PCT: A Clinician's View Part IV - Post-Cycle Pharmaceutics In Practice

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Acne

While normally thought of as a skin disorder facing those in adolescence, it is not all that uncommon in the peri- and post-cycle time frames for similar reasons to the adolescent era. Androgen-stimulated (androgen receptors are present in skin and subcutaneous tissues) sebum production is the starting point of our acneiform cascade. Sebum consists of a mixture of follicular keratin and secretions of the sebaceous glands.

Bacteria (Propionibacterium acnes) in the follicles use substrate from the sebum to stimulate a white blood cell response. The white blood cell activity releases a variety of hydrolytic enzymes, which cause a local inflammatory reaction.

Comedo formation is the next step and its presence is the initial observable change in acne and one that is likely present early during a cycle. A comedo is simply the byproduct of the inflammatory reaction as discussed above which leads to hyperkeratosis of the follicular epithelium which leads to formation of one of two prototypical response element formations that many AAS/PH/PS users are all too familiar with – the so-called “whiteheads” and/or “blackheads.”

Timeout for definitions:
• Whiteheads: closed comedones that appear as slightly elevated papules in the skin.
• Blackheads: a later stage of enlarged comedones containing melanin (dark skin pigment) that may open and cause further inflammatory responses.

Whiteheads and blackheads, while annoying tend not to go on to cause further grief for a post-cycler with essential resolution in the post-cycle realm with return of androgen production to pre-cycle status. However, there is the potential for some to go forward (particularly those that extend their cycle length or use a highly androgenic substance) and form cyctic acneiform lesions. Cystic acne is NOT actually composed of cysts but of nodules formed during the inflammatory reaction; these develop into erythematous papules (pimples) or pus-filled papules (pustules).

Subsequent gradual resolution may lead to scarring you are NOT immune from in the post-cycle era.





Anti-Acne Therapy

We have thus far NOT discussed acneiform treatments in our previous discussion of post-cycle supplements because there were simply NO effective agents to speak of in this regard. Pharmaceutic acne therapy is therefore the standard should lesions not be self-limited (complete resolution upon cycle completion). Such therapy is aimed at the four following sites:

(1) Comedo Formation
(2) Bacterial involvement
(3) Sebum Production
(4) Inflammatory Reaction (less-frequent aim in post-cycle as we will see in PCT:ACV Part V)

as suggested in the diagram above. We will talk about each in turn and discuss prototypical agents that may be employed for each step in the pathogenic pathway.

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1. Comedolytic / Antikeratolytic Agents

This first category of agents includes 3 items: Benzoyl Peroxide, Trentinoin and the systemic Isotrentinoin. Isotrentinoin also possesses sebaceous gland inhibiting action as well and will be deferred until that particular discussion section.


Benzoyl Peroxide

This is what you have likely grown accustomed to in many of the over-the-counter preparations you have become familiar with. It has gained popularity due to its efficacious potential in most cases of prototypical acne vulgaris.

Mechanism of Action: Usually supplied as a topical ointment (alone or in combination with antibiotic preparations), it penetrates the stratum corneum or follicular openings unchanged and is converted into benzoic acid within the epidermis and dermis. It has been postulated that benzoyl peroxide possesses antimicrobial activity against P acnes itself, however, the more widely accepted view is that its benefits are more appropriately assigned to its peeling (dermabrative) and comedolytic effects.


Trentinoin (RETIN-A, others)

Mechanism of Action

Primary Use: reduction of hyperkeratinization that leads to comedone formation (the initial lesion of acne as described above)

How Accomplished: shedding desmosomes leads to follicular corneocytes becoming less cohesive, decreasing tonofilaments and increasing keratinocyte autolysis (self-destruction) and intracellular deposition of glycogen

What’s More: additionally improves photodamaged human skin which we will actually see how this pans out as an imperative added benefit in the peri- and post-cycle time frame in PCT: ACV Part V.

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2. Antibiotics

Both topical (local) and systemic antibiotics have gained acceptance in use in this category. The basic premise of therapy is that the deeper the extension into the skin, the likelihood of greater need for potential use of a systemic versus a topical.

We described above that the agent thought to be responsible for contribution to the pathogenesis of acne vulgaris is affectionately described as Propionibacterium acnes. It is important to understand that alone, this bacteria is NOT anything more than a normal resident of your skin as part of the normal flora (fancy way to say that this bacteria is there among other bacteria on a daily basis – a symbiotic relationship if you will). When you couple this particular bug with an obstructed, lipid-rich lumen of the pilosebaceous unit (essentially the hair follicle combined with the sebaceous glands), where oxygen tension is low, this bug runs rampant – proliferating well beyond normal capacity. P. acnes generates free fatty acids that are irritants and may lead to comedo formation and finally result in the inflammatory lesions of acne (the global description of this pathogenic process was described above). Suppression of P. acnes with antibiotic therapy is correlated with clinical improvement.

