Pharmacology
Central Nervous System
Intravenous phenytoin is contraindicated in which of the following:
Answer:
Phenytoin is contraindicated in acute porphyrias. Intravenous phenytoin is additionally contraindicated in second- and third-degree heart block, sinoatrial block, sinus bradycardia and Stokes-Adams syndrome.Phenytoin
Pharmacology / Central Nervous System
Last Updated: 4th April 2019
Indications
Phenytoin is licensed for tonic-clonic and focal seizures but may exacerbate absence or myoclonic seizures and should be avoided if these seizures are present. It is also used in status epilepticus refractory to benzodiazepines, given intravenously.
Mechanism of Action
Carbamazepine, lamotrigine, valproate and phenytoin act by producing a use-dependent block of neuronal Na+ channels. Their anticonvulsant action is a result of their ability to prevent high-frequency repetitive activity. The drugs bind preferentially to inactivated (closed) Na+ channels, stabilising them in the inactivated state and preventing them from returning to the resting (closed) state, which they must re-enter before they can again open.
It has a narrow therapeutic index and the relationship between dose and plasma drug concentration is non-linear; small dosage increases in some patients may produce large increases in plasma concentration with acute toxic side-effects. Similarly, a few missed doses or a small change in drug absorption may result in a marked change in plasma-drug concentration. Monitoring of plasma drug concentration improves dosage adjustment; the usual total plasma-phenytoin concentration for optimum response is 10 – 20 mg/litre (or 40 – 80 micromol/ litre).
Contraindications
Phenytoin is contraindicated in acute porphyrias. Intravenous phenytoin is additionally contraindicated in second- and third-degree heart block, sinoatrial block, sinus bradycardia and Stokes-Adams syndrome.
Side Effects
Adverse effects include:
- Generally
- Nausea and vomiting
- Drowsiness, lethargy, and loss of concentration
- Headache, dizziness, tremor, nystagmus and ataxia
- Gum enlargement or overgrowth
- Coarsening of facial features, acne and hirsutism
- Skin rashes
- Blood disorders
- Intravenously
- Alterations in respiratory function or respiratory arrest
- Arrhythmias, hypotension and cardiovascular collapse
- CNS depression
Symptoms of phenytoin toxicity include nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia.
Interactions
Phenytoin is an enzyme-inducing drug and can accelerate the metabolism of certain drugs result in reduced therapeutic effect of that drug, such as corticosteroids, warfarin, doxycycline, oral contraceptive pill and thyroid hormones amongst others.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
