AySab
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Before you read this thread, just know this is going to be extremely long and in-depth, so people who have low dopamine and low comprehension ability, refrain from reading a single molecule of this thread.
INTRODUCTION:
Isotretinoin also known as 13-cis retinoic acid, is a drug commonly used/prescribed for the treatment of acne.
It’s labeled as the most effective drug when used for the treatment of acne as it impacts all major aetiological factors present in the pathogenesis of acne.
It influences cell-cycle progression, cellular differentiation, cell survival and apoptosis.
Not to mention, the effects it has on inhibiting sebum production, its influence on comedogenesis, its anti-inflammatory properties and its ability to lower surface and ductal P.acnes; Which are a gram-positive commensal bacterium that causes acne on the skin by releasing lipase which produce fatty acids by the ingestion of sebum resulting in inflammation of the skin.
The dosage of Isotretinoin varies on your weight, it’s commonly distributed through a 0.5-1.0mg per KG which is taken once a day.
Within 6 weeks of use, the drug can induce a 90% total reduction of sebum excretion.
Unlike topical retinoic acid (retinoids), Isotretinoin doesn’t bind to celluar retinol-binding proteins or retinoic acid nuclear receptors such as RARs and RXRs.
Isotretinoin has at least five biologically important metabolites;
cis-4-oxo-retinoic acid, all-trans-RA, all-trans-4-oxo-retinoic acid, 9-cisretinoic acid and 9-cis-4-oxo-retinoic acid.
When compared to 4-oxo-isotretinoin, 9-cis-retinoic acid and all trans-retinoic acid, oral isotretinoin was found superior.
Only Tretinoin and 4-oxo-tretinoin bind to RAR-y which is the receptor targeted specifically for retinoids in the treatment of acne. Although this information isn’t too important since Isotretinoin mogs.
ALTHOUGH, data has suggested that tretinoin may be the active intracellular form of isotretinoin.
Without the use of the RAR receptor, Isotretinoin has been concluded to cause apoptosis in sebocytes which of course, lead to a decreased amount of sebum production.
In addition, isotretinoin produces a reduction in comedogenesis by decreasing hyperkeratinisation, although the exact mechanism is unclear.
Isotretinoin has no direct antimicrobial properties, although by reducing SER and the sizes of pilosebaceous duct, it can alter the microflora of the skin which causes P.acnes to less likely colonise a lesion. What’s funny is that the reduction is so great that it literally has greater results at reducing P.acnes than antibiotics (oral and topical).
It’s also suggested that all-trans-retinoic acid have the chance to increase host defense mechanisms and modifies monocyte chemotaxis, which explains the potential anti-inflammatory properties, not accounting the reduction of P.acnes which of course also contributes to reducing inflammation.
Now, when referring to clinical trials, most patients who receive an optimal dosage of Isotretinoin will be “acne-free” by the end of the 4-6 month mark.
Since this is a evaluation on the drug, it can be treated for many other things, such as; acne fulminans, rosacea fulminans, Gram-negative folliculitis, dissecting cellulitis of the scalp, hidradenitis suppurativa and acne conglobata.
The half life is 22 hours and the bioavailability ranges around 25%, although, the absorption is effected by the presence of fat and pharmacokinetic studies show that the absorption can be doubled by taking isotretinoin with, or after, a meal compared to fasting state. I personally take it with 2 teaspoons of peanut-butter if i’m missing the necessary 20G of fat needed for optimal absorption. If you have a lot of money and have a stable income + are on a diet with low amounts of fat, try micronised Isotretinoin as it can be took in fasted conditions and when taken in fasted conditions, absorption supersedes absorption of oral Isotretinoin when took with a meal.
Relapse rates is dependent on many things such as the amount you’re taking and the duration of treatment although, it can be impacted by demographic factors such as, sex, age and duration of acne.
Patients, especially males, are more likely to relapse, this can be increased if they had more severe acne, extensive truncal acne and if they have suffered acne for less than 7 years.
Slow response to the drug is possible, and can be due to the presence of macrocomedones and hyperandrogensim.
