Atropine dose response

Sinus rhythm with a rate of less than 60/min is defined as sinus bradycardia. This bradycardia is usually a physiological response. Pathological and/or symptomatic sinus bradycardia may suggest sinus node dysfunction (see sick sinus syndrome). Vagally induced sinus bradycardia may be responsive to atropine, but only needs to be treated if symptomatic. Atropine doses of less than 0.5 mg may cause a paradoxical increase in vagal bradycardia. 

Modified and reproduced, with permission, from Wellstein A, Pitschner HF Complex dose-response curves of atropine in man explained by different functions of M-l and M2 cholinoceptors. Naunyn Schmiedebergs Arch Pharmacol 1988 338 19.)... 

Effects of increasing doses of atropine on heart rate (A) and salivary flow (B) compared with muscarinic receptor occupancy in humans. The parasympathomimetic effect of low-dose atropine is attributed to blockade of prejunctional muscarinic receptors that suppress acetylcholine release. (Modified and reproduced, with permission, from Wellstein A, Pitschner HF Complex dose-response curves of atropine in man explained by different functions of Mi and M2 cholinoceptors. Naunyn Schmiedebergs Arch Pharmacol 1988 338 19.)... 

Grainger S L, Smith S E 1983 Dose-response relationships of intravenous hyoscine butylbromide and atropine sulphate on heart rate in healthy volunteers. British Journal of Clinical Pharmacology 16 ... 

Koplovitz, I., Menton, R., Matthews, C., Shutz, M., Nalls, C., and Kelly, S., Dose-response effects of atropine and HI-6 treatment of organophosphorus poisoning in guinea pigs, Drug Chem. Toxicol., 18,119-136,1995. 

The elderly are particularly prone to develop dangerous hyperthermia when given atropine Atropine often causes excessive vasodilation and hypotension in tlie elderly 11. When a dose-response study of atropine is car ried out in young adults, which of the following effects may be observed ... 

Figure 1. Dose response for DSCG (A) or lodoxatmde (B) in FicoU-purified rat mast cells vs. 48/80-induced histamme release. Atropine loas added to incubations (25°C) 5 min before DSCG or lodoxamide.DSCG or lodoxamide was prepared in distilled water and added immediately before 48/80. Histamine was determined in supernatants by an automated Technicon histamine assay and was compared to histamine content of boiled cells (boiled in O.JN HCl for complete release). The results are expressed as net histamine release. ((A) Atrophine jO M alone inhibited 48/80 release 2.8% 0.5 pg/ mL 48180—26.8%histamine release)...

These data indicate that DSCG and lodoxamide tromethamine exhibit biphasic dose responses for inhibition of mediator release and that both a portion of the bell-shaped curve and a part of the multiple dose tachyphylaxis can be blocked by prior treatment with atropine. 

The extract produced a contraction of the preparation which was rapid both in onset and inactivation (see inset. Fig. 1). The dose-response relationship is shown in Fig. 1. In the presence of atropine (lO M), the effect of 0.3 mg/ml of the extract was depressed by 40.7 6.3% of control (n=4) and for 1 mg/ml the depression was 19.9 7.2% of control (n=4). On the other hand, atropine in the same concentration (lO M) abolished the responses to equieffective doses of acetylcholine (3-10 pM). Furthermore, pretreatment with HC-3 (lO M) depressed the stimulatory actions of the extract, with the effects at the two highest doses being significantly different from control (P<0.05) (Fig. 1). 

Acute treatment of patients with second- or third-degree AV nodal blockade consists primarily of administration of atropine, which maybe administered in the same doses as recommended for management of sinus bradycardia. In patients with hemodynamically unstable or severely symptomatic AV nodal blockade that is unresponsive to atropine and in whom temporary or transvenous pacing is not available or is ineffective, epinephrine (2 to 10 mcg/minute, titrate to response) and/or dopamine (2 to 10 mcg/kg/minute) maybe administered.14... 

Chiidren Use with caution signs of atropinism may occur with recommended doses, particularly in Down syndrome patients. Use with caution in young children because of variable response. Not recommended in children less than 2 years of age. 

Although atropine and scopolamine share many properties, an important difference is the easier entry of scopolamine into the CNS. Typical doses of atropine (0.2-2 mg) have minimal central effects, while larger doses can produce a constellation of responses collectively termed the central anticholinergic syndrome. At intermediate doses (2-10 mg), memory and concentration may be impaired, and the patient may be drowsy. If doses of 10 mg or more are used, the patient may exhibit confusion, excitement, hallucinations, ataxia, asyn-ergia, and possibly coma. 

Even low doses of scopolamine have central effects. Sedation, amnesia, and drowsiness are common during the clinical use of this drug. Large doses of scopolamine can produce all of the responses seen with atropine. Other tertiary amine compounds with muscarinic receptor blocking activity have similar central effects. 

Antimuscarinic drugs block contraction of the iris sphincter and ciliary muscles of the eye produced by ACh. This results in dilation of the pupil (mydriasis) and paralysis of accommodation (cycloplegia), responses that cause photophobia and inability to focus on nearby objects. Ocular effects are produced only after higher parenteral doses. Atropine and scopolamine produce responses lasting several days when applied directly to the eyes. 

Hypotensive activity. Essential oil, administered intravenously to dogs at a dose of 3 p,L/kg, was active. The ethanol (70%) extract, administered intravenously to dogs at a dose of 75 mg/kg, was active. There was a dip followed by rise in blood pressure° . Ethanol (80%) extract of the aerial parts, at a dose of 10 mg/kg, was not blocked by atropine. The extract did not inhibit pressor response of norepinephrine either . Ethanol (95%) extract of the seed, administered intravenously to dogs at a dose of 10 mg/kg, produced a transient effect that was blocked by atropine ". Petroleum ether fraction chromatographed and fraction eluted with chloroform, administered intravenously to rabbits at a dose of 0.80 mg/kg, was inactive. Methanol extract, administered intravenously to dogs and rabbits at a... 

Overdose may result in cholinergic crisis, characterized by severe nausea, increased salivation, diaphoresis, bradycardia, hypotension, flushed skin, abdominal pain, respiratory depression, seizures, and cardiorespiratory collapse, increasing muscle weakness may result in death if respiratory muscles are involved. The antidote is 1 -2 mg IV atropine sulfate with subsequent doses based on therapeutic response. 

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