OSCE QUESTION AND ANSWER
Q1) Discuss about therapeutic index of phenytoin.
PHENYTOIN maintains a narrow therapeutic range of 10 to 20 mcg/ml.
Pharmacokinetics:
In therapeutic doses, phenytoin is absorbed entirely and reaches peak plasma concertation at 1.5 to 3 hours.
Distribution:
Phenytoin is usually 90% bound to plasma proteins (mostly albumin), and only its unbound form is pharmacologically active. The fraction of protein binding may be lower in neonates, pregnant patients, hypoalbuminemia, and uremia. It is distributed in all tissues and becomes firmly tissue-bound with a large volume of distribution.
Its levels are higher in the central nervous system as compared to the serum.
Metabolism:
The hepatic P450 enzyme system metabolizes phenytoin (predominantly CYP2C9 and CYP 2C19) to inactive metabolites and is an inducer of CYP3A4, which accounts for many of its drug-drug interactions.
The metabolism of phenytoin is predominantly by the cytochrome P450 enzyme system, drugs that alter the function of these enzymes either by inducing or inhibiting phenytoin would require monitoring and possible medication adjustments to phenytoin based on resulting follow-up phenytoin levels.
Medications that inhibit these enzymes increase the phenytoin plasma concentrations. Some of These drugs include amiodarone, cimetidine, cotrimoxazole, disulfiram, fluconazole, metronidazole, chloramphenicol, sodium valproate, 5-fluorouracil, and sulphonamides ->low Serum concentration.
Medications that induce the enzyme system to decrease plasma phenytoin concentrations include alcohol, barbiturates, carbamazepine, theophylline, rifampin, and other medications -> phenytoin toxicity.
Hence it is essential to monitor closely when treated with phenytoin.
2)Effect of hyperglycemia in an episode of seizure
Elevated extracellular glucose levels is associated with neuronal hyperexcitablity which indicates the importance of glucose balance in neurotransmition.
The following article explains the impact of raised glucose levels lowering the seizure threshold levels.
The above conclusion was drawn as a result of Randomized Control Trial.
Objective: Objective was to determine in the adult rats the correlation between seizure susceptibility and extracellular glucose concentration in two models of seizures.
Method:
•Male rats were injected with two doses of streptozocin (40 mg/kg, IP) on consecutive days to induce diabetic hyperglycemia. Controls either received vehicle or were not injected.
•After 2 weeks, blood glucose concentration was measured, and the rats were subjected to flurothyl seizure test. Another group of rats received glucose solution (20%, 5 mL, IP) 30 minutes before testing to induce nondiabetic hyperglycemia.
•Thresholds for flurothyl-induced clonic and tonic–clonic seizures were determined. Finally, in vitro epileptiform activity was induced in the entorhinal cortex–hippocampal slices from naive rats by perfusing with magnesium-free medium with various glucose concentrations.
•In additional slices, the paired-pulse paradigm was determined in the perforant path
Inference:
Susceptibility to clonic and tonic-clonic flurothyl-induced seizures positively correlated with blood glucose concentrations, as the increased glucose concentration was associated with proconvulsant effects.
Similarly in the invitro experiments, epileptiform activity was promoted by increased and suppressed by decreased glucose concentrations.
Data indicates that, in the adult rats, high glucose concentrations are associated with proconvulsant effects.
B] Another article displaying clinico- radiodiagnosis due to hyperglycemia induced seizures
Pathophysiology:
MRI findings in hyperglycemia induced seizures : Subcortical T2 hypo intensity
Hypotheses:
Due to free radical deposition due to excitotoxic axonal damage during hyperglycemia induced seizures and intracellular dehydration in glial cells and supporting tissues are postulated.
Q3) Why urinary catheterization done in a seizure case?
The following describes about central regulation of micturition and its association with epilepsy
Link:
Physiological Control of Micturition
Urinary dysfunction in Epilepsy
•Patients with epilepsy displayed various urinary dysfunctions, including incontinence, urgency, and retention, although the micturition itself can also trigger seizures.
• These patients showed increased activities in the frontal cortex, the insula, and the temporal cortex, supporting that suprapontine micturition centers have critical contribution to fine regulation of the voiding process.
Hence urinary catheterization is done to avoid urinary incontinence, urgency, retention which can trigger a seizure.
LEARNING POINTS FROM THIS CASE:
1) Once again got an opportunity to understand the art of case taking.
2) How to communicate with a geriatric age group patient.
3) Importance of adequate dose of drug administration ( phenytoin in this case) and effects of prescribing underdosage of phenytoin.
4) PHENYTOIN - effect, adverse effects, therapeutic window.
5) Line of Management in status epilepticus and calculation of adequate dosage of loading dose of first line drugs in mg/ kg.
6) First line assessment of metabolic derangement of blood glucose levels upon hospital admission indicates possibility of underlying diabetes.
7) Indications for urinary catheterization.
8)Possible adverse effects of unwanted administration of antibiotics and iv Fluids.
LEARNING POINTS FROM OTHER CASES:
1) Effect of iv paracetamol over oral - A randomized control trial ( Experimental study)
2)What is orthostatic hypotension and its pathophysiology.
3) What are curable and non curable infections with examples and its management.
4) Dengue infection- Pathophysiology and its clinical features.
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