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Ajmaline
Clinical data
Trade namesGilurytmal, Ritmos, Aritmina
AHFS/Drugs.comInternational Drug Names
ATC code
Identifiers
  • (17R,21R)-ajmalan-17,21-diol
    OR
    (1R,9R,10S,13R,14R,16S,18S)- 13-ethyl- 8-methyl- 8,15-diazahexacyclo [14.2.1.01,9.02,7.010,15.012,17] nonadeca- 2(7),3,5-triene- 14,18-diol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.022.219 Edit this at Wikidata
Chemical and physical data
FormulaC20H26N2O2
Molar mass326.440 g·mol−1
3D model (JSmol)
  • CC[C@H]1[C@H]5C[C@@H]4N([C@@H]1O)[C@H]6C[C@]3(c2ccccc2N(C)[C@H]34)[C@H](O)C56
  • InChI=1S/C20H26N2O2/c1-3-10-11-8-14-17-20(12-6-4-5-7-13(12)21(17)2)9-15(16(11)18(20)23)22(14)19(10)24/h4-7,10-11,14-19,23-24H,3,8-9H2,1-2H3/t10-,11+,14-,15-,16?,17-,18+,19+,20+/m0/s1 checkY
  • Key:CJDRUOGAGYHKKD-SXKXKDIKSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Ajmaline (also known by trade names Gilurytmal, Ritmos, and Aritmina) is an alkaloid that is classified as a 1-A antiarrhythmic agent. It is often used to induce arrhythmic contraction in patients suspected of having Brugada syndrome. Individuals suffering from Brugada syndrome will be more susceptible to the arrhythmogenic effects of the drug, and this can be observed on an electrocardiogram as an ST elevation.

The compound was first isolated by Salimuzzaman Siddiqui in 1931 [1] from the roots of Rauvolfia serpentina. He named it ajmaline, after Hakim Ajmal Khan, one of the most illustrious practitioners of Unani medicine in South Asia.[2] Ajmaline can be found in most species of the genus Rauvolfia as well as Catharanthus roseus.[3] In addition to Southeast Asia, Rauvolfia species have also been found in tropical regions of India, Africa, South America, and some oceanic islands. Other indole alkaloids found in Rauvolfia include reserpine, ajmalicine, serpentine, corynanthine, and yohimbine. While 86 alkaloids have been discovered throughout Rauvolfia vomitoria, ajmaline is mainly isolated from the stem bark and roots of the plant.[3]

Due to the low bioavailability of ajmaline, a semisynthetic propyl derivative called prajmaline (trade name Neo-gilurythmal) was developed that induces effects similar to those of its predecessor but which has better bioavailability and absorption.[4]

Biosynthesis

[edit]

Ajmaline is widely dispersed among 25 plant genera, but is of significant concentration in the Apocynaceae family.[5] Ajmaline is a monoterpenoid indole alkaloid, composed of an indole from tryptophan and a terpenoid from iridoid glucoside secologanin. Secologanin is introduced from the triose phosphate/pyruvate pathway.[6] Tryptophan decarboxylase (TDC) remodels tryptophan into tryptamine. Strictosidine synthase (STR), uses a Pictet–Spengler reaction to form strictosidine from tryptamine and secologanin. Strictosidine is oxidized by P450-dependent sarpagan bridge enzymes (SBE); to make polyneuridine aldehyde. Of the sarpagan-type alkaloids, polyneuridine is a key entry into the ajmalan-type alkaloids.[7][6] Polyneuridine Aldehyde is methylated by polyneuridine aldehydeesterase (PNAE), to synthesize 16-epi-vellosimine, which is acetylated to vinorine by vinorine synthase (VS). Vinorine is oxidized by vinorine hydroxylase (VH) to make vomilenine. Vomilenine reductase (VR) conducts a reduction of vomilenine to 1,2-dihydrovomilenine, using the cofactor NADPH. 1,2-dihydrovomilenine, is reduced by 1,2-dihydrovomilenine reductase (DHVR) to 17-O-acetylnorajmaline, with the same cofactor as VR: NADPH. 17-O-acetylnorajmaline is deacetylated by acetylajmalan esterase (AAE), to form norajmaline. Finally, norajmaline methyl transferase (NAMT) methylates norajmaline resulting in our desired compound: ajmaline.[6]


Ajmaline Biosynthesis

Mechanism of action

[edit]
Schematic diagram of normal sinus rhythm for a human heart as seen on ECG (with English labels)
Schematic diagram of normal sinus rhythm for a human heart as seen on an electrocardiogram.

