Transplantation

Drug
Presented BY:
1-Sajad abbas Fadhil
Therapy
2-Sajad jamel salim
3-Sajad mohammed hasan
4-Sabaa ali jamel
5-Sarah redha sadam
6-Sarah Saleem muhsen
7-Sarah Abdulsalam abdulsaed
8-Sarah ali matrood
9-Sami laith sami
10-Saja Hussain fadhil
 Transplantation

➢ Is a life-saving surgical procedure in patients with

end-stage organ failure in which an organ, tissue are
removed from one person (the donor) and
transplanted into another person (the recipient).

➢ It's critical to restore the function to improve quality

of life.
 Transplantation
drug therapy

➢ Is the use of drugs to prevent the body from rejecting a

transplanted organ or tissue to ensure the success of
the transplant.

➢ These drugs are called immunosuppressants or anti-

rejection drugs

➢ They work by suppressing the immune system and

preventing it from attacking the transplanted organ or
tissue.
➢ There are two main types of immunosuppressants:

1. Induction drugs: Powerful anti-rejection

medications used at the time of the organ
transplantation, this helps ensure transplant
success.

2. Maintenance drugs: Anti-rejection

medications used for the long term to prevent
rejection.
The preoperative During transplantation
Post-operative drug :
medications : surgery :

1.Immunosuppressive 1.Anesthetics 1.Immunosuppressiv

drugs 2.Antibiotics e drugs
2.Antibiotics 3.Anticoagulants: 2.Antibiotics
3.Antifungal drugs 4.Immunosuppressants 3.Antifungal drugs
4.Anti-thrombotic drugs 5.Steroids 4.Pain medication
5.Pain medication 6.Fluids and electrolytes 5.Anti-hypertensive drugs
6.Anti-anxiety medication 6.Diuretics
7.Corticosteroids
 classes of transplantation drug therapy used to prevent transplant
rejection:

1.Calcineurin
inhibitors: This
class of drugs,
including
cyclosporine
and tacrolimus
2.Antiproliferative agents:
This class of drugs, 4.mTOR inhibitors: This
including azathioprine, 3.Monoclonal antibodies: class of drugs, including
mycophenolate,and This class of drugs, sirolimus and everolimus
methotrexate including basiliximab and
rituximab
 TYPES OF TRANSPLANTATION DRUG
1- Cyclosporine:
is an immunosuppressive agent used to treat organ rejection post-transplant. It
also has use in certain other autoimmune diseases.

Mechanism of action:
THERAPEUTIC USE :

•In solid organ transplantation, it has clinical use to treat organ rejection in kidney,
liver, and heart allogeneic transplants.
•In patients with rheumatoid arthritis, it is indicated when the disease has not
adequately responded to methotrexate.

• In patients with amyotrophic lateral sclerosis (ALS), cyclosporin is approved to

treat amyotrophic lateral sclerosis and its variants.
• In nephrotic syndrome, it is indicated to treat focal segmental glomerulosclerosis
not responding to corticosteroids.
Pharmacokinetic
Administration: oral or intravenous (IV)
Metabolism: Via hepatic CYP3A4 have half life 8 to 27 hours
Excretion: Mainly bile and feces.

Adverse Effects:
hypertension ,hyperglycemia, hyperlipidemia
headache ,fever and increase risk of malignancy
 2. azathioprine

● is an immunosuppressive agent that acts

through its effects as an antagonist of purine
metabolism, resulting in the inhibition of
deoxyribonucleic acid (DNA), ribonucleic acid
(RNA), and protein synthesis
Mechanism of action
● Pharmacokinetic
● Administration: Oral azathioprine is well absorbed.
● half life of azathioprine is approximately 5 hours and elimination in
urine

● Drug interaction:
● Azathioprine cannot use xanthine oxidase inhibitors (allopurinol) use
to treatment of gout which lead to increase level of 6MP and loxicity
of azathioprine greater .
● Clinical use:
● azathioprine can be use after kidney transplantation it can also be used
autoimmune disorder include glomerular nephritis and hemolytic anemia

