Hair4u Med

8/14/2019 Hair4u Med

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TOPICAL MINOXIDIL AND

AMINEXIL SOLUTION

Medical Preview


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Hair Growth Cycle


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Hair Growth Cycle

Stages

Anagen = growth

Catagen = involution

Telogen = rest


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Hair Growth Cycle

Normal scalp activity Anagen = 90-95%

Catagen =


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Hair has two important partsHair shaft

Hair follicle

Visible part ofhair


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Hair Follicle

Dermal Papilla CellsDPCs)

Contain

Responsible for growth of hair


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Dermal papilla cells DPCs)rapidly divide and produce thehair shaft up out of the hairfollicle.

GROWING PAHSELast for 2-8 yrs


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The hair stops growing but does not fall out.The lower part is destroyed and the dermalpapilla breaks awayThe blood supply cuts off and the hair shafteventually is pushed up

Transitional Phase2-4 weeks


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The hair still does not grow but remainsattached to the hair follicle while thedermal papilla is in a resting phase below.Approximately 10-15 percent of all hairsare in this phase at any one time.

Resting Phase2-4 months


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After the Telogen phase the cycle is complete and the hair fallsbecause a new hair shaft is forming and the old hair is pushedout and losthe hair follicle enters into anagen phase and the cycle again begins


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Pathophysiology of Hair Loss

Dihydrotestosterone

Formed by peripheral conversion oftestosterone by 5-alpha reductase

Binds to androgen receptor on susceptiblehair follicles

Hormone-receptor complex activatesgenes responsible for gradualtransformation of large terminal follicles tominiaturized follicles


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Pathophysiology of Hair Loss:

Miniaturization
http://www.sixdifferentways.com/gallery/becg/AUSTINPOWERS2?full=1


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Pathophysiology of Hair Loss:

Miniaturization

Progressive diminution of hair shaft diameter

and length in response to systemic androgens


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Alopecia


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Alopecia

Definition:

Origin: Gr. Alepekia = a disease in which the

hair falls out

Loss of hair.

Absence of hair from skin areas where it is

normally present


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Alopecia

Related forms of alopecia, based on location &distribution are as follows:

Alopecia totalis - loss of all facial & scalp hair.

Alopecia universalis - loss of all body hair.

Alopecia postpartum - loss of significant hair following

pregnancy & is usually

temporary.

Alopecia diffusa - diffuse loss of hair.Alopecia barbae - affects a man's beard area.

Alopecia aerata - patchy hair loss.

Androgenetic alopecia: male pattern baldness


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Androgenetic Alopecia (AGA)

Definition

Hereditary thinning of the hair induced by

androgens in genetically susceptible men and

women

Also known as

Male-pattern hair loss or common baldness in

men Female-pattern hair loss in women


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Androgenetic Alopecia

Thinning of hair usually begins between 12

and 40 years old in males and females

Approximately half the population

expresses this trait to some degree before

age 50

Inheritance is polygenic


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Male-pattern baldness

Hair loss occurs on the temples and crownof the head with sparing of the sides and

back.

hair thinning in an "M"-shaped pattern pattern reflects the distribution of

androgen-sensitive follicles

androgens shorten the anagen phase andpromote follicular miniaturization, leading

to gradual hair thinning


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Progression of male pattern

baldness


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Progression of male pattern

baldness


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Androgenetic Alopecia

Women also may experience AGA, often with

thinning in the central and frontal scalp area but

usually without frontal temporal recession

conditions of hyperandrogenism, such ashirsutism, ovarian abnormalities, menstrual

irregularities, acne, and infertility are

responsible.

Concomitant decrease in estrogens may also

contribute to AGA.


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AGA IN FEMALES

Topical minoxidil and aminexil

Hormonal contraceptives: estrogens +

progestins with anti androgen action

(drosperinone)

Anti androgen - Cyproterone acetate

Blocks androgen receptor.

Spironolactone- has 5 - inhibitor action.


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Pathophysiology

Normally;

On the top: Androgen-sensitive follicles

On the sides and back of the scalp: androgen-

independent follicles

In genetically predisposed individuals;(Under Influence

of Androgens)

Terminal hair follicles are transformed into vellus.

(terminal and intermidiate hairs) Shortened anagen and an increased telogen.

Decreased growth of hair on the scalp as well as axilla


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PATHOGENESIS

1. Inc reased telogen hair coun t:

During successive passages through the hair cycle

the anagen phase becomes shorter and the

telogen phase elongates.