Ajmaline [8] was first discovered to lengthen the refractory period of the heart by blocking sodium ion channels,[3] but it has also been noted that it is also able to interfere with the hERG (human Ether-a-go-go-Related Gene) potassium ion channel.[9] In both cases, Ajmaline causes the action potential to become longer and ultimately leads to bradycardia. When ajmaline reversibly blocks hERG, repolarization occurs more slowly because it is harder for potassium to get out due to less unblocked channels, therefore making the RS interval longer. Ajmaline also prolongs the QR interval since it can also act as sodium channel blocker, therefore making it take longer for the membrane to depolarize in the first case. In both cases, ajmaline causes the action potential to become longer. Slower depolarization or repolarization results in a lengthened QT interval (the refractory period), and therefore makes it take more time for the membrane potential to get below the threshold level so the action potential can be re-fired. Even if another stimulus is present, action potential cannot occur again until after complete repolarization. Ajmaline causes action potentials to be prolonged, therefore slowing down firing of the conducting myocytes which ultimately slows the beating of the heart.

Diagnosis of Brugada syndrome

[edit]
Normal electrocardiograms compared to electrocardiograms of people with Brugada Syndrome
(A) Normal electrocardiogram pattern in the precordial leads, (B) changes in Brugada syndrome. The arrow indicates the characteristic elevated ST segment.

Brugada syndrome is a genetic disease that can result in mutations in the sodium ion channel (gene SCN5A) of the myocytes in the heart.[10] Brugada syndrome can result in ventricular fibrillation and potentially death. It is a major cause of sudden unexpected cardiac death in young, otherwise healthy people.[11] While the characteristic patterns of Brugada syndrome on an electrocardiogram may be seen regularly, often the abnormal pattern is only seen spontaneously due to unknown triggers or after challenged by particular drugs. Ajmaline is used intravenously to test for Brugada syndrome since they both affect the sodium ion channel.[12] In an afflicted person who was induced with ajmaline, the electrocardiogram would show the characteristic pattern of the syndrome where the ST segment is abnormally elevated above the baseline. Due to complications that could arise with the ajmaline challenge, a specialized doctor should perform the administration in a specialized center capable of extracorporeal membrane oxygenator support.[13]

See also

[edit]


References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Ajmaline

View on Grokipedia
from Grokipedia
Ajmaline is a naturally occurring monoterpenoid extracted from the roots of the plant ( family), with the C20H26N2O2 and a pentacyclic structure featuring an core. As a class Ia , it is primarily recognized for its role in , where it exerts potent effects on ion channels to modulate heart rhythm. The pharmacological mechanism of ajmaline involves selective blockade of voltage-gated s (particularly Nav1.5 encoded by ) in cardiac myocytes, which prolongs the action potential duration, slows conduction velocity, and increases the , thereby suppressing abnormal electrical activity. It also influences other currents, including (e.g., Ito, HERG) and calcium (ICa-L) channels, in a dose-dependent manner, contributing to its overall antiarrhythmic profile, though these effects are secondary to sodium channel inhibition. Ajmaline exhibits a short plasma and poor oral , necessitating intravenous administration for acute use, and its metabolism is primarily hepatic via enzymes like , with genetic polymorphisms potentially affecting efficacy and safety. Clinically, ajmaline is employed to treat various tachyarrhythmias, including , , , and conditions associated with Wolff-Parkinson-White syndrome, by restoring normal . Its most prominent application, however, is in the diagnostic provocation testing for (BrS), a hereditary predisposing to sudden cardiac death; intravenous ajmaline unmasks the characteristic type 1 ECG pattern (coved ST-segment elevation ≥2 mm in leads V1-V3) in susceptible individuals with higher sensitivity than alternative agents like . The test is conducted under continuous ECG monitoring in specialized centers, with administration halted if QRS duration widens by ≥30% or arrhythmias occur, due to risks of . While effective, ajmaline is not approved by the U.S. FDA and has been withdrawn in some countries owing to availability of newer therapies, though it remains in use in and elsewhere. Historically, ajmaline was first isolated in 1931 by Salimuzzaman Siddiqui from R. serpentina, a plant long utilized in traditional Indian and Ayurvedic medicine for and mental disorders due to its alkaloid content, including . Its in the plant involves a complex pathway of 10 enzymatic steps from precursors and secologanin, fully elucidated through decades of research beginning in the 1980s. Early studies highlighted its potential beyond antiarrhythmics, such as antihypertensive effects, but cardiac applications dominate its modern profile.