Some other factors can be when a early post isotretinoin flare is present, the drug is poorly absorbed, presence of Staphylococcal aureus, severe acne and unusual variants of acne.
Macrocomedones should be detected before Isotretinoin therapy is started as a flare up of acne will be induced if left untreated.
If a flare up of acne is ensued and it wasn’t caused by macrocomedones, a antibiotic can be prescribed such as erythromycin and trimethoprim.
Tetracyclines (doxycycline) should be avoided when combined with Isotretinoin as a increased risk of benign intracranial hypertension will be present.
If the acne is extremely inflamed, then isotretinoin is reduced to a lower dosage and a oral/topical steroid may be required.
Side effects revolving with the mucocutaneous system usually indicate good absorption. Although more will be touched on this.
SIDE EFFECTS:
Isotretinoin of-course has many side effects due to it’s potent effects on the pathogenesis of acne.
Mucocutaneous side effects will always be present, no matter the dosage, but the severity will be different depending on dosage amounts.
Teratogenicity is obviously a side effect, a serious one at most.
Although I don’t think we can get pregnant
, so we will just ignore this.
Mood changes can be present, increased aggression, depression and passive suicidal intentions are also present.
Although this may be from the thought of having acne and not the drug itself, your dermatologist should do regular check-ups including the evaluation of your behaviour and skin.
If eczema is is a present skin condition, refrain from this treatment as it can further worsen it.
Retinoid dermatitis, retinoid cheilitis or conjunctivitis can occur, if they do, consult to your dermatologist immediately as drugs need to be prescribed to subside the side effects.
Now, let’s also break down the common mucocutaneous side effects that may arise from isotretinoin use; cheilitis, conjunctivitis/blepharitis, dermatitis, desquamation, facial erythema, epistaxis, epidermal atrophy, fragility of skin, hair loss, itching, mucositis, vestibulitis and xerosis.
Hair loss being the rarest at only a 5% of incidences being reported.
Here are some less likely side effects, achilies tendonitis, isotretinoin-induced-acne fulminans (KYS immediately if you get this, or just go to the hospital as it’s labelled as an emergency condition), depression, diarrhoea/colitis, headaches/benign intracranial hypertension, high-tone deafness, mood changes, night blindness, paronychia, pyogenic granulomas, sticky palms, urticaria and vasculitis.
Acne flare ups are actually somewhat rare at only 6% cases have been reported (I personally didn’t get a flare up).
If you do get a acne flare up, consult to your dermatologist immediately as these can become extremely aggressive and can cause psychological harm.
I already went over how these can happen, but i’ll repeat it again, it’s caused by the presence of macrocomedones and nodules, so make sure to get those treated beforehand.
Now, time for the evaluation of Isotretinoin’s effect on the liver.
Honestly there has been debate if liver function tests and lipids should be monitored whilst on therapy. In my experience I got a blood test before and during Isotretinoin treatment and all my lipids were in normal range and my liver wasn’t affected at all.
However, tests should be done before and 2 weeks after therapy to ensure no abnormalities are present.
Personally, I don’t believe that Isotretinoin can significantly reduce IGF-1 levels or even reduce them at all. If someone wants to educate me on this, feel free to.
The treatment is cost-effective too. Especially in areas with a nation-wide health scheme, such as Australia, which uses a Medicare system to significantly reduce the cost of prescribed medications.
DRUG INTERACTIONS:
Alcohol; Do I really have to explain why? Alcohol is shit anyways, you shouldn’t be drinking it in the first place.
Ketoconazole (or any imidazoke fungistatics); Isotretinoin is metabolised by cytochrome P450 enzymes, these are also inducible by ethanol.
Salicylic acid and indomethacin; These acidic drugs represent a high affinity for albumin, so if present in blood, it can displace Isotretinoin from protein binding sites resulting in an increase in the unbound concentration of the drug.
Carbamazepine; Carbamazepine plasma levels decrease when Isotretinoin is consumed.
Oral tetracyclics; Isotretinoin can increase benign intracranial hypertension, taking both (an oral tetracyclic) will significantly increase the severity and commonality of it.
