Atropine heart rate effects

The vagus nerve acts to decelerate heart rate via a cholinergic input to the sinoatrial node, and atropine blocks this action, leading to an increase in heart rate. Effects are noted at doses as low as 0.6 mg per 70 kg of body weight, and the maximum increase of 35 to 50 beats per min is achieved at doses of 2 to 3 mg per 70 kg of body weight. Heart rate begins to increase within 15 min of an IM injection, peaks at 60 to 90 min, and can persist for 4 hr (Penetar, 1990 Penetar, Haegerstrom-Portnoy, Jones, 1988). 

Isoproterenol. Isoproterenol hydrochloride is an nonselective P-adrenoceptor agonist that is chemically related to NE. It mimics the effects of stimulation of the sympathetic innervation to the heart which are mediated by NE. It increases heart rate by increasing automaticity of the SA and AV nodes by increasing the rate of phase 4 diastoHc depolarization. It is used in the treatment of acute heart block and supraventricular bradyarrhythmias, although use of atropine is safer for bradyarrhythmias foUowing MI (86). 

The antimuscarinic drug atropine, and its derivative ipratropiumbromide, can also be used for antiarrhyth-mic treatment. Muscarinic receptors (M2 subtype) are mainly present in supraventricular tissue and in the AV node. They inhibit adenylylcyclase via G proteins and thereby reduce intracellular cAMP. On the other hand, activation of the M2 receptor leads to opening of hyperpolarizing Ik.acii and inhibits the pacemaker current If probably via the (3y-subunit of the Gi protein associated with this receptor. The results are hyperpolarization and slower spontaneous depolarization. Muscarinic receptor antagonists like atropine lead to increased heart rate and accelerated atrioventricular conduction. There are no or only slight effects on the ventricular electrophysiology. 

Atropine generally increases heart rate, but it may briefly and mildly decrease it initially, due to Ml receptors on postganglionic parasympathetic neurons. Larger doses of atropine produce greater tachycardia, due to M2 receptors on the sinoatrial node pacemaker cells. There are no changes in blood pressure, but arrhythmias may occur. Scopolamine produces more bradycardia and decreases arterial pressure, whereas atropine has little effect on blood pressure (Vesalainen et al. 1997 Brown and Taylor 1996). 

Atropine Sulfate Dose Effects on Heart Rate... 

Atropine s peripheral effects on heart rate (Fig. 63) and blood pressure (not shown) are substantial and very rapid in onset, peaking at about 30-60 minutes. In this graph, baseline heart rate is shown as zero. Maximum heart rate at the ID50 is thus about 125 (60 + 65). It remains at this level for about 3 hours and returns to normal at about 9 hours. At the ID50, minor changes in the electrocardiogram were noted in a study by Hayes et al.. These changes rapidly revert to normal as HR declines. 

Atropine, increases, but scopolamine actually decreases, heart rate at low doses and at higher doses it does not produce elevations as high as atropine at the ID50 (Fig. 64). This is probably attributable to medullary mechanisms that tend to reduce heart rate. Similar effects also occur with atropine but they are quickly overwhelmed by atropine s much greater peripheral potency. (Low dose studies of atropine reveal this more clearly.) Note that the duration of scopolamine s effects is very similar to that of atropine. 

We used an additional analysis to support the estimated LD50/ID50 ratio for BZ. Upon reviewing the LD50 of several glycolates in the mouse, it appeared that the lethality of each closely paralleled its peripheral (as reflected in heart rate changes) rather than central effects (as reflected in performance decrements). This calls into doubt the opinion, voiced in previous textbooks of pharmacology, that death from belladonnoids such as atropine results from respiratory paralysis -primarily a central nervous system effect. 

Norepinephrine opens the pupil of the eye acetylcholine narrows it. Note that an antagonist of acetylcholine at the muscarinic receptor, atropine, has the same outcome as norepinephrine (see above). Norepinephrine is a bronchodilator in contrast, acetylcholine is a bronchoconstrictor. Norepinephrine increases the heart rate, chronotropy, whereas acetylcholine slows the heart rate, bradycardy. Norepinephrine decreases the rate of intestinal movements, whereas acetylcholine increases them. In all these cases, the effects of these neurotransmitters are opposed. 

