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
Anticonvulsants: include carbamazepine (use when lithium not tolerated; may not be as effective) .
valproic acid (use when lithium not tolerated; rapid onset)
Use of local anesthetics during pregnancy
Local anesthetics (injectable)
Drug FDA category
Articaine C
Bupivacaine C
Lidocaine B
Mepivacaine C
Prilocaine B
Vasoconstrictors
Epinephrine 1:200,000 or 1:100,000 C (higher doses)
Levonordefrin 1:20,000 Not ranked
Local anesthetics (topical)
Benzocaine C
Lidocaine B
Loop (High Ceiling) Diuretics
Loop diuretics are diuretics that act at the ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.
Agent: Furosemide
Mechanism(s) of Action
1. Diuretic effect is produced by inhibit of active 1 Na+, 1 K+, 2 Cl- co-transport (ascending limb - Loop of Henle).
o This produces potent diuresis as this is a relatively important Na re-absorption site.
2. Potassium wasting effect
a. Blood volume reduction leads to increased production of aldosterone
b. Increased distal Na load secondary to diuretic effect
c. a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting (same as thiazides but more likely)
3. Increased calcium clearance/decreased plasma calcium
o secondary to passive decreases in loop Ca++ reabsorption.
o This is linked to inhibition of Cl- reabsorption.
o This is an important clinical effect in patients with ABNORMAL High Ca++
SYMPATHOMIMETICS
β2 -agonists are invariably used in the symptomatic treatment of asthma.
Epinephrine and ephedrine are structurally related to the catecholamine norepinephrine, a neurotransmitter of the adrenergic nervous system
Some of the important β 2 agonists like salmeterol, terbutaline and salbutamol are invariably used as bronchodilators both oral as well as
aerosol inhalants
SALBUTAMOL
It is highly selective β2 -adrenergic stimulant h-aving a prominent bronchodilator action.
It has poor cardiac action compared to isoprenaline.
TERBUTALINE
It is highly selective β2 agonist similar to salbutamol, useful by oral as well as inhalational route.
SALMETEROL
Salmeterol is long-acting analogue of salbutamol
BAMBUTEROL
It is a latest selective adrenergic β2 agonist with long plasma half life and given once daily in a dose of 10-20 mg orally.
METHYLXANTHINES (THEOPHYLLINE AND ITS DERIVATIVES)
THEOPHYLLINE
Theophylline has two distinct action:
smooth muscle relaxation (i.e. bronchodilatation) and suppression of the response of the airways to stimuli (i.e. non-bronchodilator prophylactic effects).
ANTICHOLINERGICS
Anticholinergics, like atropine and its derivative ipratropium bromide block cholinergic pathways that cause airway constriction.
MAST CELL STABILIZERS
SODIUM CROMOGLYCATE
It inhibits degranulation of mast cells by trigger stimuli.
It also inhibits the release of various asthma provoking mediators e.g. histamine, leukotrienes, platelet activating factor (PAF) and interleukins (IL’s) from mast cell
KETOTIFEN
It is a cromolyn analogue. It is an antihistaminic (H1 antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate.
It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria.
LEUKOTRIENE PATHWAY INHIBITORS
MONTELUKAST
It is a cysteinyl leukotriene receptor antagonist indicated for the management of persistent asthma.
Distribution
Three major controlling factors:
Blood Flow to Tissues: rarely a limiting factor, except in cases of abscesses and tumors.
Exiting the Vascular System: Occurs at capillary beds.
- Typical Capillary Beds - drugs pass between cells
- The Blood-Brain Barrier- Tight junctions here, so drugs must pass through cells. Must then be lipid soluble, or have transport system.
- Placenta - Does not constitute an absolute barrier to passage of drugs. Lipid soluble, nonionized compounds readily pass.
- Protein Binding: Albumin is most important plasma protein in this respect. It always remains in the blood stream, so drugs that are highly protein bound are not free to leave the bloodstream. Restricts the distribution of drugs, and can be source of drug interactions.
Entering Cells: some drugs must enter cells to reach sites of action.
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)