Immunosuppressive drugs are essential in managing various medical conditions, particularly in preventing organ transplant rejection and treating autoimmune diseases. They can be classified into five main groups:

1. Glucocorticoids: These are steroid hormones that reduce inflammation and suppress the immune response. They work by inhibiting the production of inflammatory cytokines and reducing the proliferation of immune cells. Common glucocorticoids include prednisone and dexamethasone. Their effects include:

   • Mechanism of Action: Glucocorticoids inhibit the expression of genes coding for pro-inflammatory cytokines (e.g., IL-1, IL-2, TNF-α).

   • Clinical Uses: They are used in conditions like rheumatoid arthritis, lupus, and to prevent transplant rejection.

   • Side Effects: Long-term use can lead to osteoporosis, weight gain, diabetes, and increased risk of infections.

2. Cytostatic Drugs: These agents inhibit cell division and are often used in cancer treatment as well as in autoimmune diseases. They include:

   • Examples: Cyclophosphamide, azathioprine, and methotrexate.

   • Mechanism of Action: They interfere with DNA synthesis and cell proliferation, particularly affecting rapidly dividing cells.

   • Clinical Uses: Effective in treating cancers, systemic lupus erythematosus, and other autoimmune disorders.

   • Side Effects: Can cause bone marrow suppression, leading to increased risk of infections and anemia.

3. Antibodies: This group includes monoclonal and polyclonal antibodies that target specific components of the immune system.

   • Types:

     • Monoclonal Antibodies: Such as basiliximab and daclizumab, which target the IL-2 receptor to prevent T-cell activation.
     • Polyclonal Antibodies: These are derived from multiple B-cell clones and can broadly suppress immune responses.

   • Clinical Uses: Used in organ transplantation and to treat autoimmune diseases.

   • Side Effects: Risk of infections and allergic reactions due to immune suppression.

4. Drugs Acting on Immunophilins: These drugs modulate immune responses by binding to immunophilins, which are proteins that assist in the folding of other proteins.

   • Examples: Cyclosporine and tacrolimus.

   • Mechanism of Action: They inhibit calcineurin, a phosphatase involved in T-cell activation, thereby reducing the production of IL-2.

   • Clinical Uses: Primarily used in organ transplantation to prevent rejection.

   • Side Effects: Nephrotoxicity, hypertension, and increased risk of infections.

5. Other Drugs: This category includes various agents that do not fit neatly into the other classifications but still have immunosuppressive effects.

   • Examples: Mycophenolate mofetil and sirolimus.

   • Mechanism of Action: Mycophenolate inhibits lymphocyte proliferation by blocking purine synthesis, while sirolimus inhibits mTOR, affecting T-cell activation and proliferation.

   • Clinical Uses: Used in transplant patients and in some autoimmune diseases.

   • Side Effects: Gastrointestinal disturbances, increased risk of infections, and potential for malignancies.

Effects and Toxic Actions on Organ Systems

1. Local anesthetics (dose dependent) interfere with transmission in any excitable tissue (e.g. CNS and CVS).

2. CNS effects

 a. Central neurons very sensitive.

 b. Excitatory-dizziness, visual and auditory disturbances, apprehension, disorientation and muscle twitching more common with ester type agents.

 c. Depression manifested as slurred speech, drowsiness and unconsciousness more common with amide type agents (e.g. lidocaine).

 d. Higher concentrations of local anesthetic may eventually produce tonic-clonic[grand mal]  convulsions.

 e. Very large doses may produce respiratory depression which can be fatal. Artificial respiration may be life-saving.

 3.CVS effects

 a. Local anesthetics have direct action on the myocardium and peripheral vasculature by closing the sodium channel, thereby limiting the inward flux of sodium ions.

 b. Myocardium usually depressed both in rate and force of contraction. Depression of ectopic pacemakers useful in treating cardiac arrhythmias.

 c. Concentrations employed clinically usually cause vasodilation in area of injection.

 d. Vasoconstrictors such as epinephrine may counteract these effects on myocardium and vasculature.

4.  Local Tissue Responses

 a. Occasionally focal necrosis in skeletal muscle at injection site, decreased cell motility and delayed wound healing.

 b. Tissue hypoxia may be produced by action of excessive amounts of vasoconstrictors.

Lithium carbonate: 1st choice (controls mania in bipolar disorders); delay before onset of therapeutic benefit; no psychotropic effects in normal humans

i. Mechanism: blocks enzymes in inositol phosphate signaling pathway; no consistent effects of lithium on NE, 5-HT, and DA
ii. Side effects: severe CNS (ataxia, delirium, coma, convulsions) and CV (cardiac dysrhythmias)

Kinins
Peptide that are mediated in the inflammation.
Action of kinin:
On CVS: vasodilatation in the kidneys, heart, intestine, skin, and liver. It is 10 times active than histamine as vasodilator.

On exocrine and endocrine glands: kinin modulate the tone of pancreas and salivery glands and help regulate GIT motility, also affect the transport of water and electrolytes, glucose and amino acids through epithelial cell transport.

Sympatholytics (Antiadrenergic Agents)

PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent 

It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension. 
It increases the cardiac output and decreases the total peripheral resistance.

It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.

Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.

ERGOT ALKALOIDS

 Ergotamine is an  important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.

METHYSERGIDE

It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine. 

SUMATRIPTAN

It is a potent selective 5-HT 1D  receptor agonist used in the treatment of migraine.

PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1  receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.

TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½

DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.

TAMSULOSIN
It is uroselective α1A  blocker and has been found effective in improving BPH symptoms.

Other drugs used for erectile dysfunction

Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.

Methyl salicylate

also known as oil of wintergreen, betula oil, methyl ester) is a natural product of many species of plants Structurally, it is methylated salicylic acid It is used as an ingredient in deep heating rubs