Thursday, November 15, 2007

Miscellaneous drug facts most people do not know

 Antiepileptic drug random facts
1. Phenytoin (more misc. on than we already new)- a.   increases HDL levels.
    b. Formula to adjust PTN dose.  In zero order kinetics, a fixed AMOUNT not percentage of phenytoin is metabolized.  Vd= .7 L/kg     Loading dose = (Vd) x (desired change in concentration)  so eg. raise the level from 5 to 18 in a 100 kg man would mean Vd=70L, loading dose = 70 x 13= 910 mg.  Phenytoin is saturably absorbed in duodenum and affected by food and by antacids

2.  Cerebyx has the same Tmax as Dilantin due to time required to cleave the "fos" of fos phenytoin. Cerebyx also has some cardiac toxicity despite the absent phenylene glycol adjuvant.  Infusion can be faster than Dilantin but not more than 150 mg/min. It prevents the purple glove but not time to treat SE.

3. PTN, CBZ and PB block efficacy of some chemotherapeutic agents (see post)

4. Depakote
a.  may be useful in brain tumor treatment irrespective of AED effect (see post)
b.  Depakote is highly bound but not to albumen; and free levels are difficult to measure.  Its level rises in cirrhosis.  Its path is 80 % direct glucuronidation, 17 % is in same oxidative path as free fatty acids and enters the carnitine shuffle, leading to 4, en VPA.  Many ICU patients are carnitine deficient which shunts VPA to toxic metabolism so give these patients carnitine 25 mg/kg png over six hours leads to less NH4+.

5. Vimpat can cause angioedema


1. Rivastigmine patches can be left on for more than 24 hours as they have a 24 hour half life (in effect, patients are throwing away active drug). Wearing multiple patches, duly labelled, is one way to dispense a higher dose, usually with limited adverse effects

 2. Memantine has histamine blocking properties and its use may limit GI adverse events of individuals taking rivastigmine or other drugs.

3. Cholinesterase inhibitors inhibit metabolism of suxamethonium, prolonging neuromuscular blockade

1. Prazosin is highly effective for post-traumatic stress disorder
2. Levodopa-carbidopa and gabapentin are two rare drugs that are gastric absorbed and in fact compete with each other. Better to stop the gabapentin in Parkinson patients.3. Protease inhibitors potentiate toxicity of GHB, so HIV patients attending circuit parties are at extra high risk of coma and death.
4. Drug rash to Sinemet is due to yellow dye not levodopa carbidopa (see post)
 5. Natalizumab also blocks trafficking of B cells into CNS
 6. . Atorvastatin, even brief exposure, causes a marked decrease in blood Co Q 10 concentration (shares the synthetic pathway of cholesterol). Primary CoQ10 deficiency causes mitochondrial encephalomyopathy with recurrent myoglobinuria; this may pertain to AE's of atorvastatin. Also, CoQ10 is an excellent free radical scavenger and the effects on degenerative disease are not known. Rundek et al,. Arch Neurol 2004; 61: 889-892.

A 16 year old girl with progressive weakness of the let leg

Hahn AF, Mauermann ML, Dyck PJB, Keegan BM/ CPC. Neurology2007;69:84-90. Insidious onset of left LE weakness started at age 13, progressing to complete footdrop. She had normal sensation and reflexes. She had gobs of negative tests. Motor exam showed mild weakness in posterior tibialis and hamstring, severe weakness in the tibialis anterior, to extensors and peroneii, and normal gastrocnemius and toe flexors. She had mild pes cavus. EMG showed normal left tibial nerve conductions, left peroneal motor and surals were absent or severely abnormal. Needle testing showed marked denervation distal to the short head of the biceps. QST's were normal. MRI showed mild increase int he size and signal intensity of the left peroneal nerve in the peroneal division only. Anatomic localization implicated the common peroneal nerve or divisional sciatic nerve. Discussant notes that the tibial and peroneal divisions of the sciatic nerve are segregated as the sciatic nerve passes from the sciatic notch, so a sciatic lesion can mimic a peroneal neuropathy. In such cases needle EMG of the short head of the biceps is crucial. MRI neuronography showed enlarged peroneal nerve ipsilaterally. The diagnosis on biopsy of the nerve was intraneural perineuroma (aka localized hypertrophic mononeuropathy). It presents as a painless motor mononeuropathy in younger patients in a variety of nerves (posterior interosseous, radial ulnar). MRI differentiates from fibrolipomatous hamartoma, but not intraneural ganglion cysts. Intraoperatively, internal neurolysis can suggest the diagnosis also. Unlike true onion bulbs, which are S100 positive, these are S100 negative and EMA positive.

Friday, November 09, 2007


Cole AJ, Henson JW, Roehrl MHA et al. Case 24-1007: A 20 year old pregnant woman with altered mental status. NEJM 2007; 357: 589-600.

Case showed a young pregnant woman with clinical presentation of aseptic meningitis: confusion, lymphocytic pleocytosis in CSF, FIRDA on EEG, ,MRI showing dysfunction in a non hSVE pattern affecting internal capsule and cerebellar outflow tract, gads of negative tests. MRI affected left temporal lobe and pons. The patient had chorea which brought up Strep infection and Syndenham's chorea but ASO was only minimally positive and ACL's were negative. There was marked increase in CSF IgG levels, IgG index and oligoclonal bands. According to Dr. Cole, that narrowed it to syphilis, chronic rubella encephalitis, and SSPE.

Measles causes 3 different CNS diseases: postinfectious encephalomyelitis, subacute measles encephalitis, and SSPE. SSPE occurs 7-10 years after infection with behavioral changes, headache, adventitious movements, and sometimes seizures. Myoclonic jerks and PLEDs on EEG may occur. It may occur from childhood until fifth decade of life. It persists in places where measles vaccination remains uncommon. It is more common if measles occurred at age < 2 years, and may be more common in pregnancy. The diagnostic test is measles specific CSF IgG antibody index compared to serum. Iit maybe compared to a control infection such as mumps. This patients was treated with interferon and pranobex for eight weeks, delivered a healthy baby and then expired. SSPE is considered almost always a progressive disease. This patient may have shown signs in a prior pregnancy of a movement disorder.

Saturday, November 03, 2007

Drug interactions,enzyme inducers and anticancer

PTN, CBZ and PB induce cytochome P450 and reduces bioavailability of many chemotherapeutic drugs and warfarin. The former include camptothecins (topotecan and irinotecan) and taxanes (paclitaxol).

Mayo Clin Prcds combination of risperidol and gingko caused priaprism