NEET MDS Lessons
Pharmacology
Laxatives and cathartics (purgatives)
Constipation is a common problem in older adults and laxatives are often used or overused. Non drug measures to prevent constipation (e.g. increasing intake of fluid and high–fiber foods, exercise) are much preferred to laxatives.
Laxatives and cathartics are drugs used orally to evacuate the bowels or to promote bowel elimination (defecation). Both terms are used interchangeably because it is the dose that determines the effects rather than a particular drug. For example, Castor oil laxative effect = 4ml while Cathartic effect = 15-60ml
The term laxative implies mild effects, and eliminative of soft formed stool. The term cathartic implies strong effects and elimination of liquid or semi liquid stool.
Laxatives are randomly classified depending on mode of action as:
1. Bulk-forming laxatives: are substances that are largely unabsorbed from the intestine.
They include psyllium, bran, methylcellulose, etc. When water is added, the substances swell and become gel-like which increases the bulk of the faecal mass that stimulates peristalsis and defecation.
2. Osmotic laxatives such as magnesium sulphate, magnesium hydroxide, sodium phosphate, etc. These substances are not efficiently absorbed and cause water retention in the colon. The latter causes increase in volume and pressure which stimulates peristalsis and defecation.
Lactulose is a semisynthetic disaccharide sugar that also acts as an osmotic laxative.
Electrolyte solutions containing polyethylene glycol(PEG) are used as colonic lavage solutions to prepare the gut for radiologic or endoscopic procedures
3. Stimulant (irritant) laxatives: these are irritant that stimulate elimination of large bowel contents. Individual drugs are castor oil, bisacodyl, phenolphthalein, cascara sagrada, glycerine, etc. The faeces are moved too rapidly and watery stool is eliminated. Glycerine can be administered rectally as suppositories.
4. Faecal softeners: they decrease the surface tension of the faecal mass to allow water to penetrate into the stool. They have detergent– like property e.g. docusate(docusate sodium, docusate calcium, and docusate spotassium. )
5. Lubricant laxatives e.g. liquid paraffin (mineral oil). It lubricates the intestine and is thought to soften stool by preventing colonic absorption of faecal water. They are used as retention enema.
6. Chloride channel activators
Lubiprostone works by activating chloride channels to increase fluid secretion in the intestinal lumen. This eases the passage of stools and causes little change in electrolyte balances. Nausea is a relatively common side effect with lubiprostone.
Clinical indications of laxatives
1. To relieve constipation.
2. To prevent straining.
3. To empty the bowel in preparation for bowel surgery or diagnostic procedures.
4. To accelerate elimination of potentially toxic substances from the GI tract.
5. To accelerate excretion of parasite after anti-helmintic drugs have been administered.
Diclofenac
Short half life (1‐2 hrs), high 1stpass metab., accumulates in synovial fluid after oral admn., reduce inflammation, such as in arthritis or acute injury
Mechanism of action
inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX). There is some evidence that diclofenac inhibits the lipooxygenase pathways, thus reducing formation of the
leukotrienes (also pro-inflammatory autacoids). There is also speculation that diclofenac may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain the high potency of diclofenac - it is the most potent NSAID on a molar basis.
Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid. This is also the main side effect of diclofenac and other drugs that are not selective for the COX2-isoenzyme.
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.
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.
Metabolism
Hepatic Drug-Metabolizing Enzymes: most drug metabolism in the liverperformed by the hepatic microsomal enzyme system.
Therapeutic Consequences of Drug Metabolism
- Accelerated Renal Drug Excretion: The most important consequence of drug metabolism is the promotion of renal drug excretion. Metabolism makes it possible for the kidney to excrete many drugs that it otherwise could not.
- Drug Inactivation
- Increased Therapeutic Action: Metabolism may increase the effectiveness of some drugs.
- Activation of Prodrugs: A prodrug is a compound that is inactive when administered and made active by conversion in the body.
- Increased or Decreased Toxicity
Factors that influence rate of metabolism:
- Age: Hepatic maturation doesn't occur until about a year old.
- Induction of Drug-Metabolizing Enzymes: Some drugs can cause the rate of metabolism to increase, leading to the need for an increased dosage. May also influence the rate of metabolism for other drugs taken at the same time, leading to a need for increased dosages of those drugs as well.
- First-Pass Effect: Hepatic inactivation of certain oral drugs. Avoided by parentaral administration of drugs that undergo rapid hepatic metabolism.
- Nutritional Status
- Competition between Drugs
Aspirin
Mechanism of Action
ASA covalently and irreversibly modifies both COX-1 and COX-2 by acetylating serine-530 in the active site Acetylation results in a steric block, preventing arachidonic acid from binding
Uses of Aspirin
Dose-Dependent Effects:
Low: < 300mg blocks platelet aggregation
Intermediate: 300-2400mg/day antipyretic and analgesic effects
High: 2400-4000mg/day anti-inflammatory effects
Often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant (blood thinning) effect and is used in long-term low-doses to prevent heart attacks
Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks
Its primary undesirable side effects, especially in stronger doses, are gastrointestinal distress (including ulcers and stomach bleeding) and tinnitus. Another side effect, due to its anticoagulant properties, is increased bleeding in menstruating women.
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.