Anagen to telogen ratio : 12:1 to 5:1

Telogen hairs are more loosely anchored to the

follicle

The new anagen hair is shorter than its predecessor


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PATHOGENESIS

Increased telogen count explains the

increased hair shedding

latency period between telogen hair

shedding and anagen regrowth becomes

longer


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3. Sys tem ic effec ts o f

androgens:Geographical patterning : quantitative differences

no. androgen receptor and 5-reductase activity

in balding and non-balding areas of the scalp

Local control by androgens: Follicle regulates its

own response to androgens by modulating

expression of 5-reductase and androgen

receptors.


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Role of DHT

Testosteroneconverted to DHTwith the help of5 -reductase.

Persons with an inherited deficiency of type II

5 -reductase & castrated prepubertal boys or

eunuchs do not develop androgenic alopecia Under the influence of DHT, the terminal follicle

is converted to a vellus follicle

High concentrations of DHT seen in the scalp of

patients with androgenic alopecia.


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4. Inheritance

AD gene with variable penetrance,

polygenic inheritance has not been

excluded.

Genes are those involved in androgen

production and conversion of androgen to

dihydrotestosterone.


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Diagnosis & Evaluation

Androgenetic alopecia diagnosis

Characteristic pattern of hair loss

Miniaturization in thinning areas

Family history is supportive but not necessary


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Patient Evaluation

Evaluate for miniaturization using a

densitometer to observe small area of

clipped scalp


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Evaluation

Normal scalp

Thick terminal hair

Fine vellus hair

Miniaturization Thick terminal hair

Fine vellus hair

Intermediate diameter hair


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Evaluation

Regions of the scalp


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Evaluation

Norwood Classification

Most widely used classification of male-

pattern hair loss

2 types Common type

Type A variant


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Patient Evaluation


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Patient Evaluation


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Patient Evaluation

Studies reveal negative psychosocialimpact with hair loss

Body image dissatisfaction

Negative stereotype: Older

Weaker

Less attractive

Counselling patients on expectations withtreatment


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Medical Treatment


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Medical Treatment

Goals Increase coverage of the scalp

Retard further hair thinning

Drugs:

Twotreatments approved by the FDA for AGA.1. Topical Minoxidil: unknown mechanism for hair

growth stimulation

2. Oral Finasteride: competitive inhibitor of type 2

5-alpha reductase

Dutasteride: competitive inhibitor of type 1 and 2

5-alpha reductase


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Finasteride

Has been available since 1997 5-Alpha Reductase Inhibitor

first and only oral medication approved by

the FDA for the treatment of male patternhair loss.

Dose: 1 mg ORALLY once daily

It has not been proven effective in womenand is not approved for women.

3 to 12 mnth treatment. Expensive.


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Finasteride

Gynecomastia

Constipation

Testicular pain and sexual dysfunctions

including decreased libido, impotence, and adecrease volume in ejaculation .

Teratogenic : contraindicated in pregnancy and nursing

mothers

Many times stoppage of treatment leads to loss of hairgained during therapy

More useful for vertex type than frontal type alopecia


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Surgical Techniques

Goal

Achieve the greatest hair density while retaining

complete undetectability and natural appearance

Surgical Techniques

- Scalp Reduction

- Scalp Flaps

- Hair Transplantation


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Minoxidil

Therapeutic class: Orally: Antihypertensive, PeripheralVasodilator

Topically: For alopecia The 2% product was first marketed in 1986 in the United States

the 5% product became available in 1993.

Indication and dose :ALOPECIA ANDROGENETICARecommended dose is 1 ml of the (2%) or the extra strength (5%) solution

applied to the affected areas of the scalp twice daily.

(maximum total daily dose is 2 ml).Hair and scalp should be dry prior to application.

Duration: till adequate clinical response.

M h i f i idil


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Mechanism of minoxidil

1. increase the linear growth rate of hair

2. increase the diameter of the hair fibre

3. alter the hair cycle, either shorteningtelogen or prolonging anagen,

4. or act through a combination of theseeffects.

Present evidence suggests that minoxidilacts mainly on the hair cycle; it may alsoincrease hair diameter.


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Mechanism of action

Minoxidil stimulates hair growth by more than one

mechanism;

1. Direct stimulation of the hair follicle cells

to enter into a proliferative phase2. Resting phase (telogen) follicles being

stimulated to pass into active phase

(anagen) follicles3. Alteration of the effect of androgens on

genetically predetermined hair follicles


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Mechanisms of action

Minoxidil may affect the androgen metabolism in the scalp

by inhibiting the capacity of androgensto affect the hair

follicles.

Acts at the level of the hair follicle, as a potassium-

channel agonist or a direct stimulant

Minoxidil sulfate is active metabolite responsible for

stimulating hair follicles

reverse the miniaturization process of androgenetic

alopecia by normalizing the hair follicle cycle.


