Chemistry of Peels Flashcards
1
Q
chemical peel
definition
A
- treatment technique used to improve and smooth facial and/or body skin’s texture
- using a chemical solution that causes the dead skin to slough off & eventually peel off
2
Q
3 separate MoA for chemical peeling solutions
A
- Acidity
- Toxicity
- Metabolic interactions
3
Q
All peeling agents assume to induce 3 stages of tissue replacement
A
- destruction
- elimination
- regeneration
- all accompanied by a controlled stage of inflammation
4
Q
Acid
A
- compound that donates a hydrogen ion (H+) to another compound (called a base)
- Acids can occur in solid, liquid, or gaseous form, depending on the temperature
5
Q
Arrhenius Acids
A
- substance that increases concentration of the hydronium ion, H3O+, when dissolved in water
- definition stems from the equilibrium dissociation of water into hydronium and hydroxide (OH−) ions:
- H2O(l)+H2O(l)⇌ H3O+(aq)+OH–(aq)
6
Q
Arrhenius base
A
- molecule that increases the concentration of the hydroxide ion when dissolved in water
7
Q
Brønsted Acids
A
- act by donating a proton to water
- differently than Arrhenius acids, can also be used to describe molecular compounds
- whereas Arrhenius acids must be ionic compounds
8
Q
Brønsted–Lowry acid
A
- is a species that donates a proton to a Brønsted–Lowry base
9
Q
example of Brønsted acid
A
10
Q
Lewis Acids
A
- species that accepts a pair of electrons from another species
- in other words, it is an electron pair acceptor
11
Q
- Bronsted acid-base vs Lewis reactions
- Bronsted vs Lewis acids
A
- Brønsted acid–base reactions are proton transfer reactions
- whereas Lewis acid–base reactions are electron pair transfers
- All Brønsted acids are also Lewis acids
- but not all Lewis acids are Brønsted acids
12
Q
Reaction of acids
A
- Reactions of acids are often generalized in the form:
- HA ⇌ H+ + A−
- where HA represents the acid and A− is the conjugate base
- Acid–base conjugate pairs differ by one proton and can be interconverted by the addition or removal of a proton (protonation & deprotonation)
13
Q
equilibrium constant K
A
- expression of the equilibrium concentrations of the molecules or the ions in solution
- The acid dissociation constant Ka is generally used in the context of acid–base reactions
14
Q
numerical value of Ka
A
- numerical value of Ka is equal to the concentration of the products divided by the concentration of the reactants
- where the reactant is the acid (HA) and the products are the conjugate base and H+
15
Q
more useable constant than Ka
A
- pKa
- pKa = −log10Ka
- Stronger acids have a smaller pKa than weaker acids
16
Q
acid strength and Ka/pKa
A
- stronger acids have a higher K and a lower pK than weaker acids
17
Q
2 parameters to be taken into consideration for peelers
A
- pKa, a synonym of the acid’s strength
- pH, a synonym of the penetration for the selected acid
18
Q
Two key factors that contribute to the ease of deprotonation
A
- polarity of the H–A bond and
- size of atom A, which determines the strength of the H–A bond
19
Q
Do all medical peels have pKa<3 ?
A
- No
- Caution is advised against simply classifying “cosmetic peels” for acids with pKa > 3 and “medical peels” for acids with pKa < 3
- because some acids like phenol can be toxic substances even with a pKa > 3
20
Q
Carboxylic acids
A
- organic acids that contain an acidic hydroxyl group and a carbonyl (C–O bond)
21
Q
Property of carboxylic acids
A
- can be reduced to the corresponding alcohol
- the replacement of an electronegative oxygen atom with two electropositive hydrogens yields a product that is essentially nonacidic
- reduction of acetic acid to ethanol using LiAlH4 (lithium aluminum hydride or LAH), and ether is an example of such a reaction
22
Q
Difference btw monoprotic & polyprotic acids
A
- monoprotic acids (having one unique pKa)
- polyprotic acids (having two or more pKa)
23
Q
Monoprotic acid
definition
A
- those acids that are able to donate one proton per molecule during the process of dissociation (sometimes called ionization), as shown below (symbolized by HA):
- HA(aq)+H2O(1) ⇌ H3O (aq)+A(aq)Ka
24
Q
Examples of monoprotic organic acids
A
- acetic acid (CH3COOH)
- glycolic acid
- lactic acid
25
Polyprotic acid
definition
* are **able to donate more than one proton per acid molecule**
* in contrast to monoprotic acids that only donate one proton per molecule
* Specific types of polyprotic acids have more specific names, such as **diprotic acid (two potential protons to donate) and triprotic acid (three potential protons to donate)**
* A diprotic acid can undergo one or two dissociations depending on the pH
* Each dissociation has its own dissociation constant, Ka1 and Ka2
26
Diprotic acids used for peelings
* **malic, tartaric, azelaic acids**
27
2 or 3 dissociations mean that...?
