Part B
Q1.
The normal dose of paracetamol is very safe to use and it is not over 4g per 24 hours; however, when the patient take more than 6g per 24 hours of paracetamol, the liver necrosis will happen within 10 to 12 hours and liver damage may occur within 24 to 48 hours. For the metabolism, most of the paracetamol is converted to nontoxic metabolites by the phase II conjugation of glucuronide and sulfate and a small amount of paracetamol is oxidized by the Cytochrome P450 (CYP) enzymes in the phase I metabolism. In this phase, CYP1A2 and CYP2E1 enzymes convert paracetamol to N-acetyl-p-benzoquinoneimine (NAPBQI) which is highly toxic substances. NAPBQI will rapidly enter the phase II conjugation of glucuronide and detoxified in the liver …show more content…
When the tablet is swallowed, the overcoat of the drug will dissolve quickly and the initial release can increase the drug concentration rapidly and it is similar to the stranded release formulation. Then, the beneath layer of drug is a coat with a semi-permeable membrane which can absorb water by osmosis and some of the drugs are a polymer-based coat with a hole on one side or a porous membrane. In the interior of the tablet, the compartment will dissolve from low concentration to high concentration. Therefore, the initial release from the outer coat causes a rapid rise in the plasma concentration which ensures the quick onset of action occurred. The interior part keep releasing by the concentration, therefore, it makes the plasma drug concentration stable and stays between the minimum effective concentration (MEC) and toxic concentration (MTC). The most outstanding benefit is no significant fluctuation in concentration will occur, in other words, the concentration will not suddenly reach to MTC and drop into MEC and it keep the drug at an effective level, as a result ,it will have a better therapeutic effect and less side effect. Comparing with the common tablet, the common tablet needs to be taken three times a day for it to be effective in 24 hours but the modified release tablet only need to take once a day. On the other hand, the tablet also …show more content…
Those CYP enzymes can be induced or inhibited by the enzyme induction or inhibition and it can effectively change the rate of metabolism, as a result, the level of CX in the blood is affected and the therapeutic effect can be increase or decrease. When genetic polymorphisms occur, the specific CYP enzymes of CX are determined by a specific gene and the genotype decide rather the function of the enzyme is normal, reduced or non-existent. Moreover, there are four main phenotypes, firstly, the extensive metabolizer has two normal alleles and the intermediate metabolizer has one normal and one variant allele. Turning to the poor metabolizer, it has two variant alleles and the rarest one is the ultra-rapid metabolizer which has multiple copies of the normal gene. In the case of ultra-rapid metabolizer, it can cause the CYP enzymes function greater than normal. As CX is a prodrug, the body will convert the CX prodrug into an active metabolite and the CYP enzymes are too active for ultra-rapid metabolizer, as a result, the drug level in plasma will increase rapidly. Hence, it can explain some patients may experience CX overdose symptoms when they take only one drug and CX with the
Q1.
The normal dose of paracetamol is very safe to use and it is not over 4g per 24 hours; however, when the patient take more than 6g per 24 hours of paracetamol, the liver necrosis will happen within 10 to 12 hours and liver damage may occur within 24 to 48 hours. For the metabolism, most of the paracetamol is converted to nontoxic metabolites by the phase II conjugation of glucuronide and sulfate and a small amount of paracetamol is oxidized by the Cytochrome P450 (CYP) enzymes in the phase I metabolism. In this phase, CYP1A2 and CYP2E1 enzymes convert paracetamol to N-acetyl-p-benzoquinoneimine (NAPBQI) which is highly toxic substances. NAPBQI will rapidly enter the phase II conjugation of glucuronide and detoxified in the liver …show more content…
When the tablet is swallowed, the overcoat of the drug will dissolve quickly and the initial release can increase the drug concentration rapidly and it is similar to the stranded release formulation. Then, the beneath layer of drug is a coat with a semi-permeable membrane which can absorb water by osmosis and some of the drugs are a polymer-based coat with a hole on one side or a porous membrane. In the interior of the tablet, the compartment will dissolve from low concentration to high concentration. Therefore, the initial release from the outer coat causes a rapid rise in the plasma concentration which ensures the quick onset of action occurred. The interior part keep releasing by the concentration, therefore, it makes the plasma drug concentration stable and stays between the minimum effective concentration (MEC) and toxic concentration (MTC). The most outstanding benefit is no significant fluctuation in concentration will occur, in other words, the concentration will not suddenly reach to MTC and drop into MEC and it keep the drug at an effective level, as a result ,it will have a better therapeutic effect and less side effect. Comparing with the common tablet, the common tablet needs to be taken three times a day for it to be effective in 24 hours but the modified release tablet only need to take once a day. On the other hand, the tablet also …show more content…
Those CYP enzymes can be induced or inhibited by the enzyme induction or inhibition and it can effectively change the rate of metabolism, as a result, the level of CX in the blood is affected and the therapeutic effect can be increase or decrease. When genetic polymorphisms occur, the specific CYP enzymes of CX are determined by a specific gene and the genotype decide rather the function of the enzyme is normal, reduced or non-existent. Moreover, there are four main phenotypes, firstly, the extensive metabolizer has two normal alleles and the intermediate metabolizer has one normal and one variant allele. Turning to the poor metabolizer, it has two variant alleles and the rarest one is the ultra-rapid metabolizer which has multiple copies of the normal gene. In the case of ultra-rapid metabolizer, it can cause the CYP enzymes function greater than normal. As CX is a prodrug, the body will convert the CX prodrug into an active metabolite and the CYP enzymes are too active for ultra-rapid metabolizer, as a result, the drug level in plasma will increase rapidly. Hence, it can explain some patients may experience CX overdose symptoms when they take only one drug and CX with the