Sympathomimetics ,

DIRECT ANAESTHETICS-GENERAL 1. Risk of arrhythmias when inhalational anaesthetics are coadministered with epinephrine or norepinephrine 2. Case report of marked t BP when phenylephrine eye drops given during general anaesthesia 

INDIRECT ANALGESICS Dexamfetamine and methylphenidate t the analgesic effects and 1 the sedation of opioids when used for chronic pain Uncertain complex interaction between the sympathetic nervous system and the opioid receptors Opioid requirements may be 1 when patients also take indirect sympathomimetics 

SYMPATHOMIMETICS ANTACIDS-SODIUM BICARBONATE Possibly t ephedrine/ pseudoephedrine levels Alkalinising urine 1 excretion of these sympathomimetics Watch for early features of toxicity 

SYMPATHOMIMETICS LINEZOLID Risk of t BP when linezolid is co-ingested with either direct or indirect sympathomimetics Linezolid causes accumulation of norepinephrine at the nerve ends sympathomimetics stimulate the release of these T reserves of norepinephrine, which in turn causes vasoconstriction and a rise in BP Monitor BP closely watch for t BP. Warn patients taking linezolid not to take OTC remedies containing sympathomimetics 

Apart from receptors, adrenergic neu-rotransmission involves mechanisms for the active re-uptake and re-storage 

Inhibitors of MAO (A). The enzyme is located predominantly on mitochondria, and serves to scavenge axoplasmic free NE. Inhibition of the enzyme causes free NE concentrations to rise. Likewise, dopamine catabolism is impaired, making more of it available for NE synthesis. 

Consequently, the amount of NE stored in granular vesicles will increase, and with it the amount of amine released per nerve impulse. 

In the CNS, inhibition of MAO affects neuronal storage not only of NE but also of dopamine and serotonin. 

These mediators probably play significant roles in CNS functions consistent with the stimulant effects of MAO inhibitors on mood and psychomotor drive and their use as antidepressants in the treatment of depression (A). Tranylcypromine is used to treat particular forms of depressive illness as a covalently bound suicide substrate, it causes long-lasting inhibition of both MAO isozymes, (MAOa, MAOb). Moclobemide reversibly inhibits MAOa and is also used as an antidepressant. The MAOb inhibitor selegiline (deprenyl) retards the cat-obolism of dopamine, an effect used in the treatment of parkinsonism (p. 188). 

Raising the concentration of norepinephrine in the synaptic space intensifies the stimulation of adrenoceptors. In principle, this can be achieved by  

Chemically altered derivatives differ from norepinephrine with regard to the relative af nity for these systems and affect these functions differentially. 

Indirect sympathomimetics (B) in the narrow sense comprise amphetamine-like substances and cocaine. Cocaine blocks the norepinephrine transporter (NAT), besides acting as a local anesthetic. Amphetamine is taken up into varicosities via NAT, and from there into storage vesicles (via the vesicular monoamine transporter), where it displaces NE into the cytosol. In addition, amphetamine blocks MAO, allowing cytosolic NE concentration to rise unimpeded. This induces the plasmalemmal NAT to transport Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms 

NE in the opposite direction, that is, to liberate it into the extracellular space. Thus, amphetamine promotes a nonexocytotic release of NE. The effectiveness of such indirect sympathomimetics diminishes quickly or disappears (tachyphylaxis) with repeated administration. 

Pralidoxime has a very high affinity for the phosphorus atom in organophosphate insecticides. The answer is (G). 

The case description is typical of antimuscarinic drug poisoning. A common source of such agents in nature is Jimson weed (Datura stramonium). The patient had ingested several of the 2-3 mm round black seeds from the pods of this plant. 

Skill Keeper Answer Drug Ionization (see Chapter 1) 

Therefore, about 99% of the drug is in the protonated form, 1% in the unprotonated form. Since atropine is a weak base, it is the unprotonated form that is lipid-soluble. Therefore, about 1% of the atropine in the urine is lipid-soluble. 

List tissues that contain significant numbers of alpha receptors of the a, or types. 

LoD was 0.5 pgL (2nmolL ) using a 1 mL sample. The A-(l,l-dimethyl)ethyl analogue of prenalterol was selected as the internal standard. 

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Tetrahydro2oline [84-22-0] 2-(l,2,3,4-tetrahydro-l-naphthyl)2-imida2olin, (Tysine, Visine) (40), a sympathomimetic and nasal decongestant, is made by the condensation of 1,2,3,4-tetrahydro-l-naphthoic acid or its methyl ester with 1,2-ethylenediamine. 

