Atropine, heart rate

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. 

THE PATIENT WITH HEART BLOCK. The patient receiving atropine for third-degree heart block is placed on a cardiac monitor during and after administration of the drug. The nurse watches the monitor for a change in pulse rate or rhythm. Tachycardia, other cardiac arrhythmias, or failure of the drug to increase the heart rate must be reported to the primary health care provider immediately because other dm or medical management may be necessary. 

The answer is d. (Hardman, pp 212—213.) Only isoproterenol will lower mean blood pressure, decrease peripheral vascular resistance, and increase heart rate. Methacholine decreases heart rate as does propranolol. Atropine has no action on peripheral resistance. Norepinephrine causes intense vasoconstriction and raises the mean blood pressure. 

Naunyn-Schmiedeberg s Archives of Pharmacology Figure 10. Blood pressure and heart frequency in an anaesthetized cat with sectioned vagi and pretreatment with atropine (1 mg/kg). Decrease of blood pressure and heart rate in beats/min (S/min) after intracisternal (i.ci.) and intravenous (i.v.) injection... 

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. 

Ditran is intermediate between atropine and scopolamine with respect to heart rate changes, with a slight dip below baseline at the low dose of 50 mcg/kg (Fig. 65). Peak FIR elevation occurs at about 30 min, somewhat later than both atropine and scopolamine. The tachycardia is short-lived, with recovery at 5-6 hours. No doubt, the short duration of Ditran was an advantage when used by Ostfeld et al. in their Ditran coma therapy, which was perhaps inspired by Forrer s atropine coma therapy introduced a few years earlier. 

As shown in Fig. 74, belladonnoids vary greatly in both their relative peripheral and eentral poteneies. " BZ is approximately 7x as potent as atropine, while 302196 is about 40% less potent than atropine. The peripheral potencies of 27349, 302282, 3443, 302668, 3443, 3580, 226086 and 3167 (Fig. 74) Ml between 20% and 60% of BZ s potency in terms of their tendency to produce elevation of heart rate and blood pressure. 

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 sinus bradycardia or incomplete heart block, lidocaine administration for the elimination of ventricular ectopy without prior acceleration in heart rate (eg, by atropine, isoproterenol or electric pacing) may promote more frequent and serious ventricular arrhythmias or complete heart block. Use with caution in patients with hypovolemia and shock, and all forms of heart block. 

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. 

B. Phenylephrine is an aj-selective agonist. It causes an increase in peripheral vascular resistance. The major cardiovascular response to this drug is a rise in blood pressure associated with reflex bradycardia. The slowing of the heart rate is blocked by 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.)... 

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