NEET MDS Lessons
Pharmacology
Sedative-Hypnotic Drugs
Sedative drug is the drug that reduce anxiety (anxiolytic) and produce sedation and referred to as minor tranquillisers.
Hypnotic drug is the drug that induce sleep
Effects: make you sleepy; general CNS depressants
Uses: sedative-hypnotic (insomnia ), anxiolytic (anxiety, panic, obsessive compulsive, phobias), muscle relaxant (spasticity, dystonias), anticonvulsant (absence, status epilepticus, generalized seizures—rapid tolerance develops), others (pre-operative medication and endoscopic procedures, withdrawal from chronic use of ethanol or other CNS depressants)
1- For panic disorder alprazolam is effective.
2- muscle disorder: (reduction of muscle tone and coordination) diazepam is useful in treatment of skeletal muscle spasm e.g. muscle strain and spasticity of degenerative muscle diseases.
3-epilepsy: by increasing seizure threshold.
Clonazepam is useful in chronic treatment of epilepsy while diazepam is drug of choice in status epilepticus.
4-sleep disorder: Three BDZs are effective hypnotic agents; long acting flurazepam, intermediate acting temazepam and short
acting triazolam. They decrease the time taken to get to sleep They increase the total duration of sleep
5-control of alcohol withdrawals symptoms include diazepam, chlordiazepoxide, clorazepate and oxazepam.
6-in anesthesia: as preanesthetic amnesic agent (also in cardioversion) and as a component of balanced anesthesia
Flurazepam significantly reduce both sleep induction time and numbers of awakenings and increase duration of sleep and little rebound insomnia. It may cause daytime sedation.
Temazepam useful in patients who experience frequent awakening, peak sedative effect occur 2-3 hr. after an oral dose.
Triazolam used to induce sleep in recurring insomnia and in individuals have difficulty in going to sleep, tolerance develop within few days and withdrawals result in rebound insomnia therefore the drug used intermittently.
Drugs and their actions
1. Benzodiazepines: enhance the effect of gamma aminobutyric acid (GABA) at GABA receptors on chloride channels. This increases chloride channel conductance in the brain (GABA A A receptors are ion channel receptors).
2. Barbiturates: enhance the effect of GABA on the chloride channel but also increase chloride channel conductance independently of GABA, especially at high doses
3. Zolpidem and zaleplon: work in a similar manner to benzodiazepines but do so only at the benzodiazepine (BZ1) receptor type. (Both BZ1and BZ2 are located on chloride channels.)
4. Chloral hydrate: probably similar action to barbiturates.
5. Buspirone: partial agonist at a specific serotonin receptor (5-HT1A).
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine):
mechanisms not well-described. Several mechanisms may be involved.
7. Baclofen: stimulates GABA linked to the G protein, Gi , resulting in an increase in K + conductance and a decrease in Ca2+ conductance. (Other drugs mentioned above do not bind to the GABA B receptor.)
8. Antihistamines (e.g., diphenhydramine): block H1 histamine receptors. Doing so in the CNS leads to sedation.
9. Ethyl alcohol: its several actions include a likely effect on the chloride channel.
Neurolept Anesthesia
An antipsychotic agent such as droperidol plus an opiate analgesic agent such as fentanyl or sufentanil. This latter agent is approximately eight to ten times more potent than fentanyl.
NATURAL ANTICOAGULANTS:
1. PGI-2.
2. Antithrombin.
3. Protein-C.
4. TFPI.
5. Heparin.
6. Fibrinolytic system.
Clotrimazole: Clotrimazole is a potent, specific inhibitor of p450 enzymes.
It is used in some antifungal medications, and in the treatment of yeast infections.
Macrolide
The macrolides are a group of drugs (typically antibiotics) whose activity stems from the presence of a macrolide ring, a large lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, are attached. The lactone ring can be either 14, 15 or 16-membered. Macrolides belong to the polyketide class of natural products.
The most commonly-prescribed macrolide antibiotics are:
Erythromycin, Clarithromycin, Azithromycin, roxithromycin,
Others are: spiramycin (used for treating toxoplasmosis), ansamycin, oleandomycin, carbomycin and tylocine.
There is also a new class of antibiotics called ketolides that is structurally related to the macrolides. Ketolides such as telithromycin are used to fight respiratory tract infections caused by macrolide-resistant bacteria.
Non-antibiotic macrolides :The drug Tacrolimus, which is used as an
immunosuppressant, is also a macrolide. It has similar activity to cyclosporine.
Uses : respiratory tract infections and soft tissue infections.
Beta-hemolytic streptococci, pneumococci, staphylococci and enterococci are usually susceptible to macrolides. Unlike penicillin, macrolides have shown effective against mycoplasma, mycobacteria, some rickettsia and chlamydia.
Mechanism of action: Inhibition of bacterial protein synthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl-tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations
Resistance : Bacterial resistance to macrolides occurs by alteration of the structure of the bacterial ribosome.
Thiazide diuretics
Chlorothiazide, Hydrochlorothiazide
Mechanism(s) of Action
1. Block facilitated Na/Cl co-transport in the early distal tubule. This is a relatively minor Na absorption mechanism and the result is modest diuresis
2. Potassium wasting effect
a. Blood volume reduction leads to increased production of aldosterone
b. Increased distal Na load secondary to diuretic effect
c. a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting
3. Increase distal Ca re-absorption (direct effect)
o causes an increase in plasma calcium.This is unimportant NORMALLY but makes thiazides VERY inappropriate choice for hypercalcemic patients.
4. Anti-diuretic effect in nephrogenic diabetes insipidus patients secondary to depletion of Na and Water.
Toxicity
• Electrolyte imbalance (particularly hypokalemia) ,Agranulocytosis , Allergic reactions
• Hyperuricemia , Thrombocytopenia
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.