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Other mechanisms of action

Minoxidil is a potent activator of the

cytoprotective isoform of prostaglandin

endoperoxide synthase-1, which is the main

isoform present in the dermal papilla. Incorporation of cysteine into the follicle is

measurably increased.

There is no apparent antiandrogen effect on hair

follicle epithelium.


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Other mechanisms of action

Increased scalp blood flow

Prolongation of the anagen phase may

result in follicular hypertrophy.

Minoxidil appears to work only on

suboptimal follicles, with no further

stimulation of normal hair follicles.

Minoxidil-induced hair growth mediated by adenosine


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g y

Minoxidil SulfateATPAdenosineK+

Ecto-ATPase KirSUR

Adenosine Receptors

Dermal PapillaABC transporter Cells

PIP3 , cAMP KATP channel

Ca2+

c-fos

Hair growthVEGF

Release to extra-cellar

Li et al.,J Invest Dermatol, 117, 1594-, 2001

Pl i th


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Place in therapy Topical minoxidil appears to be effective in producing

moderate hair regrowth in 30% of men and 45% to60% of women with alopecia androgenica

(Price, 1987a; DeVillez et al, 1994; Jacobs et al, 1993).

Response is best in patients less than 35- to 40-years-old, vertex balding of less than 10 cm diameter,

and more than 100 intermediate hairs within the

balding area at baseline

(DeVillez, 1990; Karam, 1993).

The American Academy of Dermatology guidelines

for androgenetic alopecia list topical minoxidil 2%

solution as first-line medical treatment for both men

and women (Drake et al, 1996).

Pl i th


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Place in therapy Minoxidil has been tested in hundreds of clinical studies on

thousands of volunteers and has been shown effective in thetreatment of hair loss particularly on the vertex of the head.

Minoxidil has been approved for use in treating male-pattern hairloss for more than 15 years.

Clinical studies of the effects of 5% Minoxidil in treating male-patternhair loss report that a majority of patients found Very effective toeffective results in promoting new hair growth over the period oftreatment

Decreased hair lossMinimal side effects


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Ol t l [JAAD 2002]


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Olsen et al. [JAAD 2002]

B. change from baseline in hair count


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Clinical trials LONG-TERM EFFICACY OF TOPICAL MINOXIDIL IN

MALE PATTERN BALDNESS.

Katz et al JAAD 1987.

A 24-month clinical trial, in 153 men compared placebo,

2% minoxidil, or 3% minoxidil solution.

Both 2% minoxidil, and 3% minoxidil solution showed

significant improvement. 2% & 3%minoxidil did nothave significant difference in the groups .

Both strengths were well tolerated.


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Karam et al, :Int J Dermatol, 1993

A 48-week open label trial was conducted

in five Middle-Eastern countries to

determine the safety and efficacy of 2%

minoxidil . 195 men, 48-week open label trial.

80% showed moderate to dense growth.


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Lucky AW et al. JAAD. 2004

In this 48-week study of 381 women with female patternhair loss, 5% topical minoxidil was superior to placeboon each of the 3 primary efficacy end points:

1. promoting hair growth as measured by change in

nonvellus hair count and2. patient/investigator assessments of hair growth and

3. scalp coverage.

Both concentrations of topical minoxidil were well toleratedby the women in this trial without evidence of systemicadverse effects.


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Pharmacokinetics

A = Minoxidil is poorly absorbed from normal intact skin.with an average of 1.4% (range 0.3 to 4.5%) of the total

applied dose reaching the systemic circulation.

5% minoxidil once or twice daily for up to 30 months,serum levels < 6.2 ng/mL or undetectable

8 times daily application of 3% minoxidil < 2 ng/mL.

TRETINOIN and ANTHRALIN have been shown to

substantially increase (up to 3-fold) the amount of

MINOXIDIL percutaneous absorption when used in

combination

Pharmacokinetics


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Pharmacokinetics

Elimination half-life of minoxidil is 22 hours; due to

the rate of percutaneous absorption.

Topical absorption of minoxidil is increased by

increasing the dose applied, increasing thefrequency of dosing and decreasing the barrier

function of stratum corneum.

Minoxidil is metabolized mainly in the liver and its

metabolites are excreted in the urine.

Adverse effects


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Adverse effects

itching and skin irritation of the treatedarea of scalp

Dryness, irritation and pruritis was noted in

less than 5% of patients. Contact dermatitis, scaling of the scalp,

and inflammation or erythema of the scalp

could also occur. Changes in hair pigments (reddish tint in

dark hair; salt-and-pepper appearance in

dark hair; yellowish color in white hair.


