Pathophysiology and Management of Acute Mountain Sickness (AMS)
Megh R. Goyal, Hafiz Ansar Rasul Suleria, Ademola Olabode Ayeleso, T. Jesse Joel, Sujogya Kumar Panda in The Therapeutic Properties of Medicinal Plants, 2019
Acetazolamide, a carbonic anhydrase inhibitor, @ 125 mg per day, has been suggested sufficient for preventing symptomatic AMS [32, 91]. Acetazolamide has been reported to cause bicarbonate dieresis and metabolic acidosis resulting in stimulation of ventilator responses to hypobaric hypoxia at high altitude exposure [33, 81]. On the other hand, intravenous therapy of acetazolamide has also been found to increase cerebral blood flow and respiration by causing carbonic acidosis in brain tissue [42]. Dexamethasone, a synthetic glucocorticoid, has been reported to be the best alternative to acetazolamide [45]. The molecular mechanism of dexamethasone was found to be acting on a reduction of capillary bed permeability by inhibiting the production of prostaglandins [13, 14, 91]. The use of dexamethasone over acetazolamide is still debatable [62]. However, dexamethasone has been found highly effective as compare to acetazolamide in cases, where rapid ascend for a short period is required [21–23]. Non-steroidal anti-inflammatory drug (viz., ibuprofen) has also been found to be effective for preventing symptoms associated with AMS [45, 59].
Treatment of Chronic Fatigue Syndrome
Jay A. Goldstein in Chronic Fatigue Syndromes, 2020
It is suggested that locus ceruleus inhibition of hippocampal activity produces anxiety. Benzodiazepines may reduce generalized anxiety but not sodium lactate induced panic. Since benzodiazepine receptors are dense in limbic structures, it may be that these anxiolytics act there but not in the brain stem. There are well-known pathways from the limbic system to the locus ceruleus. Gorman et al. suggest that “repeated stimulation of limbic neurons by brain stem discharge lowers the threshold to excitatory postsynaptic stimulation in the limbic lobe until `subpanic’ stimulation is capable of maintaining the ‘kindled’ anticipatory anxiety. Thus, even without the further occurrence of panic, the limbic area continues to have a reduced threshold for response to various stressors.” It may be that the hyperventilation that accompanies panic attacks causes reduced cerebral blood flow in the limbic system and is thereby responsible for the symptoms of hyperventilation syndrome. In our CFS SPECT scan population, the patients who chronically hyperventilated (as determined by end-tidal pCO2) could be symptomatically distinguished from those who did not only by the presence of fibromyalgia tender points. Addition of agents which markedly increase cerebral blood flow, such as calcium channel blockers (except for nimodipine) and acetazolamide, do not often reduce such symptoms. Patients with anxiety disorders, however, have normal, or increased, cerebral blood flow.89 Acetazolamide lowers brain pH but causes hyperventilation.
Epidemiology and genetic associations of neonatal tumors
Prem Puri in Newborn Surgery, 2017
Drugs may act as carcinogens or cocarcinogens in association with other agents or a particular genetic background. There is also clear evidence that tumors may arise in the children of mothers taking medication. One of the best examples of this is the fetal hydantoin syndrome.74 There is some evidence of tumors arising from estrogens taken during pregnancy, and sacrococcygeal tumors have also been associated with maternal intake of acetazolamide.75 This may be a greater problem than was initially thought. Satgé et al.76 showed a history of medications being taken in 39 out of 89 (44%) neonatal tumor patients. Out of the 39 tumors, 9 were malignant, of which the main types were neuroblastomas and teratomas. Three groups of drugs were identified: IARC group 1, diethylstilboestrol and oral contraceptives; IARC group 2, possibly carcinogenic to humans; and IARC group 3, where no association has been proven. To date, the association of vitamin K with carcinogenesis remains uncertain.77
Contemporary management of the pseudotumor cerebri syndrome
Published in Expert Review of Neurotherapeutics, 2019
Carbonic anhydrase is a metalloenzyme which catalyzes the reversible hydration and dehydration of carbon dioxide and bicarbonate [23]. The human brain and choroid plexus contain many carbonic anhydrase isoforms. The secretion of CSF involves the transport of Na+, Cl- and HCO3- from the blood to the brain ventricles which is driven by an osmotic gradient [24]. Carbonic anhydrase inhibitors maintain pH and bicarbonate homeostasis and most of them incorporate a sulfonamide as a zinc binding group and act systemically, leading to off-target side effects (e.g. nausea, fatigue, depression). The inhibitory effect of acetazolamide on CSF secretion and flow was demonstrated in 1954 by Tschirigi et al. and confirmed in a cat model by Kister, who infused intravenous acetazolamide at various doses into cats and recorded CSF flow [25]. He found a decline in CSF flow to about 30% of control rates which occurred within 5 min, reached a maximum in 30 min and persisted for several hours, independent of the dose infused. Methazolamide is a lipophilic, methylated analogue of acetazolamide and an equally potent carbonic anhydrase inhibitor. Acetazolamide is more likely to cause metabolic acidosis, has greater urinary secretion and a longer duration of action in the proximal tubule than methazolamide [26]. The most common side effects of acetazolamide are paresthesias, weight loss, diarrhea, dyspepsia, nausea, and vomiting [20].
Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses
Published in Pharmaceutical Biology, 2021
Yunhui Hu, Jia Sun, Tongxing Wang, Hairong Wang, Chunlai Zhao, Wenjia Wang, Kaijing Yan, Xijun Yan, He Sun
Acute high-altitude hypoxia affects the blood flow and the efficiency of oxygen utilization, causing multi-organ injury and ultimately leading to life-threatening high-altitude cerebral edoema (HACE) or high-altitude pulmonary edoema (HAPE) (Imray et al. 2010). Decreased barometric pressure and subsequent reduction in available oxygen are the primary causal factors in these medical conditions (Clarke 2006). Acetazolamide, dexamethasone and montelukast are widely used to prevent acute altitude sickness. However, they produce a variety of adverse effects, including headache, sensory abnormalities, cardiopalmus osteoporosis and increased risk of infection (Fagenholz et al. 2007; Nieto Estrada et al. 2017). Thus, there is an increasing need for the development of alternative therapies to treat and prevent these conditions.
Oral acetazolamide for intraocular pressure lowering: balancing efficacy and safety in ophthalmic practice
Published in Expert Review of Clinical Pharmacology, 2021
Given its broad set of indications and often pronounced IOP-lowering effect, acetazolamide has become a foundational medication in ophthalmic practice, with particular importance among glaucoma care providers. As such, it is important for practitioners to have a solid understanding of how best to use the medication for their patients. Herein, we aim to provide a comprehensive review of the use of systemic acetazolamide to lower IOP with the following: (1) mechanism of action, (2) methods of observing efficacy, (3) indications for IOP lowering, (4) side effects, (5) allergy information including assessment of cross-reactivity with antimicrobial sulfonamides, (6) formulations and dosing, and (7) monitoring.
Related Knowledge Centers
- Altitude Sickness
- Carbonic Anhydrase
- Glaucoma
- Idiopathic Intracranial Hypertension
- Tinnitus
- Epilepsy
- Heart Failure
- Periodic Paralysis
- Oral Administration
- Intravenous Therapy