February 8, 2023

Duloxetine is a Serotonin Norepinephrine Reuptake Inhibitor (SNRI) that is useful various clinical conditions such as major depressive disorder (MDD), generalized anxiety disorder (GAD) and pain disorders like fibromylalgia and neuropathic pain.

Hi everyone today in this video we are going to discuss about duloxetine what is this drug duloxetine geloxide is a drug related to serotonin as well as norepinephrine reuptake inhibitor commonly known as snri this drug inhibits the reuptake of both norepinephrine as well as phi hd that is serotonin that’s why it is called as snri serotonin and norepinephrine

Reuptake inhibitor and here by the suffix we cannot classify this drag into snri because we have the other drugs with similar suffix such as fluoxetine peroxitin both of these drugs are not snris they are ssris select two serotonin reuptake inhibitors so these two drugs are going to inhibit reuptake of serotonin only without any significant activity on reuptake of

Norepinephrine so even these drugs are having a similar suffix they are not completely equivalent to durocity so duloxetin is an snri which inhibits the reuptake of both norepinephrine as well as serotonin so today in this video we are going to discuss about this duloxetine how this drug acts what are the important precautions drug interactions contraindications

Side effects and clinical use of this drag we will discuss in this video so duloxetin is one of the rag which is hang white clinical uses mainly this drug is indicated to treat major depressive disorder mdd so this is the mental disorder where the patient can have fear of the depressive symptoms such as pessimism feeling of guilt lack of initiation insomnia loss

Of appetite all these symptoms are collectively called as major depressive disorder in such conditions duroxidine can be prescribed similarly this drug can also be used in the anxiety disorder particularly duloxetine is useful in the treatment of generalized anxiety disorder gad this is one of the anxiety disorder without any proper reason in such conditions zero

Oxygen can be used similarly another clinical indication of uloxidine is in the painful conditions since this drug is an snra geloxidine can be used for fear of the pain disorders such as fibromyalgia we have another drug like venous vaccine which is also used in the fibromyalgia which is again snri and another important indication of duloxetine is that this

Drug is useful in diabetic peripheral neuropathic pain so neuropathic pain is the pain produced within the neurons without any external damage and this neuropathic pain is associated with the diabetic neuropathy in such conditions dual oxidation can be used to control the neuropathic pain and this can also be used to treat chronic musculoskeletal pain in this

Way dual oxidant is one of the drug which is used as antidepressant as well as anxiolytic and it can also be used to control the pain conditions associated with the central nervous system now let us see the chemical nature of this duloxetine so this is the structure of duloxetine and here the amine is the principal function group so we can start the numbering

From the amine so this is one two three this amine group is attached to the profile chain so the suffix of the name is propane 1 amine now to this proper mine at the third portion one of the heterocyclic ring system is present this is nothing but thiophene let us give the numbering to this thiophane this is one this is true now thiophene is attached by second

Position to the third portion of the main chain so we can write this as three dash thiophene two isle similarly at the third portion naphthalene ring is attached through the oxygen so we can write this as three dash naphthalene one i’ll oxy and finally one of the methyl group is present on the amine group so it is n-methyl this is the complete name of duloxetine

Now let us see how this drug acts so within the central nervous system norepinephrine is one of the important mediator which can be released and it can act on the post-synaptic neurons at the post-synaptic neurons adrenergic receptors are present such as alpha beta receptors and this norepinephrine can be released by calcium mediated exocytosis so when the action

Potential reaches to the presynaptic neurons calcium can enter and it can produce the exocytosis and release of norepinephrine and this norepinephrine can bind to norepinephrine receptors resulting in the postsynaptic stimulation but the action of norepinephrine can be controlled by its reuptake into the nerve terminal here one of the transporter is present nat

Norepinephrine transporter through this transporter norepinephrine can be uptaken into the nerve terminals in this way the action of norepinephrine depends on its reuptake into the nerve terminal similarly another important mediator within the cns is the serotonin again at the post-synaptic neurons serotonin energy receptors are present such as phi ht2 receptors

Now this 5ht can be released and can act on the five st2 receptors to produce post-synaptic stimulation just like the norepinephrine the action of feisty is again controlled by its reuptake into the neural terminal so one of the transporter is present this is the serotonin transporter through this transporter serotonin can be reuptake into the new terminal so again

