General Pharmacology:
- In angina pectoris, nitroglycerin is administered through the sublingual route.
Angina pectoris is a clinical condition characterised by an acute onset of chest pain resulting from myocardial ischemia (caused by atherosclerotic narrowing of coronary vessels), leading to an imbalance in oxygen supply and demand. Nitroglycerine reduces preload and afterload, thereby decreasing oxygen demand.
Nitroglycerine has high first-pass metabolism, so the oral route is not preferred. In the sublingual route, the drug is placed undersurface of the tongue. It bypasses first-pass metabolism as the drug from the alveolar vessels directly enters the systemic circulation.
Additionally, it induces a rapid onset of action (within 3 minutes) and relieves pain in patients with angina.
- Levodopa is used in the treatment of Parkinsonism.
Parkinsonism is a neurodegenerative movement disorder of the brain (substantia nigra) with a deficiency of dopamine.
Dopamine, a catecholamine (polar compound), though useful in the treatment of Parkinsonism, fails to penetrate the blood-brain barrier. Levodopa, a precursor of dopamine, easily crosses the blood-brain barrier and is decarboxylated into dopamine in the CNS to replenish the depleted dopamine stores. Hence, levodopa is the first choice of drug in Parkinsonism.
To prevent peripheral conversion of dopamine and increase the bioavailability of central dopamine concentration, the normal practice is to add carbidopa in combination with levodopa.
- Phenobarbitone is used to treat neonatal jaundice.
Preterm labour can cause neonatal jaundice because the immature baby cannot convert bilirubin to glucuronic acid.
Phenobarbitone is indicated in preterm pregnancy. Phenobarbitone, an enzyme inducer, if given 1-2 weeks before labor, upregulates hepatic UDP-glucuronyl transferase, a key enzyme for conjugation of bilirubin. It leads to a decrease in bilirubin deposition and the risk of development of neonatal hyperbilirubinemia.
It is essential to administer phenobarbitone before the development of hyperbilirubinemia, as it does not have any pharmacotherapeutic role later.
Drugs acting on ANS:
- Adrenaline is the drug of choice in Anaphylactic shock.
Anaphylaxis is an IgE-mediated type I hypersensitivity reaction that occurs due to exposure to certain drugs (allergens), such as Penicillin or Cephalosporins. The antigen-antibody reactions lead to the degranulation of mast cells and the release of various chemical mediators like histamine, bradykinin, PAF, and leukotrienes.
Histamine primarily causes vasodilatation and bronchoconstriction (H1-mediated action). Adrenaline is a physiological antagonist of histamine, which causes vasoconstriction and bronchodilatation. Additionally, it decreases the release of mediators from mast cells and basophils. (β2-mediated action), increase force of contraction and AV conduction (β1-mediated action), and decrease mucosal edema in the airway (α1-mediated action).
The peculiar action of preventing mast cell release, dominant bronchodilator action, and marked vasoconstrictor property make adrenaline the first choice of drug in anaphylactic shock.
- Why is dopamine preferred in cardiogenic shock in patients with renal dysfunction?
In patients with myocardial ischemia/necrosis, there is pump failure that reduces cardiac output, leading to severe shock.
The aim of dopamine in cardiogenic shock is to improve cardiac function by increasing cardiac output. Dopamine, with a dose rate of 5-10 μg/kg/min, acts as an inotropic agent by stimulating β1 receptors present in ventricular myometrium. Dopamine induces its positive ionotropic effect (β1-mediated action on the ventricular myometrium) more than the chronotropic effect (β1-mediated action through the SA node) in patients with cardiogenic shock. Dopamine, with a dose rate of 3-5 μg/kg/min, induces renal vasodilatation. It enhances systemic blood pressure without altering renal blood flow and urine output; hence, it is the preferred agent in cardiogenic shock with renal compromise.
- Atropine is contraindicated in glaucoma.