* **such acids can generate 2 or 3 peelings, depending on the pH**, with the second one less acidic than the first one
* In this case, **we consider one peeling reaction per one dissociation**
28
triprotic acid (H3A)
definition
* acid that can undergo one, two, or three dissociations
* has 3 dissociation constants, where **Ka1 > Ka2 > Ka3**
29
organic example of a triprotic acid
* **citric acid**
* which can successively lose three protons to finally form the citrate ion
30
**Buffer Solution**
definition
* **aqueous solution consisting of a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid**
31
property of buffer solutions
* **the pH of the solution changes very little when a small amount of acid or base is added to it**
* Buffer solutions are used as a means of keeping pH at a nearly constant value in a wide variety of chemical applications
32
example of buffer solution
**blood**
33
Le Chatelier’s Principle
34
Henderson–Hasselbach Equation
## Footnote
when the concentrations of acid and conjugate base are equal, often described as half-neutralization, pH = pKa
35
Buffer Capacity
* quantitative measure of the resistance of a buffer solution to pH change with the addition of hydroxide ions
36
Buffer capacity features
37
ideal buffer
* **ideal buffer for a particular pH has a pKa equal to that pH**
* since such a solution has maximum buffer capacity
38
Useful Buffer Mixtures
* **Citric acid**, sodium citrate, pH range 2.5 to 5.6
* **Acetic acid**, sodium acetate, pH range 3.7 to 5.6
39
Neutralization
* **chemical reaction whereby an acid & a base react to form water and a salt**
40
the timing of neutralization of chemical peeling agent is determined by...?
* **frost in the skin or**
* **how much contact time the peel has with the skin**
41
Neutralization is achieved by...?
* applying cold water or wet, cool towels to the face following the frost
42
using water just after the frost provokes...?
* an exothermic reaction that can provoke a “cold” burn
43
neutralization reactions are often...?
* **exothermic**
* giving out heat to the surroundings (the enthalpy of neutralization)
44
Other neutralizing agents
* **bicarbonate spray or soapless cleansers**
45
Peeling agents for which this neutralization step is less important?
* salicylic acid
* Jessner’s solution
* TCA
* phenol
46
partially neutralized alpha-hydroxy acid (AHA) solutions
* the acid and a lesser amount of base are
combined in a **reversible chemical reaction that yields unneutralized acid and a salt**
* resulting solution has less free acid & a higher
pH than a solution that has not been neutralized
* **salt functions as a reservoir of acid that is available for second-phase penetration**
* This means that **partially neutralized formulas can deliver as much, if not more, AHA than free acid formulas, but in a safer, “time-released” manner**
47
advantage of partially neutralized glycolic acid solutions
* better safety profile than low-pH solutions containing only free glycolic acid
* releases glycolic acid in a safer, “time-released” manner
* stimulates fibroblast proliferation—an index of tissue regeneration
48
skin can be considered..?
* **aqueous solution into which are dissolved a certain number of molecules**
* These are molecules of proteins, lipids, and carbohydrates in variable quantities and proportions
49
which stratum of skin contains more water & why ?
* There is **more water in the dermis** than in the epidermis
* due to the **presence of blood, glycosaminoglycans (GAGs), and lymph in the dermis**, all of which have a high water content
* as well as the fact that the epidermis is in contact with a more or less dehydrated environment
50
which stratum of skin contains more proteins & why?
* There are **more proteins (keratin) in the epidermis than in the dermis**
* whereas more carbohydrates & lipids exist in the dermis, and there are even more in the
subcutaneous layer than in the dermis
51
most important molecule in the epidermis
* **keratin**
* that protects & takes part, through its continuous production by the keratinocytes, in the **complete replacement of the epidermis every 27 days**
52
most important molecules of the dermis
* collagen
* elastin
* GAGs
* proteoglycans
53
* collagen & elastin vs GAGs?
