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.
Prostaglandines:
Every cell in the body is capable of synthesizing one or more types of PGS. The four major group of PGs are E, F, A, and B.
Pharmacological actions:
stimulation of cyclicAMP production and calcium use by various cells
CVS
PGE2 acts as vasodilator; it is more potent hypotensive than Ach and histamine
Uterous
PGE2 and PGF2α Contract human uterus
Bronchial muscle
PGF2α and thromboxan A2 cause bronchial muscle contraction.
PGE2 & PGI2 cause bronchial muscle dilatation
GIT: PGE2 and PGF2α cause colic and watery diarrhoea
Platelets
Thromboxan A2 is potent induce of platelets aggregation
Kidney
PGE2 and PGI2 increase water, Na ion and K ion excretion (act as diuresis) that cause renal vasodilatation and inhibit
tubular reabsorption
USE
PGI2: Epoprostenol (inhibits platelets aggregation)
PGE1: Alprostadil (used to maintain the potency of arterioles in neonates with congenital heart defects).
PGE2: Dinoproste (used as pessaries to induce labor)
Synthetic analogue of PGE1: Misoprostol (inhibit the secretion of HCl).
Aquaretics
An aquaretic is a class of drug that is used to promote aquaresis, the excretion of water without electrolyte loss.
Lithium, demeclocycline
Mechanism of Action
1. Block ADH action on distal tubule and collecting duct. Blocking ADH decreases H2O permeability. H2O is not recovered (distal tubule) using osmotic draw of counter-current multiplier so aquaretics reduce water reabsorption (tubule to blood stream).
2. Net effect is an increase in free water clearance
Nalidixic acid:
Nalidixic acid is the basis for quinolone antibiotics. It acts bacteriostatically (that is, it inhibits growth and reproduction) or bactericidally (it kills them) on both Gram positive and Gram negative bacteria, depending on the concentration. It is especially used in treating urinary tract infections, caused for example by Escherichia coli, Proteus, Enterobacter and Klebsiella.
Treatment modifications to consider if there are concerns regarding vasoconstrictors
- Monitor blood pressure and heart rate preoperatively
- Minimize administration of epinephrine or levonordefrin
- Monitor blood pressure and heart rate 5 min after injection
- May re-administer epinephrine or levonordefrin if blood pressure and heart rate are stable
- Continue to monitor as required
- Consider limiting epinephrine to 0.04 mg, levonordefrin to 0.2 mg
- Avoid epinephrine 1:50,000
- Never use epinephrine-impregnated retraction cord
Routes of Drug Administration
Intravenous
- No barriers to absorption since drug is put directly into the blood.
- There is a very rapid onset for drugs administered intravenously. This can be advantagous in emergency situations, but can also be very dangerous.
- This route offers a great deal of control in respect to drug levels in the blood.
- Irritant drugs can be administer by the IV route without risking tissue injury.
- IV drug administration is expensive, inconvenient and more difficult than administration by other routes.
- Other disadvantages include the risk of fluid overload, infection, and embolism. Some drug formulations are completely unsafe for use intravenously.
Intramuscular:
- Only the capillary wall separates the drug from the blood, so there is not a significant barrier to the drug's absorption.
- The rate of absorption varies with the drug's solubility and the blood flow at the site of injection.
- The IM route is uncomfortable and inconvenient for the patient, and if administered improperly, can lead to tissue or nerve damage.
Subcutaneous
Same characteristics as the IM route.
Oral
- Two barriers to cross: epithelial cells and capillary wall. To cross the epithelium, drugs have to pass through the cells.
- Highly variable drug absorption influenced by many factors: pH, drug solubility and stability, food intake, other drugs, etc.
- Easy, convenient, and inexpensive. Safer than parenteral injection, so that oral administration is generally the preferred route.
- Some drugs would be inactivated by this route
- Inappropriate route for some patients.
- May have some GI discomfort, nausea and vomiting.
- Types of oral meds = tablets, enteric-coated, sustained-release, etc.
- Topical, Inhalational agents, Suppositories
Serotonin or 5-hydroxytryptamine (5-HT)
It is a neurotransmitter, widely distributed in the CNS, beginning in the midbrain and projecting into thalamus, hypothalamus, cerebral cortex, and spinal cord. CNS serotonin is usually an inhibitory neurotransmitter and is associated with mood, the sleep-wake cycle.
Serotonin is thought to produce sleep by inhibiting CNS activity.
In the blood, 5-HT is present in high concentration in platelets (regulator of platelets function) and also high concentration in intestine
Pharmacological effects:
Smooth muscles. 5-HT stimulates the G.I smooth muscle; it increases the peristaltic movement of intestine.
Serotonin contracts the smooth muscle of bronchi;
Blood vessels. If serotonin is injected i.v, the blood pressure usually first rises, because of the contraction of large vessels and then falls because of arteriolar dilatation. Serotonin causes aggregation of platelets.
Specific agonists
- Sumatriptan a selective 5-HT1D used in treatment of acute migraine.
- Buspirone a selective 5-HT1A used in anxiety.
- Ergotamine is a partial agonist used in migraine. It acts on 5-HT1A receptor.
Nonspecific 5-HT receptor agonist
o Dexfenfluramine used as appetite suppressant.
Specific antagonists
o Spiperone (acts on 1A receptor) and
o Methiothepin (acts on 1A, 1B, 1D receptors)