Pathogenesis
The pathogenesis underlying the development of costochondritis remains unclear. Proposed mechanisms of pain include neurogenic inflammation, muscular imbalances, neuropathy of the intercostal nerves, myofascial pain, or mechanical dysfunction. Diagnosis
Costochondritis is predominately a clinical diagnosis only after life-threatening conditions have been ruled out, with physical examination and medical history being considered. Before a costochondritis diagnosis is made, other serious causes of chest pain are investigated. Further evaluation for cardiopulmonary or neoplastic causes is typically based on history, age, and risk factors, with diagnostic imaging and tests, completed to assess for life-threatening emergencies. If there is a suspicion of infection or a rheumatoid condition, laboratory work may be conducted.A physical exam will assess for tenderness or pain upon palpation, with an absence of heat, erythema, or swelling. The physical exam may assess if the pain is worsened with movements of the upper body or breathing, and may be reproduced upon using the crowing rooster maneuver, the hooking maneuver, or the horizontal flexion maneuver. Medical history is considered in diagnosing costochondritis, such as inquiry regarding any recent trauma, coughing, exercise, or activity involving the upper body that may have caused the symptoms. Differential diagnosis
Cardiopulmonary
Life-threatening medical emergencies that may be associated with chest wall pain include acute coronary syndrome, aortic dissection, pneumothorax, or pulmonary embolism. Other cardiopulmonary causes of chest pain similar to that produced by costochondritis may include but are not limited to myocardial infarction, angina, and pericarditis. With costochondritis, the pain is typically worse with respiration, with movement, or within certain positions.
It is a reversible inhibitor of acetylcholinesterase, the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft of the neuromuscular junction. It indirectly stimulates both nicotinic and muscarinic acetylcholine receptors. Physostigmine has an LD50 of 3 mg/kg in mice. Bioactivity
Physostigmine functions as an acetylcholinesterase inhibitor. Its mechanism is to prevent the hydrolysis of acetylcholine by acetylcholinesterase at the transmitted sites of acetylcholine. This inhibition enhances the effect of acetylcholine, making it useful for the treatment of cholinergic disorders and myasthenia gravis. More recently, physostigmine has been used to improve the memory of Alzheimers patients due to its potent anticholinesterase activity. However, its drug form, physostigmine salicylate, has poor bioavailability. Physostigmine also has a miotic function, causing pupillary constriction. It is useful in treating mydriasis. Physostigmine also increases outflow of the aqueous humor in the eye, making it useful in the treatment of glaucoma. Side effects
An overdose can cause cholinergic syndrome. Other side effects may include nausea, vomiting, diarrhea, anorexia, dizziness, headache, stomach pain, sweating, dyspepsia, and seizures. The carbamate functional group readily hydrolyses in water, and in bodily conditions. The metabolite thus formed from physostigmine and some other alkaloids (e.g. cymserine) is eseroline, which research has suggested may be neurotoxic to humans. Death can occur rapidly following overdose as a result of respiratory arrest and paralysis of the heart. Synthesis
Physostigmine has two stereocenters—the two carbons where the five-membered rings join—so any attempt at the total synthesis must pay attention to obtaining the correct stereoisomer.