Chapter 9 anti inflammatory and immunomodulating agents -- immunosuppressive drugs for specific autoimmune diseases

Question 1

traditional medications

psoriasis drugs

Answer 1

• typically t’d with variety of topical meds (psoriasis — immune system becomes overactive, causing skin cells to multiply too quickly. Patches of skin become scaly and inflamed, most often on the scalp, elbows, or knees, but other parts of the body can be affected as well.)
  1) corticosteroids
  2) retinoids (slow down skin cell growth)
  3) coal tar
  4) tacrolimus (It can prevent organ rejection after transplant in its oral form. When applied topically it can treat a skin rash and type of eczema called atopic dermatitis.)
  5) pimocrolimus (treat mild to moderate atopic dermatitis (eczema) in patients who have already been treated with other medicines that did not work well)

oral meds – risk of systemic toxicity — vitamin D, methotrexate, cyclosporine (It can prevent organ rejection after transplant in its oral form. It can also treat rheumatoid arthritis and psoriasis. In eye drop form it can treat chronic dry eye.), retinoids, apremalast (treatment of certain types of psoriasis and psoriatic arthritis)

newer therapies — can target IL23 and IL17 that drive cascades in psoriasis

Question 2

risankizumab
guselkumab
tidrakizumab (ilumya)
//////
secukinumanb (cosentyx)
ixekizumab (taltz)
brodalumab (siliq)

psoriasis drugs

Answer 2

• IL23 inhibitors (top)
• IL17a inhibitors (bottom)
• activated meyloid dendritic cells release IL23, IL17 and other cytokines to activate T cells and other immunes cell in a pro inflammatory cascade that l/t keratainocyte proliferation (basal layer of the epidermis and start differentiating on their way to the surface, undergoing gradual differentiation), angiogenesis (formation of new blood vessels), and mvmt of immune cells into psoriatic lesions [scaly, inflamed]

monoclonal antibodie delievered subcutaneously at multi-week intervals

Question 3

interferon beta 1 (avonex,, betaseron, extavia, plegridy, rebif)

injectiable meds

Answer 3

• same as human interferon beta
• mech unknown

indication
* 1st line in relasping remitting multiple sclerosis (In MS, resulting nerve damage disrupts communication between the brain and the body.
Multiple sclerosis causes many different symptoms, including vision loss, pain, fatigue, and impaired coordination. The symptoms, severity, and duration can vary from person to person.)

• trail results showed ===> fewer exacerbations, reduce risk of disability progression, and less MS lesions in brain

effects
* depression
* suicide
* psychotic d/o
* hepatic injury
* seizures

Question 3

glatiramer (copaxone)

injectable med

Answer 3

• induce + activates drug-specific suppressor T cells that downregulate autoimmune response against myelin (lipid sheat that coats neurons and is damaged in MS) antigens
• 1st line in relapsing remitting MS

effects
* allergic rxn
* chest pain after 1 month of tx

Question 4

terflunomide (aubagio)

oral med - prioritize convenience

Answer 4

• pyramidine synthesis inhibitor
• mechanism for MS unclear

used safetly in combinatoin with interferon beta and glatiramer

effects
* severe hepatotoxicity
* alopecia
* paraesthesia
* diarrhea/nausea

Question 5

fingolimod (gilenya)

oral - convenience

Answer 5

• blocks lymphocyte from being released from lymph nodes — via spingosine 1-phosphate (S1P) receptor
• l/t less lymphocytes in circulation — l/t less autoimmune attacks on mylein sheaths in MS

effects
* severe infection risk
* arrhtymias
* progressive multifocal leukoencephalopathy (disease of the white matter of the brain)
* macular edema
* encephalopathy (any disturbance of the brain’s functioning that leads to problems like confusion and memory loss.)
* respiratory decline
* liver injury

Question 6

diemthyl fumarate (tecfidera)

oral - convenience

Answer 6

• reduces CD8 t cells
• mechanism unclear
• better tolerated than finglimod and may be the most effective (more than teriflunomide)

effects
* anaphylaxis
* progressive multifocal leukoencepahlopathy
* lymphopenia (which your blood doesn’t have enough white blood cells called lymphocytes — B cells, T cells, and natural killer cells. )
* flushing

Question 7

alemtuzumab (campath)

continuous IV – active and priortize efficacy

Answer 7

monoclonal antibody against CD52

for those who did not respond well to 2 or more dsiease modifying drugs

Question 8

ocrelizumab (ocrevus)

continuous IV - active disease

Answer 8

• monocloanl antibody against CD20

Question 9

natalizumab (tysabri)

continuous IV - active disease

Answer 9

• monoclonal antibody against a4-integrin
• data showed more efficacy over interferon beta 1 for reducing relapses

Question 10

mitoxantrone (novatone)

continuous IV

Answer 10

• cancer chemotherapy drug that interferes with topoisomerase II
• l/t impaired proliferation of b cells, t cells and macrophages
• impairs antigen presentation and blocks cytokine secretion