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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Sympatholytics (Antiadrenergic Agents)
PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent
It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension.
It increases the cardiac output and decreases the total peripheral resistance.
It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.
Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.
ERGOT ALKALOIDS
Ergotamine is an important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.
METHYSERGIDE
It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine.
SUMATRIPTAN
It is a potent selective 5-HT 1D receptor agonist used in the treatment of migraine.
PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1 receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.
TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½
DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.
TAMSULOSIN
It is uroselective α1A blocker and has been found effective in improving BPH symptoms.
Other drugs used for erectile dysfunction
Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.
EPHEDRINE
It act indirectly and directly on α and β receptors. It increases blood pressure both by peripheral vasoconstriction and by increasing the cardiac output. Ephedrine also relaxes the bronchial smooth muscles.
Ephedrine stimulates CNS and produces restlessness, insomnia, anxiety and tremors.
Ephedrine produces mydriasis on local as well as systemic administration.
Ephedrine is useful for the treatment of chronic and moderate type of bronchial asthma, used as nasal decongestant and as a mydriatic without cycloplegia. It is also useful in preventing ventricular asystole in Stokes Adams syndrome.
Antiarrhythmic Drugs
Cardiac Arrhythmias
Can originate in any part of the conduction system or from atrial or ventricular muscle.
Result from
– Disturbances in electrical impulse formation (automaticity)
– Conduction (conductivity)
– Both
MECHANISMS OF ARRHYTHMIA
ARRHYTHMIA – absence of rhythm
DYSRRHYTHMIA – abnormal rhythm
ARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
- Block results from severely depressed conduction
- Re-entry or circus movement / daughter impulse
Types of Arrhythmias
• Sinus arrhythmias
– Usually significant only
– if they are severe or prolonged
• Atrial arrhythmias
– Most significant in the presence of underlying heart disease
– Serious: atrial fibrillation can lead to the formation of clots in the heart
• Nodal arrhythmias
– May involve tachycardia and increased workload of the heart or bradycardia from heart block
• Ventricular arrhythmias
– Include premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation
|
Class |
Action |
Drugs |
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I |
Sodium Channel Blockade |
|
|
IA |
Prolong repolarization |
Quinidine, procainamide, disopyramide |
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IB |
Shorten repolarization |
Lidocaine, mexiletine, tocainide, phenytoin |
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IC |
Little effect on repolarization |
Encainide, flecainide, propafenone |
|
II |
Beta-Adrenergic Blockade |
Propanolol, esmolol, acebutolol, l-sotalol |
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III |
Prolong Repolarization (Potassium Channel Blockade; Other) |
Ibutilide, dofetilide, sotalol (d,l), amiodarone, bretylium |
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IV |
Calcium Channel Blockade |
Verapamil, diltiazem, bepridil |
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Miscellaneous |
Miscellaneous Actions |
Adenosine, digitalis, magnesium |
Indications
• To convert atrial fibrillation (AF) or flutter to normal sinus rhythm (NSR)
• To maintain NSR after conversion from AF or flutter
• When the ventricular rate is so fast or irregular that cardiac output is impaired
– Decreased cardiac output leads to symptoms of decreased systemic, cerebral, and coronary circulation
• When dangerous arrhythmias occur and may be fatal if not quickly terminated
– For example: ventricular tachycardia may cause cardiac arrest
Mechanism of Action
• Reduce automaticity (spontaneous depolarization of myocardial cells, including ectopic pacemakers)
• Slow conduction of electrical impulses through the heart
• Prolong the refractory period of myocardial cells (so they are less likely to be prematurely activated by adjacent cells
CENTRAL NERVOUS SYSTEM PHARMACOLOGY
Antipsychotic Drugs
1. Phenothiazines
a. Aliphatic derivatives
(1) Chlorpromaxine
b. Piperidine derivatives
(1) Thioridazine
(2) Mesoridazine
c. Piperazine derivatives
(1) Fluphenazine
(2) Perphenazine
(3) Prochlorperazine
(4) Trifluoperazine
2. Haloperidol resembles the piperazine phenothiazines.
3. Thiothixene resembles the piperazine phenothiazines.
4. Others (e.g., loxapine, pimozide).
5. Newer and more atypical antipsychotic drugs:
a. Clozapine
b. Olanzapine
c. Quetiapine
d. Risperidone
e. Ziprasidone
f. Aripiprazole
Antidepressant Drugs
Drug treatment of depression is based on increasing serotonin (5-HT) or NE (or both) at synapses in selective tracts in the brain. This can be accomplished by different mechanisms.
Treatment takes several weeks to reach full clinical efficacy.
1. Tricyclic antidepressants (TCAs)
a. Amitriptyline
b. Desipramine
c. Doxepin
d. Imipramine
e. Protriptyline
2. Selective serotonin reuptake inhibitors (SSRIs)
a. Fluoxetine
b. Paroxetine
c. Sertraline
d. Fluvoxamine
e. Citalopram
3. Monoamine oxidase inhibitors (MAOIs)
a. Tranylcypromine
b. Phenelzine
4. Miscellaneous antidepressants
a. Bupropion
b. Maprotiline
c. Mirtazapine
d. Trazodone
e. St. John’s Wort
Antimania Drugs
These drugs are used to treat manic-depressive illness.
A. Drugs
1. Lithium
2. Carbamazepine
3. Valproic acid
Sedative Hypnotics
1. Benzodiazepines
2. Barbiturates
3. Zolpidem and zaleplon
4. Chloral hydrate
5. Buspirone
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine)
7. Baclofen
8. Antihistamines (e.g., diphenhydramine)
9. Ethyl alcohol
Antiepileptic Drugs
Phenytoin
Carbamazepine
Phenobarbital
Primidone
Gabapentin
Valproic acid
Ethosuximide
Anti-Parkinson Drugs
a. L-dopa plus carbidopa (Sinemet).
b. Bromocriptine, pergolide, pramipexole, ropinirole.
c. Benztropine, trihexyphenidyl, biperiden, procyclidine.
d. Diphenhydramine.
e. Amantadine.
f. Tolcapone and entacapone.
g. Selegiline.
Mucosal protective agents.
These are locally active agents that help heal gastric and duodenal ulcers by forming a protective barrier between the ulcers and gastric acid, pepsin, and bile salts. They do not alter the secretion of gastric acid. These drugs include sucralfate and colloid bismuth compounds. (e.g. tripotassium, dicitratobismuthate). Colloidal bismuth compounds additionally exert bactericidal action against H.pylori. Also, Prostaglandins have both antisecretory and mucosal protective effects.
Example: Misoprostol- used for prevention of NSAID – induced ulcer.
- Drugs that exert antimicrobial action against H.pylori such as amoxicillin, metronidazole, clarithromycin and tetracycline are included in the anti-ulcer treatment regimens.
PLASMA FRACTIONS:
a) Fresh frozen plasma.
b) Platelets.
c) Plasma concentrates.
d) Non-plasma recombinant factor concentrates.