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Pharmacology > Retinoids > Flashcards

Retinoids Flashcards

1
Q

What are the contraindications for retinoids?

A

Absolute
* Pregnancy or a woman who is likley to become pregnant
* Non-compliance with contraception
* Breast-feeding
* Hypersensitivity to parabens (in isotretinoin capsules)

Relative
* Leukopaenia
* Hypothyroidism (in bexarotene patients)
* Moderate to severe cholestrol / or triglycerides elevation
* Significant hepatic dysfunction
* Significant rental dysfunction

Wolverton

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2
Q

What are the severe adverse effects of systemic retinoid?

A
  1. Teratogenicity
    * Spontaneous abortions (1/3 of pregnancies
    * Congential heart defects, defects in the cranium and face, thymic abnormalties, CNS malformation

Occur in 50% of full term pregnancies, where exposure was in the first trimester

  1. Ocular side effects:
    * Reduced night vision
    * Dry eyes
    * Staph infections
  2. Lipids
    * Hypercholestrolaemia
    * Hypertriglycerideamia
  3. Gastrointestinal
    * Inflammatory bowel disease
    * Pancreatitis
  4. Hepatic
    * Transaminase elevations
    * Toxic hepatitis
  5. Neurologic
    * Psudotumour cerebri
    * Depression
  6. Muscular
    * Myopathy
  7. Bones
    * Skeletal hypostosis
    * Osteophyte formation
    * Premature epiphyseal closure

*6. Endocrine
Hypothyroidism (for bexarotene)
Diabetes Mellitus (controversial)

  1. Haematologic
    Leukopaenia
    Agranulocytosis (for bexarotene)*

Wolverton

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3
Q

How long after stopping isotretinoin is it safe to conceive?

A

1 month

wolverton

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4
Q

How long after stopping acitretin is it safe to conceive?

A

3 years, hence it is not given to pre-menopausal women

This is due to the ‘re-esterification’ to etretinate (which has an extremely long half life) that can occur with concomitant alcohol and acitretin use.

This risk is theoretical, and the magnitude of the actual risk is unknown (likely to be small)

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5
Q

Is there any risk to a fetus fathered by a man taking systemic retinoids?

A

There is limited data, however it appears there is little, if any risk f retinoid embryopathy to fetus fathered by men taking systemic retinoids

wolverton

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6
Q

What the common (or minor) side efects of taking systmic retinoids?

A

Cutaneous
** Xerosis
Palmoplantar digital desqumation **
* Photosensitivity
* Pyogenic granulomas
* Stickiness sensation on the palms and soles

Ocular:
* Dry eyes with visual blurring
* Blepharitis
* Photophobia

Oral / mucocutaneous
* chelitis
* dry mouth
* dry nose
* nose bleeding

Hair
* telogen effluvium
* abnormal texture / dryness

Nails
* Fragility
* Paronychia
* Onycholysis

MSK
* Arthralgia
* Myalgia
* Fatigue
* Tendinitis

Neurologic
* Headache
* Mild depression

GI
* Nausea
* Diarrhoea
* Abdo pain

Wolverton

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7
Q

What is the most common lab abnormality in patients taking isotretinoin?

A

Elevated serum lipids - especially triglycerides

Isotretinoin and acitretin elevates TGs in 50% of patients, and cholestrol in 30%

For TGs >5, consider reducing dose or adding a lipid lowering agent

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8
Q

Does isotretinion cause IBD?

A

There is conflicting evidence (similar to depression)

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9
Q

What is the effect of isotretinoin on the liver?

A

15% of patients develop mild transmintitis

This typically returns to normal despite continuing therapy

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10
Q

What is the effect of acitretin on the liver?

A

30% of patients develop mild transmintitis

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11
Q

When do you need to consider discontinuing acitretin, in regard to abnormal LFTs?

A

Only for severe, > 3 fold elevatiosn in AST / ALT.

