NEET MDS Lessons
Pharmacology
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.
Immunosuppressive antibodies can be classified mainly into monoclonal and polyclonal antibodies, targeting specific components of the immune system.
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Monoclonal Antibodies:
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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.
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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.
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Rituximab: Targets CD20 on B cells, leading to B-cell depletion. It is used in various conditions, including non-Hodgkin lymphoma and rheumatoid arthritis.
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Daclizumab: Targets the IL-2 receptor (CD25) and is used in renal transplantation to prevent acute rejection.
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Eculizumab: Targets complement component C5, inhibiting the complement cascade. It is used in conditions like paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.
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Polyclonal Antibodies:
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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.
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Equine Antithymocyte Globulin (eATG): Similar to rATG, it targets T cells and is used in transplantation settings.
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Mechanisms of Action:
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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.
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Blocking Activation Signals: Some antibodies block key receptors involved in T-cell activation, preventing the immune response from being initiated.
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Inhibition of Complement Activation: Antibodies like eculizumab inhibit the complement system, which can contribute to tissue damage in antibody-mediated rejection.
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Clinical Applications:
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Organ Transplantation: Antibodies are commonly used to prevent rejection in kidney, liver, and heart transplants.
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Autoimmune Diseases: They are also used in treating conditions like rheumatoid arthritis, lupus, and multiple sclerosis.
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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.
Organic Nitrates
Relax smooth muscle in blood vessel
Produces vasodilatation
– Decreases venous pressure and venous return to the heart Which decreases the cardiac work load and oxygen demand.
– May have little effect on the coronary arteries CAD causes stiffening and lack of
– responsiveness in the coronary arteries
– Dilate arterioles, lowering peripheral vascular resistance Reducing the cardiac workload
Main effect related to drop in blood pressure by
– Vasodilation- pools blood in veins and capillaries, decreasing the volume of blood that the heart has to pump around (the preload)
– relaxation of the vessels which decreases the resistance the heart has to pump against (the afterload)
Indications
- Myocardial ischemia
– Prevention
– Treatment
Nitroglycerin (Nitro-Bid)
• Used
– To relive acute angina pectoris
– Prevent exercise induced angina
– Decrease frequency and severity of acute anginal episodes
Type
• Oral - rapidly metabolized in the liver only small amount reaches circulation
• Sublingual – Transmucosal tablets and sprays
• Transdermal – Ointment s
– Adhesive discs applied to the skin
• IV preparations
Sublingual Nitroglycerine
• Absorbed directly into the systemic circulation, Acts within 1-3 minutes , Lasts 30-60 min
Topical Nitroglycerine
• Absorbed directly into systemic circulation, Absorption at a slower rate. , Longer duration of action
Ointment - effective for 4-8 hours
Transdermal disc - effective for 18-24 hours
Isosorbide dinitrate
• Reduces frequency and severity of acute anginal episodes
• Sublingual or chewable acts in 2 min. effects last 2-3 hours
• Orally, systemic effects in about 30 minutes and last about 4 hours after oral administration
Tolerance to Long-Acting Nitrates
• Long-acting dosage forms of nitrates may develop tolerance
– Result in episodes of chest pain
– Short acting nitrates less effective
Prevention of Tolerance
• Use long-acting forms for approximately 12-16 hours daily during active periods and omit them during inactive periods or sleep
• Oral or topical should be given every 6 hours X 3 doses allowing a rest period of 6 hours
Isosorbide dinitrate (Isordil, Sorbitrate) is used to reduce the frequency and severity of acute anginal episodes.
When given sublingually or in chewable tablets, it acts in about 2 minutes, and its effects last 2 to 3 hours. When higher doses are given orally, more drug escapes metabolism in the liver and produces systemic effects in approximately 30 minutes. Therapeutic effects last about 4 hours after oral administration
Isosorbide mononitrate (Ismo, Imdur) is the metabolite and active component of isosorbide dinitrate. It is well absorbed after oral administration and almost 100% bioavailable. Unlike other oral nitrates, this drug is not subject to first-pass hepatic metabolism. Onset of action occurs within 1 hour, peak effects occur between 1 and 4 hours, and the elimination half-life is approximately 5 hours. It is used only for prophylaxis of angina; it does not act rapidly enough to relieve acute attacks.
Propoxyphene
- A methadone analog.Used orally to relieve mild to moderate pain.
- A typical opiate, it does not possess anti-inflammatory or antipyretic actions, but has little or no antitussive activity.
- Cannot be used parenterally because of irritant properties.
- Has a low addiction potential primarily due to its lack of potency as an opiate.
- The most common adverse side effects are:• dizziness, drowsiness, and nausea and vomiting. • these effects are more prominent in ambulatory patients.
- Withdrawal symptoms have occurred in both adults and in neonates following use of the drug by the mother during pregnancy.
- CNS depression is additive with other CNS depressants.
Neomycin
used as a topical preparation
Neomycin is not absorbed from the gastrointestinal tract, and has been used as a preventative measure for hepatic encephalopathy and hypercholesterolemia. By killing bacteria in the intestinal tract, it keeps ammonia levels low and prevents hepatic encephalopathy, especially prior to GI surgery. It is not given intravenously, as neomycin is extremely nephrotoxic (it causes kidney damage), especially compared to other aminoglycosides.
Valdecoxib
used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhoea
Etoricoxib new COX-2 selective inhibitor
Stimulants:
Amphetamines: amphetamine is a substrate of serotonin and NE uptake transporters so in cytoplasm, it competes for transport into storage vesicles → ↑ [ ] in cytoplasm then excess amines bind to membrane transporter and are transported out of cell
Drugs:
a. Dextroamphetamine: psychomotor stimulant (↓ fatigue), short-term weight loss, prevents narcolepsy
b. Methylphenidate (Ritalin): prevents narcolepsy, treatment for ADD and ADHD
c. Methamphetamine: psychomotor stimulant, abused widely (cheap, easy to make)
Side effects:
a. CNS: euphoria, anxiety, agitation, delirium, paranoia, panic, suicidal/homicidal impulses, psychoses, tolerance (develops rapidly to most CNS effects), physical dependence (not clinically relevant)
b. CV: headache, chills, arrhythmias and HTN (may be fatal)