PHRM 6-7

• Immunomodulators


  Drugs that can support the immune function by modifying, in a beneficial way, the immune system's response to a threat
• Conditions treated with immunomodulators


  • Multiple sclerosis
  • Hereditary angioedema
  • Rheumatoid arthritis
  • Cryopyrin-associated periodic syndromes
• How immunomodulators work


  1. Decreasing inflammation and preventing nerve damage

  2. Preventing the immune system from attacking the nerves in the brain and the spinal cord

  3. Blocking a natural substance "kallikrein" which acts to increase another natural substance "bradykinin"

  4. Helping to slow down or stop the growth of the cancer cells

  5. Blocking the activity of interleukin, a substance in the body that causes inflammation

  6. Blocking a natural protein "interleukin-1" that may worsen the symptoms
• Conditions that use immunomodulators

  • Multiple Sclerosis
  • Hereditary Angioedema
  • Acute Lymphatic leukemia
  • Rheumatoid arthritis
  • Crohn's disease
  • Ulcerative Colitis
  • Condylomata acuminata
  • Cryopyrin-associated periodic syndromes
  • Deficiency of Interleukin-1 receptor antagonist
  • Pericarditis
  • Bronchiolitis obliterans
  • Kidney transplant rejection
  • Capillary leakage syndrome
  • Friedreich's ataxia
  • Amyotrophic Lateral Sclerosis (ALS)
  • Hemophagocytic Lymphohistiocytosis
  • Demyelinating Polyneuropathy
  • Multicentric Castleman disease
  • Familial Cold Auto-inflammatory Syndrome
  • Muckle Wells Syndrome
  • Neonatal-onset multisystem inflammatory disease
• Side effects of immunomodulators

  • Abdominal Pain
  • Asthenia (Physical Weakness Or Lack Of Energy)
  • Chills
  • Diarrhea
  • Constipation
  • Dyspnea (Shortness Of Breath)
  • Fever
  • Headache
  • Malaise (A Feeling Of Weakness, Overall Discomfort, And Illness)
  • Nausea
  • Vomiting
  • Flushing
  • Muscle Cramps
  • Back/Joint Pain
  • Drowsiness
  • Pain, Redness, Swelling, Itching, Or Lump At The Injection Site
• Other rare side effects of immunomodulators

  • Leukopenia (reduced number of WBC)
  • Peripheral edema (swelling of lower legs and hands
  • Tachycardia (a fast heart rate – more than 100 beats per minute)
  • Thrombocytopenia (low blood platelet count)
  • Dizziness (feeling faint, weak, or unsteady)
  • Elevated liver function test
  • Increased sweating
  • Alopecia (a condition that causes hair to fall out in small patches)
  • UTI
  • Mental/mood changes (depression, thoughts of suicide)
  • Rapid and swallow breathing
  • Chest pain/heaviness
  • Swelling of the ankles, feet, and hands
  • Trouble sleeping
  • Hallucinations (involves hearing, seeing, feeling, smelling, or even tasting things that are not real)
  • Hives (itchy, raised welts that are found on the skin)
  • Wheezing
  • Skin rash on the arms or cheeks
  • Unusual weight gain
  • Liver problems
  • Signs of kidney problems
• Immunosuppressants


  Drugs that suppress the immune response
• Classification of immunosuppressants


  • Calcineurin inhibitor
  • Antiproliferative and Cytotoxic agents
  • mTOR (mammalian target of rapamycin) inhibitors
  • Glucocorticoids
  • Biologics
• Calcineurin inhibitors


  Immunosuppressants used to manage autoimmune conditions
• Modes of administration for calcineurin inhibitors

  • Oral
  • Intravenous
  • Topical
  • Ophthalmic
• Cyclosporine use is associated with premature births and low birth weight
• Oral tacrolimus is associated with premature delivery, low birth weight, high potassium, and kidney dysfunction in the fetus
• Lupkynis should not be used in women who are pregnant or breastfeeding due to lack of safety data
• Topical calcineurin inhibitors and cyclosporine eye drops do not pose any risk to the fetus and are safe to use during pregnancy and breastfeeding
• How calcineurin inhibitors work

  1. Blocking the activity of calcineurin

  2. Preventing T cells from producing interleukin-2 (IL-2)

  3. Making T cells less responsive to antigens
• Side effects of calcineurin inhibitors (oral administration)

  • Diarrhea
  • Nausea
  • Vomiting
  • Stomach upset
  • Headache
  • cough
  • Nephrotoxicity (kidney damage)
  • Hepatotoxicity (liver damage)
  • Infections
  • Increased risk of lymphomas
  • Increased risk of cutaneous squamous cell carcinoma
  • High blood pressure
  • High cholesterol
  • High potassium
  • Elevated uric acid levels
  • Low magnesium
  • Tremors (shaking)
  • Alopecia (hair loss)
  • Acne
• Side effects of calcineurin inhibitors (cream & ointment)