Vitamin A supplements; Vitamin A supplements can induce additive toxic effects and the supplement of additional Vitamin A, can mess with both the metabolism and absorption of Isotretinoin.
SUMMARY+ADDITIONAL INFORMATION:
If you have acne scars and or severe cystic acne, this is your only resolution or should be your first call to significantly reduce the chance of more acne scarring appearing.
People with mild acne but permanently want to resolve it, the treatment of Isotretinoin may be suitable if the understanding of risks and pre-factors have been assessed.
Isotretinoin can cause be slowed/ineffective, the chance is increased if male, have severe acne, acne has been present for less than 7 years, an 21-hydroxylase deficiency is present and if hyperandrogenism is present.
Isotretinoin will cause a flare if macrocomedones are present, please resolve this before treatement if you don’t want the increased chance of scarring, psychological damage and obviously the gay flare up.
Some ways to decrease inflammation are to take NSAIDs, for example Ibuprofen; Ibuprofen works by reducing your body’s ability to create prostaglandins, specifically the sub-type prostaglandin H2 (PGH2) as it is a non-selective inhibitior of the enzyme called cyclooxgenase (COX). COX is needed to convert arachidonic acid to PGH2. In acne sebaceous glands, it was found that high expressed levels of cyclooxygenase-2 (COX2) which led to increased levels of prostaglandin E2 (PGE2), this then resulted in sebaceous gland hyperplasia and overshooting sebum production. PGH2 serves as the substrate for the isomerization to PGE2.
Anti-histamines; Acne inflammation response is due to the release of inflammatory mediators such as histamine and leukotrienes. So, taking a anti-histamine can effectively prevent the formation of lesions and even resolve old acne lesions.
In addition, a H3 receptor can inhibit histamine release and also regulate the functioning of the NLRP-3 inflammasome which is a another extremely important factor when it comes to the formation of lesions.
Lactobacillus plantarum MH-301 is a bacteria strain thats under the class of probiotics which of-course helps increasing gut health. In reference to acne, a study was conducted and concluded that the amount of Lactobacillus planarum MH-301 was actually decreased in patients afflicted by acne. This of-course logically implies that the exaggeration of metabolic inflammation, immunologic derangement and impaired cell proliferation is present. Moreover, when being treated with Isotretinoin, it may exert a inhibitory response that impacts liminal bacterial stimulation by impairing innate immune response, potentially implying that it can result in a excessive immune reaction, metabolic dysregulation and gastrointestinal inflammation. Not only that, Lactobacillus plantarum MH-301 can restore and reverse the disturbances in the skin-flora caused by acne. This was further backed up with the use of mice as they found weakened intestinal mucosa resulting in the formation of ulcers which can in turn break the gut microbial homeostasis. L. plantarum MH-301 was then used in a trial with the drug Isotretinoin and when taken together, it was found to increase the efficacy of Isotretinoin and also decrease the amount lesions present on the face when compared to the stand-alone Isotretinoin group.
USAGE OF ISOTRETINOIN FOR AESTHETICS:
Even though Isotretinoin should’t be used for aesthetics because of the side effects, it can provide many aesthetic benefits.
Reduced pore size and oiliness; As sebum production is almost inhibited and the size is shrunk, Isotretinoin can induce a “poreless” effect on the skin, this also may be caused by the reduction of comedones resulting in smooth skin texture.
In addition, Isotretinoin can reduce hair oiliness making your perceived cleanliness more pleasant.
Not only that, I also eat like a dog whilst microdosing Isotretinoin and don’t get any breakouts anymore.
Potential reduced nose width and bulbosity; As skin is more oily, enlarged sebaceous glands are often present which causes the overproduction of oil visually making the skin seem thicker and bigger. This indirectly makes the nose seem bigger and more bulbous. So, logically taking isotretinoin (or microdosing it) can reduce alar width and nasal tip bulbosity.
I personally microdose 5mg of Isotretinoin everyday and experience no sides except for dry lips which is easily negated by the usage of a lip-balm.
