Acetylcholine cardiac effects

Rare adverse cardiac effects have been reported secondary to ranitidine. These effects may be either due to direct ranitidine blockade of cardiac H2 receptors or due to potentiation of acetylcholine activity on the heart by ranitidine-induced inhibition of acetylcholinesterases. Ranitidine-induced hepatic injury is thought to be secondary to an idiosyncratic reaction or a hypersensitivity reaction. 

Elucidation of the stmctural requirements for dmg interaction at the recognition site is by the study of stmcture—activity relationships (SAR), in which, according to a specific biologic response, the effects of systematic molecular modification of a parent dmg stmcture are determined. Such studies have permitted the classification of discrete classes of pharmacological receptors. For example, the neurotransmitter acetylcholine acts at both peripheral and central receptors which are of at least three distinct types. The effects of acetylcholine are mimicked in smooth and cardiac muscles and secretory... 

The Class I agents decrease excitability, slow conduction velocity, inhibit diastoHc depolarization (decrease automaticity), and prolong the refractory period of cardiac tissues (1,2). These agents have anticholinergic effects that may contribute to the observed electrophysiologic effects. Heart rates may become faster by increasing phase 4 diastoHc depolarization in SA and AV nodal cells. This results from inhibition of the action of vagaHy released acetylcholine [S1-84-3] which, allows sympathetically released norepinephrine [51-41-2] (NE) to act on these stmctures (1,2). 

In the following, the cardiac action potential is explained (Fig. 1) An action potential is initiated by depolarization of the plasma membrane due to the pacemaker current (If) (carried by K+ and Na+, which can be modulated by acetylcholine and by adenosine) modulated by effects of sympathetic innervation and (3-adrenergic activation of Ca2+-influx as well as by acetylcholine- or adenosine-dependent K+-channels [in sinus nodal and atrioventricular nodal cells] or to dqjolarization of the neighbouring cell. Depolarization opens the fast Na+ channel resulting in a fast depolarization (phase 0 ofthe action potential). These channels then inactivate and can only be activated if the membrane is hyperpolarized... 

Inhibition of the Na+/K+-ATPase leads to a loss of potassium and an increase of sodium within the cell. Secondary intracellular calcium is increased via the Na VCa -exchanger. This results in a positive inotropic effect in the myocardium, with an increase of peak force and a decrease in time to peak tension. Besides this, cardiac glycosides increase vagal activity by effects on the central vagal nuclei, the nodose ganglion and increase in sensitivity of the sinus node to acetylcholine. 

The histamine H2-receptor (359 amino acids) is best known for its effect on gastric acid secretion. Histamine H2-receptor activation, in conjunction with gastrin and acetylcholine from the vagus, potently stimulate acid secretion from parietal cells. High concentrations of histamine are also present in cardiac tissues and can stimulate positive chronotropic and inotropic effects via H2-receptor stimulation and activation of adenylyl... 

A G-protein-mediated effect has an absolute requirement for GTP. Reference has already been made to the requirement for GTP in reconstituting hormone-stimulated adenylate cyclase activity. A similar requirement can be demonstrated when the effector is an ion channel, such as the cardiac atrial inward-rectifier K+ channel which is activated following stimulation of the M2 muscarinic acetylcholine receptor. Thus, in the experiment illustrated in Figure 7.8, the channel recorded with a cell-... 

With severe intoxication by all routes, an excess of acetylcholine at the neuromuscular junctions of skeletal muscle causes weakness aggravated by exertion, involuntary twitchings, fasciculations, and eventually paralysis. The most serious consequence is paralysis of the respiratory muscles. Effects on the central nervous system include giddiness, confusion, ataxia, slurred speech, Cheyne-Stokes respiration, convulsions, coma, and loss of reflexes. The blood pressure may fall to low levels, and cardiac irregularities, including complete heart block, may occur. ... 

The action of administered acetylcholine on effector systems innervated by parasympathetic postganglionic neurons (smooth muscle cells, cardiac muscle cells, and exocrine gland cells) resembled the actions produced by the naturally occurring plant alkaloid muscarine. The actions of both acetylcholine and muscarine on the visceral effectors are similar to those produced by parasympathetic nerve stimulation. Furthermore, the effects of acetylcholine, muscarine, and parasympathetic nerve stimulation on visceral effectors are antagonized by atropine, another plant alkaloid. 

Transmembrane action potential of a sinoatrial node cell. In contrast to other cardiac cells, there is no phase 2 or plateau. The threshold potential (TP) is -40 mV. The maximum diastolic potential (MDP) is achieved as a result of a gradual decline in the potassium conductance (gK+). Spontaneous phase 4 or diastolic depolarization permits the cell to achieve the TR thereby initiating an action potential (g = transmembrane ion conductance). Stimulation of pacemaker cells within the sinoatrial node decreases the time required to achieve the TR whereas vagal stimulation and the release of acetylcholine decrease the slope of diastolic depolarization. Thus, the positive and negative chronotropic actions of sympathetic and parasympathetic nerve stimulation can be attributed to the effects of the respective neurotransmitters on ion conductance in pacemaker cells of the sinuatrial node. gNa+ = Na+ conductance. 

Mechanism of Action An acetylcholine antagonist that inhibits the action of acetylcholine by competing with acetylcholine for common binding sites on muscarinic receptors, which are located on exocrine glands, cardiac and smooth-muscle ganglia, and intramural neurons. This action blocks all muscarinic effects. Therapeutic Effect Decreases GI motility and secretory activity, and GU muscle tone (ureter, bladder) produces ophthalmiccycloplegia, and mydriasis. 

Mechanism of Action Competitive inhibitors of the muscarinic actions of acetylcholine, acting at receptors located in exocrine glands, smooth and cardiac muscle, and intramural neurons. Composed of 3 main constituents atropine, scopolamine, and hyoscyamine. Scopolamine exerts greater effects on the CNS, eye, and secretory glands than the constituents atropine and hyoscyamine. Atropine exerts more activity on the heart, intestine, and bronchial muscle and exhibits a more prolonged duration of action compared to scopolamine. Hyoscyamine exerts similar actions to atropine but has more potent central and peripheral nervous system effects. TherapeuticEffect Peripheral anticholinergic and antispasmodic action, mild sedation. Pharmacokinetics None known... 

It is a potent alpha-adrenergic blocking agent and only haloalkylamine used clinically. It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease. It interferes with the reflex adjustment of blood pressure and produces postural hypotension. It increases the cardiac output and decreases the total peripheral resistance. It also antagonizes cardiac arrhythmias provoked by catecholamines. Apart from these effects, phenoxybenzamine has other actions also e.g. antagonism of acetylcholine, histamine, 5-hydroxytryptamine (serotonin). However, the vasodilatation produced by phenoxybenzamine is because of alpha blockage. Adverse reactions are miosis, dryness of mouth, inhibition of ejaculation, palpitation, nasal stuffiness and in higher doses, postural hypotension and reflex bradycardia. 

VIP exerts significant effects on the cardiovascular system. It produces marked vasodilation in most vascular beds and in this regard is more potent on a molar basis than acetylcholine. In the heart, VIP causes coronary vasodilation and exerts positive inotropic and chronotropic effects. It may thus participate in the regulation of coronary blood flow, cardiac contraction, and heart rate. 

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