Sympathomimetics syndromes

Drug overdose Acute toxicity requiring emergency medical treatment is rare. When it occurs there is a typical sympathomimetic syndrome, which should be treated with fluids, control of hyperthermia, bed rest, and, if necessary, sedation with benzodiazepines (1). 

Sympathomimetic syndromes include tachycardia, hypertension, hyperthermia, sweating, mydriasis, hyperreflexia, agitation, delusions, paranoia, seizures and cardiac arrhythmias. These are commonly caused by amphetamine and its derivatives, cocaine, proprietary decongestants, e.g. ephedrine, and theophylline (in the latter case, excluding psychiatric effects). 

Infection, acute coronary syndrome, cerebrovascular accidents, trauma, noncompliance with insulin pharmacotherapy, new-onset diabetes mellitus, and medications (e.g., corticosteroids and sympathomimetics)... 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

Medications with serotonergic activity may also have other monaminergic or sympathomimetic activity. Combining MAOIs with these medications may result in a complex side effect profile. For example, combining meperidine or dextromethorphan with MAOIs may result in respiratory depression, in addition to symptoms of serotonin excess. Furthermore, interactions between MAOIs and tricyclic antidepressants (TCAs) more commonly result in potentiating shared adverse events such as othostatic hypotension, as opposed to hyperadrenergic crises or the serotonin syndrome. 

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

Shock is a complex acute cardiovascular syndrome that results in a critical reduction in perfusion of vital tissues and a wide range of systemic effects. Shock is usually associated with hypotension, an altered mental state, oliguria, and metabolic acidosis. If untreated, shock usually progresses to a refractory deteriorating state and death. The three major mechanisms responsible for shock are hypovolemia, cardiac insufficiency, and altered vascular resistance. Volume replacement and treatment of the underlying disease are the mainstays of the treatment of shock. Although sympathomimetic drugs have been used in the treatment of virtually all forms of shock, their efficacy is unclear. 

Phenylephrine is an effective mydriatic agent frequently used to facilitate examination of the retina. It is also a useful decongestant for minor allergic hyperemia and itching of the conjunctival membranes. Sympathomimetics administered as ophthalmic drops are also useful in localizing the lesion in Horner s syndrome. (See An Application of Basic Pharmacology to a Clinical Problem.)... 

If the lesion of Horner s syndrome is postganglionic, indirectly acting sympathomimetics (eg, cocaine, hydroxyamphetamine) will not dilate the abnormally constricted pupil because catecholamines have been lost from the nerve endings in the iris. In contrast, the pupil dilates in response to phenylephrine, which acts directly on the a receptors on the smooth muscle of the iris. 

Phenelzine Blockade of MAO-A and MAO-B (phenelzine, nonselective) MAO-B irreversible selective MAO-B inhibition (low dose selegiline) Transdermal absorption of selegiline achieves levels that inhibit MAO-A Major depression unresponsive to other drugs Very slow elimination Toxicity Hypotension, insomnia Interactions Hypertensive crisis with tyramine, other indirect sympathomimetics serotonin syndrome with serotonergic agents, meperidine... 

Clinical syndromes from LSD-25, mescaline, and the indoleamincs arc similar, Somatic symptoms are nausea, dizziness, loss of appetite, blurred vision, paresthesia, weakness, drowsiness, and trembling. These result frequently and are usually associated with sympathomimetic effects, such as increased pulse rate and slight temperature elevation. Perceptual and psychic changes are marked. Visual illusions and vivid hallucinations, decreased concentration, slow thinking, depersonalization, dreamy states, changes in mood, and often anxiety are commonly found. 

The diagnosis of GHB withdrawal may be difficult because it is similar to sedative or alcohol withdrawal syndromes, as well as to withdrawal from sympathomimetic agents such as cocaine, methamphetamine, and ecstasy. GHB withdrawal may also be confused with serotonin syndrome (a reaction caused by a combination of drugs, one of which increases serotonin levels in the body, such as Prozac) and neuroleptic malignant syndrome (a rare reaction to an antiseizure medication). 