Dose reduction and frequent monitoring can be trialled first.

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12
Q

What investigations should you do for a paitent starting acitretin or isotretinoin?

A

Baseline:
* FBC
* LFTs
* UECs
* Lipids
* For women of childbearing age - pregnancy test

Monitoring:
* LFTs
* Lipids
* FBC
For isotretinoin - when reaches max dose
For Acitretin - every 3 months

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13
Q

Is acitretin bioavialability affected by food intake?

A

Yes, best to have a dose with food.

Wolverton

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14
Q

How are retinoids metabolised and excreted?

A

Hepatic metabolism (induced by the retinoids themselves, rather than liver enzymes)

Excreted in the urine and faeces (bilary)

Wolverton

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15
Q

What is the role of retinoids in the skin?

A

Vitamin A and its bioactive metabolites play a major role in promoting
the keratinocyte differentiation that occurs from the epidermal basal
layer to the stratum corneum.

Retinoids have:
* anti-keratinisation effects
* alter cellular cohesiveness
* anti-acne / anti-seborrheic effects
* anti-inflammaotry effects
* modulation of ECM production

Bolognia

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16
Q

What are the first generation retinoids? second generation? third generation? fourth generation?

A

First generation:
* Tretinoin
* Isotretinoin
* Alitretinoin

Second Generation:
* Acitretin

Third Generation:
* Adapalene
* Tazarotene
* Bexarotene

Fourth Generation:
* Trifarotene

Bolognia

17
Q

What are the main side effects of topical retinoids?

A

Local skin irritation
* reduced by titrating concentration of retinoid
* reduced by titrating frequency of applicaiton
* reduced by concominant emolliant use and suncream use

bolognia

18
Q
A
19
Q

What is the mechanism of aciton of topical steroids in acne?

A

normalization of differentiation and proliferation of the follicular epithelium

leads to the loosening and unseating of microcomedones, preventing obstruction of the pilosebaceous unit

Also have antiinflammatory activity

Bolognia

20
Q

What topical retinoids can be used in Acne?

A

Tretinoin
* photolabial

Adapalene
* Slightly better tolerability than tretinoin

Tazarotene

Trifarotene

Bolognia

21
Q

How are topical retinoids applied? What instructions should you give patients?

A

Applied to the entire face or all acne prone areas once a day as tolerated
* can start with less frequent applicaiton to improve tolerability
* Apply to dry skin
* Can apply moisturiser on top

Need to use for 6 - 8 weeks before benificial effects are evident

Bolognia

22
Q

What is the concentration of topical **tretinoin **commonly used for acne?

What is the concentration of topical **adapalene **commonly used for acne?

What is the concentration of topical **tazarotene **commonly used for acne?

What is the concentration of topical **trifaratene **commonly used for acne?

A

Tretinoin = 0.01 or 0.05% cream or gel

Adapalene = 0.1% cream or gel

Tazarotene = 0.05% or 0.1% cream or gel

Trifarotene = 0.005% cream

23
Q

What is the standard isotretinoin dosing?

What is the suggested cumulative dose of isotretinoin for a treatment course?

A

10 - 40mg a day (can go up to 1mg / kg /day however side effect profile much worse)

Cumulitative dose:
120 - 150 mg / kg

Bolognia

24
Q

Can topical adapalene be used in pregnancy?

A

According to the TGA it is catergory D = use should be avoided.

However, given very minimal systemic absorption, JAAD CME Dec 2024 - suggests low risk and ok in Pregnancy

Would need to be a discussion with the patient

JAAD Dec 2024 - CME

25
Q

Can topical tretinoin be used in pregnancy?

A

According to the TGA it is catergory D = use should be avoided.

However, human data suggests low risk and given very minimal systemic absorption, JAAD CME Dec 2024 - suggests low risk and ok in Pregnancy

Would need to be a discussion with the patient

26
Q
A

Pharmacology (5 decks)

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