Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, pethidine, tetrahydrocannabinol (THC), ethanol (drinking alcohol), cimetidine, lidocaine, and chlorpromazine.
What is the first-pass effect of diazepam?
With diazepam, a nonbasic lipophilic amine, there was 30% uptake during the first pass through the human lung–significantly less than that observed with verapamil. With thiopental, an acidic lipophilic barbiturate, only 14% of the injected drug accumulated in the lung during the first pass.
Which drug routes undergo first pass metabolism?
Drugs that are administered orally (as opposed to intravenously, intramuscularly, sublingually, or transdermally) must first pass from the intestine to the liver before reaching the general circulation.
How is diazepam metabolized?
Diazepam is primarily metabolized via CYP2C19 and CYP3A4 to the major active metabolite (desmethyldiazepam), which is found in the plasma at concentrations equivalent to diazepam. Two minor active metabolites include temazepam and oxazaepam, which are usually not detectable.
Which drug avoids first pass metabolism?
Drug: Nitroglycerin- is typically taken sublingually (buccal cavity) where it enters the circulation and is rapidly delivered directly to the heart (without having to go through the liver first), thus avoiding the First Pass Effect.
What is the effect of a significant first pass effect on the metabolism of a medication?
The first pass effect is a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation.
How can first-pass metabolism be circumvented?
Bypassing First Pass Metabolism
Two ways to bypass first pass metabolism involve giving the drug by sublingual and buccal routes. The drugs are absorbed by the oral mucosa in both methods. In sublingual administration the drug is put under the tongue where it dissolves in salivary secretions.
Which route is most affected by first pass effect?
It happens most commonly when the drug is administered orally. The drug then is absorbed in the GIT and enters enters the portal circulation before entering the systemic circulation.
Which drug Cannot given by oral route due to first-pass metabolism Mcq?
Commonly used drugs that undergo extensive first pass metabolism are cimetidine, lidocaine, propranolol, nitroglycerin, diazepam, midazolam, morphine, pethidine, imipramine, and buprenorphine. Some drugs like insulin are destroyed by the gastric secretions and therefore cannot be given orally.
Which routes of administration can be used to avoid the first pass effect?
Intravenous injection is the most common parental route of medication administration and has the benefit of bypassing the first-pass metabolism by the liver.
Is diazepam metabolized by the liver?
Diazepam is metabolized in the liver to its active metabolite which is excreted in the urine.
Does diazepam metabolized to temazepam?
Diazepam is metabolized to either nordiazepam by CYP 2C19 or temazepam by CYP3A4.
What is the active metabolites of diazepam?
Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-desmethyldiazepam and temazepam are both further metabolized to oxazepam. Temazepam and oxazepam are largely eliminated by glucuronidation.
Do all oral drugs undergo first-pass metabolism?
All drugs given by the oral route undergo a degree of first pass metabolism either in the gut or the liver, with some drugs being destroyed before they reach the systemic circulation.
Do IV drugs undergo first-pass metabolism?
First pass metabolism determines what fraction of an oral dose will reach the circulation – the bioavailable fraction. Intravenous drugs don’t experience this first pass effect and are, by definition, 100% bioavailable. Drugs administered orally or inhaled demonstrate less than 100% bioavailability.
What is first phase metabolism?
Phase I metabolism consists of reduction, oxidation, or hydrolysis reactions. These reactions serve to convert lipophilic drugs into more polar molecules by adding or exposing a polar functional group such as -NH2 or -OH.