  • Burning, redness, itching at the application site
  • Fever
  • Headache
  • Nausea
  • Cough
  • Nasal congestion
  • Sinusitis (inflamed sinuses)
  • Upper respiratory tract infection
  • Sore throat
  • Acne
  • Worsening of asthma symptoms
  • Folliculitis (inflamed hair follicles)
  • Skin infections
• Side effects of calcineurin inhibitors (eye drops)

  • Blurred vision
  • Burning, stinging, or itching of the eyes
  • Discharge from the eyes
  • Headache
  • Lacrimation (excessive tears)
• Nursing responsibilities for calcineurin inhibitors

  • Patients should not receive vaccines containing live viruses during treatment
  • Patients must report signs of infection promptly
  • Liver and kidney function must be monitored
  • Check patient's blood pressure regularly
  • Monitor for allergic reaction
  • Patients with severe gout should not take cyclosporine
  • Advise patients to wear sunscreen and avoid sun exposure with tacrolimus
  • Avoid certain interactions with other medications
• Antiproliferative agents


  Disease-modifying anti-rheumatic drugs (DMARDs) that reduce the activity of the immune system
• Azathioprine


  An example of an antiproliferative agent, also known as Imuran or Azapress
• Mechanism of action of antiproliferative agents

  1. Taken up into the immune cells

  2. Activated to 6-mp

  3. Inhibits purine synthesis

  4. Inhibition of cell proliferation and impairment of lymphocyte function
• Indications for antiproliferative agents


  • Kidney transplant rejection
  • Rheumatoid arthritis
  • Crohn's disease
  • Ulcerative colitis
• How to use azathioprine


  1. Take by mouth as directed, usually once or twice daily

  2. Take with food to reduce stomach upset
• Drugs that should not be taken with Lupkynis


  • cyclophosphamide
  • ketoconazole
  • itraconazole
  • clarithromycin
• Drugs that may not be safe to take with cyclosporine

  • Simvastatin
  • dronedarone
  • cisapride
• Antiproliferative agents


  A disease-modifying anti-rheumatic drug (DMARD) that works by reducing the activity of the body's immune system, which may be overactive in some conditions
• Antiproliferative agent


  • Azathioprine
• Azathioprine


  It is a purine antimetabolite, sometimes known as Imuran or Azapress
• Mechanism of action of azathioprine

  1. Taken up into the immune cells

  2. Activated to 6-mp

  3. Inhibits purine synthesis

  4. Inhibition of cell proliferation and impairment of lymphocyte function
• Indications for antiproliferative agents

  • Kidney transplant rejection
  • Rheumatoid arthritis
  • Crohn's disease
  • Ulcerative colitis
• Side effects of azathioprine

  • Nausea/vomiting
  • Abdominal pain
  • Temporary hair loss
  • Diarrhea
  • Worsening joint/muscle pain
• More serious side effects of azathioprine


  • Dark urine
  • Yellowing eyes/skin (jaundice)
  • Loss of balance/coordination
  • Weakness
  • Confusion
  • Difficulty concentrating
  • Clumsiness
  • Difficulty talking/walking
  • Seizure
  • Vision changes
  • Rash
• Nursing responsibilities for azathioprine

  • Advise patient to limit time under the sun, wear sunscreen and protective clothing
  • Tell patient to avoid contact with people who have infections
  • Avoid receiving live vaccine
  • Pregnant women should not take this drug or even breathe the dust from the tablet
  • Advise female patients who are planning to become pregnant not to become pregnant while using azathioprine
  • Watch out for any allergic reaction
  • This medication passes into breast milk, ask patient to consult a doctor before breast-feeding
  • Some products may interfere with azathioprine, tell patient not to combine with these drugs
  • CBC, liver/kidney function should be monitored while taking this drug
  • If the patient missed a dose, take it as soon as the patient remember, do not double the dose
• mTOR inhibitors


  A class of drugs that inhibit the mechanistic target of rapamycin (mTOR), a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinase (PIKKs)
• mTOR inhibitors


  • Sirolimus and Everolimus
• Adverse drug reactions of mTOR inhibitors


  • Hyperlipidemia
  • Impaired wound healing
  • Thrombocytopenia
• Mechanism of action of mTOR inhibitors


  1. It forms complex with an immunophilin

  2. Inhibits a key enzyme in cell cycle progression

  3. Inhibits the response of interleukin-2

  4. Blocks activation of T-cells and B-cells
• Sirolimus


  An mTOR inhibitor
• Indications for sirolimus


  • Kidney transplant rejection
  • Lymphangioleiomyomatosis (LAM) - lung disease