* **Collagen & elastin are proteins**
* whereas **GAGs (eg, hyaluronic acid) and the proteoglycans are biological polymers formed mainly by sugars that retain
water**
54
collagen constituents
* most abundant protein in the human body
* formed mainly by glycine, proline, hydroxyproline
55
Elastin
* similar to collagen
* but it is an extensible protein responsible for elasticity
* has **2 unique polypeptides, desmosine & isodesmosine**
56
GAGs
* **contain specific sugars** such as glucosamine sulfate, N-acetylglucosamine, and glucosamine hydrochloride
* **all very capable of attracting water**
* They form long chains of molecules, such as hyaluronic acid, keratin sulfate, heparin, dermatin, & chondroitin, that retain up to 1000 times their weight in water
57
hypodermis or subcutaneous tissue consists mainly of...?
* **fat**
* although this tissue accounts for a completely different chemical interaction with peeling solutions
58
pH of epidermis
* epidermal acid layer or mantel is the result of
sebum secretion and sweat
It protects the skin and makes it less vulnerable from attacks by microorganisms (bacteria & fungi)
* A healthy epidermis has a **slightly acidic pH with a range between 4.2 - 5.6**
* varies from one part of the skin to another
* in general, is **more acidic in men than in women**
59
Anatomy of the skin with penetration depths of the various peels
60
Approximate Skin Composition
61
cell membrane of nearly all organisms is primarily made up of...?
* **a phospholipid bilayer**
* a micelle of hydrophobic fatty acid esters with polar, hydrophilic phosphate “head” groups
62
which molecules have more difficulty passing through the skin cell membrane?
* Cell membranes are generally **impermeable to charged or large, polar molecules** because of the lipophilic fatty acyl chains comprising their interior
* Many biologically important molecules, including a number of pharmaceutical agents, are **organic weak acids that can cross the
membrane in their protonated, uncharged form but not in their charged form** (i.e., as the conjugate base)
* The charged form, however, is often more soluble in blood & cytosol, both aqueous environments
63
3 categories of Substances used in chemical peeling
* metabolic
* caustic
* toxic
64
Classification of Chemical Peels
65
**Alpha Hydroxy Acids (AHAs)**
* definition
* examples
* class of chemical compounds that consist of a carboxylic acid with a hydroxy group on the adjacent carbon
* may be either naturally occurring or synthetic
* most common and simple are **glycolic acid, lactic acid, citric acid, mandelic acid**
* AHAs are weak acids that induce their rejuvenation activity by either metabolic or caustic effect
66
**AHA peels include..?**
* **aliphatic** (lactic, glycolic, tartaric, malic)
* **aromatic** (mandelic) acids
67
effect of AHAs in low vs high concentration?
* At **low concentration**, <30% they reduce sulfate and phosphate groups from the surface of corneocytes. By decreasing corneocyte cohesion, they **induce exfoliation of the epidermis**
* At **higher** concentration, their effect is mainly **destructive**
68
can AHAs neutralize themselves & why?
* Because of the **low acidity** of AHAs, they **do not induce enough coagulation of the skin proteins**
* and therefore **cannot neutralize themselves**
* They **must be neutralized using a weak buffer**
69
AHAs MCy used in cosmetic applications are typically derived from?
* **fruit products**
* glycolic acid (sugar cane)
* lactic acid (sour milk)
* malic acid (apples)
* citric acid (citrus fruits)
* tartaric acid (grapes and wine)
70
properties that any topical compound must have?
* **must penetrate into the skin, where it can act on living cells**
* **Bioavailability** (influenced primarily by small molecular size) is one characteristic that is important in determining the compound’s ability to
penetrate the top layer of the skin
71
AHA with greatest bioavailability that penetrates skin most easily?
**Glycolic acid** , has the smallest molecular size
72
Epidermal effects of AHAs
* **profound effect on keratinization**, which is clinically detectable by the **formation of a new stratum corneum**
* AHAs modulate this formation through **diminished cellular cohesion between corneocytes at the lowest levels of the stratum corneum**
73
Dermal effects of AHAs
* **AHAs with greater bioavailability appear to have deeper dermal effects**
* Glycolic acid, lactic acid, and citric acid, on topical application to photodamaged skin, have been shown to **produce increased amounts of mucopolysaccharides and collagen and increased skin thickness without detectable inflammation**, as monitored by skin biopsies
74
MC side effects of AHAs
* mild skin irritation, redness
* flaking
75
Cosmetic Actions of the Alpha-Hydroxy Acids
76
Aliphatic AHAs with pKa >3 ?
* Glycolic
* Lactic
* Malic
* Tartaric
* Citric
77
Glycolic acid (or hydroxyacetic acid)
* **smallest** AHA
* **colorless, odorless**, hygroscopic crystal line solid is highly soluble in water
* Formulated from **sugar cane**, glycolic acid creates a mild exfoliating action
* Glycolic acid peels work by **loosening up the horny layer** & exfoliating the superficial top layer
78
glycolic acid in low concentrations 5-10%
* **reduces cell adhesion in the top layer of the skin**
* This action **promotes exfoliation of the outermost layer of the skin**, accounting for smoother texture following regular use of topical glycolic acid
79
how does glycolic act once applied on the skin?
