NEET MDS Lessons
Pharmacology
Histamine:
Involved in inflammatory and anaphylactic reactions
Local application causes swelling redness, and edema, mimicking a mild inflammatory reaction.
Large systemic doses leads to profound vascular changes similar to those seen after shock or anaphylactic origin.
Storage: widely distributed; in tissues, primarily in mast cells; in blood- in basophils, platelets; non-mast cell sites (epidermis, CNS, regenerating cells)
Histamine Stored in complex with:
Heparin
Chondroitin Sulfate
Eosinophilic Chemotactic Factor
Neutrophilic Chemotactic Factor
Proteases
Release: during type I (IgE-mediated) immediate hypersensitivity rxns, tissue injury, in response to some drugs
a. Process: Fcε receptor on mast cell or basophil binds IgE, when Ag binds → ↑ PLC activity → histamine
Symptoms: bronchoconstriction, ↓ Pa, ↑ capillary permeability, edema
Action
H1 receptors are located mainly on smooth muscle cells in blood vessels and the respiratory and GI tracts. When histamine binds with these receptors producing the following effects.
-Contraction of smooth muscle in the bronchi and bronchioles producing bronchoconstraction.
-stimulation of vagus nerve endings to produce reflex bronchoconstraction and cough.
-Increased permeability of veins and capillaries, which allows fluid to flow into subcutaneous tissues and form edema (little lower blood pressure).
-Increased secretion of mucous glands. Mucosal edema and increased nasal mucus produce the nasal congestion characteristic of allergic rhinitis and the common cold.
-Stimulation of sensory peripheral nerve endings to cause pain and pruritus.
Histamine promotes vasodilation by causing vascular endothelium to release nitric oxide. This chemical signal diffuses to the vascular smooth muscle, where it stimulates cyclic guanosine monophosphate production, causing vasodilation.
H2-receptors present mostly in gastric glands and smooth muscle of some blood vessels. When receptors are stimulated, the main effects are increased secretion of gastric acid and pepsin, increased rate and force of myocardial contraction.
The H3-receptor functions as a negative-feedback mechanism to inhibit histamine synthesis and release in many body tissues. Stimulation of H3 receptors opposes the effects produced by stimulation of H1 receptors.
The H4- receptor is expressed in only a few cell types, and their role in drug action is unclear.
Drugs cause release of histamine:
Many drugs can cause release of histamine in the body.
-Intracutaneouse morphine injection in humans produced localized redness, localized edema and a diffuse redness. This is due to release of histamine.
-I.V. inj of curare may cause bronchial constriction due to release of histamine.
-codeine , papaverine, meperidine (pethedine), atropine, hydralizine and sympathomimetic amines, histamine releases by these drugs may not be significant unless they are administered I.V in large doses
Pharmacological effects
- If injected I.V. (0.1 mg of histamine) causes a sharp decline in the blood pressure, flushing of the face and headache.
- There is also stimulation of gastric acid secretion.
- If this injection is given to an asthmatic individual, there will be a marked decrease in vital capacity and a sever attack of asthma.
Circulatory effects of histamine:
The two factors involved in the circulatory action of histamine are:
Arteriolar dilatation and
Capillary permeability
So it leads to loss of plasma from circulation
Effect on gastric secretion:
Histamine is a potent stimulant of gastric Hcl secretion.
Beta - Adrenergic Blocking Agents
Mechanisms of Action
- Initial decrease in cardiac output, followed by reduction in peripheral vascular resistance.
- Other actions include decrease plasma renin activity, resetting of baroreceptors, release of vasodilator prostaglandins, and blockade of prejunctional beta-receptors.
Advantages
- Documented reduction in cardiovascular morbidity and mortality.
- Cardioprotection: primary and secondary prevention against coronary artery events (i.e. ischemia, infarction, arrhythmias, death).
- Relatively not expensive.
Considerations
- Beta blockers are used with caution in patients with bronchospasm.
