Why need to give IV Diazepam even after given rectal Diazepam?

o Same efficacy between rectal and IV Diazepam o The lipid solubility of diazepam allows it to enter the brain readily and terminate
seizures quickly. Unfortunately, this pharmacokinetic profile means diazepam is quickly redistributed to other fatty tissues. The concentrations in the brain and serum fall rapidly.

Absorption occurs by passive diffusion through lipoidal membranes Absorbed by middle and inferior rectal veins which bypass portal circulation and avoids first-pass hepatic elimination o You also need to give 2 benzodiazepines before starting on pheytoins or phenobarbitones. Hence better give IV with higherplasma level rather than rectal as long as IV access available. What is the downside of rectal diazepam? o Time to peak plasma levels after rectal administration (about 5-10 minutes) is longer
than after intravenous injection (1-3 minutes).

o o

Loss of administered drug into stool Despite the potential for faeces to affect absorption, faecal evacuation before
giving diazepam is not recommended.

o Expulsion from cathartic effect o Social implications from administration by non-family member o Embarrassment o Commercial kit expensive Why give IV Diazepam 0.2mg/kg slow bolus (at 2 mg/min; maximum 10mg)? Why give IV Phenytoin 20 mg/kg (Max Loading dose 1.25 Gm)Dilute in 0.9% saline; Max. conc. At 10 mg/ml; Infuse over 20-30 mins, with cardiac monitoring. Why cardiac monitoring o arrythmia What are the side effects of Phenytoin? o Intravenous phenytoin can cause cardiac arrhythmias, hypotension, and cardiovascular
collapse even when infused at the recommended rate. [2] [4] Hypotension often results from a combination of factors: Direct myocardial depression, reduction in cardiac output and peripheral vasodilation. Phenytoin level in our case was higher than the reported series of patients with oral phenytoin toxicity, which may explain the arrhythmia. Charcoal hemoperfusion is reported to be effective in cases when serial serum levels are increasing or persistently elevated.
,

Pharmacology of Diazepam? Pharmacology of Phenytoin? Elaborate pathophysiology of seizure. o High frequemcy burst of action potentials of neurons o Hypersynchronisation of neuronal population o Then, seizure propagation within brain Why use Na Valproate as prophylaxis? What is Cx of NA Valproate? Sx of meningitis

In addition the rectal route bypasses around two thirds of the first-pass metabolism as the rectum's venous drainage is two thirds systemic (middle and inferior rectal vein) and one third portal(superior rectal vein). This means the drug will reach the circulatory system with significantly less alteration and [Note 3] in greater concentrations. Pharmacokinetics The lipid solubility of diazepam allows it to enter the brain readily and terminate seizures quickly. Unfortunately, this pharmacokinetic profile means diazepam is quickly redistributed to other fatty tissues. The concentrations in the brain and serum fall rapidly. The absorption of oral diazepam is slow (1-2 hours) and variable. Intramuscular diazepam has similar absorption problems, is painful and may cause muscle necrosis. Suppositories have slow and variable absorption rates and are not recommended in an emergency. Rectal administration of the intravenous form of diazepam has been used successfully for hospital and home treatment of prolonged seizures.1

Efficacy Experience suggests that rectal diazepam is rapidly effective in children, but efficacy has not been well studied in adults. Diazepam given rectally appears to be as effective as intravenous diazepam in terminating seizures. It may haveadvantages, including more prolonged action (20-30 minutes compared to 10-20 minutes), less respiratory depression, less drowsiness and little effect on blood pressure.2 Intravenous and rectal diazepam both stop seizures in more than 80% of cases within 1015 minutes.1 Time to peak plasma levels after rectal administration (about 5-10 minutes) is longer than after intravenous injection (1-3 minutes). This time difference may be important in status epilepticus where rapid seizure termination is necessary. It also possibly explains the lower incidence of respiratory depression experienced with rectal administration. The prolonged action after rectal administration may prevent seizure recurrence and allow more time to seek medical assistance. Despite the potential for faeces to affect absorption, faecal evacuation before giving diazepam is not recommended.

In conclusion, we have shown that i.v. and p.r. administration of diazepam results in the rapid achievement of therapeutic plasma diazepam concentrations with few cardiorespiratory side-effects in children with severe malaria. The p.r. route is easy to use, but the systemic absorption is more variable and does not terminate all convulsions. Both routes of administration did not prevent the recurrence of convulsions. In resource poor countries, a single dose of diazepam can be used to terminate convulsions in children with severe malaria. We recommend that diazepam (0.3 mg kg1) should be administered i.v., but in health units with no facilities for i.v. cannulation the diazepam p.r. (0.5 mg kg1) can be used cautiously as an alternative. Ideally, diazepam should be administered together with a long acting anticonvulsant in children with severe malaria and convulsions.