Psoriasis Pharmacology Flashcards

Question

Cyclosporin A, Tacrolimus, Pimecrolimus Pharmacological Effect

Answer 1

Inhibits cytokine synthesis (IL 2,4,and 10) Prevents release of mediators from mast cells

Answer 2

Increased risk of development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression Increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infection

Answer 3

``` Nephrotoxicity (long term use) Hypertension Upper respiratory tract infections Burning and irritation of skin at application site Cough and headache ``` ``` Cyclosporin only: Gingival hyperplasia (gum overgrowth also occurs with phenytoin) Multiple drug interactions through P450 3A4 ``` Anti-rejection drugs – given to patients who have organ transplant – suppress the immune system so the organ will not be rejected Ensure that the patient is not sick – opportunistic infections may arise

Answer 4

Etanercept (Enbrel) Adalimumab (Humira) Infliximab (Remicade)

Answer 5

Binds free TNFa and reduces inflammation TNFa (keeps us from getting cancer, but in autoimmune diseases TNFa is too active) is a cytokine that kills off cells in our bodies – if it occurs in higher than normal levels, kills off cells that are not harmful

Answer 6

Ustekinumab (Stelera)

Answer 7

Inhibits IL-12 and IL-23 from binding to T-cells

Answer 8

Reduces the number and size of the plaques Really work! But are expensive and not especially safe (can be lethal) yet advertised frequently like they are aspirin

Answer 9

- Injection reactions – chills and site pain and inflammation - Serious infections and malignancies (make sure the person does not have any serious illness – TB) - Blood dyscrasias (reduces the # of RBC/WBC) - Upper respiratory tract infections and headache - Can worsen Chrone’s disease

Answer 10

Acitretin Tazarotene Calcipotriene Steroids

Answer 11

Binds to either RAR or RXR retinoid receptors A homodimer or heterodimer is formed which alters DNA transcription (Direct) binding RARE A single receptor complex binds to a transcription factor to alter DNA transcription (indirect) stops TRE binding

Answer 12

Reduces proliferation and enhances differentiation of keratinocytes Does not suppress sebum production as effectively as the other retinoids – not used in acne

Answer 13

Half life is 49 hours Drug is still detectable in the serum from 1 to 3 years after discontinuation You can’t give blood for 1 month after discontinuing accutane Cannot give blood or get pregnant for 3 years if you have taken soriatane (therefore is typically used in older, post menopausal)

Answer 14

``` Lip inflammation Alopecia Peeling on palms, soles and fingertips Dry nose and epitaxis Dry mouth and stomatitis ```

Answer 15

``` Ophthalmic: Eye irritation Dryness or thickening of conjunctiva Blurred vision Loss of eyelashes or brow ``` ***Pseudotumor cerebri*** (benign intercranial pressure) Smaller changes in blood lipids than isotretinoin (good for older patients) Everything dries up SEs are less severe than accutane

Answer 16

Teratogenic Should not be given to woman in child bearing years More teratogenic than isotretinoin Should not become pregnant or give blood up to 3 years after use Warnings Do not drink alcohol with this drug – increases the half-life Do not use any of the retinoids in patients with atopic dermatitis – further skin drying RAR – in the skin RXR – one that involves reproduction These drugs bind to both (RXR linked to teratogenicity) Soritane is oral

Answer 17

Tazorac (topical retinoid)

Answer 18

Same as Acitretin Binds to either RAR or RXR retinoid receptors A homodimer or heterodimer is formed which alters DNA transcription (Direct) binding RARE A single receptor complex binds to a transcription factor to alter DNA transcription (indirect) stops TRE binding

Answer 19

Same as Acitretin Reduces proliferation and enhances differentiation of keratinocytes Does not suppress sebum production as effectively as the other retinoids – not used in acne

Answer 20

Pruritis, burning, stinging, erythema, irritation, rash, peeling and dry skin Photosensitivity No known systemic side effects

Answer 21

Teratogenic Do not use in pregnancy While it doesn’t cross the skin, it should not be used in pregnancy to be safe Basically topical soritane

Answer 22

Calipotriene-VDR complex forms a heterodimer with retinoid receptors to alter DNA function – see nuclear receptor mechanism Binds with GRE, RAR, RXR, TRE Vitamin D drug The VDR binds RAR or RXR to form a heterodimer which then binds the RARE

Answer 23

Inhibits proliferation and promotes epidermal differentiation Decreases inflammation by decreasing inflammatory cytokine release

Answer 24

Topical side effects: Burning, itching, erythema, dry skin Hypercalcemia (Vit D regulates calcium) 6% of drug is absorbed through the skin Rare side effects: Skin atrophy, hyperpigmentation and folliculitis Pretty good drug – not as many side effects as retinoids Synthetic derivative of vitamin D3 which can cause an increase in calcium absorption and cause hypercalcemia

Answer 25

Steroids are called corticosteroids because they are formed in the adrenal cortex (WATCH FOR TEST SAYING MEDULLA=INCORRECT) Corticosteroids have two main effects - Na+ retention: mineralocorticoids - Hepatic glycogen storage: glucocorticoid Most corticosteroids have a mixture of these activities

Answer 26

Steroid Aldosterone is the endogenous steroid Acts on the kidneys to retain Na+ and thus retains water These usually have little anti-inflammatory activity

Answer 27

Steroid Cortisol and cortisone are the endogenous steroids Have significant effect on metabolism to help the body through stressful times (mobilize sugars) such as trauma, surgery, car accident etc These compounds usually have greater anti-inflammatory action

Answer 28

Glucocorticoids modulate inflammation either directly or indirectly by increasing the transcription of anti-inflammatory proteins or decreasing the transcription of inflammatory proteins Direct Mechanism – a homodimer binds to the Glucocorticoid Response Element (GRE) in the DNA Indirect Mechanism – a single receptor/steroid complex binds to AP-1 and NF-kB and prevents binding to the TRE

Answer 29

(Efficacy) A vasoconstrictor assay is used to measure efficacy 7 degrees of potency : ``` Steroids in each class have the same relative efficacy (they are all at a concentration that produces maximal response) Exception: Cutivate (clobetasol) – the strongest steroid = highest efficacy ```

Answer 30

