Characteristics of Opioid Receptors

mu₁

Agonists : morphine phenylpiperidines

Actions:  analgesia bradycardia sedation

mu₂

Agonists : morphine phenylpiperidines

Actions:  respiratory depression euphoria physical dependence  

delta

Actions:  analgesia-weak,  respiratory depression

kappa

Agonists: ketocyclazocine dynorphin nalbuphine butorphanol

Actions:  analgesia-weak respiratory depression sedation

Sigma

Agonists: pentazocine

Action: dysphoria -delerium hallucinations tachycardia hypertension

epsilon:

Agonists: endorphin

Actions: stress response acupuncture

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.

Carbenicillin

Antibiotic that is chemically similar to ampicillin. Active against gram-negative germs. It is well soluble in water and acid-labile.

Mefenamic acid

Analgesic, anti‐inflammatory properties less  effective than aspirin 

Short half‐lives, should not be used for longer  than one week and never in pregnancy and in  children. 

Enhances oral anticoagulants

Used to treat pain, including menstrual pain. It decreases inflammation (swelling) and uterine contractions.

Ofloxacin : It is a quinolone antibiotic and similar in structure to  levofloxacin. It is an alternative treatment to ciprofloxacin for anthrax.

Pharmacokinetics

Pharmacokinetics is the way that the body deals with a drug - how that drug moves throughout the body, and how the body metabolizes and excretes it.  The factors and processes involved in pharmacokinetics must be considered when choosing the most effective dose, route and schedule for a drug's use.

The four processes involved in pharmacokinetics are:

Absorption:  The movement of a drug from its site of administration into the blood.

Several factors influence a drug's absorption:

• Rate of Dissolution:  the faster a drug dissolves the faster it can be absorbed, and the faster the effects will begin.
• Surface Area:  Larger surface area = faster absorption.
• Blood Flow:  Greater blood flow at the site of drug administration = faster absorption.
• Lipid Solubility:  High lipid solubility = faster absorption
• pH Partitioning:  A drug that will ionize in the blood and not at the site of administration will absorb more quickly.

Distribution:  The movement of drugs throughout the body.

Metabolism:  (Biotransformation) The enzymatic alteration of drug structure.

Excretion:  The removal of drugs from the body.

As a drug moves through the body, it must cross membranes.  Some important factors to consider here then are:

Body's cells are surrounded by a bilayer of phospholipids (cell membrane).

There are three ways that a substance can cross cell membranes:

• Passing through channels and pores: only very small molecules can cross cell membranes this way.

• Transport Systems:   Selective carriers that may or may not use ATP.

• Direct Penetration of the Cell Membrane: