UMEM Educational Pearls - Pharmacology & Therapeutics

• We often see seizure patients on phenytoin therapy who have subtherapeutic levels.  Most patients do not require intravenous loading and can be adequately managed with oral treatment.
• To estimate what dose to prescribe, use the following equation: [0.7 x IBW x (15 - current level)].  For example if a 70 kg patient has a level of 8 mcg/mL (mg/L), we would need ~400 mg loading dose to achieve a level of 15.
• Phenytoin is known for its erratic absorption and propensity for causing GI upset with doses too high.  The recommended strategy is to avoid administering more than 400 mg at one time and separate the doses by 2 hours.  This would take three doses over 4 hours for a 1 gm load.
  • In the ED, an effective strategy for a 1 gm oral load is 500 mg now and 500 mg in 2 hours at discharge.  Patients tolerate it well, it cuts down on ED length of stay, and still achieves therapeutic levels.  Remember that an oral suspension formulation is also available.

Patients requiring anticoagulation for HIT or with a history of HIT may be initiated on argatroban.  We have recently been seeing increased utilization.  Here are some important points to remember.

• MOA: Direct thrombin inhibitor – reversibly binds to the active thrombin site of free and clot-associated thrombin
• Monitoring parameters:
  • aPTT prior to starting therapy (similar to heparin)
  • aPTT two hours after initiation of therapy or after dose change
  • Signs/symptoms of bleeding, LFTs, CBC, Hgb/Hct
• Dosing (general): 2 mcg/kg/min (actual body weight)
• Important notes:
  • Discontinue all heparin products including hep locks and coated catheters.  This includes all LMWH such as enoxaparin.
  • Causes false elevation of INR by cross-reacting with the INR assay

Pathophysiology: Angiotensin converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II.  It also degrades bradykinin.  Thus, ACE inhibitors have the effects of decreasing angiotensin II and increasing bradykinin.  In the presence of ACE inhibition, bradykinin can accumulate and interact with vascular bradykinin B2 receptors, causing vasodilation, increased vascular permeability, increased c-GMP, and release of nitric oxide.

Treatment: Even though we generally treat with standard allergic reaction medications, none counteract the mechanism causing the problem.  Steroids, H1-blockers, and H2-blockers should still be considered but may not alter the progression.  Airway monitoring and management is paramount.

IV acetaminophen has been approved for use since November 2010

It is indicated for the:

• Treatment of mild to moderate pain
• Combination therapy with opioids for treatment of moderate to severe pain
• Fever reduction

The results of studies demonstrating opoid sparing effects have been mixed; some studies have not demonstrated either a reduction in opioid dose or opioid side effects.

The dose is the same for acetaminophen administered by other routes.

It must be administered over 15 minutes, and onset of activity is 15 minutes. Peak effect occurs at one hour.

The MAJOR drawback is the cost, which is $13 dollars per vial. This is compared to oral acetaminophen and ibuprofen, which are pennies.

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For patients with normal renal function, enoxaparin dosing for treatment of VTE is 1 mg/kg subcut every 12 hours OR 1.5 mg/kg subcut every 24 hours.

Studies have evaluated dosing for patients weighing up to 190 kg and found the 1 mg/kg q 12 hours dose to be safe and effective.  It can even be used for patients heavier than 190 kg, but anti-Xa monitoring is recommended.

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Sulfamethoxazole (SMX)/trimethoprim (TMP) is the treatment of choice for PCP pneumonia. The IV formulation has been unavailable for almost a year due to shortage. It is contraindicated in patients with sulfa allergy. Here are the alternatives with adverse effects. You'll quickly see why pentamidine should generally be reserved for those with sulfa allergy and G6PD deficiency.

Mild-to-moderate disease:

1. Primaquine 15-30 mg PO PLUS Clindamycin 600 mg IV or 300-450 mg PO
2. Dapsone 100 mg PO PLUS TMP 5 mg/kg PO
3. Atovaquone suspension 750 mg PO

Moderate-to-severe disease:

1. Primaquine 15-30 mg PO PLUS Clindamycin 600 mg IV or 300-450 mg PO
2. Pentamidine 4 mg/kg IV

Adverse Effects:

• Primaquine: Rash, fever, methemoglobinemia, hemolytic anemia (check for G6PD deficiency)
• Clindamycin: Rash, diarrhea, Clostridium difficile colitis, abdominal pain
• Dapsone: Rash, fever, gastrointestinal upset, methemoglobinemia, hemolytic anemia (check for G6PD deficiency)
• TMP: Rash, gastrointestinal distress, transaminase elevation, neutropenia
• Atovaquone: Rash, fever, transaminase elevation
• Pentamidine: Nephrotoxicity, hyperkalemia, hypoglycemia, hypotension, pancreatitis, dysrhythmias, transaminase elevation

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Many patients report an allergy to iodinated RCM, sometimes adding to the complexity of diagnostic decision making.  Here are a few pearls to help:

• Seafood or shellfish allergy is NOT a risk factor for IHR to RCM
• Iodine and iodide are small molecules that do NOT cause anaphylactic or anaphylactoid reactions
• Life-threatening reactions occur in only 0.004 to 0.04 percent of nonionic low osmolality RCM infusions
  • Our radiology department uses primarily iohexol (Omnipaque) for IV contrast with a low osmolality of 844
  • Iodixanol (Visipaque) is the iso-osmotic alternative with an osmolality of 290

Bottom line: Despite the lack of cross reactivity with shellfish/iodine allergies AND the very low risk associated with today’s low osmolality agents, premedication is still indicated in patient’s with a history of IHR to RCM.

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