Adrenergic storm | |
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Other names | Sympathomimetic toxicity Sympathomimetic toxidrome |
Complications | Tachycardia, hypertension |
Causes | Cocaine, stimulant abuse, subarachnoid hemorrhage, methamphetamine, foods high in tyramine, rabies |
Treatment | diazepam, benzodiazepines, beta blockers, anti-hypertensives |
An adrenergic storm is a sudden and dramatic increase in serum levels of the catecholamines adrenaline and noradrenaline (also known as epinephrine and norepinephrine respectively), with a less significant increase in dopamine transmission. It is a life-threatening condition because of extreme tachycardia and hypertension, and is especially dire for those with prior heart problems. If treatment is prompt, prognosis is good; typically large amounts of diazepam or other benzodiazepines are administered alongside beta blockers. Beta blockers are contraindicated in some patients, so other anti-hypertensive medication such as clonidine may be used. [1] Antipsychotics are also used to treat the most severe psychiatric reactions such as psychosis, paranoia or terror, after their use was formerly discouraged because of their potential to prolong the QT interval; however, more recent research performed since 2019 has revealed that this and other severe side effects are rare and their occurrence does not warrant banning antipsychotics from the treatment of adrenergic crises for which they can be extremely useful. [2] [3] [4] [5] [6] [7] [8]
Adreneric storms are usually caused by overdoses of stimulants, especially cocaine or methamphetamine, or eating foods high in tyramine while taking monoamine oxidase inhibitors. [9] A subarachnoid hemorrhage can also cause an adrenergic storm. [9] A catecholamine storm is part of the normal course of rabies infection, and is responsible for the severe feelings of agitation, terror, and dysautonomia present in the pre-coma stage of the disease. [10]
The behavioral symptoms are similar to those of an amphetamine, cocaine or caffeine overdose. Overstimulation of the central nervous system results in a state of hyperkinetic movement and unpredictable mental status including mania, rage and suicidal behavior; hyperthermia is also prominently present. [11] Delirium can also be present but rarely. [12]
Physical symptoms are more serious and include heart arrhythmias as well as outright heart attack or stroke in people who are at risk of coronary disease. Breathing is rapid and shallow while both pulse and blood pressure are dangerously elevated. [13]
Other complications would include rhabdomyolysis, a breakdown of the voluntary muscles because of the excessive physical movement, causing the components of the muscle, most notably myoglobin, to be released into the bloodstream and then clog the kidneys, causing renal failure. [14] In all, rhabdomyolysis is especially common in adrenergic storms caused by the use of stimulant drugs, most notably those of the phenethylamines such as cathinones or amphetamines. [15]
There are several known causes of adrenergic storms; in the United States, cocaine overdose is the leading cause. [16] Any stimulant drug has the capacity to cause this syndrome if taken in sufficient doses, but even non-psychotropic drugs can very rarely provoke a reaction. [17]
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the enzyme monoamine oxidase. This enzyme is responsible for breaking down many compounds; basically, anything with a primary amine moiety is likely to be oxidized by monoamine oxidase. An important substrate of the enzyme MAO is tyramine. MAOIs inhibit the enzyme either reversibly, in which MAO is inhibited only until the drug is cleared from the system, or irreversibly, in which the substrate binds permanently to the enzyme, rendering it inactive and effectively destroying it. Irreversible MAOIs are potentially more dangerous, because the body takes about two weeks to regenerate MAO enzymes to functional levels. [18] Two subtypes of MAO exist: MAO-A and MAO-B; this is relevant to adrenergic storms, as there are significant differences between the two types, such as their differential expression throughout the body, and range of substrates. While both MAO-A and MAO-B metabolize tyramine, only MAO-A is present in the gastrointestinal tract and singularly metabolizes the majority of consumed tyramine. [9] (The small portion normally passing into circulation is mostly degraded in the liver where both MAO types act. [9] ) Consequently, MAOIs that irreversibly inhibit MAO-A will permit high levels of circulating tyramine able to cause tyramine-induced hypertensive crisis. Aged cheese, beer, red wine, some mushrooms, and fermented products such as pickles are foods containing high levels of tyramine that passed into circulation can cause such a hypertensive crisis.[ citation needed ]
Adrenergic storms are not provoked often from MAOI-tyramine interactions; hypertensive crisis alone does not diagnose adrenergic storm, although there will always be hypertension in an adrenergic storm, along with tachycardia and rapid, shallow breathing. However, if a patient on MAOIs uses recreational quantities of any drug with stimulant effects on the CNS, it can provoke an adrenergic crisis (along with the inevitable hypertensive crisis). Deaths have occurred from individuals attempting to combine MAOIs with various entheogens to attain a stronger psychedelic experience, both from adrenergic storms and serotonin syndrome. Combining drugs like MDMA, 2C-B, mescaline, 2C-T-7, etc. with even small quantities of MAOIs - small quantities of both drugs - is still extremely risky. Nevertheless, some users claim to use certain combinations successfully.[ citation needed ]
Subarachnoid hemorrhage is an extremely serious condition in which a neural membrane is breached and the brain itself is compromised. The onset is sudden, described as "the worst headache of one's life," and many grave symptoms follow. Adrenergic storm is often present among these symptoms, and is responsible for some of the dangers, both long-term and short, of subarachnoid hemorrhage adrenergic storm, through a complex cascade of processes starting with the movement of subarachnoid blood into the brain. Apparently, as the intracranial pressure increases, the brain is squeezed and catecholamines are forced out of their vesicles into the synapses and extracellular space. [19]
Rarely, a pheochromocytoma (tumor of the medullar tissue of the adrenal glands, which are located anterior to the kidney), may result in an adrenergic storm. [20] This type of tumor is not common to begin with, and furthermore, the subtype that can cause massive adrenaline release is rarer still. Patients with pheochromocytoma can unexpectedly fly into a rage or sink into trembling fear, possibly dangerous to themselves and others as their judgment is impaired, their senses and pain threshold are heightened, and the level of the adrenaline in their bloodstream is more than most people ever experience; pheochromocytoma can, very rarely, kill by internal adrenaline overdose. [21] But overall, adrenergic storm is an uncommon but certainly not rare phenomenon associated with the also uncommon condition of pheochromocytoma. [22]
Because the adrenergic storm overlaps with so many other similar conditions, such as hypertensive crises, stimulant intoxication or overdose, or even panic attack, and because the treatments for these overlapping conditions are largely alike, it is not necessary to obtain a differential and definitive diagnosis before initiating treatment. However, analysis of the patient's medical history, checked against the possible causes of the adrenergic storm such as those above, should be done, because some adrenergic storms can be caused by serious underlying conditions. [10] If a patient has an adrenergic storm and all or most of the other factors are ruled out, the adrenergic storm could lead to the discovery of a pheochromocytoma, which can become malignant. However, not all cases of adrenergic storm have an identifiable cause. Like a seizure, sometimes a patient has a single one, or perhaps a few, and then does not for the rest of their life. [23] The mechanisms of idiopathic adrenergic storm are very poorly understood.
