Certain antimicrobial medications specifically disrupt the creation of bacterial cell walls, a feature absent in mammalian cells. These cell walls are constructed from a substance called peptidoglycan, made up of glycan units linked together by peptide cross-links. To work optimally, inhibitors of cell wall synthesis need to target actively multiplying microorganism. Structure of pencillins Penicillins […]

Chloramphenicol, a broad-spectrum antibiotic, functions by binding reversibly to the bacterial ribosomal subunit, inhibiting protein synthesis and ATP production in bacteria. Its removal from the US market was due to its potential for bone marrow toxicity and mitochondrial dysfunction. While effective against various microorganisms including bacteria, chlamydiae, rickettsias, spirochetes, and anaerobes, its bacteriostatic or bactericidal […]

Aminoglycosides are utilized to treat serious infections caused by aerobic gram-negative bacteria, but their usage is restricted due to significant toxicities. Aminoglycosides are a class of potent bactericidal antibiotics primarily used to treat serious infections caused by aerobic Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa. They work by irreversibly binding to the 30S […]

Introduction Direct-acting cholinergic agonists mimic the effects of acetylcholine (Ach) by binding directly to cholinoceptors, which can be muscarinic or nicotinic. These classified into two categories: 1) choline esters, which consist of both endogenous Ach and synthetic esters such as carbachol and bethanechol; and 2) naturally occurring alkaloids as nicotine and pilocarpine. All these drugs […]

Catechol-O-Methyltransferase Inhibitors General Information Typically, the methylation of levodopa by catechol-O-methyltransferase (COMT) to 3-O-methyldopa is a minor pathway for levodopa metabolism. However, when peripheral dopamine decarboxylase is inhibited by carbidopa, a significant amount of 3-O-methyldopa is produced, which competes with levodopa for transport into the central nervous system (CNS). Entacapone and tolcaponeare the medicines that […]

Ganglionic Blockers Ganglionic blockers target nicotinic receptors in both parasympathetic and sympathetic autonomic ganglia, and some also inhibit ion channels within these ganglia. These drugs do not distinguish between parasympathetic or sympathetic ganglia and are ineffective as neuromuscular antagonists. Consequently, they block all autonomic nervous system output at the nicotinic receptor. Apart from nicotine, the […]

Introduction Cholinergic antagonists are drugs that bind to muscarinic or nicotinic receptors, inhibiting the effects of acetylcholine and other cholinergic agonists. The most clinically relevant are those that target muscarinic receptors, often referred to as antimuscarinic agents or parasympatholytics. They interrupt parasympathetic innervation, leaving sympathetic actions unopposed. Ganglionic blockers preferentially target nicotinic receptors in sympathetic […]

Introduction Alzheimer’s disease is characterized by three main features: the buildup of senile plaques (B-amyloid accumulations), the formation of numerous neurofibrillary tangles, and the loss of cortical neurons, especially cholinergic neurons. Current treatments aim to enhance cholinergic transmission in the central nervous system (CNS) or to prevent excitotoxic effects due to the overstimulation of NMDA-glutamate […]

 Toxicology of Anticholinesterase Agents Irreversible acetylcholinesterase (AChE) inhibitors, primarily organophosphate compounds, are widely employed as agricultural insecticides in the United States. This widespread use has resulted in numerous accidental poisoning incidents. Additionally, these compounds are often utilized for suicide and homicide. Organophosphate nerve agents, such as sarin, are deployed in warfare and acts of chemical […]

Overview Acetylcholinesterase (AChE) is an enzyme responsible for breaking down acetylcholine (Ach) into acetate and choline, terminating its action. Located both pre- and postsynaptically in the nerve terminal, AChE is membrane-bound. Inhibiting AChE (using anticholinesterase agents or cholinesterase inhibitors) indirectly enhances cholinergic action by preventing Ach degradation, leading to its accumulation in the synaptic space. […]