As of late, as many bacteria tend to do, ole P. acnes has wised up and resistant strains to antibiotic therapy are emerging making this particular mode of therapy a difficult sell in isolation. However, as we will see in PCT: ACV Part V, judicious use of retinoids combined with antibiotics may still prove effective in lieu of this resistance. While there are over 30 agents that would effectively cover this bug, we will limit our current discussion to brief description of select representatives from the top five agents in both topical (local) and oral (systemic) classes.

Topicals (Local)
1. Erythromycin
2. Clindamycin (CLEOCIN-T)
3. Antibiotic-Benzoyl Peroxide Combos (BENZAMYCIN, BENZACLIN, others)
4. Metronidazole (METROCREAM, METROGEL, NORITATE)
5. Sulfacetamide (KLARON – 10% lotion; OVACE – 10% wash)

Oral (Systemic)
1. Tetracycline (SUMYCIN, others)
2. Minocycline (MINOCIN, others)
3. Erythromycin (ERYC, others)
4. Clindamycin (CLEOCIN)
5. Trimethoprim-Sulfamethoxazole (BACTRIM, others)

Select Pharm Profiles

Clindamycin (CLEOCIN, CLEOCIN-T)

This agent possesses in vitro activity against P. acnes; this has therefore been postulated as its mechanism of action affording it efficacious activity both in oral and topical (T) forms. Approximately 10% of the applied T form is absorbed. It is also available in a fixed-combination topical gel with benzoyl peroxide (BENZACLIN).

Erythromycin (ERYC)

Only the second agent (aside from Clindamycin) to make appearances on the topical and systemic lists as well is Erythromycin. In topical preparations, the base of erythromycin rather than a salt is used to facilitate penetration. Again, the mechanism of action centers on activity against P. acnes, however, a direct action in this regard is a struggle to support via the available literature as we will see in PCT:ACV Part V.

Metronidazole (METROCREAM, METROGEL, NORITATE)

Post-cyclers have attempted to use this agent, however, there is no known activity against P. acnes. The mechanism to combat acneiform lesions likely centers more on an anti-inflammatory action (through direct effects on neutrophil action) rather than antibacterial. In PCT:ACV Part V, we will take a much more in-depth look here as it may be a better target in those seemingly resistant to other antibacterial regimes.

Sodium Sulfacetamide (KLARON, OVACE)

Topical sulfacetamide may either be supplied alone or in combo preps with sulfur. The mechanism of action is thought to be due to the inhibition of P. acnes via competitive inhibition of p-aminobenzoic acid utilization.

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3. Sebaceous Gland Inhibitor Agents

While this particular category in the fight against acne usually consists of two potential categories of agents, it is imperative to see how the second does NOT apply to the post-cycler. In addition, it may become evident as to why many cases of acne see in the on cycle mode actually remain self-limited and undergo complete cessation with discontinuation of the cycle.

2 categories:
(1) Systemic isotrentinoin (as described above with dual action in the comedeolytic category)
-and-
(2) Antiandrogenic aids

Provided you have subscribed to a short cycle duration, the essential need of the latter category may in fact be employed, however, with the potential of suffering HPTA suppression, antiandrogenic aids could in fact pose potential threats for the unopposed estrogen rationale supplied earlier in this article. As you can see, the use of antiandrogen may supply the same effect as taking away the androgenic agent that was used while on cycle in the first place leading to essential resolution of the symptoms. We will, therefore, concentrate on the former item while foregoing discussion of the latter.

Isotrentinoin (ACCUTANE)

Isotrentinoin is a synthetic retinoid currently restricted to the treatment of severe cystic acne that is recalcitrant to standard therapies. While gaining increasing popularity in post-cyclers with simple non-cystic varieties, one must consider the potential pitfalls with this therapeutic modality which we will address very thoroughly in the next part of this series.

The precise mechanism of action in cystic acne is NOT KNOWN, although guesstimates have suggested inhibition of sebaceous gland size and function through normalization of keratinization. Additional hypotheses include: reduction in sebocyte number with subsequent decreased sebum synthesis as well as even a minor anti-bacterial role against P. acnes.

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4. Anti-Inflammatory Agents

I bring this category up solely for completion’s sake. We will challenge efficacy in the post-cycler during the next part of this series. The 3 agents that comprise this category showing efficacy against acne in the normal setting of acne vulgaris amongst other dermatologic conditions are:

(1) Topical corticosteroids
(2) Immunosuppressive Agents
(3) Tar Preparations

The latter two categories have shown minor efficacy and can actually worsen acneiform lesions and the corticosteroids are marginal at best. We will explore their full efficacy from various clinical trials in the next part of this series.

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Conclusion

So, what we have done here is set the theoretical stage for PCT: ACV V clinical show, much like PCT: ACV II set the stage for PCT: ACV III. For the non-science types, my apologies in advance as this one was not exactly written the way you may have desired. It is that point of view that often brings fear that many may view part V as the superior piece, but without the foundation, it is just my views without true rationale as to why they exist – there is already enough of this mentality out there. Minimally, it is my hope that this particular piece gave an appreciation for the actual thought that goes into such agents and hopefully displayed why putting together a particular PCT regime should NOT be well thought out first and foremost. I will see you again, real soon…





Author’s Note: All pharmaceutical trade names are property of the respective registered trademark holders.

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