The action of serotonin can be controlled by its reuptake into the nerve terminal now here duloxetine can act on both norepinephrine as well as fasting neurons that’s why it is called snri serotonin as well as norepinephrine reuptake inhibitor this drug can bind to this non-epinephrine transporter thereby it can inhibit its activity so that norepinephrine cannot

Enter the nerve terminals which results in the accumulation of norepinephrine within the synaptic cleft similarly geloxide can also block serotonin transporter so that serotonin cannot be uptaken into the nerve terminals by these actions gelox gene can increase the levels of norepinephrine as well as 5ht within the cns which improves the symptoms of depression

As well as pain disorders such as fibromyalgia and neuropathic pain what are the precautions one of the important precaution of zero oxygen is that this drug can produce hepatotoxicity in the patients so when this drug is going to prescribe after two months of the treatment hepatotoxicity may be developed and few of the symptoms can be observed in the patients such

As abdominal pain hepatomegaly enlargement of the liver and polystatic jaundice similarly increased transaminase levels such as increased alt alanine transaminase increased asd aspartate transaminase so these liver enzymes are elevated because of duloxetine which indicates hepatic injury so this drug should be carefully given in the patients who are having the more

Risk for hepatic damage just like other ssris as well as snris this drug can also present serotonin syndrome so this is one of the syndrome which is associated with increased physit levels so when this drug is given with other drugs which increase the further levels of ist it may lead to severe serotonin syndrome so few of the drugs like ssris such as fluoxetine

Peroxide similarly snris such as acetyl oprom venlafaxin mouvin bitters like phenyl giant transipromine and isocarboxate these mammal inhibitors can inhibit the metabolism of ist thereby increase of highest levels and trypton drugs which are used to treat the migraine such as sumatripton all these drugs can further increase the serotonin syndrome when they are

Given with dulcety so within the syndrome the patients can observe you have the symptoms such as agitation hallucinations confusion anxiety and some tachycardia increased heart rate hyperthermia increased body temperature their forces sweating flushing tremor and muscle rigidity in the patients another important precaution of duloxetine is that this drug can

Produce orthostatic hypotension this orthostatic hypotension may lead to syncope in the patients this condition can be observed within first week of treatment so caution should be taken in order to prevent orthostatic hypotension as well as syncope in the patients and when the patient is treated with other vasodilators such as calcium channel blockers ccbs as well

As alpha blockers they can further increase the orthostatic hypotension similarly gelox gene can increase the risk of bleeding in the patients so this may lead to echemosis the pulling of the blood under the skin epistaxis nasal bleeding hematoma blood in the urine as well as gastrointestinal bleeding all this can be observed with duloxetine along with other

Ssris as well as snris and this risk of bleeding can be further increased with other drugs such as aspirin warfarin and anasites all these drugs can increase the risk of bleeding when they are combined with duloxetine another important precaution of duloxetine commonly observed with many of the antidepressants is the risk of suicidal initiation so adolescence

With a is less than 18 years and young patients with is 18 to 24 years there is an increased risk of suicidal initiation in these patients we can observe you have the symptoms such as anxiety hesitation irritability some aggressiveness restlessness insomnia all this can further increase the risk of suicidal initiation so geologically should be carefully given

To these patients similar another important precaution is that this study is used as an antidepressant so this can produce a manic phase in the patients otherwise it can also produce hypomania due to fluctuations of the physical levels as well as norepinephrine levels within the cns and this drug can also increase your urinary retention finally it can also induce

The seizures in the patients just like other agents durocity can also increase the neuroleptic malignant syndrome so it may produce muscle rigidity and hyperthermia some confusing the patients and particularly this risk is more pronounced with other drugs like dopamine antagonise gelox gene can also produce the hyponatremia and the serum sodium levels may be

Reduced less than 110 millimoles per liter this results in few of the symptoms such as headache confusion impaired memory as well as weakness in the patients and this hyponatremia produced by duloxetine is mainly attributed to inhibitory effect on anti-diuretic hormone so when this anti-diuretic hormone is not working properly it increase the diuresis which

Results in the decreased serum sodium levels and in the patients who are having the volume depletion otherwise the patients using loop diuretics or elder patients they may have further risk of hyponatremia when they are prescribed with duloxetine what are the drug interactions duloxetine is going to be metabolized by cytochrome p450 system one of the important

Metabolic enzyme is cyp1a2 so if you have the drags like phloxamine cemented in which is a h2 antagonist ciprofloxacin anoxazine these two are quinoline antibiotics all these drugs can inhibit the cyp1e2 activity thereby they can increase the dual oxidant levels within the serum similarly this drug is also metabolized by cyp2d6 few of the tracks like peroxidine