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Adverse effects

unwanted hair growth on other parts of the

body, including facial hair growth in

women , local erythema, scalp flaking and

rarely exacerbation of hair loss. LEUKODERMA of the scal, darkening of

skin.

Rarely changes in BP, Hypotension andM.I have occured


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AMINEXIL SP94 In people subject to hair loss, an abnormal build-up of

thick, rigid, collagen often hinders new hair growth.

The hair becomes less deeply rooted in the scalp.

It falls out prematurely and as the cycles proceed

becomes little more than a soft down.

Hair loss is linked to the stiffening of the hair roots and

Aminexil has been specifically developed to prevent the

stiffening and premature aging of the roots.


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Perifollicular Fibrosis Condition that accompanies all alopecia

Research shows - abnormal build-up of thick, rigid, collagenoften hindered new hair growth.

Collagen around the hair root becomes rigid and tightens,pushing the root to the surface and causing premature hairloss.

This causes the roots to become rigid and compresses theblood vessels that nourish and stimulate themleads toaccelerated aging of hair roots.

In men, stiffening of roots spreads;

roots produce hair that is increasingly fine and has

an ever shorter life span.


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AMINEXIL

Aminexil, patented research product of

L'Oral's laboratories, came on the

international market on June 20, 1996.

Aminexil has been shown to increase hairdensity and hair growth by preventing

perifollicular fibrosis.


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Aminexil

Hair thickness increased by 6%

Many people suffer from hair loss after the

summer or wintertime. Aminexil showed

that such persons are no longer troubledby seasonal hair loss.


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Clinical trials

In one world-wide placebo controlled study

(1994 -1995) Aminexil was used for 42

consecutive days.

130 test participants; aged between 18and 55 years, with Alopecia type II to V;


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Increase in number of hair.


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Hair thickness

The hair growth thickness investigation showed that byusing Aminexil hair thickness increased by 6%.


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Hair preservation

Thus aminexil controls seasonal hair loss

Cli i l di


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Clinical studies

Study was done to evaluate whether topicalAminexil lotion prevents or reduces hair loss

which occurs after stoppage of oral finasteride

treatment.

18 male patients aged from 20 to 43 years

Evaluation from global photographs showed a moderate

decrease in 3 patients, a slight decrease in 6 patients

and no changes in the remaining 9 patients. Conclusion : may be helpful in preventing hair loss after

stopping finasteride treatment.


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Bi dh i l


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Bioadhesive polymer

been recommended that after minoxidilreaches the scalp, it must remain incontact for at least four hours for full

absorption. Addition of the bioadhesive polymer would

prolong the contact time of the drug withthe scalp.

Keep minoxidil in solution form andprolong the time of absorption

Bi dh i l


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Bioadhesive polymer

Marketed preparation contains alcohol and propylene glycol thatevaporates resulting in a supersaturated solution.

This leads to precipitation of minoxidil and thus abrupt absorption

pattern

addition of the polymer would not allow the thermodynamic activity

of the formulation to change as quickly as the plain solution.

It would keep minoxidil and aminexil in a solution form.

In a study with excised mouse skin it was found that in a formulation

(gel) containing the polymer, minoxidil was released over a

prolonged period of 24 h.

H d l ll l


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Hydroxypropyl cellulose

derivative of cellulose soluble in both water and organic solvents.

It is particularly good at trapping water andproducing a film that serves as a barrier to waterloss.

Hydroxypropyl cellulose possesses goodsurface activity but does not gel as it forms openhelical coils.

In general Hydroxypropyl cellulose is a water-soluble thickener, emulsifier and film-former.

C t i di ti


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Contraindications

individuals with a history of sensitivityreactions to any of its components.

Pregnancy and breast feeding.

WARNINGS


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WARNINGS Low blood pressure or are taking blood pressure lowering

medications. People with heart failure or significant coronary heartdisease

not be used in patients using occlusive dressings or other medicines

on the scalp, a red, inflamed, infected, irritated or painful scalp

(including psoriasis and sun burn)

DISCONTINUE: RAPID HEART BEAT, DIZZINESS ORSHORTNESS OF BREATH

To prevent growth in unwanted areas: application only to

the scalp, wash hands with soap and water immediately

after use.

D


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Dosage

Applied directly to the scalp twice a day,every day, without skipping applications.

1 ml of the regular strength (2%) or the

extra strength (5%) solution applied to theaffected areas

The hair and scalp should be dry prior to

topical application of minoxidil.

HOW TO USE


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HOW TO USE

Shake the solution well before use.

care should be taken to rub the

medicine on the scalp along with

application on hair.

Not to apply on other areas

Wash hands after use.

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