Glaucoma is a clinical disorder with progressive degeneration of retinal cells, visual field impairment, and an increase in intraocular pressure.
Aqueous humor is typically drained out by two pathways, namely the trabecular pathway (90 % drainage) and the uveoscleral pathway (10% drainage). In narrow-angle glaucoma, the posterior chamber forces the iris in a forward direction, leading to narrowing of the ocular angle and blockade of the trabecular meshwork and canal of Schlemm. While in open-angle glaucoma, trabecular meshwork patency is lost; hence, outflow is blocked.
There are two significant muscles (sphincter pupillae and ciliary muscles) present in the eye. Atropine is a muscarinic receptor antagonist that blocks the M3 action of the sphincter pupillae, leading to pupillary dilatation, which in turn causes the iris to fall back and block the canal of Schlemm. This leads to obstruction of the drainage. Further, relaxation of ciliary muscles causes the sensory ligaments to tighten and flattening of the lens, leading to cycloplegia. Now the eye is focused for distant vision.
Atropine causes both mydriasis and cycloplegia, which can trigger an attack of glaucoma. Hence, its use is strictly avoided in patients with glaucoma.
4. Neostigmine is preferred over physostigmine in the management of myasthenia gravis.
Myasthenia gravis is a chronic autoimmune peripheral nervous system disorder characterized by skeletal muscle weakness and fatigue due to defective NM transmission at the nicotinic Ach receptor. Neostigmine and physostigmine are reversible anticholinesterase inhibitors that enhance the availability of Ach. Both drugs can increase the number of receptors and enhance transmission at the nicotinic Ach receptor.
Being cholinergic drugs, both have similar clinical profiles. But, due to pharmacokinetic variability, they diverge in selected indications. Neostigmine, a quaternary ammonium compound, does not cross the blood-brain barrier, produces peripheral action, and does not induce central side effects. This property makes neostigmine a safer and more appropriate choice in the management of myasthenia gravis as compared to physostigmine, which crosses the BBB and induces central side effects.
5. Why is glycopyrrolate preferred over atropine in pre-anesthetic medication?
Atropine and Glycopyrrolate are antimuscarinic drugs used in pre-anaesthetic medications due to their vagolytic and anti-sialagogue action. Glycopyrrolate, administered with a dose of 0.1-0.3 mg via intramuscular injection, is a commonly used pre-anesthetic medication for the following advantages.
- Minimal Cardiac Action: It causes less tachycardia.
- Better efficacy profile: It reduces bronchial and salivary secretions more effectively (longer anti-sialagogue action), which helps in preventing laryngospasm and makes endotracheal intubation easy.
- Better safety profile: Central CNS side effects (sedation, confusion, delirium) are not seen, as it does not cross the blood–brain barrier. It is less likely to precipitate glaucoma and rarely causes postoperative urinary retention in elderly patients.
6. Why is phenylephrine used as a nasal decongestant?
Phenylephrine is a non-catecholamine with selective α₁ agonistic action without β receptor-mediated action. It causes nasal decongestion by inducing local vasoconstriction in the nasal mucosa without any systemic side effects.
Additionally, it is not metabolized by COMT, resulting in a prolonged duration of action compared to other catecholamines.
7. Why is physostigmine used in atropine poisoning but not neostigmine?
Atropine is a muscarinic antagonist. Its overdose/toxicity causes central (delirium, disorientation, seizures) as well as peripheral actions (dry mouth, fever, hot flush, photophobia, blurring of vision, tachycardia, etc.).
Neostigmine can inhibit only peripheral actions. However, physostigmine, a tertiary amine that crosses the blood–brain barrier, neutralizes the central and peripheral toxicity of atropine.
Furthermore, physostigmine is used for the diagnosis of atropine poisoning. In atropine poisoning, when physostigmine (0.5-1.0 mg IM) is administered, the parasympathetic actions of physostigmine (salivation, lacrimation) are not observed.