Muscle relaxants interaction

Used mainly in anesthesia protocols or in the ICU to afford muscle relaxation and/or immobility. Occasionally used to treat tetanus. These muscle relaxants interact with nicotinic receptors at the skeletal muscle end plate. Nicotinic receptors are comprised of five subunits, two of which (alpha) bind ACh, a requirement for opening of the Na+ channel. Most drugs in this class bind competitively to one of the alpha subunits to prevent depolarization (receptor antagonists) one drug (succinylcholine) binds noncompetitively and opens the Na+ channel, causing excessive depolarization and desensitization. 

Muscle relaxants interact with nicotinic ACh receptors at the neuromuscular junction. Drugs ... 

The major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

The clinical consequences of the currently used benzodiazepines range from sedation, muscle relaxation, seizure reduction, anxiolysis, and hypnosis. Clearly, it would be highly desirable to be able to separate some of these effects. In addition, it would be useful to reduce other undesirable consequences such as development of tolerance and dependence, abuse, synergistic interaction with ethanol, and memory impairment (for a comprehensive review see [22]). Animal models for some of the aforementioned conditions, in combination with transgenic mouse technology, have recently led to a deeper understanding of the contribution some of the individual a subunits make to these behaviors. 

Spinal anesthesia Spinal anesthesia is the introduction of local anesthetics directly into the spinal fluid, which causes a sympathetic blockage, or loss of feeling as well as muscle relaxation resulting from the interaction of anesthetic with every spinal nerve tract. This method is used during major surgical interventions. As a rule, lidocaine, mepivacaine, and bupivacaine are used for this purpose. 

Other drugs that may interact with cardiac glycosides include the following Albuterol, amphotericin B, beta-blockers, calcium, disopyramide, loop diuretics, nondepolarizing muscle relaxants, potassium-sparing diuretics, succinylcholine, sympathomimetics, thiazide diuretics, thioamines, and thyroid hormones. 

Drugs that may interact with nitrates include alcohol, alteplase, aspirin, beta-blockers, calcium channel blockers, dihydroergotamine, heparin, nondepolarizing muscle relaxants, phenothiazines, phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil), and vasodilators. 

Drugs that may interact with vancomycin include aminoglycosides, anesthetics, neurotoxic/nephrotoxic agents, and nondepolarizing muscle relaxants. 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

Cydobenzaprine (Flexeril) [Skeletal Muscle Relaxant/ANS A nt] Uses Relief of muscle spasm Action Centrally acting skeletal muscle relaxant reduces tonic somatic motor activity Dose 5-10 mg PO bid-qid (2-3 wk max) Caution [B, ] Shares the toxic potential of theTCAs urinary hesitancy, NAG Contra Do not use concomitantly or w/in 14 d of MAOIs hyperthyroidism heart failure arrhythmias Disp Tabs SE Sedation anticholinergic effects Interactions t Effects of CNS d ression W/ CNS dqjressants, TCAs, barbiturates, EtOH t risk of HTN convulsions W/MAOIs EMS Use caution w/ other CNS depressants concurrent EtOH use can t CNS d ession OD May cause N/V,... 

Dexrazoxane (Zinecard) [Chelating Agent] Uses Prevent anthracycline-induced (eg, doxorubicin) cardiomyopathy Action Chelates heavy metals binds intracellular iron prevents anthracycline-induced free radicals Dose 10 1 ratio dexrazoxane doxorubicin 30 min prior to each dose, 5 1 ratio w/ CrCl <40 mL/min Caution [C, ] Contra Component sensitivity Disp Inj SE -1-BM (esp leukopenia), fever, Infxn, stomatitis, alopecia, NA /D Interactions t Length of muscle relaxation Wf succinylcholine EMS Given concurrent w/a chemo agent for treating CA to prevent cardiotox monitor for Infxn and reduced cardiac Fxn use caution w/ succinylcholine, reduced doses may be needed OD May cause extreme BM suppression symptomatic and supportive... 

Methocarbamol (Robaxin) [Skeletal Muscle Relaxant/ Centrally Acting] Uses Relief of discomfort associated w/ painful musculoskeletal conditions Action Centrally acting skeletal muscle relaxant Dose Adults. 1.5 g PO qid for 2-3 d, then 1-g PO qid maint therapy IV form rarely indicated Peds. 15 mg/kg/dose IV, may repeat PRN (OK for tetanus only), max 1.8 g/mVd for 3 d Caution Sz disorders [C, +] Contra MyG, renal impair Disp Tabs, inj SE Can discolor urine drowsiness, GI upset Interactions T Effects Wf CNS depressant, EtOH EMS May cause blurred vision and orthostatic hypotension use caution w/ CNS depressants concurrent EtOH use can T CNS depression OD May cause drowsiness, light-headedness, syncope, and slow shallow breathing symptomatic and supportive... 

On the other hand, if a chemical is somewhat less similar to acetylcholine, it may interact with the receptor but be unable to induce the exact molecular change necessary to allow the inward movement of sodium. In this instance the chemical does not cause contraction, but because it occupies the receptor site, it prevents the interaction of acetylcholine with its receptor. Such a drug is termed an antagonist. An example of such a compound is d-tubocurarine, an antagonist of acetylcholine at the end-plate receptors. Since it competes with acetylcholine for its receptor and prevents acetylcholine from producing its characteristic effects, administration of d-tubocurarine results in muscle relaxation by interfering with acetylcholine s ability to induce and maintain the contractile state of the muscle cells. 

Buspirone does not appear to have a major effect on the BZ-GABA-chloride ionophore complex and, if anything, has some antagonistic interactions with GA-BAergic transmission (although it does not induce seizures) (Jann, 1988 Baldessarini, 1996). The lack of GABAergic effects is evident in the fact that buspirone does not consistently cause sedation, it is not a muscle relaxant, it is not an anticonvulsant, and it does not relieve BZ withdrawal (Jann, 1988 Cole and Yonkers, 1995). 

NO released by GTN activates soluble, cytosolic form of guanylyl cyclase in vascular smooth muscles by interacting with haem group in the enzyme. This converts GTP to cGMP. cGMP dephosphorylates myosin light chain kinase and prevent myosin interaction with actin leading to relaxation. 

Bethanechol Muscarinic agonist t negligible effect at nicotinic receptors Activates Mi through M3 receptors in all peripheral tissues causes increased secretion, smooth muscle contraction (except vascular smooth muscle relaxes), and changes in heart rate Postoperative and neurogenic ileus and urinary retention Oral and parenteral, duration 30 min does not enter central nervous system (CNS) Toxicity Excessive parasympathomimetic effects, especially bronchospasm in asthmatics Interactions Additive with other parasympathomimetics... 

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