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Pharmacology

Aspirin

Mechanism of Action

ASA covalently and irreversibly modifies both COX-1 and COX-2 by acetylating serine-530 in the active site Acetylation results in a steric block, preventing arachidonic acid from binding

Uses of Aspirin

Dose-Dependent Effects:

Low: < 300mg blocks platelet aggregation

Intermediate: 300-2400mg/day antipyretic and analgesic effects

High: 2400-4000mg/day anti-inflammatory effects

Often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant (blood thinning) effect and is used in long-term low-doses to prevent heart attacks

Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks

Its primary undesirable side effects, especially in stronger doses, are gastrointestinal distress (including ulcers and stomach bleeding) and tinnitus. Another side effect, due to its anticoagulant properties, is increased bleeding in menstruating women.

Diphenoxylate (present in Lomotil)

  • A meperidine congener
  • Not absorbed very well at recommended doses.
  • Very useful in the treatment of diarrhea.

Immunosuppressive antibodies can be classified mainly into monoclonal and polyclonal antibodies, targeting specific components of the immune system.

  1. Monoclonal Antibodies:

    • Basiliximab: Targets the IL-2 receptor on T cells, inhibiting T-cell activation. It is FDA approved for use in renal transplantation to prevent acute rejection.

    • Alemtuzumab: Targets CD52, a protein found on the surface of mature lymphocytes. It is used for treating chronic lymphocytic leukemia and as an induction agent in kidney transplantation.

    • Rituximab: Targets CD20 on B cells, leading to B-cell depletion. It is used in various conditions, including non-Hodgkin lymphoma and rheumatoid arthritis.

    • Daclizumab: Targets the IL-2 receptor (CD25) and is used in renal transplantation to prevent acute rejection.

    • Eculizumab: Targets complement component C5, inhibiting the complement cascade. It is used in conditions like paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

  2. Polyclonal Antibodies:

    • Rabbit Antithymocyte Globulin (rATG): A polyclonal antibody that targets multiple T-cell surface markers, leading to T-cell depletion. It is used as an induction agent in kidney transplantation and for treating acute rejection.

    • Equine Antithymocyte Globulin (eATG): Similar to rATG, it targets T cells and is used in transplantation settings.

  3. Mechanisms of Action:

    • Depletion of Immune Cells: Many antibodies work by depleting specific immune cell populations (e.g., T cells or B cells) to reduce the immune response against transplanted organs or in autoimmune diseases.

    • Blocking Activation Signals: Some antibodies block key receptors involved in T-cell activation, preventing the immune response from being initiated.

    • Inhibition of Complement Activation: Antibodies like eculizumab inhibit the complement system, which can contribute to tissue damage in antibody-mediated rejection.

  4. Clinical Applications:

    • Organ Transplantation: Antibodies are commonly used to prevent rejection in kidney, liver, and heart transplants.

    • Autoimmune Diseases: They are also used in treating conditions like rheumatoid arthritis, lupus, and multiple sclerosis.

  5. Potential Side Effects:

    • Infections: Due to immune suppression, patients are at increased risk of infections.
    • Allergic Reactions: Some patients may experience allergic reactions to antibody therapies.
    • Infusion Reactions: These can occur during the administration of monoclonal antibodies, leading to symptoms like fever, chills, and hypotension.

Gabapentin (Neurontin): newer; for generalized tonic-clonic seizures and partial seizures (partial and complex)

Mechanism: unknown but know doesn’t mimic GABA inhibition or block Ca currents

Side effects: dizziness, ataxia, fatigue; drug well-tolerated and no significant drug interactions

TRIMETHOPRIM

It is a diaminopyrimidine. It inhibits bacterial dihydrofolate reductase( DHFRase).

In combination with sulphamethoxzole it is called Co-trimoxazole.

Spectrum of action

 S. Typhi. Serratia. Klebsiela and many sulphonamide resistant strains of Staph.aureus. Strep pyogens

Adverse effects

Megaloblastic anemia. i.e.. due to folate defeciency.

Contraindicated in pregnancy.

Diuretics if given with co-trimoxazole cause thrombocytopenia.

Uses

I. UTI. 2. RTI. 3. Typhoid. 5. Septicemias. 5. Whooping cough

 

Piroxicam:

Half‐life of 45 hrs. Once‐daily dosing. Delay onset of  action.

High doses inhibits PMN migration, decrease oxygen  radical production, inhibits lymphocyte function. 

used to relieve the symptoms of  arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic,non-selective  cyclooxygenase (COX) inhibitor

The risk of adverse side efects is nearly ten times higher than with other NSAIDs. Peptic ulcer (9.5 higher)

Carbapenems: Broadest spectrum of beta-lactam antibiotics.

imipenem with cilastatin

meropenem

ertapenem

Monobactams: Unlike other beta-lactams, there is no fused ring attached to beta-lactam nucleus. Thus, there is less probability of cross-sensitivity reactions.

aztreonam

Beta-lactamase Inhibitors No antimicrobial activity. Their sole purpose is to prevent the inactivation of beta-lactam antibiotics by beta-lactamases, and as such, they are co-administered with beta-lactam antibiotics.

clavulanic acid

tazobactam

sulbactam

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