● Adverse effects:
● because it effect on nucleic acid it can lead to bone marrow suppression
● skin cancer and lymphoma
● nausea and vomiting
 3 . Tacrolimus

● Tacrolimus, sold under the brand name

Prograf among others, is an
immunosuppressive drug. This medicine is
used for: Suppressing immunity after
transplanting organs such as the heart, kidney
or liver (used by mouth or by injection)
Mechanism of action
● Pharmacokinetics :

● The absorption of tacrolimus occurs in the small intestine

and is decreased substantially by the presence of food. The
bioavailability ranges from 5-93% with a mean of 25% in the
adult population . Tacrolimus is completely metabolised prior
to elimination. The mean disposition half-life is 12hours .
● The elimination of tacrolimus is decreased in the presence of
liver impairment and in the presence of several drugs
 Therapeutic use
1. Tacrolimus is an immunosuppressive drug
whose main use is after organ transplant to
reduce the activity of the patient’s immune
system and so the risk of organ rejection.

2. Tacrolimus topical is used on the skin to

treat moderate to severe atopic dermatitis
in patients who have received other
medicines that have not worked well.
• Common side effects :
• Nephrotoxicity , stomach
pain , headache .
• oral Tacrolimus may
increase your risk of
getting skin cancer or
cancer of the lymph
system (lymphoma)
Prednisone :

➢ Classified as a corticosteroid or a steroid hormone, prednisone

is similar to the steroid hormone your body produces naturally.
Prednisone might be given along with other immunosuppressive
medicines to prevent and treat rejection.

Side effects:

➢ Increased appetite, which might result in weight gain.

➢ Excess hair growth on the face, back, arms, and legs.
➢ Increased swelling of the face, hands, or ankles.
➢ Mouth sores..
Mechanism of action :

➢ Prednisone decreases inflammation via suppression of the migration of

polymorphonuclear leukocytes and reversing increased capillary
permeability. It also suppresses the immune system by reducing the activity
and the volume of the immune system
 Pharmacokinetics :

➢ Prednisone is absorbed in the gastrointestinal tract and has a half life of 2–3 hours.it
has a volume of distribution of 0.4–1 L/kg.

➢ The drug is cleared by hepatic metabolism using cytochrome P450 enzymes.

Metabolites are excreted in the bile and urine

Medical uses :

➢ As part of a drug regimen to prevent rejection after organ transplant

➢ Allergic disorders

➢ Adrenocortical insufficiency
 Sirolimus
➢ is a mammalian target of rapamycin (mTOR)
inhibitor that inhibits cell cycle progression and
has proven to be a potent immunosuppressive
agent for use in solid organ transplant recipients.

➢ The drug was initially studied as an adjunct to

ciclosporin (cyclosporine) to prevent acute
rejection in kidney transplant recipients.

➢ The most common adverse effects of

sirolimus are hyperlipidaemia and
myelosuppression.
Pharmacodynamics :

➢ Unlike the similarly named tacrolimus, sirolimus is not a calcineurin inhibitor, but it has a
similar suppressive effect on the immune system.

➢ Sirolimus inhibits IL-2 and other cytokine receptor-dependent signal transduction

mechanisms, via action on mTOR, and thereby blocks activation of T and B cells.
Ciclosporin and tacrolimus inhibit the secretion of IL-2, by inhibiting calcineurin.
Medical uses :

➢ Sirolimus is indicated for the prevention of organ transplant rejection and for the
treatment of lymphangioleiomyomatosis (LAM).

➢ Sirolimus (Fyarro), as protein-bound particles, is indicated for the treatment of adults

with locally advanced unresectable or metastatic malignant perivascular epithelioid cell
tumor (PEComa)
Mehanism of action :

The mode of action of sirolimus is to bind the cytosolic protein FK-binding protein
12 (FKBP12) in a manner similar to tacrolimus. Unlike the tacrolimus-FKBP12 complex,
which inhibits calcineurin (PP2B), the sirolimus-FKBP12 complex inhibits
the mTOR (mammalian Target Of Rapamycin, rapamycin being another name for
sirolimus) pathway by directly binding to mTOR Complex 1 (mTORC1).
 Common drug interactions
● The necessity for polypharmacy increases the potential for
serious drug interactions. Drug interactions, by definition, occur
when substances alter the nature, the magnitude, or the duration
of the pharmacologic effect of another drug.

● Interactions affecting drug metabolism are common and typically

involve the cytochrome P-450 enzyme system (CYP450)

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● Fungal infections are estimated to occur in 5% of kidney transplant
recipients and up to 40% of liver recipients.8 The azole antifungals
(ketoconazole, fluconazole, itraconazole, voriconazole) are well-
documented to inhibit the clearance of the calcineurin
immunosuppressants, often producing toxic drug levels

● Bacterial infections are among the leading complications occurring

posttransplant.10 Whereas numerous agents are available for the
treatment of these infections, one must keep in mind the potential for
drug interactions. Macrolide antibiotics (erythromycin, clarithromycin)
and the new ketolide (telithromycin) are strong CYP3A4 inhibitors

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● Hypertension is a common comorbidity affecting a large proportion of
transplant patients. Of the many different approved antihypertensives, only
calcium channel blockers complicate immunosuppressive management.
Nondihydropyridine calcium channel blockers (verapamil, diltiazem) are well-
known inhibitors of immunosuppressant metabolism.

● Posttransplant depression is associated with medication noncompliance, and

treatment may be complicated by multiple drug interactions. Most selective
serotonin reuptake inhibitors (SSRIs)? such as fluvoxamine, fluoxetine,
paroxetine, sertraline, and escitalopram?are weak inhibitors of CYP3A4.
● Nefazodone, a mixed SSRI and norepinephrine reuptake inhibitor, is a potent
CYP3A4 inhibitor and should be avoided in transplant patients due to the
potential for severe toxicity.

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 Side effects
The most significant side effect of immunosuppressant
drugs is an increased risk of infection such as urinary tract
infections (UTIs), colds and flu, are common after kidney
transplants.
You can also get more serious infections, such as
pneumonia and cytomegalovirus (CMV), Other
less serious side effects can
include loss of appetite, nausea, vomiting, increased hair
growth,and hand trembling.
The following side effects indicate the need for
immediate attention:
➢ A feeling of being unusually tired or weak.
➢ Fever above 100 degrees or chills.
➢ Frequent urination or burning when you pass your urine.
➢ A cold or cough that will not go away.
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Side effects of drug for kidney transplant
•Immunosuppressants prevent your body's immune system from attacking the new kidney,
Which would cause the transplanted kidney to be rejected.

• A combination of 2 or 3 different immunosuppressants is usually taken long term

These can cause a wide range of side effects, including:
➢ An increased risk of infections
➢ An increased risk of diabetes
➢ High blood pressure
➢ Weight gain
•Abdominal pain
•Diarrhoea
•Extra hair growth or hair loss
•Swollen gums
•Bruising or bleeding more easily
•Thinning of the bones
•Acne
•Mood swings
The long-term use of Immunosuppressants also Increases your risk of developing some
types •
of cancer, particularly types known to be caused by viruses (as you will be more
vulnerable to the effects of infection)
•An increased risk of certain types of cancer, particularly skin cancer
•Side effects should Improve once the right dosage Is identified. Even if your
side effect
become troublesome, never suddenly stop taking your medicine because your
kidney could be rejected.
 Conclusion

● The results of organ transplantation has majorly

improved since the development of
immunosuppressive drugs.

● Because it helped ensure that the transplanted organ

or tissue was not rejected by the body, and it could
help reduce the risk of complications.
But there is problem with side effects of these drugs
can be severe, resulting in a shorter life expectancy
for transplant patients compared to the general
population

So pharmacists work to develop new therapists that

can induce immune tolerance in combination with no
or limited side effects .
Fortunately, many new strategies for induction of
immune tolerance are being explored. For example,
therapy based on Treg. cells and novel
immunosuppressive bio similar (such as anti-IL-6) is
emerging to prevent rejection after transplantation.
THANK You