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.
Streptomycin
Streptomycin was the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus.
Streptomycin cannot be given orally, but must be administered by regular intramuscular injection.
Anticonvulsants: include carbamazepine (use when lithium not tolerated; may not be as effective) .
valproic acid (use when lithium not tolerated; rapid onset)
Roxithromycin
It is used to treat respiratory tract, urinary and soft tissue infections. Roxithromycin is derived from erythromycin, containing the same 14-membered lactone ring. However, an N-oxime side chain is attached to the lactone ring.
Roxithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Legionella pneumophilae.
When taken before a meal, roxithromycin is very rapidly absorbed, and diffused into most tissues and Phagocytes Only a small portion of roxithromycin is metabolised. Most of roxithromycin is secreted unchanged into the bile and some in expired air
Anti-Histamines:
The effect of histamine can be opposed in three ways:
1. Physiological antagonism: by using a drug to oppose the effect (e.g adrenaline). Histamine constricts bronchi,
causes vasodilatation which increases capillary permeability. Adrenaline opposes this effect by a mechanism unrelated to histamine.
2. By preventing histamine from reaching its site of action (receptors), By competition with H1-H2 receptors (Drug antagonisms).
3. By preventing the release of histamine. (adrenal steroids and sodium-cromoglycate can suppress the effect on the tissues)
Types of Anti-histamine drugs
Selected H1 antagonist drugs
First-generation H1 receptor antagonists:
Chlorpheniramine (Histadin) & Dexchlorpheniramine
Diphenhydramine (Allermine)
Promethazine (Phenergan) - strong CNS depressants
Cyproheptadine (Periactin)
ACTION
These drugs bind to both central and peripheral H1 receptors and can cause CNS depression or stimulation.
- They usually cause CNS depression (drowsiness,sedation) with usual therapeutic doses
- Cause CNS stimulation (anxiety, agitation)
with excessive doses, especially in children.
They also have Anticholinergic effects (e.g. dry mouth, urinary retention, constipation, blurred vision).
Second-generation H1 receptor antagonists (non-sedating) agents
Terfenadine
Fexofenadine
Loratadine
Acravistine and Cetirizine
Astemizol
Action
They cause less CNS epression because they are selective for peripheral H1 receptors and do not cross the blood brain barrier.
Indications for use
The drugs can relieve symptoms but don’t relieve hypersensitivity.
1) Allergic rhinitis. Some relief of sneezing, rhinorrhea, nasal airway obstruction and conjunctivitis are with the use of antihistamine.
2) Anaphylaxis. Antihistamine is helpful in treating urticaria and pruritus.
3) Allergic conjunctivitis. This condition, which is characterized by redness, itching and tearing of the eyes.
4) Drug allergies. Antihistamines may be given to prevent or treat reactions to drugs (e.g, before a dignostic test that
uses an iodine preparation).
5) Transfusions of blood and blood products.
6) Dermatologic conditions. Antihistamines are the drug of choice for treatment of allergic contact dermatitis and
acute Urticaria. Urticaria often occurs because the skin has many mast cells to release histamine.
7) Miscellaneous. Some antihistamines are commonly used for non-allergic disorder such as motion sickness, nausea, vomiting, sleep, cough or add to cough mixtures.
Contraindication
hypersensitivity to the drugs, narrow-angle glaucoma, prostatic hypertroph, stenosing peptic ulcer, bladder neck obstruction, during pregnancy and lactating women
Adverse effects:
Drowsiness and sedation
Anticholinergic
Some antihistamines may cause dizziness, fatigue, hypotention, headache, epigastric distress and photosensitivity
Serious adverse reaction including cardiac arrest & death, have been reported in patients receiving high dose astemizole
H2-receptor antagonists
Cimetidine (Tagamate), Ranitidine (Zantac), Fomatidine, Nizatidine.
Mechanism of action
Numerous factors influence acid secretion by the stomach, including food, physiological condition and drugs. H2 receptor blockers reduce basal acid-secretion by about 95% and food stimulated acid-secretion by about 70%. Both conc. and vol. of H ions will decrease.
Pharmacokinetics:
1) They are all well absorbed after oral dose.
2) Antacids decrease their absorption in about 10-20%
Uses
Cimetidine - reduction of gastric secretion is beneficial, these are in main duodenal ulcer, benign gastric ulcer, stomach ulcer and reflux eosophagitis.
Rantidine -used as alternative for duodenal ulcer
Adverse effects:
headache, dizziness, constipation, diarrhoea, tiredness and muscular pain.
OXYMETAZOLINE
It is a directly acting sympathomimetic amine used in symptomatic relief in nasal congestion which increases mucosal secretion.
It is used:
- As a nasal decongestant in allergic rhinitis, with or without the addition of antazoline or sodium chromoglycate.
- As an ocular decongestant in allergic conjunctivitis.
Compounds like naphazoline and xylometazoline are relatively selective α2 agonists, which on topical application produce local vasoconstriction.
Nitrous Oxide (N2O)
MAC 100%, blood/gas solubility ratio 0.47
- An inorganic gas., low solubility in blood, but greater solubility than N2
- Inflammable, but does support combustion.
- Excreted primarily unchanged through the lungs.
- It provides amnesia and analgesia when administered alone.
- Does not produce muscular relaxation.
- Less depressant to both the cardiovascular system and respiratory system than most of the other inhalational anesthetics.
- Lack of potency and tendency to produce anoxia are its primary limitations.
- The major benefit of nitrous oxide is its ability to reduce the amount of the secondary anesthetic agent that is necessary to reach a specified level of anesthesia.