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.
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.
Antiemetics
Antiemetic drugs are generally more effective in prophylaxis than treatment. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting centre, dopamine receptors, chemoreceptors trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination of these.
Drugs used in the treatment of nausea and vomiting belong to several different groups. These include:
1. Phenothiazines, such as chlorpromazine, act on CTZ and vomiting centre, block dopamine receptors, are effective in preventing or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy).
They are generally ineffective in motion sickness.
Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines
2. Antihistamines such as promethazine and Dimenhyrinate are especially effective in prevention and treatment of motion.
3. Metoclopramide has both central and peripheral antiemetic effects. Centrally, it antagonizes the action of dopamine. Peripherally metoclopramide stimulates the release of acetylcholine, which in turn, increases the rate of gastric. It has similar indications to those of chlorpromazine.
4. Scopolamine, an anticholinergic drug, is very effective in reliving nausea & vomiting associated with motion sickness.
5. Ondansetron, a serotonin antagonist, is effective in controlling chemical-induced vomiting and nausea such those induced by anticancer drugs.
6. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties
Class III Potassium Channel Blockers
Prolong effective refractory period by prolonging Action Potential
Treatment: ventricular tachycardia and fibrillation, conversion of atrial fibrillation or flutter to sinus rhythm, maintenance of sinus rhythm
– Amiodarone (Cordarone) – maintenance of sinus rhythm
– Bretylium (Bretylol)
– Ibutilide (Corvert)
– Dofetilide (Tykosyn)
– Sotalol (Betapace)
Amiodarone
- Has characteristics of sodium channel blockers, beta blockers, and calcium channel blockers
- Has vasodilating effects and decreases systemic vascular resistance
- Prolongs conduction in all cardiac tissue
- Decreases heart rate
- Decreases contractility of the left ventricles
Class III - Adverse Effects
- GI- Nausea vomiting and GI distress
- CNS- Weakness and dizziness
- CV-Hypotension, CHF, and arrhythmias are common.
- Amiodarone associated with potentially fatal Hepatic toxicity, ocular abnormalities and serious cardiac arrhythmias.
Drug – Drug Interactions
These drugs can cause serious toxic effects if combined with digoxin or quinidine.
Kinins
Peptide that are mediated in the inflammation.
Action of kinin:
On CVS: vasodilatation in the kidneys, heart, intestine, skin, and liver. It is 10 times active than histamine as vasodilator.
On exocrine and endocrine glands: kinin modulate the tone of pancreas and salivery glands and help regulate GIT motility, also affect the transport of water and electrolytes, glucose and amino acids through epithelial cell transport.
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
Pharmacology is the study of drugs and the way they interact with living systems. Clinical pharmacology is the study of drugs in humans.
A drug is any chemical that can effect living processes.
Therapeutics: the medical use of drugs.
An ideal drug has several important properties. Three of these properties are of utmost importance: effectiveness, safety and selectivity.
Effectiveness: This is the most important quality that a drug can have. Effectiveness refers to the drug's ability to do what it is supposed to do.
Safety: Although no drug can be totally safe, proper usage can lessen the risks of adverse effects.
Selectivity: A truly selective drug would have no side effects, and would effect only the body process' for which it is designed and given. Therefore, there is no such thing as a selective drug.
Pharmacokinetics: The way the body deals with a drug. Pharmacokinetics is concerned with the processes of absorption, distribution, metabolism and excretion.
Pharmacodynamics: What a drug does to the body.
Pharmacokinetics and pharmacodynamics are two of the processes that determine how a person will respond to a drug. Other factors include how a drug is administered (dose, route, and timing of administration), interactions with other drugs, and individual physiological variables (weight, age, function of body systems).