Fluoxetine and quinidine they can inhibit the activity of cyp2d6 thereby they inhibit the metabolism of dual oxity and here flow oxamine can block both cyp1e2 as well as cyp2d6 which significantly inhibits the metabolism of duloxetine thereby increase the serum levels of juloxidine to a higher level so again these drug interactions should be closely monitored

When this geologic strain is given with these drugs duloxetine is metabolized by cyp2d6 but at the same time this drug is also inhibit the acuity of cyp2d6 so this duct can inhibit the metabolism and increase the serum levels of other drugs such as not tryptophan hemitripline imepramine all these are tcas similarly phenotypes and antipsychotics like chlorpromzine

And thio redesign class 1c antiarrhythmics like propafenone flakkinite all these drugs are affected by duloxity and their levels are increased in prince of zuloxide and particularly thiodesign is contraindicated with the jewellox gene because of this drug interaction what are the contraindications this drug dulongstein can increase the medriace’s pupillary

Dialetation which may increase the intraocular pressure so it is contraindicated in uncontrolled narrow angle glaucoma similarly vista can preset serotonin syndrome so it is contraindicated with mao inhibitors which are inhibiting the metabolism of ist thereby they further increase the serotonin syndrome now let’s see the side effects of dual oxity the important

Side effects mainly include dry mouth nausea soma fatigue constipation some loss of appetite dizziness headache palpitations blood vision parasthesis loss of sensation and hyperhidrosis increased sweating in the patients can be absurd how it is given this truck is available as delayed release capsule and it is available at different strengths like 20 mg 30 mg

40 mg as well as 60 mg the dose of the drug depends on the type of clinical indication for the treatment of major depressive disorder the starting dose of this drag is 20 to 30 mg twice daily that means the dose per day is variable from 40 to 60 mg and the maximum dose that can be achieved is 120 mg per day similarly for the treatment of generalized anxiety

Disorder as well as neuropathic pain the initial dose is 60 mg once daily so the starting dose is same for both basal repressive disorder as well as generalized anxiety disorder 60 mg is given once daily for the treatment of fibromyalgia as well as other musculoskeletal disorders the initial dose is 30 mg once daily but the dose can be increased up to 60 mg

Per day so in all these clinical conditions the 60 mg per day is the one of the suitable dose which is effective so that’s about this dual oxygen dual oxidation snri serotonin norepinephrine reuptake inhibitor this drug inhibits the reuptake of both norepinephrine as well as 5ht there will increase their levels within the cns which results in the antidepressant

Activity as well as reducing the pain stimulation within the cns so this drug is useful in the treatment of major depressive disorder as well as generalized anxiety disorder it can also be useful in the pain disorder such as fibromyalgia diabetic peripheral neuropathic pain and chronic musculoskeletal pain disorders in all these conditions geologic strain can

Be used this reg may produce hypotoxin in the patients so case should be taken the patients who are having the risk of hepatic failure and you can also produce orthostatic hypotension and syncope so along with other vasodilators this drug should be carefully given just like the other drugs within this category this drug can also present euro-electric malignant

Syndrome and serotonin syndrome it can also increase the suicidal risk in the in the adolescents as well as young patients hyponatremia is another important precaution because of inhibition of antibiotic hormone activity and this can also present manic phase or hypomania some seizures and urinary retention in the patients this drug should be carefully given with

Other drugs which are inhibiting the cyp1e2 activity such as fluoxamine symmetrine ciprofloxacin and another and an oxygen similarly cyp2d6 inhibitors such as fluoxamine peroxide in quinidine they can also increase the levels of geloxide by inhibition of its metabolism this drug also inhibits the cyp26 activity thereby it can inhibit the metabolism of many drugs

Such as tcas phenothiazines and tryptontrax so these drugs should be carefully combined with duloxetine this drug is available as delayed release capsule and for most of the disorders the initial dose is 60 mg per day but for fibromyalgia and other painful conditions the dose the initial dose may be 30 mg per day which may be increased up to 60 mg per day so

That’s about this julo exiting hope you have enjoyed this video if you like this video please subscribe to our channel share this video with your friends post your comments in the comment box thank you for watching this video

Transcribed from video
Duloxetine – Mechanism, precautions, interactions & uses By egpat