Pharmacology: Immunosuppressive Drugs

Question 1

List the possible Indications for Immunosuppression.

Answer 1

1. Organ Transplants(Kidney, Heart, Liver, Lung)
2. Auto-immune disease
3. severe **allergies. **

Question 2

Describe the general procedure for Organ Transplants

Answer 2

1. Sequential Immunotherapy
2. Antibodies are used as induction agents
3. Mantainabce therapy-using multiple drugs

(NB) There can be rejection episodes, when high doses of glucocorticoids are used

Question 3

List the drugs (classes) available for use as Immunosuppressive Drugs

not specif drugs, but classes of the drugs

Answer 3

1. GLucocorticoids
2. Calcineurin (CAL-CI-NEURIN) Inhibitors (Includes Cyclosporin and Tacrolimus)
3. mTOR Inhibitors (includes Sirolimus)
4. Mycophenolate Mofetil
5. Cytostatics (includes Azathioprine)
6. Antibodies

Question 4

Calcineurin Inhibitors

Describe the MOA, Pharmacokinetics and adverse effects of Cyclosporine and Tacrolimus

Answer 4

Mech. Of Action (for both)
They penetrate T cells, bind to immunophilin and form heterodimer, which inhibits phosphatase activity and prevents translocation of NFATc to nucleus, which prevents transcription of cytokine genes[Gm-CSF, IL-2,3,4, TNF-a, IFN-y]

Adverse Effects(for both)
1. Nephrotoxicity (which is common)
2. Hypertension
3. Neurological: tremor–>seizures
4. CI pregnacy
5. Haemolytic Uremic Syndrome
6. Gingival hyperplasia

NB: Therepeutic Drug Monitoring is required for CYCLOSPORIN

Pharmacokinetics
Both]]
1. Given ORALLY or IV
2. Metabolised in the LIVER
3. food impairs absorption
4. Drug Interactions
Decrease metabolism- HIV Protein Inhibitors, Antifungals, Antibiotics, Grapefruit Juice
Increase Metabolism- Rifampicin

Question 5

mTOR inhibitors

Discuss the MOA, Pharmacokinetics, Indications and adverse effects of mTOR inhibitors

The mTOR inhibitor you should know is Sirolimus

-limus is an mTOR inhibitor

Answer 5

Pharmacokinetics
Oral Admin, food interefers,
it is synergisitc with CsA(Cyclosporin)
Indications
Post-transplant
Adverse Effects
Increased triglycerides and cholesterol
Increase nephrotoxicity when with CSA
Anaemia
Leukopaenia
Thrombocytopenia
Delayed wound healing
MOA
Binds FKBP12 and inhibits mTOR

mTOR= molecular Target of Rapamycin

Question 6

Mycophenolate Mofetil

Describe the Indications, Adverse effects and immunosuppressive effects of Mycophenolate Mofetil

Answer 6

Indications
used with sirolimus to monitor blood levels
Combination therapy with Glucocorticoid and CSA
Adverse Effects
Leukopenia
Diarrhaoe
Vomiting
CMV infections common

Question 7

Cytostatic Agents

Name the cytostatic agent commonly used, its Mech, Of Action, Drug Interactions and its adverse effects.

Answer 7

Azathioprine

Mech. Of Action
Inhibits Purine Biosynthesis(Adenine and Guanine)
Only activated in immune cells
Drug Interactions
Allopurinol–inhibits the metabolism of 6-MP leading to toxic effects
Adverse Effects
Myelosuppression
Hepatotoxicity
GIT
Pancreatitis

Question 8

Antibodies

Describe the Use, MOA and problems with use of Muromonab-CD3

Answer 8

USE
Acute Rejection

MOA
Modulates T-cell receptor
Leads to rapid depletion of T-cells
Depletes cytokine levels

Problems
Cytokine storm
Pulmonary Oedema
Acute renal failure
Opportunistic Infections
Hypersensitivity