In the cardiovascular system the effect on the heart rate is prominent. The depressive influence of the nervus vagus on the pacemaking activity in the heart is concentration dependently reduced and thereby the heart rate increases. This can be therapeutically useful in various forms of bardycardia, especially if they are caused by a vagus overstimulation, for example in the carotis-sinus syndrom. There is hardly any effect on the vasculature except a vasodilatation in the thoracic region after very high doses of atropine. 

A 77-year-old man is admitted to the hospital for a coronary artery bypass. He has been treated with a (3-blocker (Tenormin 100 mg per day), which he took every morning. He is induced with propofol 1 mg/kg, fentanyl 5 jjig/kg and vecuronium 8 mg for muscle relaxation. After 3 minutes a decreasing heart rate becomes a worry for the anesthesiologist. The heart rate continues to fall until it reaches 38 BPM. At this point the patient s blood pressure is 80/60 and the anesthesiologist gives atropine 0.4 mg and ephedrine 10 mg. This treatment results in a stable patient. What effects were most likely produced by the anesthesia procedure Could this have been avoided ... 

Sldell, F.R., Magness, J.S., and Bollen, T.E. Modification of the effects of atropine on human heart rate by pralidoxlme. 

Atropine initially decrease the heart rate due to stimulation of vagal centre followed by tachycardia due to peripheral vagal block on SA node. It also shortens effective refractory period of AV node and facilitates AV conduction. In therapeutic doses, atropine completely blocks the peripheral vasodilatation and decrease in blood pressure produced by cholinergic agents. 

Heart rate In CHF patients, the heart rate is decreased. Digitalis produce a decrease in heart rate by stimulation of vagus. The vagal effect is probably evoked by sensitization of carotid baroreceptors, and by direct stimulation of vagal centre. The vagal action can be blocked by atropine but after full digitalising dose the effect can not be blocked by atropine and it is due to its direct cardiac action. In CHF patients, the sympathetic activity is increased as a compensatory phenomenon which leads to tachycardia. Digitalis decreases the... 

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. 

Effects of subcutaneous injection of atropine on salivation, speed of micturition (voiding), heart rate, and accommodation in normal adults. Note that salivation is the most sensitive of these variables, accommodation the least. 

Cardiovascular System. Atropine is sometimes used to block the effects of the vagus nerve (cranial nerve X) on the myocardium. Release of acetylcholine from vagal efferent fibers slows heart rate and the conduction of the cardiac action potential throughout the myocardium. Atropine reverses the effects of excessive vagal discharge and is used to treat the symptomatic bradycardia that may accompany myocardial infarction.4 Atropine may also be useful in treating other cardiac arrhythmias such as atrioventricular nodal block and ventricular asystole. 

The effect of atropine upon chromosomal abnormalities24 has been studied. A significant dose-dependent reduction of heart rate and blood pressure has been observed.25 A possible effectiveness of atropine on Prinzmetal s variant form of... 

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.)... 

CANNABIS ANTIMUSCARINICS -ATROPINE, FLAVOXATE, HYOSCINE, OXYBUTYNIN, TOLTERODINE t risk of tachycardia. Heart rate may t to 100-160 beats per minute, with some records of 300 beats per minute resistant to verapamil therapy Additive antimuscarinic effect Ask patients about cannabis use if they present with otherwise unexplained tachycardias while taking these drugs... 

Based on the experience of Iranian physicians who treated sarin toxicity during the Iran-Iraq war (Newmark, 2004), PAM was not available on the front lines and atropine alone was used for treatment. The doses of atropine used were considerably higher than those used in the Tokyo subway sarin attack, or that are generally recommended in the USA (Medical Letter, 2002). The Iranian protocol called for initial administration of 4 mg intravenously. If no atropine effects (improvement in dyspnea or decrease in airway secretions) were seen after 1 to 2 min, 5 mg was then administered intravenously over 5 min while heart rate was monitored. A rise in heart rate of 20 to 30 beats per min was regarded as an atropine effect. In severe cases, 20 mg to 200 mg was given. Regardless of dose, the key to saving lives, in their opinion, was how soon the atropine was administered. 