If you have additional information or questions (or if I stated wrong information) LMK. Thanks for reading.
Tag:
@silencio
INTRODUCTION:
Isotretinoin also known as 13-cis retinoic acid, is a drug commonly used/prescribed for the treatment of acne.
It’s labeled as the most effective drug when used for the treatment of acne as it impacts all major aetiological factors present in the pathogenesis of acne.
It influences cell-cycle progression, cellular differentiation, cell survival and apoptosis.
Not to mention, the effects it has on inhibiting sebum production, its influence on comedogenesis, its anti-inflammatory properties and its ability to lower surface and ductal P.acnes; Which are a gram-positive commensal bacterium that causes acne on the skin by releasing lipase which produce fatty acids by the ingestion of sebum resulting in inflammation of the skin.
The dosage of Isotretinoin varies on your weight, it’s commonly distributed through a 0.5-1.0mg per KG which is taken once a day.
Within 6 weeks of use, the drug can induce a 90% total reduction of sebum excretion.
Unlike topical retinoic acid (retinoids), Isotretinoin doesn’t bind to celluar retinol-binding proteins or retinoic acid nuclear receptors such as RARs and RXRs.
Isotretinoin has at least five biologically important metabolites;
cis-4-oxo-retinoic acid, all-trans-RA, all-trans-4-oxo-retinoic acid, 9-cisretinoic acid and 9-cis-4-oxo-retinoic acid.
When compared to 4-oxo-isotretinoin, 9-cis-retinoic acid and all trans-retinoic acid, oral isotretinoin was found superior.
Only Tretinoin and 4-oxo-tretinoin bind to RAR-y which is the receptor targeted specifically for retinoids in the treatment of acne. Although this information isn’t too important since Isotretinoin mogs.
ALTHOUGH, data has suggested that tretinoin may be the active intracellular form of isotretinoin.
Without the use of the RAR receptor, Isotretinoin has been concluded to cause apoptosis in sebocytes which of course, lead to a decreased amount of sebum production.
In addition, isotretinoin produces a reduction in comedogenesis by decreasing hyperkeratinisation, although the exact mechanism is unclear.
Isotretinoin has no direct antimicrobial properties, although by reducing SER and the sizes of pilosebaceous duct, it can alter the microflora of the skin which causes P.acnes to less likely colonise a lesion. What’s funny is that the reduction is so great that it literally has greater results at reducing P.acnes than antibiotics (oral and topical).
It’s also suggested that all-trans-retinoic acid have the chance to increase host defense mechanisms and modifies monocyte chemotaxis, which explains the potential anti-inflammatory properties, not accounting the reduction of P.acnes which of course also contributes to reducing inflammation.
Now, when referring to clinical trials, most patients who receive an optimal dosage of Isotretinoin will be “acne-free” by the end of the 4-6 month mark.
Since this is a evaluation on the drug, it can be treated for many other things, such as; acne fulminans, rosacea fulminans, Gram-negative folliculitis, dissecting cellulitis of the scalp, hidradenitis suppurativa and acne conglobata.
The half life is 22 hours and the bioavailability ranges around 25%, although, the absorption is effected by the presence of fat and pharmacokinetic studies show that the absorption can be doubled by taking isotretinoin with, or after, a meal compared to fasting state. I personally take it with 2 teaspoons of peanut-butter if i’m missing the necessary 20G of fat needed for optimal absorption. If you have a lot of money and have a stable income + are on a diet with low amounts of fat, try micronised Isotretinoin as it can be took in fasted conditions and when taken in fasted conditions, absorption supersedes absorption of oral Isotretinoin when took with a meal.
Relapse rates is dependent on many things such as the amount you’re taking and the duration of treatment although, it can be impacted by demographic factors such as, sex, age and duration of acne.
Patients, especially males, are more likely to relapse, this can be increased if they had more severe acne, extensive truncal acne and if they have suffered acne for less than 7 years.
Slow response to the drug is possible, and can be due to the presence of macrocomedones and hyperandrogensim.
Some other factors can be when a early post isotretinoin flare is present, the drug is poorly absorbed, presence of Staphylococcal aureus, severe acne and unusual variants of acne.