* glycolic acid **reacts with the upper layer of the epidermis, weakening the binding properties of the lipids that hold the dead skin cells together**
* This allows the outer skin to “dissolve,” revealing the underlying skin
80
what can irritation from glycolic acid do?
* may result in **worsening of any pigmentary problems**
81
newer formulations of glycolic acid
* **combine glycolic acid with an amino acid** such as **arginine**
* and **form a time-release system that reduces the risk of irritation** without affecting glycolic acid efficacy
* use of an anti-irritant like allantoin is also helpful
82
effect of medium concentrations of glycolic , between 10% and 50%
* **benefits are more pronounced**
* but are **limited to temporary skin smoothing without much long-lasting results**
* **can prepare the skin for more efficacious glycolic acid peels at higher concentrations (50%–70%)**
* as well as to prime the skin for deeper chemical peels such as TCA peel
83
effect of high concentrations of glycolic acid 50-70%
* **50% to 70% applied for 3 to 8 minutes** glycolic acid **promotes disruption of the bonds between keratinocytes**
* **can be used to treat acne or photo damage** (such as mottled dyspigmentation, or fine wrinkles)
* Although single application of 50% to 70% GA will produce beneficial results, multiple treatments every 2 to 4 weeks are required for optimal results
84
Lactic acid
85
Malic acid
86
Tartaric Acid
87
Citric Acid
* usually derived from **lemons, oranges, limes, pineapples**
* **citric acid is triprotic**, having 3 pKa values
* It is quite interesting, because the first pKa is lower than the pKa of the monoprotic glycolic acid on one hand, and the three reactions are made of two peelings (pKa1 = 3.15, pKa2 = 4.77) that end with a buffer (third reaction) of a pKa3 = 6.40
88
Aromatic AHA with pKa >3
Mandelic acid
89
Mandelic acid
* aromatic AHA with the molecular formula C8H8O3
* larger molecule than glycolic acid, which makes it better tolerated on the skin
* **possesses antibacterial properties**, whereas glycolic acid does not
90
Pyruvic Acid
91
Azelaic acid
* saturated dicarboxylic acid naturally found in wheat, barley, and rye
* It is active in a concentration of **20%** in topical products used mainly in **mild to moderate acne & papulopustular rosacea**
* works in part by **inhibiting the growth of skin bacteria** that cause acne and by keeping skin pores clear
92
Properties of azelaic acid
* **Antibacterial**: reduces the growth of bacteria in the follicle (P. acnes, St. epidermis)
* **Keratolytic & comedolytic**: It returns to normal the disordered growth of the skin cells, lining the follicle
* Scavenger of free radicals, reduces inflammation
* Nontoxic, well tolerated by most patients
* does not result in bacterial resistance to
antibiotics, reduction in sebum production, photosensitivity (easy sunburn), staining of skin or clothing, or bleaching of normal skin or clothing
93
Beta Hydroxy Acid Peels With pKa Around 3
* Salicylic Acid
* Jessner’s Peel
* Retinoic Acid Peels
94
Salicylic Acid
* MCy used peeling currently is **30% salicylic acid in ethanol**
* lipid soluble (**lipophilic**)
* therefore good peeling agent for **comedonal acne**
* works as **both a keratolytic & comedolytic agent** by causing the cells of the epidermis to shed more readily, opening clogged pores and killing bacteria within, preventing pores from clogging up again by constricting pore diameter, and stimulating new cell growth
* found naturally in certain plants (Spiraea ulmaria, Andromeda leschenaultii), particularly fruits
95
Jessner’s Peel
* pioneered by Max Jessner, a dermatologist
* **14% salicylic acid, 14% lactic acid,
14% resorcinol in an ethanol base**
* Its main effect is to **break intracellular bridges between keratinocytes**, whereas the salicylic acid component also allows better penetration across sebum-rich skin
* It is a stronger peel than 30% salicylic acid
96
modified Jessner peel composition
* **lactic acid(17%), salicylic acid(17%), citric acid(8%) and ethanol**
97
Retinoic Acid Peels
* **Retinoic acid or vitamin A acid is not soluble in water but is soluble in fat**
* therefore **retinyl palmitate or vitamin A palmitate** is the elected retinoic agent for chemical peels
* **Tretinoin** is the acid form of vitamin A and so also known as all-trans retinoic acid (ATRA)
98
retinoids of relevance in chemical peelings
* only natural retinoids
* retinol, ATRA, and retinoic acid
99
substance with mainly caustic activity
**trichloroacetic acid**
100
TCA