Lonnerholm, G., Widerlov, E. (1975). Effect of intravenous atropine and methyl atropine on heart rate and secretion of saliva in man. Eur. J. Clin. Pharmacol. 8 233 0. 

Cullumblne e al. (115) studied the effects of atropine sulfate on healthy men. Twenty men each received 1 mg of atropine sulfate by subcutaneous and Intramuscular injection and 0.5 mg by intravenous Injection. Forty men received double doses by the same three routes of administration. The first sign of action by atropine In many subjects was a slight, temporary decrease In heart race, followed by a gradual Increase. Intravenous Injection produced effects more rapidly chan the other routes of administration. The Increase In heart rate Induced by 1 mg of atropine sulfate Injected Intravenously Was similar to, but of shorter duration than, that Induced by subcutaneous or Intramuscular Injection of 2 mg. Subcutaneous Injection of atropine sulfate Induced acceleration of the pulse more rapidly, but less lastingly, than the same dose Injected Intramuscularly. 

The effects of mechylscopolammonium bromide and atropine sulfate on heart rate became evident (18-19 min) and reached their greatest intensities (37-40 min) at about the same times, despite the fact chat the dose of mechylscopolammonium bromide was only 22 5% chat of atropine sulfate. When equally effective doses of the compounds were administered, methylscopolammonlum bromide was slower chan scopolamine hydrobromide and atropine sulfate in exerting its maximal effect on salivation and on Che iris The effects of scopolamine l drobromide on the iris and on accommodation for near vision lasted considerably longer than those of equal doses of methylscopolammonltim bromide and atropine sulfate. 

Holland et al. (133,134) gave men intramuscular Injections of sterile water, 2 mg of atropine sulfate with 500 mg of methyl-2-hydroxylmlnomethylpyrldlnlum methyl sulfonate TP2S), 750 mg of P2S, 750 mg of P2S with 2 mg of atropine sulfate, or 2 mg of atropine sulfate. The Initial rate of absorption was judged by the time after Injection required for attainment of the maximal reduction In heart rate. Five volunteers were used to examine the effects of water, 750 mg of P2S, 750 mg of P2S with atropine sulfate, and atropine sulfate alone seven were used to determine the effects of 750 mg of P2S with atropine sulfate and atropine sulfate alone 10 were used to compare the effects of 500 mg of F2S with atropine sulfate and atropine sulfate alone. 

One can conclude that 750 mg of P2S alone had no significant effect on heart rate and that addition of either 500 or 750 mg of P2S to 2 mg of atropine sulfate had no striking effect on absorption of atropine from a site or intramuscular injection. The initial rate of absorption of atropine seems to have been increased slightly by both doses of P2S (mean time to maximal bradycardia was decreased from 18.7 min to 12.9 min by 500 mg of P2S and from 15.3 min to 12.2 min by 750 mg of P2S). 

Gcob al. (147) compared the effects of atropine administered intravenously and Intramuscularly. Four subjects were used. Two received injections of 2 mg of atropine sulfate by the Intramuscular route only one of these subjects received only one Injection, and the other, two. A third subject received 1 mg of atropine sulfate intravenously on one occasion, 1 mg of atropine sulfate intramuscularly on another occasion, and 2 mg of atropine sulfate intramuscularly on four other occasions. The fourth subject received 1 mg of atropine sulfate Intravenously on two occasions and 2 mg of atropine sulfate Intramuscularly on three occasions Atropine sulfate by either route of administration induced an Increase In heart rate, an Increase In skin resistance, an Increase In pupil size, dryness of the skin, and an Increased sensation of dryness of the mouth. In general, the effects appeared earlier after Intravenous chan after intramuscular Injection. Prior administration of sufficient TEPP to Increase sweating and salivation and to Induce anorexia and mild nausea slightly delayed the onset of the effects of atropine and slightly reduced the extent of chose effects. 

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