Naltrexone and Bupropion combination for obesity, let us discuss the combination of drugs naltrexone and Bupropione. Naltrexone is one of the drug which is classified as opioid antagonist, whereas Bupropione is another category of drug which is classified as atypical antidepressant. So these two drugs belongs to the different chem categories as well as clinical categories.
But both of these drugs can be combined in a single tablet. Naltrexone can be mixed with bupropione as a single doses form, but this tablet is not given as immediate releasing. Here endercode is present on the tablet which releases the drug in a slow as well as extended way.
So Naltrex Zone and Bupropione are available in single doses form as extended release tablets and these two drugs are combined in their salt form as HCL. So Naltrexone HCL and Bupropion HCL are combined to form extended release tablet.
Then what is use of this combination? Since both of these drugs are going to control the appetite within the hypothalamus, this combination can be used in the management of chronic obesity. So in those patients with body mass index greater than 30 kilogram per square meter, this combination can be used even this combination can be used in control.
of overweight in the patients with body mass index greater than 27 kg per square meter who are associated with any risk factors related to cardiovascular system. So in those patients, this naltrexone and bupropione can be given as extended release tablet. But since this drug is given as er tablet, it should not be cut open.
It should not be crushed even it should not be chewed because any of these can release the drug in immediate way, which results in the overdoses of the drug. So this drug should be swallowed with water in order to release the drug in an extended way and even these doses forms are not equivalent with the immediate release tablets.
Now let us see how this combination acts. Within the CNS, in the mesolimbic pathway, dopaminegic neurons are present which are storing the DOP mine. On the postsynaptic neurons dopamine receptors are present but the action of release dopamine is controlled by its reuptake.
So dopamine transporters are present on the presynaptic neurons which will take the DOP mine which is released in the synaptic cleft. Now bupropione is one of the drug which can block these dopamine transporters at the presynaptic neurons. Thereby it can increase the dopamine transmission.
So when the presynaptic neurons are exited, dopamine can be more released in Prince of Bupropion so this released dopamine can act on the postsynaptic dopamine receptors resulting in their activation. This activation is more increased in brains of propion.
So this can stimulate the POMC neurons. Pre Opio melanocartin Neurons these are the neurons which are storing poamc which is one of the precursor peptide. This peptide can be cleaved and can be released into two mediators.
One is alpha MSH alpha melanocyte stimulating hormone and second one is the beta endorphin which is one of the indigenous opioid peptide. These are the two important mediators which can control the AppTite.
So, within the Hypothalamus, alpha, MSH can act on the MC four or receptors melanocoten four receptors. By action on these receptors, it can decrease the appetite as well as it can increase the energy consumption. By all of this, the food intake is going to be reduced, which results in the weight loss. In this way, bupropione can increase the activity of POMC there, but can reduce the appetite, resulting in the weight loss. Here, beta endorphin plays quite opposite role on the POMC neurons.
Mu receptors are present. Now, beta endorphin can act on these mu receptors resulting in the inhibition of POMC activity. Now, naltrexone is one of the opioid antagonists. It can block these mu receptors, thereby it can remove auto inhibitory effect of beta endorphin. In this way, naltrexone can further increase the POMC activity, thereby can reduce the appetite.
That’s why this combination bupropion plus naltrex zone is one of the effective combination in the management of obesity. Now, let us the precautions of these combinations. So, when this naltrexone and bupropion are used, one of the important precautions on the seizures. So in those patients, this combination can induce the seizures. So in those patients with any history of seizures, this combination should be carefully used.
Particularly, bupropion is more associated with induction of seizures. Again, this combination should be carefully used in those patients who are using CNS stimulants, because these drugs can further increase the seizure tendency.
Similarly, in the patients with any previous head injury or stroke, which again induce the seizures are those patients who are having abrupt withdrawal of alcohol intake. All these conditions can further increase the seizure induction produced by this combination. Second important precaution is that this combination should be carefully given with the opioid uses because it may lead to opiate intoxication.
Since naltrexone is a opiate antagonist, it can reduce the opiate activity. So in such patients, opiate dose may be increased in order to produce the effective response. This may lead to opiate intoxication. So, naltrexone may lead to opioid intoxication. That’s why low dose of opiate should be used.
And if it is required, the gap should be maintained between the use of this combination as well as the opioids. Similarly, this combination can increase the heart rate, which may increase the blood pressure. So patients may feel palpitations hypertension. So, these pawns should be considered when this combination is used for longer periods. Similarly, this combination can produce some allergic reactions resulting in proritis uticaria.
Even it can produce angioedema. So, if any allergic reactions are observed with this drug, then this combination should not be used. Finally, this combination can produce hepatotoxity. So liver functionality should be checked when this combination is used at max and dose for longer periods. Similarly, it can increase the risk of angle closure glaucoma.
So in such patient, this combination should be avoided and it can also increase the manic phase because bupropion is a antidepressant. Similarly, bupropione can also increase the suicidal tendency. So in the young patients this combination should be carefully used. What are the side effects? So this combination can produce constipation, nausea and vomiting, headache, Digness, insomnia, dry mouth, fatigue, tremor, hypertension, abdominal pain can be observed, tinnitus and excessive sweating can be observed with this combination.
How it is given as we have discussed earlier, this drug is available as external release tablet. This tablet contains two drugs. One is a naltrexone, as hydrochloride and bupropione. Again, as hydrochloride naltrexone is given at a dose of eight mg whereas bupropione as 90 mg. The dose of the drug should be slowly escalated as morning and evening dose.
In the first week, morning one tablet should be given, but evening no tablet is given. Second week morning one tablet as well as evening one tablet. Third week morning two tablets evening one tablet and finally at the fourth week morning two tablets as well as evening two tablets. So on the fourth week we can observe four tablets of this combination. That means 32 mg of nalatrexone and 360 mg of bupropione.
So this is the maximum dose that can be given and at this dose the therapy should be continued until the effectiveness of the combination is absurd. So that’s about this combination nanotrexone plus.