* can be found directly in the environment because it is used as a herbicide (as sodium salt) and indirectly as a metabolite derived from chlorination reactions for water treatment
* much stronger acid than any other current acids used for peelings
* Like glycolic acid, TCA does not have general toxicity, even when applied in concentrated form on the skin
101
TCA effect on the skin
* When applied to the skin, it is not transported into the blood circulation
* TCA’s destructive activity is a consequence of its acidity in aqueous solutions, but **in peels acid is rapidly “neutralized” as it progresses through the different skin layers, leading to a coagulation of skin proteins**
* As the proteins become coagulated, TCA is used up
* To penetrate deeper, more TCA must be applied (volume) or a higher concentration of TCA needs to be used
* TCA action is simple, reproducible, and proportional to the concentration and to the amount applied
102
visual signs unique to TCA & phenol
* **light speckling to white frost**
* following cutaneous application **indicate the degree of coagulation of protein
molecules & the depth of acid penetration**
103
* TCA 20-50%
* TCA >50%
* 20-50% intermediate to deep peeling agent
* TCA >50% penetrates into the reticular dermis
104
Hints on phenol & TCA
* Both phenol & TCA are caustic, and adding both of them will not reduce the toxicity
* Phenol can be diluted into TCA or vice versa to reduce the concentration of the phenol and/or TCA
105
Calculations in peeling should be made in weight/weight or volume/volume & why ?
* **All calculations have to be made in w/w and never in v/v (volume/volume)**
* **because only mass are additive**
106
main caustic effect of phenol is due to ?
**croton oil and not the phenol itself**
107
substances with mainly toxic activity
* Phenol
* Resorcinol
108
schematic difference of skin reactivity
to the coating with TCA
109
Phenol
* aromatic alcohol with the properties
of a weak acid
* sometimes called **carbolic acid when in water solution**
* reacts with strong bases to form the salts called phenolates
* Its **pKa is high, at 9.95**
* Phenol has antiseptic, antifungal, anesthetic
pharmacological properties
110
which one is more acidic phenol or carbolic acid?
* **Carbolic acid** is more acidic than phenol
111
Resorcinol
aka resorcin
* Resorcinol is a phenol substituted by a hydroxyl in position meta
* Hydroquinone is a phenol substituted by a hydroxyl in position para
* Like phenol, resorcinol is a protoplasmic poison
that works through enzymatic inactivation and protein denaturation with production of insoluble proteins both phenol and resorcinol act on the
cellular membrane, modifying its selective permeability by changing its physical properties
* This change in permeability then leads to cell death
112
Phenol & resorcinol side effects
* Phenol alone is a more powerful poison, with a **secondary anesthetic effect** due to inhibition of sensory nerve endings
* **Phenol and (to a lesser extent) resorcinol are cardiac,renal, and hepatic toxins** that are eliminated from the body at 80% concentration either unchanged or conjugated with glucuronic or sulfuric acid
113
Classification of Substances Used for
Chemical Peels (L. Dewandre)
* **Caustic**: trichloroacetic acid
* **Metabolic**: AHAs, azelaic acid, retinoic acid
* **Toxic: phenol, resorcinol, salicylic acid**
114
Toxins, particularly phenol, have little if any caustic action unless...?
**solutions are used that contain croton oil**
115
Monheit’s formula
* **version of a modified Jessner’s solution with the resorcinol replaced with citric acid**
* followed by the application of a TCA peel
116
Proposed MoA of Tranexamic acid
* well-known plasmin inhibitor
* Plasmin formation is inhibited by TXA,
resulting in plasmin downregulation and inability to
cleave the fibrin clot
* decreasing the melanogenic activity of the melanocytes, resulting in a reduced synthesis of melanin
* since it has similar molecular structure to tyrosine, functions as a competitive inhibitor to the enzyme tyrosinase, which is responsible for melanin production
117
Proposed actions of TXA on the skin
118
Ways of Delivery of Tranexamic Acid to the Skin
* TXA can be delivered to the skin via various modes: **topical, intradermal, oral delivery**
* with the topical and oral routes most
widely studied
119
Oral Tranexamic acid
* 250 mg twice daily (BID) is an effective dose for the observance of skin lightening within
2 months
120
Topical Tranexamic acid
Topical serum 5% TXA in a suitable
base for use BID
