Parasympatholytics,

Excitation of the parasympathetic division of the autonomic nervous system causes release of acetylchoUne at neuro-effector junctions in different target organs. The major effects are summarized in A (blue arrows). Some of these effects have therapeutic appUcations, as indicated by the clinical uses of parasympa-thomimetics (p. 102). 

Substances acting antagonistically at the M-cholinoceptor are designated parasympatholytics (prototype the alkaloid atropine actions shown in red in the panels). Therapeutic use of these agents is complicated by their low organ selectivity. Possibilities for a targeted action include  

Bronchial secretion. Premedication with atropine before inhalation anesthesia prevents a possible hypersecretion of bronchial mucus, which cannot be expectorated by coughing during intubation (anesthesia). 

Gastric secretion. Stimulation of gastric acid production by vagal impulses involves an M-cholinoceptor subtype (M -receptor), probably associated with enterochromaffin cells. Pirenzepine (p. 106) displays a preferential affinity for this receptor subtype. Remarkably, the HCl-secreting parietal cells possess only Ma-receptors. Mi-receptors have also been demonstrated in the brain however, these cannot be reached by pirenzepine because its lipophilicity is too low to permit penetration of the blood-brain barrier. Pirenzepine was formerly used in the treatment of gastric and duodenal ulcers (p. 166). 

Bronchodilation can be achieved by the use of ipratropium in conditions of increased airway resistance (chronic obstructive bronchitis, bronchial asthma). When administered by inhalation, this quaternary compound has Uttle effect on other organs because of its low rate of systemic absorption. 

Spasmolysis by N-butylscopolamine in biliary or renal colic (p. 130). Because of its quaternary nitrogen atom, this drug does not enter the brain and requires parenteral administration. Its spasmolytic action is especially marked because of additional ganglionic blocking and direct muscle-relaxant actions. 

Lowering of pupillary sphincter tonus and pupillary dilation by local administration of homatropine or tropicamide (mydriatics) allows observation of the ocular fundus. For diagnostic uses, only short-term pupillary dilation is needed. The effect of both agents subsides quickly in comparison with that of atropine (duration of several days). 

---

Atropiae (41), isolated from the deadly nightshade Airopa belladonna L.) is the racemic form, as isolated, of (—)-hyoscyamine [which is not isolated, of course, from the same plant but is typically found ia solanaceous plants such as henbane (HyosQiamus mgerl. )]. Atropiae is used to dilate the pupil of the eye ia ocular inflammations and is available both as a parasympatholytic agent for relaxation of the intestinal tract and to suppress secretions of the saUvary, gastric, and respiratory tracts. In conjunction with other agents it is used as part of an antidote mixture for organophosphorus poisons (see Chemicals in war). 

Parasympathetic Nervous System Parasympatholytics Parasympathomimetics Parathyroid Hormone Paraventricular Nucleus Parkin... 

Tropane alkaloids, long known to have anticholinergic, antiemetic, parasympatholytic, anesthetic, and many other actions, have been featured in an extremely wide number of pharmacological reports. The section Pharmacology in Chemical Abstracts (Vols. 90-105) lists over 600 articles. To deal in an adequate way with these articles would go far beyond the scope of the present chapter, and interested readers are referred to Chemical Abstracts. Many of the same articles are mentioned in Periodical Reports (9a-9h). Only a few papers (vide infra) will receive comment here. 

The family Solanaceae consists of about 85 genera and 2800 species of plants, of which, 80 are of medicinal value in the Asia-Pacific region. Solanaceaeare well known for their parasympatholytic tropane alkaloids, such as hyoscyamine. Classic examples are Atropa belladonna L. (belladona herb, British Pharmacopoeia 1963), Datura stramonium L. (stramonium, British Pharmacopoeia, 1963), and the dried leaves and flowering tops of Hyoscyamus... 

The consequences of lack of selectivity can often be avoided if the drug does not require the blood route to reach the target organ, but is, instead, applied locally, as in the administration of parasympatholytics in the form of eye drops or in an aerosol for inhalation. 

Parasympatholytics have a wide therapeutic margin Rarely life-threatening, poisoning with atropine is characterized by the following peripheral and central effects ... 

Bronchodilators. Narrowing of bronchioles raises airway resistance, e.g in bronchial or bronchitic asthma Several substances that are employed as bronchodilators are described elsewhere in more detail P2-sympathomimetics (p. 84, given by pulmonary, parenteral, or oral route), the methylxanthine theophylline (p. 326, given parenterally or orally), as well as the parasympatholytic ipratropium (pp. 104, 107, given by inhalation). 

