NEET MDS Lessons
Pharmacology
Acid-Peptic disorders
This group of diseases include peptic ulcer, gastroesophageal reflux and Zollinger-Ellison syndrome.
Pathophysiology of acid-peptic disorders
Peptic ulcer disease is thought to result from an imbalance between cell– destructive effects of hydrochloric acid and pepsin on the one side, and cell-protective effects of mucus and bicarbonate on the other side. Pepsin is a proteolytic enzyme activated in gastric acid (above pH of 4, pepsin is inactive); also it can digest the stomach wall. A bacterium, Helicobacter pylori, is now accepted to be involved in the pathogenesis of peptic ulcer.
In gastroesophageal reflux the acidic contents of the stomach enter into the oesophagus causing a burning sensation in the region of the heart; hence the common name heartburn or other names such as indigestion and dyspepsia.
However, Zollinger-Ellison syndrome is caused by a tumor of gastrin secreting cells of the pancreas characterized by excessive secretion of gastrin that stimulates gastric acid secretion.
These disorders can be treated by the following classes of drugs:
A. Gastric acid neutralizers (antacids)
B. Gastric acid secretion inhibitors (antisecretory drugs)
C. Mucosal protective agents
D. Drugs that exert antimicrobial action against H.pylori
Neurophysiology
Nerve fibers exhibit wide range of sensitivity to nerve blockade-in order of increasing resistance to block are the sensations of pain, cold, warmth, touch, pressure, proprioception and motor function
Nerve Fibers:
|
Types |
Size |
Speed |
Occurrence |
|
A (α) |
20 µm |
80 - 120 |
Myelinated (Primarily for muscular activity). |
|
β |
8 - 15 µm |
|
Myelinated (Touch and pressure) |
|
γ |
4 - 8 µm |
|
Myelinated (Muscle spindle tone) |
|
δ |
3 - 4 µm |
10-15 |
Myelinated (Pain and temperature sensation) |
|
B |
4 µm |
10-15 |
Myelinated (Preganglionic autonomic) |
|
C |
1-2 µm |
1 - 2 |
Unmyelinated (Pain and temperature sensation) |
Myelinated = faster conducting
Unmyelinated = slower conducting
- Small non-myelinated fibers (C- pain fibers) and smaller myelinated pre-ganglionic B fibers are more readily blocked than are larger myelinated fibers responsible for muscle activity and touch [A-alpha and A-beta].
- Clinically, a person would notice complete lack of sensation to a pinprick, while at the same time still be able to move their fingers.
Types of Neurons (Function)
•There are 3 general types of neurons (nerve cells):
1-Sensory (Afferent ) neuron:A neuron that detects changes in the external or internal environment and sends information about these changes to the CNS. (e.g: rods and cones, touch receptors). They usually have long dendrites and relatively short axons.
2-Motor (Efferent) neuron:A neuron located within the CNS that controls the contraction of a muscle or the secretion of a gland. They usually have short dendrites and long axons.
2-Interneuron or association neurons: A neuron located entirely within the CNS in which they form the connecting link between the afferent and efferent neurons. They have short dendrites and may have either a short or long axon.
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.
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).
Methicillin
Methicillin is an antibiotic related to penicillin and other beta-lactam containing antibiotics. It is often used to treat infections caused by bacteria carrying an antibiotic resistance, e.g., staphylococci. As methicillin is deactivated by gastric acid, it has to be administered by injection.
Uses Methicillin serves a purpose in the laboratory to determine antibiotic sensitivity in microbiological culture.
Nystatin
Candida spp. are sensitive to nystatin.
Uses: Cutaneous, vaginal, mucosal and esophageal infections.
Candida infections can be treated with nystatin.
Cryptococcus is also sensitive to nystatin.
Nystatin is often used as prophylaxis in patients who are at risk for fungal infections, such as AIDS patients with a low CD4+ count and patients receiving chemotherapy.
MOA
nystatin binds to ergosterol, the main component of the fungal cell membrane. When present in sufficient concentrations, it forms a pore in the membrane that leads to K+ leakage and death of the fungus.