As of the mid-1990s, use of MAOIs for the treatment of depression is severely restricted because of potential side effects, the most serious of which is hypertensive crisis, which results primarily from the presence of dietary tyramine. Tyramine, a naturally occurring amine present in cheese, beer, wine, and other foods, is an indirecdy acting sympathomimetic, that is, it potently causes the release of norepinephrine from sympathetic neurons. The norepinephrine that is released interacts with adrenoceptors and, by interacting with a-adrenoceptors, causes a marked increase in blood pressure the resultant hypertension may be so severe as to cause death. 

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

Appetite suppressants have been widely used as an adjunct to dietary restriction and sympathomimetic amines have traditionally been used for this purpose. These agents have not proven particularly useful and frequentiy cause unacceptable side effects, hence their popularity has been waning for several years. The most promising newer dmgs work through a serotoninergic mechanism and hold considerable promise at least for certain obese patients. 

The sympathetic or adrenergic nervous system operates in juxtaposition to the parasympathetic nervous system to maintain homeostasis in response to physical activity and physical or psychological stress. Sympathomimetic neurotransmission is generally mediated by norepinephrine [51-41 -2] (1), CgH NO, released from presynaptic storage granules upon stimulation. A second endogenous sympathomimetic agent, epinephrine [51-43-4] (2),... 

Compounds stmcturaHy related to the endogenous sympathomimetic amines epinephrine and norepinephrine have classically been employed as appetite suppressants. These agents, of which amphetamine [300-62-9], is the prototypical example, generally retain the phenethyl amine, but lack... 

Some P-adrenoceptor blockers have intrinsic sympathomimetic activity (ISA) or partial agonist activity (PAA). They activate P-adrenoceptors before blocking them. Theoretically, patients taking P-adrenoceptor blockers with ISA should not have cold extremities because the dmg produces minimal decreases in peripheral blood flow (smaller increases in resistance). In addition, these agents should produce minimal depression of heart rate and cardiac output, either at rest or during exercise (36). 

P-Adrenoceptor blockers for the treatment of hypertension include (/) the cardioselective P -adrenoceptor blockers without intrinsic sympathomimetic activity (ISA), ie, atenolol (Table 3), bisoprolol (Table 3), and metoprolol (Table 1) (2) the cardioselective with ISA, ie, acebutolol (Table 1) (J) the noncardioselective without ISA, ie, propranolol (Table 1) and timolol [26839-75-8] C23H24N4O2S and (4) the noncardioselective with ISA, ie, oxprenolol [6452-71-7] C 3H23N03, and pindolol. 

Acutrim 16 Hour Steady Control Tablets. Acuttim is an appetite suppressant diet aid available without a prescription and marketed by CIBA Consumer Pharmaceuticals. The active ingredient is phenylpropanolamine hydrochloride [154-41 -6] a sympathomimetic amine (see Antiobesity drugs). Acutrim dehvers its dosage at a precisely controlled rate for up to 16 hours. This is achieved through the OROS technology. 

Sympathomimetics with free amino groups e g carbadrine, norfenefnne, noradrenaline, norephednne... 

Polyethylene glycol primary amines, indole derivatives, sympathomimetics stabilization and enhancement dipping solution, 20% in methanol [270]... 

As already stated, the number of substances made by chemists for pharmacological examination as possible sympathomimetic amines is enormous and the literature voluminous. Fortunately the latter has been reviewed from time to time, and most recently in the symposium in which Hartung dealt with the correlation of structure and pharmacological action in )3-phenylethylamine derivatives, which includes the more impor-... 

Omission of the side chain hydroxyl group from molecules based on epinephrine or ephedrine does not abolish the sympathomimetic activity of the resulting compounds. Many of these agents exert a considerable stimulant action on the central nervous system. As such, drugs in this class have been widely used—and... 

Sympathomimetic. A drug that produces effects similar to stimulating the sympathetic nervous system, that is, increased blood pressure, dilated bronchi, and mydriasis. 

Amphetamine and related compounds are indirect acting sympathomimetic agents that are frequently abused due to their stimulant properties on the central nervous system. Amphetamines act by inducing the... 

The appetite-suppressing effect of (3-phenylethylamine drugs is either related to their sympathomimetic effect (metamphetamine, phentermine, diethylpropion), to... 

Hypertensive reaction resulting from release of noradrenaline by tyramine and other sympathomimetic amine as a consequence of irreversible inhibition of MAO-A. 

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