- Contraindicated in more than grade I AV, heart block.
- Do not discontinue abruptly.
Side Effects
- Bronchospasm and obstructive airway disease.
- Bradycardia
- Metabolic effects (raise triglyerides levels and decrease HDL cholesterol; may worsen insulin sensitivity and cause glucose intolerance). Increased incidence of diabetes mellitus.
- Coldness of extremities.
- Fatigue.
- Mask symptoms of hypoglycemia.
- Impotence.
Indications
- First line treatment for hypertension as an alternative to diuretics.
- Hypertension associated with coronary artery disease.
- Hyperkinetic circulation and high cardiac output hypertension (e.g., young hypertensives).
- Hypertension associated with supraventricular tachycardia, migraine, essential tremors, or hypertrophic cardiomyopathy.
Beta adrenergic blocker Drugs
Atenolol 25-100
Metoprolol 50-200
Bisoprolol 2.5-10
Paracetamol
Paracetamol or acetaminophen is analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains.
paracetamol acts by reducing production of prostaglandins, which are involved in the pain and fever processes, by inhibiting the cyclooxygenase (COX) enzyme.
Metabolism Paracetamol is metabolized primarily in the liver. At usual doses, it is quickly detoxified by combining irreversibly with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is eventually excreted by the kidneys.
Factors affecting onset and duration of action of local anesthetics
pH of tissue
pKa of drug
Time of diffusion from needle tip to nerve
Time of diffusion away from nerve
Nerve morphology
Concentration of drug
Lipid solubility of drug
Needle selection
Nerve blocks:
Inferior alveolar- 25 G short (LLU technique)
PSA- 25 G short
Mental/Incisive- 25 G short
Palatal- 27/30 G short/ultrashort
Gow-Gates/Akinosi- 25 G long
Infraorbital- 25 G long
Field Block:
ASA 25/27 short
Infiltration:
Infiltration/SP 25/27 short
PDL/Intraosseous
PDL 27/30 short
Intraosseous 30 short/ultrashort
Distal (Potassium Sparing) Diuretics
Agents:
spironolactone
triamterene
Mechanism of action
Inhibition of Na/K exchange at aldosterone dependent distal tubular site
Spironolactone - competes with aldosterone for regulatory site
Triamterene - decreases activity of pump directly
• Either mechanism decreases potassium wasting
• Either mechanism produces poor diuresis (when used alone)
o relatively unimportant Na recovery site
Diurectic activity increased if:
• sodium load (body) is high
• aldosterone concentrations are high
• sodium load (tubule) is high - secondary to diuresis
Other electrolytes unaffected
Toxicity
• spironolactone may produce adrenal and sex hormone effects with LONG-TERM use
• Both drugs may produce electrolyte imbalance
Cough is a protective reflex which helps in expulsion of respiratory secretion or foreign particles which are irritant to respiratory
tract. Irritation to any part of respiratory tract starting from pharynx to lungs carried impulses by afferent fibres in vagus and
sympathetic nerve to the cough centre in the medulla oblongata. \
Cough may be dry (without sputum or unproductive) or productive (with sputum production).
Classification for drugs used in cough.
I. Pharyngeal demulcents
Certain lozenges, linctus and cough drops containing glycerine, liquorice and syrups.
II. Expectorants
Sodium and potassium citrate
Sodium and potassium acetate
Potassium iodide
Ammonium chloride & carbonate
Acetylcysteine
Bromhexine
Guaiphenesin
III. Antitussive
i. Opioids
Codeine (as linctus) Pholcodeine
ii. Non-opioids
Noscapine
Dextromethorphan
Pipazethate
iii. Antihistaminics
Chlorpheniramine
Diphenhydramine
Promethazine
Erdosteine is recently introduced mucolytic with unique protective functions for the respiratory tract. It is indicated in the treatment of acute and chronic airway diseases such as bronchitis, rhinitis, sinusitis, laryngopharyngitis and exacerbations of chronic bronchitis.