiepileptics: sedation, dizziness, cognitive impairment
• Antidepressants: Cardiac arrhythmia, sedation, nausea, dry mouth, constipation, sleep disturbance

Some commonly used pharmaceuticals include:

• Tramadol (ultram): 250-300 microgm q 6hr, binds mu-opioid receptors and inhibits the noradrenaline reuptake inhibitor, has addictive/abuse potential
• Toradol (Ketorolac): 10 mg q 6hr, NSAID, risk of gastritis after 5-7 days
• Vicodin: 5/500 or 7.5/750, hydrocodone and acetaminophen, formulations which use NSAID instead of acetaminophen are also available (Vicoprofen)

Severely elevated transaminases

Severely elevated ALT/AST (>10000) indicates extensive hepatic necrosis. Common causes include:

• ischemia, shock (prolonged hypotension/circulatory collapse)
• acute toxic insult (acetaminophen toxicity, mushrooms: Amanita phalloides)
• Severe viral hepatitis

This is in contrast to:

• moderately elevated ALT/AST (high hundreds to thousands): acute viral hepatitis

• mildly elevated ALT/AST (low hundreds): chronic viral hepatitis, acute alcoholic hepatitis.

Leukopenia

Leukopenia: WBC<4-4.5X10^3/mm3
Neutropenia: most common cause of leukopenia, classified based on risk of overwhelming infection as

• mild: 1000-1500 cell/mm3
• moderate: 500-1000 cell/mm3
• severe: <500>

Mild/moderate neutropenia can be tx on outpatient basis if a clear, reversible source is identified and no clinical findings are seen. Severe neutropenia with fever should be admitted with panculture and panimaging.

Mechanisms of leukopenia

1. bone marrow injury: drugs, radiation, toxins, infections (mumps, measles, malaria, influenza, parvo, TB, typhoid, tularemia, HIV, EBV) , infiltrative disease of bone marrow (lymphoma, leukemia, and mets from lung, breast, prostate, stomach CA)

2. maturation defect : folic acid/B12 deficiency, neoplasm (ie acute myeloblastic leukemia)

3. sequestration: hypersplenism

4. destruction: autoimmune (ie Systemic lupus erythematosus)

Lymphopenia

lymphocyte count <2x10^3>

Common causes: HIV, corticosteroids, Hodgekin's lymphoma, multiple myeloma, protein-calorie malnutrition

Wernicke Encephalopathy

• Sx: confusion, ataxia, opthalmoplegia
• Mechanism: thiamine deficiency
• Affected population: alcoholism, AIDS, hyperemesis, bowel resection/gastric bypass
• Tx: thiamine c/ dextrose, often given as banana bag with folic acid and Mg sulf
• can be worsened by glucose, so glucose should not be given prior to thiamine

Myasthenia vs. Lambert-Eaton

Myasthenia Gravis
Sx: fluctuating weakness of commonly used voluntary muscles, weakness increased by activity

• diplopia
• ptosis
• difficulty swallowing
• respiratory and limb muscles may be involved

Dx: Tensilon test (edrophonium chloride test): short acting (min) anticholinesterase, transiently improves symptoms of Myasthenia gravis

Associated conditions: thymic tumor, thyrotoxicosis, rheumatoid arthritis, lupus erythematosus

Mechanism: anti-Ach-R antibodies made

Tx: 1st line: anticholinesterases (symptomatic), recommended if pt <60>

Admit indications: acute exacerbation, plasmaphoresis, thymectomy, starting corticosteroids

Interactions: aminoglycosides worsen symptoms

Lambert-Eaton

sx: variable weakness, improved with activity

• dysautonomic symptoms present

associated conditions: h/o malignant disease (small cell carcinoma)

Mechanims: antibodies against voltage gated Ca++ channel

Tx: combined plasmaphoresis and immunosuppressive therapy (prednisone, azathioprine), tx underlying malignancy, response to anticholinesterases is variable