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Pharmacology

Antiplatelet Drugs:

Whereas the anticoagulant drugs such as Warfarin and Heparin suppress the synthesis or activity of the clotting factors and are used to control venous thromboembolic disorders, the antithrombotic drugs suppress platelet function and are used primarily for arterial thrombotic disease. Platelet plugs form the bulk of arterial thrombi.

Acetylsalicylic acid (Aspirin)

• Inhibits release of ADP by platelets and their aggregation by acetylating the enzymes (cyclooxygenases or COX) of the platelet that synthesize the precursors of Thromboxane A2 that is a labile inducer of platelet aggregation and a potent vasoconstrictor.

• Low dose (160-320 mg) may be more effective in inhibiting Thromboxane A2 than PGI2 which has the opposite effect and is synthesized by the endothelium.

• The effect of aspirin is irreversible.

Celecoxib

is a highly selective COX-2 inhibitor and primarily inhibits this isoform of cyclooxygenase, whereas traditional NSAIDs inhibit both COX-1 and COX-2. Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1.

Being a sulphonamide can cause skin rash &  hypersensitivity rxn., occasional oedema& HT.

Indication

Osteoarthritis ( 100‐200mg BID ) , rheumatoid  arthritis, dysmenorrhea, acute gouty attacks,  acute musculoskeletal pain. 

Erythromycin

used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including  mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea.

Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.

Mechanism of action Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translocation of peptides.

Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or  esters. Erythromycin is very rapidly absorbed, and diffused into most tissues and  phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where during active phagocytosis, large concentrations of erythromycin are released.

Most of erythromycin is metabolised by demethylation in the liver. Its main route elimination route is in the bile, and a small portion in the urine.

Erythromycin's half-life is 1.5 hours.

Side-effects. More serious side-effects, such as reversible deafness are rare. Cholestatic jaundice, Stevens-Johnson syndrome and toxic epidermal necrosis are some other rare side effects that may occur.

Contraindications Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem)

erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time.

Procaine penicillin Procaine penicillin is a combination of benzylpenicillin with the local anaesthetic agent procaine. This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin.

Indications

respiratory tract infections where compliance with oral treatment is unlikely ,syphilis, cellulitis

Piroxicam:

Half‐life of 45 hrs. Once‐daily dosing. Delay onset of  action.

High doses inhibits PMN migration, decrease oxygen  radical production, inhibits lymphocyte function. 

used to relieve the symptoms of  arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic,non-selective  cyclooxygenase (COX) inhibitor

The risk of adverse side efects is nearly ten times higher than with other NSAIDs. Peptic ulcer (9.5 higher)

Hypothalamic - Pituitary Drugs

Somatropin

Growth hormone (GH) mimetic

Mechanism

agonist at GH receptors
increases production of insulin growth factor-1 (IGF-1)

Clinical use

GH deficiency
increase adult height for children with conditions associated with short stature 
Turner syndrome
wasting in HIV infection
short bowel syndrome

Toxicity

scoliosis
edema
gynecomastia
increased CYP450 activity


Octreotide

Somatostatin mimetic

Mechanism

agonist at somatostatin receptors

Clinical use

acromegaly
carcinoid
gastrinoma
glucagonoma
acute esophageal variceal bleed

Toxicity

GI upset
gallstones
bradycardia
Oxytocin

Mechanism

agonist at oxytocin receptor

Clinical use

stimulation of labor
uterine contractions
control of uterine hemorrhage after delivery
stimulate milk letdown

Toxicity

fetal distress 
abruptio placentae 
uterine rupture
Desmopressin
ADH (vasopressin) mimetic

Mechanism

agonist at vasopressin V2 receptors

Clinical use

central (pituitary) diabetes insipidus
hemophilia A (factor VIII deficiency)
increases availability of factor VIII
von Willebrand disease
increases release of von Willebrand factor from endothelial cells

Toxicity

GI upset
headache
hyponatremia
allergic reaction

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.

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