Serotonin syndrome, in which an excess of serotonin in the synapses causes a similar crisis of hypertension and mental confusion, could be confused with an adrenergic storm. Serotonin, being a tryptamine (non-catecholamine) involved in higher brain functions, can cause dangerous hypertension and tachycardia from its effects on the sympathetic nervous system. [23] Symptoms caused by excessive adrenergic signalling can occur alongside those of serotonergic signalling. One example would be: overdose of drug(s) influencing multiple targets including serotonin, and adrenergic systems, with concurrent MAOI use). Abnormal echocardiograms, or chest pain are indicative of adrenergic crisis. [23] On the other hand, uncontrollable slow, rhythmic, and/or jerky movements, contractions and tension-often in every part of the body, dangerously high fever, eye rolling, and bruxism are more indicative of serotonin syndrome. [10] [24]
If there is evidence of overdose or it is suspected, the patient should be given gastric lavage, activated charcoal, or both; this could make the difference between life and death in a close situation. [25] It can however aggravate the patient which should be taken into account. [10]
The first line treatments are diazepam and a non-selective beta blocker; other antihypertensive drugs may also be used. It is important to note that not all benzodiazepines and beta blockers are safe to use in an adrenergic storm; for instance, alprazolam and propranolol; [10] alprazolam weakly agonizes dopamine receptors and causes catecholamine release while propranolol mildly promotes some catecholamine release - each worsening the condition. [23]
Antipsychotics are also used to treat the psychiatric symptoms such as aggression, agitation, psychosis, paranoia or anxiety. Originally, the use of antipsychotics was discouraged because of their potential to prolong the QT interval; [3] however, newer research has revealed that their careful use does not carry the potential for any significant side effects and today their judicious use is encouraged. [3] [2] [4] [26]
Adrenergic storms are often idiopathic in nature; however if there is an underlying condition, then that must be addressed after bringing the heart rate and blood pressure down. [1]
An anxiolytic is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.
Monoamine oxidases (MAO) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase. The MAOs belong to the protein family of flavin-containing amine oxidoreductases.
Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases, body temperature can increase to greater than 41.1 °C (106.0 °F). Complications may include seizures and extensive muscle breakdown.
A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of synthetic chemical compounds and are usually prescribed in psychiatric settings, potentially involuntarily during commitment. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, thereby lowering the cost of mental health care. The recidivism or rehospitalization of the mentally ill is at a high rate in many countries, and the reasons for the relapses are under research.
A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.
Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.
Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use. It is typically available in 15 mg tablets and doses usually range from 45–90 mg per day.
Myristicin is a naturally occurring compound found in common herbs and spices, such as nutmeg. It is an insecticide, and has been shown to enhance the effectiveness of other insecticides.
Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively.
Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).
Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart rate, force of cardiac contraction, and blood pressure. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.
Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or tablet taken by mouth for Parkinson's disease and as a patch applied to skin for depression.
Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine.
Isocarboxazid is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. Along with phenelzine and tranylcypromine, it is one of only three classical MAOIs still available for clinical use in the treatment of psychiatric disorders in the United States, though it is not as commonly employed in comparison to the others.
Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.
Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the UK and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.
A spontaneous orgasm, or spontaneous ejaculation when it occurs in males, is an orgasm which occurs spontaneously and involuntarily without sexual stimulation. Nocturnal emissions may be considered a normal/physiological form of spontaneous orgasm. Pathological spontaneous orgasms can be experienced as pleasurable, non-pleasurable, or unpleasant, and can be distressing. Causes of pathological spontaneous orgasms include spinal cord lesions, psychological causes, rabies, and medications. Some cases may have no identifiable cause. Spontaneous orgasms may have no trigger or may be triggered by various non-sexual circumstances. They may occur in both males and females. Treatment of spontaneous orgasms include psychotherapy, selective serotonin reuptake inhibitors (SSRIs), the alpha-1 blocker silodosin, and anxiolytics.
Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene.
Mary Lilias Christian Bernheim was a British biochemist best known for her discovery of the enzyme tyramine oxidase, which was later renamed as monoamine oxidase. Bernheim discovered the enzyme system of tyramine oxidase during her doctorate research at the University of Cambridge in 1928, and her research has been referred to as "one of the seminal discoveries in twentieth century neurobiology".