``` Depends on: Concentration Efficacy Salt Vehicle Percutaneous absorption (Application) – goes through the plaque down into the skin to cause an effect ```

Answer 31

Optimized cream (propylene glycol) or ointment (highest efficacy) Ointment with less propylene glycol than optimized Cream less propylene glycol than optimized Alcoholic lotion (shampoo) Solution (shampoo) (lowest efficacy) Note: Sometimes the vehicle is more important than the drug itself The vehicle list is highest to lowest efficacy

Answer 32

- Proportional to the duration of use, area of coverage and thickness of skin (thin skin= increased absorption) - Abraded or inflammed skin is more permeable than regular skin - Occlusive dressing can enhance percutaneous absorption by as much as 10 fold (patient may be told to put saran wrap or an occlusive dressing over the affected area) - The skin acts as a reservoir so frequent dosing is not needed

Answer 33

High - scalp, axilla, face, eyelids, neck, perineum & genitalia (use low absorption drugs on highly permeable) Low - back, palms, and soles (use high absorption drugs on low permability)

Answer 34

Increased risk of local infection and masking of infection (change the immune system)

Answer 35

``` Atrophy of the dermis and epidermis (thin skin) Striae (stretch marks) Purpura (black and blue marks) Telangiectasia (spider veins) Acne Hypertrichosis (hair growth on face) Alopecia (hair loss on head) Cataracts and glaucoma (more frequent when steroids are used in inhalers) ```

Answer 36

Topical glucocorticoids can be absorbed in sufficient quantities to produce systemic side effects Usually only occurs under extreme use like when high potency with occlusive dressing are used over a large area of the body for a long period of time Long term oral use may cause round stomach distention Cushing’s Syndrome – excess steroids (almost entirely drug induced) - Rounding, puffiness and plethora of the face (moon face) - Fat redistributes to the face and trunk (buffalo hump) - Fine hair grows over the thighs, face and trunk - Alopecia Addison’s Syndrome – too little steroid (congenital or caused by abrupt discontinuation of overused steroids) Weakness & fatigue Weight loss Hyperpigmentation Hypotension Electrolyte imbalance Possible death if discontinued to rapidly Growth suppression in children

Answer 37

Important!! Adrenal Suppression aka HPA axis suppression: Naturally release steroids when under stress  Stress signals hypothalamus Hypothalamus releases CRH CGR stimulates anterior pituitary  anterior pituitary releases ACTH  ACTH stimulates of adrenal cortex  adrenal cortex releases cortisol  cortisol causes metabolic effects  metabolic effects cause negative feedback to turn off hypothalamus If we introduce steroids into the system, the brain thinks there are enough and doesn’t produce any more=adrenal gland atrophy (gets smaller) – if you don’t use it, you lose it  adrenal cortex will atrophy to the point that it will not function – may be lethal Adrenal suppression can occur at 14 days after beginning steroid therapy – use step-therapy Can not take for extended periods because it will kill us. Adrenal cortex is a lazy gland and if you don’t use it, it will atrophy and basically die off. If you don’t use it, you will lose it. When you need it such as in a stressful situation, it won’t work to make the steroids you need, and you die.

Answer 38

Methoxsalen

Answer 39

``` Belongs to the chemical class psoralens -Chromophore – a drug that is excited by a specific wavelength of light ``` The drug does not have activity until excited After exposure to UVA, methoxsalen combines with the DNA in epidermal cells by forming covalent linkages with pyrimidines (the linkages keep DNA from being made) Therapy with psoralens is called PUVA therapy

Answer 40

Normalizes number and arrangement of ketatinocytes Reorganizes cutaneous blood vessels Cytotoxic to T-cells Increases melanin pigmentation (darkens skin)

Answer 41

``` Pruritus Nausea Erythema & Blistering (could get sunburn) Hyperpigmentation Increased skin aging Increased risk of skin cancer Cataracts ```

Answer 42

Apremilast

Answer 43

Inhibits PDE4 which increases cAMP

Answer 44

Reduces plaques and psoriatic arthritis

Answer 45

Diarrhea, nausea and headache Use cautiously in depressed patients (screen for antidepressants etc)…could cause patient to commit suicide Weight loss (could lose 5% body weight-significant) Don’t use with strong cytochrome P450 enzyme inducers

Psoriasis Pharmacology Flashcards

(73 cards)