Macrocomedones should be detected before Isotretinoin therapy is started as a flare up of acne will be induced if left untreated.
If a flare up of acne is ensued and it wasn’t caused by macrocomedones, a antibiotic can be prescribed such as erythromycin and trimethoprim.
Tetracyclines (doxycycline) should be avoided when combined with Isotretinoin as a increased risk of benign intracranial hypertension will be present.
If the acne is extremely inflamed, then isotretinoin is reduced to a lower dosage and a oral/topical steroid may be required.
Side effects revolving with the mucocutaneous system usually indicate good absorption. Although more will be touched on this.
SIDE EFFECTS:
Isotretinoin of-course has many side effects due to it’s potent effects on the pathogenesis of acne.
Mucocutaneous side effects will always be present, no matter the dosage, but the severity will be different depending on dosage amounts.
Teratogenicity is obviously a side effect, a serious one at most.
Although I don’t think we can get pregnant
, so we will just ignore this.Mood changes can be present, increased aggression, depression and passive suicidal intentions are also present.
Although this may be from the thought of having acne and not the drug itself, your dermatologist should do regular check-ups including the evaluation of your behaviour and skin.
If eczema is is a present skin condition, refrain from this treatment as it can further worsen it.
Retinoid dermatitis, retinoid cheilitis or conjunctivitis can occur, if they do, consult to your dermatologist immediately as drugs need to be prescribed to subside the side effects.
Now, let’s also break down the common mucocutaneous side effects that may arise from isotretinoin use; cheilitis, conjunctivitis/blepharitis, dermatitis, desquamation, facial erythema, epistaxis, epidermal atrophy, fragility of skin, hair loss, itching, mucositis, vestibulitis and xerosis.
Hair loss being the rarest at only a 5% of incidences being reported.
Here are some less likely side effects, achilies tendonitis, isotretinoin-induced-acne fulminans (KYS immediately if you get this, or just go to the hospital as it’s labelled as an emergency condition), depression, diarrhoea/colitis, headaches/benign intracranial hypertension, high-tone deafness, mood changes, night blindness, paronychia, pyogenic granulomas, sticky palms, urticaria and vasculitis.
Acne flare ups are actually somewhat rare at only 6% cases have been reported (I personally didn’t get a flare up).
If you do get a acne flare up, consult to your dermatologist immediately as these can become extremely aggressive and can cause psychological harm.
I already went over how these can happen, but i’ll repeat it again, it’s caused by the presence of macrocomedones and nodules, so make sure to get those treated beforehand.
Now, time for the evaluation of Isotretinoin’s effect on the liver.
Honestly there has been debate if liver function tests and lipids should be monitored whilst on therapy. In my experience I got a blood test before and during Isotretinoin treatment and all my lipids were in normal range and my liver wasn’t affected at all.
However, tests should be done before and 2 weeks after therapy to ensure no abnormalities are present.
Personally, I don’t believe that Isotretinoin can significantly reduce IGF-1 levels or even reduce them at all. If someone wants to educate me on this, feel free to.
The treatment is cost-effective too. Especially in areas with a nation-wide health scheme, such as Australia, which uses a Medicare system to significantly reduce the cost of prescribed medications.
DRUG INTERACTIONS:
Alcohol; Do I really have to explain why? Alcohol is shit anyways, you shouldn’t be drinking it in the first place.
Ketoconazole (or any imidazoke fungistatics); Isotretinoin is metabolised by cytochrome P450 enzymes, these are also inducible by ethanol.
Salicylic acid and indomethacin; These acidic drugs represent a high affinity for albumin, so if present in blood, it can displace Isotretinoin from protein binding sites resulting in an increase in the unbound concentration of the drug.
Carbamazepine; Carbamazepine plasma levels decrease when Isotretinoin is consumed.
Oral tetracyclics; Isotretinoin can increase benign intracranial hypertension, taking both (an oral tetracyclic) will significantly increase the severity and commonality of it.