ADRENERGIC NEURONE BLOCKERS-GUANETHIDINE CENTRALLY ACTING ANTIHYPERTENSIVES-METHYLDOPA MAOIs Risk of adrenergic syndrome (see above). Reports of an enhanced hypotensive effect and hallucinations with methyldopa, which may cause depression Due to inhibition of MAOI, which breaks down sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion... 

SYMPATHOMIMETICS ANTIVIRALS-PROTEASE INHIBITORS 1. Risk of serotonin syndrome when dexamfetamine is administered with ritonavir 2. Indinavir may t phenylpropanolamine levels 1. Protease inhibitors inhibit CYP2D6-mediated metabolism 2. Likely inhibition of phenylpropanolamine metabolism 1. Avoid co-administration 2. Monitor BP closely watch for marked t BP... 

SSRIs SYMPATHOMIMETICS 1. Case report of serotonin syndrome when dexamfetamine was co-administered with citalopram 2. Case reports of psychiatric disturbances when methylphenidate was given with sertraline, and phenylpropanolamine was co-administered with phenylpropanolamine 1. Uncertain postulated that there is an additive effect of inhibition of serotonin reuptake by citalopram with release of serotonin by venlafaxine 2. Uncertain 1. Avoid co-administration of dexamfetamine and citalopram 2. Warn patients to watch for early signs such as anxiety... 

VENLAFAXINE SYMPATHOMIMETICS -INDIRECT Case of serotonin syndrome when dexamfetamine is co administered with venlafaxine Uncertain postulated that there is an additive effect of inhibition of serotonin reuptake by venlafaxine, with a release of serotonin by venlafaxine Avoid co-administration... 

LEVODOPA, SELEGILINE, POSSIBLY RASAGILINE, ENTACAPONE, TOLCAPONE MAOIs Risk of adrenergic syndrome -hypertension, hyperthermia, arrhythmias - and dopaminergic effects with selegiline Levodopa and related drugs are precursors of dopamine. Levodopa is predominantly metabolized to dopamine, and a smaller proportion is converted to epinephrine and norepinephrine. Effects are due to inhibition of MAOI, which breaks down dopamine and sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion. Carbidopa and benserazide, which inhibit dopa decarboxylase that converts L-dopa to dopamine, is considered to minimize this interaction. However, MAOIs should not be used in patients with Parkinson s disease on treatment with levodopa. Imipramine and amitriptyline are considered safer by some clinicians... 

Nonnarcotic analgesic combinations usually consist of one or more of the fitUowing agents acetaminophen, salicylates, salsalate, and saUcylamide. Some of the products contain barbiturates, meprobamate, or antihistamines to produce a sedative effect, and antacids may be included to minimize gastric upset associated with the salicylates. Caffeine, a traditional adjuvant in many analgesic combinations, may be beneficial in the treatment of certain vascular headache syndromes. Some belladonna alkaloids may be incorporated for their antispasmodic properties. Pamabrom, a diuretic, and cinnamedrine, a sympathomimetic amine, are sometimes included in products for premenstrual syndrome. 

Sympathomimetics Concurrent use may increase the risk of serotonin syndrome. 

Toxic syndromes ( toxidromes ) are clinical syndromes that are essential for the successful recognition of poisoning patterns. A toxidrome is the constellation of clinical signs and symptoms that suggests a specific class of poisoning. The most important toxidromes are (1) anticholinergic, (2) cholinergic, (3) opioid and opioid withdrawal, (4) sedative-hypnotic and sedative-hypnotic withdrawal, and (5) sympathomimetic. Symptoms for these toxidromes are listed in Table 34-2. 

The risk of serotonin syndrome may be increased shortly after dosage increases of SSRIs or when drug interactions increase serotonin activity. Concomitant or proximal use of SSRIs, tricyclic antidepressants, or monoamine oxidase inhibitors may cause serotonin syndrome. Further, the addition of certain drugs, such as tryptophan, dextromethorphan, cocaine, or sympathomimetics, to SSRI therapy may increase the risk of developing serotonin syndrome." ... 

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