Sinus bradycardia. An abnormally low sinoatrial impulse rate (<60/min) can be raised by parasympatholytics. The quaternary ipratropium is preferable to atropine, because it lacks CNS penetrability (p. 107). Sympathomimet-ics also exert a positive chronotropic action they have the disadvantage of increasing myocardial excitability (and automaticity) and, thus, promoting ectopic impulse generation (tendency to extrasystolic beats). In cardiac arrest epinephrine can be used to reinitiate heart beat... 

Muscle relaxants, opioid analgesics such as fentanyl, and the parasympatholytic atropine are discussed elsewhere in more detail. 

Secondary hypotension is a sign of an underlying disease that should be treated first. If stroke volume is too low, as in heart failure, a cardiac glycoside can be given to increase myocardial contractility and stroke volume. When stroke volume is decreased due to insufficient blood volume, plasma substitutes will be helpful in treating blood loss, whereas aldosterone deficiency requires administration of a mineralocor-ticoid (e.g., fludrocortisone). The latter is the drug of choice for orthostatic hypotension due to autonomic failure. A parasympatholytic (or electrical pacemaker) can restore cardiac rate in bradycardia. 

Rhinitis. Nasal discharge could be prevented by parasympatholytics however, other atropine-like effects (pp. 

Motion sickness. Effective prophylaxis can be achieved with the parasympatholytic scopolamine (p. 106) and H antihistamines (p. 114) of the diphenyl-methane type (e.g., diphenhydramine, meclizine). Antiemetic activity is not a property shared by all parasympatho-lytics or antihistamines. The efficacy of the drugs mentioned depends on the actual situation of the in vidual (gastric filling, ethanol consumption), environ-... 

A. Alkaloids 1. Belladonna-type solanaceous tropane alkaloids [Atropine (1), (—)-Hyoscyamine (2), Scopolamine ((—)-Hysoscine)(3)] Atropa belladonna L. (belladonna), Datura metel L., D. stramonium L. (jimson weed), Hyoscyamus niger L. (henbane), Mandragora officinarum L. (European mandrake), and other solanaceous species Anticholinergics (parasympatholytics)... 

Pharmacology Trospium is an antispasmodic, antimuscarinic agent. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium increases maximum cystometric bladder capacity and volume at first detrusor contraction. 

Pharmacology Ipratropium for oral inhalation is an anticholinergic (parasympatholytic) agent that appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine. The bronchodilation following inhalation is primarily a local, site-specific effect, not a systemic one. 

Atropine blocks muscaric cholinergic receptor competitively and has a large spectrum of clinic applications. Atropine acts as a parasympatholytic on parasym-phathetically innervated organs. Therefore, the possible applications of atropine are as a general anaesthetic and include its use in pure form or as a component. 

Atropine, an alkaloid from Atropa belladonna, is the classical parasympatholytic compound. It competes with acetylcholine for the binding at the muscarinic receptor. Its affinity towards nicotinic receptors is very low, so that it does not interfere with the ganglionic transmission or the neuromotor transmission, at least in therapeutic dosages. However, in the central nervous system muscarinic receptor do play an important role and while atropine can penetrate the blood-brain barrier it exerts pronounced central effects. Atropine, like all other antagonists of the muscarinic acetylcholine receptor inhibit the stimulatory influence of the parasympathetic branch of the autonomous nervous system. All excretory glands (tear, sweat, salivary, gasto-intestinal, bronchi) are... 

All smooth muscle activity which is physiologically under a strong parasympathetic influence is effectively inhibited by atropine, for example in the gastrointestinal, genitourinary and respiratory tract. Parasympatholytics are very useful drugs in the treatment of spastic conditions (colic) in these regions. 

Parasympatholytics are used to induce a mydriasis in the ophthalmology for the examination of the retina. They are applied locally as drops or ointment. The drug-induced inability of the eyes to accommodate results in a serious, although transient, impairment of the visus. Therefore the long-acting atropine (7-10 days) is replaced by short-acting compounds like homatropine (1-3 days), cyclopentolate (1 day) or tropicamide (6 hours). 

This holds true for the use of parasympatholytic dmgs in the therapy of bardycardia due to vagal overstimulation. Individuals with an overactive... 

---