Vitamin A supplements; Vitamin A supplements can induce additive toxic effects and the supplement of additional Vitamin A, can mess with both the metabolism and absorption of Isotretinoin.
SUMMARY+ADDITIONAL INFORMATION:
If you have acne scars and or severe cystic acne, this is your only resolution or should be your first call to significantly reduce the chance of more acne scarring appearing.
People with mild acne but permanently want to resolve it, the treatment of Isotretinoin may be suitable if the understanding of risks and pre-factors have been assessed.
Isotretinoin can cause be slowed/ineffective, the chance is increased if male, have severe acne, acne has been present for less than 7 years, an 21-hydroxylase deficiency is present and if hyperandrogenism is present.
Isotretinoin will cause a flare if macrocomedones are present, please resolve this before treatement if you don’t want the increased chance of scarring, psychological damage and obviously the gay flare up.
Some ways to decrease inflammation are to take NSAIDs, for example Ibuprofen; Ibuprofen works by reducing your body’s ability to create prostaglandins, specifically the sub-type prostaglandin H2 (PGH2) as it is a non-selective inhibitior of the enzyme called cyclooxgenase (COX). COX is needed to convert arachidonic acid to PGH2. In acne sebaceous glands, it was found that high expressed levels of cyclooxygenase-2 (COX2) which led to increased levels of prostaglandin E2 (PGE2), this then resulted in sebaceous gland hyperplasia and overshooting sebum production. PGH2 serves as the substrate for the isomerization to PGE2.
Anti-histamines; Acne inflammation response is due to the release of inflammatory mediators such as histamine and leukotrienes. So, taking a anti-histamine can effectively prevent the formation of lesions and even resolve old acne lesions.
In addition, a H3 receptor can inhibit histamine release and also regulate the functioning of the NLRP-3 inflammasome which is a another extremely important factor when it comes to the formation of lesions.
Lactobacillus plantarum MH-301 is a bacteria strain thats under the class of probiotics which of-course helps increasing gut health. In reference to acne, a study was conducted and concluded that the amount of Lactobacillus planarum MH-301 was actually decreased in patients afflicted by acne. This of-course logically implies that the exaggeration of metabolic inflammation, immunologic derangement and impaired cell proliferation is present. Moreover, when being treated with Isotretinoin, it may exert a inhibitory response that impacts liminal bacterial stimulation by impairing innate immune response, potentially implying that it can result in a excessive immune reaction, metabolic dysregulation and gastrointestinal inflammation. Not only that, Lactobacillus plantarum MH-301 can restore and reverse the disturbances in the skin-flora caused by acne. This was further backed up with the use of mice as they found weakened intestinal mucosa resulting in the formation of ulcers which can in turn break the gut microbial homeostasis. L. plantarum MH-301 was then used in a trial with the drug Isotretinoin and when taken together, it was found to increase the efficacy of Isotretinoin and also decrease the amount lesions present on the face when compared to the stand-alone Isotretinoin group.
USAGE OF ISOTRETINOIN FOR AESTHETICS:
Even though Isotretinoin should’t be used for aesthetics because of the side effects, it can provide many aesthetic benefits.
Reduced pore size and oiliness; As sebum production is almost inhibited and the size is shrunk, Isotretinoin can induce a “poreless” effect on the skin, this also may be caused by the reduction of comedones resulting in smooth skin texture.
In addition, Isotretinoin can reduce hair oiliness making your perceived cleanliness more pleasant.
Not only that, I also eat like a dog whilst microdosing Isotretinoin and don’t get any breakouts anymore.
Potential reduced nose width and bulbosity; As skin is more oily, enlarged sebaceous glands are often present which causes the overproduction of oil visually making the skin seem thicker and bigger. This indirectly makes the nose seem bigger and more bulbous. So, logically taking isotretinoin (or microdosing it) can reduce alar width and nasal tip bulbosity.
I personally microdose 5mg of Isotretinoin everyday and experience no sides except for dry lips which is easily negated by the usage of a lip-balm.
If you have additional information or questions (or if I stated wrong information) LMK. Thanks for reading.
Tag:
@silencio
Last edited:
