NEET MDS Lessons
Pharmacology
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:
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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:
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Mechanism of Action: Glucocorticoids inhibit the expression of genes coding for pro-inflammatory cytokines (e.g., IL-1, IL-2, TNF-α).
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Clinical Uses: They are used in conditions like rheumatoid arthritis, lupus, and to prevent transplant rejection.
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Side Effects: Long-term use can lead to osteoporosis, weight gain, diabetes, and increased risk of infections.
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Cytostatic Drugs: These agents inhibit cell division and are often used in cancer treatment as well as in autoimmune diseases. They include:
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Examples: Cyclophosphamide, azathioprine, and methotrexate.
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Mechanism of Action: They interfere with DNA synthesis and cell proliferation, particularly affecting rapidly dividing cells.
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Clinical Uses: Effective in treating cancers, systemic lupus erythematosus, and other autoimmune disorders.
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Side Effects: Can cause bone marrow suppression, leading to increased risk of infections and anemia.
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Antibodies: This group includes monoclonal and polyclonal antibodies that target specific components of the immune system.
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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.
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Clinical Uses: Used in organ transplantation and to treat autoimmune diseases.
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Side Effects: Risk of infections and allergic reactions due to immune suppression.
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Drugs Acting on Immunophilins: These drugs modulate immune responses by binding to immunophilins, which are proteins that assist in the folding of other proteins.
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Examples: Cyclosporine and tacrolimus.
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Mechanism of Action: They inhibit calcineurin, a phosphatase involved in T-cell activation, thereby reducing the production of IL-2.
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Clinical Uses: Primarily used in organ transplantation to prevent rejection.
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Side Effects: Nephrotoxicity, hypertension, and increased risk of infections.
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Other Drugs: This category includes various agents that do not fit neatly into the other classifications but still have immunosuppressive effects.
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Examples: Mycophenolate mofetil and sirolimus.
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Mechanism of Action: Mycophenolate inhibits lymphocyte proliferation by blocking purine synthesis, while sirolimus inhibits mTOR, affecting T-cell activation and proliferation.
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Clinical Uses: Used in transplant patients and in some autoimmune diseases.
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Side Effects: Gastrointestinal disturbances, increased risk of infections, and potential for malignancies.
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Thiopental
- A barbiturate that is generally used to induce anesthesia.
- The temporal course of effects from induction to recovery depends almost entirely upon progressive redistribution.
- Metabolic degradation or excretion during anesthesia is negligible, except in the case of methohexital.
- The barbiturates produce minimal analgesia.
- Respiratory depression may be pronounced.
- Cardiac output is reduced while total peripheral resistance is increased.
- It does not sensitize the heart to catecholamines.
- It may cause bronchiospasm, especially in asthmatics.
- It is contraindicated in acute intermittent porphyria.
Diphenoxylate (present in Lomotil)
- A meperidine congener
- Not absorbed very well at recommended doses.
- Very useful in the treatment of diarrhea.
Carbonic anhydrase inhibitors
Acetazolamide, Dichlorphenamide, Methazolamide, Ethoxzolamide
Mechanism of Action
1. Carbonic anhydrase (CA) facilitates excretion of H+ and recovery of bicarbonate by the proximal renal tubule and ciliary epithelium of the eye. Sodium is recovered in exchange for H+.
2. Inhibitors block CA block sodium recovery. A very mild diuresis is produced (this is really a side effect of their use in glaucoma) because relatively unimportant mechanism for Na recovery and because proximal tubule site means that other sodium recovery mechansims continue to process their normal fraction of the sodium load.
Antihypertensives Drugs
CATEGORIES
I. Diuretics to reduce blood volume
Chlorothiazide (Diuril)
II. Drugs that interfere with the Renin-Angiotensin System
A. Converting enzyme inhibitors Captopril , enalapril, Lisinopril
B. Angiotensin receptor antagonists Saralasin Losartan
III. Decrease peripheral vascular resistance and/or cardiac output
A. Directly acting vasodilators
1. calcium channel blockers Nifedipine , Diltiazem, amlodipine
2. potassium channel activators Minoxidil
3. elevation of cGMP Nitroprusside
4. others Hydralazin e
B. Sympathetic nervous system depressants
1. α-blockers Prazosin, phentolamine, phenoxybenzamine
2. β-blockers Propranolol ,Metoprolol, atenolol
3. norepinephrine synthesis inhibitors Metyrosine
4. norepinephrine storage inhibitors Reserpine
5. transmitter release inhibitors Guanethidine
6. centrally acting: decrease
sympathetic outflow Clonidine , methyldopa
Non-barbiturate sedatives
1- Chloral hydrate is trichlorinated derivative of acetaldehyde that is converted to trichlorethanol in the body. It induces sleep in about 30 minutes and last up to 6 hr. it is irritant to GIT and produce unpleasant taste sensation.
2- Ramelteon melatonin receptors are thought to be involved in maintaining circadian rhythms underlying the sleep-wake cycle. Ramelteon is an agonist at MT1 and MT2 melatonin receptors , useful in patients with chronic insomnia with no rebound insomnia and
withdrawal symptoms
3- Ethanol (alcohol) it has antianxiety sedative effects but its toxic potential out ways its benefits.
Ethanol is a CNS depressant producing sedation and hypnosis with increasing dose.
Absorption of alcohol taken orally is rapid, it is highly lipid soluble, presence of food delayed its absorption, maximal blood concentration depend on total dose, sex, strength of the solution, the time over which it is taken, the presence of food and speed of metabolism.
Alcohol in the systemic circulation is oxidized in the liver principally 90% by alcohol dehydrogenase to acetaldehyde and then by acetaldehyde dehydrogenase to products that enter the citric cycle.
Alcohol metabolism by alcohol dehydrogenase follows first order kinetics in the smallest doses. Once the blood concentration exceeds about 10 mg/100 ml, the enzymatic processes are saturated and elimination rate no longer increases with increasing
concentration but become steady at 10-15 ml/ 1 hr. in occasional drinkers.
Thus alcohol is subject to dose dependant kinetics i.e. saturation or zero order kinetics.
Actions
- Ethanol acts on CNS in a manner similar to volatile anesthetic.
- It also enhances GABA so stimulating flux of chloride ions through ion channels.
- Other possible mode of action involve inhibition of Ca-channels and inhibition of excitatory NMDA receptors.
- Ethanol has non selective CNS depressant activity.
- It causes cutaneous vasodilatation, tachycardia and myocardial depression
Ofloxacin : It is a quinolone antibiotic and similar in structure to levofloxacin. It is an alternative treatment to ciprofloxacin for anthrax.