Muscarinic blocker

The quaternary ammonium derivatives of the belladonna alkaloids, as well as the synthetic quaternary ammonium compounds, are incompletely absorbed from the gastrointestinal tract. Consequently, greater amounts of these compounds are eliminated in the feces following oral administration. The blood-brain barrier prevents quaternary ammonium muscarinic blockers from gaining significant access to the CNS. 

Actions Applied topically to the cornea, pilocarpine produces a rapid miosis and contraction of the ciliary muscle. The eye undergoes a spasm of accommodation, and vision is fixed at some particular distance, making it impossible to focus (Figure 4.7). [Note the opposing effects of atropine, a muscarinic blocker, on the eye (see p. 45).] Pilocarpine is one of the most potent stimulators of secretions such as sweat, tears, and saliva, but it is not used for this purpose. 

Atropine [A troh peen], a belladonna alkaloid, has a high affinity for muscarinic receptors, where it binds competitively, preventing acetylcholine from binding to that site (Figure 5.3). Atropine is both a central and peripheral muscarinic blocker. Its general actions last about 4 hours except when placed topically in the eye, where the action may last for days. 

The LD50 value of rivastigmine can be raised by the muscarinic blocker atropine almost 11-fold, while the value for the other carbamates in this series is usually about 3 (except for 5.8 for the dimethyl derivative). The quaternary drug atropine methylnitrate, which cannot penetrate the brain, raises the value about two-fold in all cases. This not only adds a safety feature to the use of rivastigmine, but also indicates that rivastigmine s activity - even at high and toxic doses - is more focused than the others in central mechanisms that either directly or indirectly stem from activation of muscarinic receptors. This might contribute to the clinical results if it is assumed that those unexplored nonmuscarinic effects are mostly detrimental to the AD treatment. 

Muscarinic blockers atropine, benztropine, ipratropium, glycopyrrolate, scopolamine Ganglionic blockers hexamethonium, mecamylamine NMJ blockers ... 

Atropine and muscarinic blockers t HR, T BP, hyperthermia (hot, dry skin), delirium, hallucinations Control CV symptoms and hyperthermia + physostigmine (crosses BBB) ... 

Include benztropine, trihexyphenidyl, and diphenhydramine, which are muscarinic blockers... 

Pharmacokinetics of atropine Atropine is the prototypical nonselective muscarinic blocker. This alkaloid is found in Atropa belladonna and many other plants. Because it is a tertiary amine, atropine is relatively lipid-soluble and readily crosses membrane barriers. The drug is well distributed into the CNS and other organs and is eliminated partially by metabolism in the liver and partially by renal excretion. The elimination half-life is approximately 2 hours, and the duration of action of normal doses is 4-8 hours except in the eye, where effects last for 72 hours or longer. 

C. Effects The peripheral actions of muscarinic blockers are mostly predictable effects derived from cholinoceptor blockade (Table 8-2). These include the ocular, gastrointestinal, genitourinary, and secretory effects. The CNS effects are less predictable. Those seen at therapeutic concentrations include sedation, reduction of motion sickness, and, as noted above, reduction of some of the signs of parkinsonism. Cardiovascular effects at therapeutic doses include an initial... 

D. Clinical Uses The muscarinic blockers have several useful therapeutic applications in the central nervous system, eye, bronchi, gut. and urinary bladder. These uses are summarized in Table 8-3. 

Gut Atropine, methscopolamine, and propantheline were used in acid-peptic disease to reduce acid secretion, but they are not as effective as H,-blockers such as cimetidine, and they cause far more frequent and severe adverse effects. Pirenzepine is an M -selective muscarinic blocker (available in Europe but not tbe USA) that may be more useful in peptic ulcer. Muscarinic blockers can also be used to reduce cramping and hypermotility in transient diarrheas, but opioids such as diphenoxylate (Chapter 31) are more effective. 

Muscarinic blockers Nonselective Atropine Scopolamine, glycopyn-olate, ipratropium, cyclopentolate, benztropine Homatropine, methscopolamine, iropicamide, oxybutynin, tolterodine... 

All of the muscarinic blockers, including scopolamine, act as reversible, competitive pharmacologic antagonists. The answer is (D). 

Ganglion blockers and muscarinic blockers can both cause mydriasis, increase resting heart rate, blur vision, and cause dry mouth and constipation, because these are determined largely by parasympathetic tone. Postural hypotension, on the other hand, is a sign of sympathetic blockade, which would occur with ganglion blockers but not muscarinic blockers (Chapter 6). The answer is (C). 

The parasympathomimetic effects of digitalis can be blocked by muscarinic blockers such as atropine. The only parasympathomimetic effect in the list provided is increased PR interval, representing slowing of AV conduction. The answer is (C). 

D. Clinical Use Asthma. Muscarinic blockers are useful in one-third to two-thirds of asthmatic patients agonists are effective in almost all. For acute bronchospasm, therefore, the beta agonists are usually preferred. However, in chronic obstructive pulmonary disease (which is often associated with acute episodes of bronchospasm), the antimuscarinic agents may be more effective and less toxic than beta agonists. 

The symptoms are likely to be alleviated by continued treatment with levodopa Dyskinesias are less likely to occur if levodopa is administered with carbidopa Coadministration of muscarinic blockers prevents the occurrence of dyskinesias during treatment with levodopa... 

The Effect of Muscarinic Blockers on the DSCXS and Lodoxamide Tromethamine Dose Response in Rat Mast Cell... 

The Effect of Pretreatment of Rats with the Muscarinic Blockers Atropine and QuinuclicHnyl Benzilate (QNB) on Multiple Dose DS and Lodoxamide Tromethamine Tachyphylaxis... 

Figure 4. Effect of muscarinic blockers atropine and QNB on multiple-dose lodoxamide tachyphylaxis. Sensitized rats were given atropine 25mglkg ip or QNB 0.01 mg/kg ip 20 min before the first iv dose of lodoxamide. One hr Utter the animals were given another iv dose of lodoxamide (0.2 mg/kg containing 2 mg egg albumin and S mg Evans blue), and 30 min later the skin sites of sensitization were scored and compared to nonpredosed rats as well as control rats. Numbers in parenthesis refer to number of animals per variable.

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