Overview

Definition and Sources

Ajmaline is a , a class of naturally occurring compounds characterized by a fused ring system derived from and a unit. It is classified as a class Ia antiarrhythmic agent due to its ability to modulate cardiac sodium channels, though its primary stems from its chemical structure within the family. First isolated in , ajmaline serves as a key example of bioactive alkaloids from , contributing to its pharmacological profile without overlapping into detailed therapeutic uses. The primary natural source of ajmaline is the roots of Rauwolfia serpentina, commonly known as Indian snakeroot, an evergreen shrub native to the and . This plant has been utilized in traditional Ayurvedic medicine, where ajmaline is extracted from root bark and stems, constituting a significant portion of the over 50 alkaloids produced by the species. Ajmaline is also present in other species within the genus, such as , highlighting the genus's role in yielding this alkaloid across tropical plants. Commercially, ajmaline is available under several trade names, including Gilurytmal, Ritmos, and Aritmina, reflecting its formulation for clinical applications in various regions. These names are associated with pharmaceutical preparations derived directly from natural extraction processes, underscoring ajmaline's reliance on botanical origins for production.

History

Ajmaline, an indole alkaloid derived from the roots of Rauvolfia serpentina (commonly known as Sarpagandha), traces its historical roots to ancient Ayurvedic medicine, where extracts of the plant have been employed for over 3,000 years to alleviate conditions such as hypertension, insomnia, epilepsy, hysteria, and snakebites. Referenced in classical texts like the Charaka Samhita (circa 2nd century CE) and by Sushruta, the plant's roots were valued for their sedative and hypotensive effects, often prepared as decoctions or powders in traditional Indian healing practices. The modern history of ajmaline began in 1931 when Indian chemist Salimuzzaman Siddiqui, working at the Ayurvedic and Unani Tibbi College (Tibia College) in Delhi, successfully isolated the compound from R. serpentina roots during systematic studies of the plant's alkaloids. Siddiqui identified at least nine distinct alkaloids, including ajmaline, and characterized their chemical structures, marking a pivotal advancement in natural product research. He named the alkaloid ajmaline in honor of Hakim Ajmal Khan, a renowned Indian physician, botanist, and Unani medicine expert who had mentored Siddiqui and advocated for integrating traditional knowledge with scientific inquiry. Post-isolation, ajmaline's pharmacological potential was explored through early studies in , with R.N. Chopra and colleagues conducting the first detailed investigations into its effects, confirming its utility as an . By the 1940s, Indian researchers like Rustom Vakil further demonstrated the therapeutic value of Rauvolfia alkaloids, including ajmaline, in managing and cardiac arrhythmias, which facilitated the transition from crude plant extracts in Ayurvedic traditions to purified compounds in Western pharmacology during the mid-20th century. This shift was underscored by global interest in the , as ajmaline's sodium channel-blocking properties were recognized for treating ventricular tachyarrhythmias.

Chemistry

Structure and Properties

Ajmaline is an with the molecular formula C₂₀H₂₆N₂O₂ and a of 326.44 g·mol⁻¹. Its structure consists of a complex pentacyclic system derived from the ajmalan skeleton, featuring an moiety fused to additional rings including a characteristic azabicyclo[3.3.1]nonane core. The compound exhibits nine chiral carbon atoms, contributing to its specific , which is crucial for its natural configuration as isolated from plant sources. This stereochemical complexity arises from the fused ring architecture, with defined configurations at key centers such as those in the tetrahydro-β-carboline and quinolizidine portions. Physically, ajmaline presents as a to off-white crystalline powder. It has a of 206 °C. In terms of , ajmaline is slightly soluble in , with a reported value of 490 mg/L at 30 °C, but it dissolves well in organic solvents such as , , and .

Derivatives

Ajmaline exhibits low oral , primarily due to extensive first-pass and poor gastrointestinal absorption, which limits its administration to intravenous routes in . To address this limitation, semisynthetic derivatives have been developed through structural modifications, particularly at the atoms, aiming to enhance pharmacokinetic properties such as absorption and duration of action while retaining the parent compound's antiarrhythmic efficacy. Prajmaline, an N-propyl derivative of ajmaline, represents a primary semisynthetic analog designed for improved . This modification results in significantly higher compared to native ajmaline, attributed to a ring-opened conformation at physiological that facilitates better permeability and reduced presystemic elimination. Prajmalium , the salt form of prajmaline, further optimizes and absorption, enabling effective oral dosing with a more favorable therapeutic profile. Other notable derivatives include lorajmine, a monochloroacetyl at the 17-position that serves as a rapidly hydrolyzed by plasma esterases to ajmaline, potentially allowing for controlled release and extended effects. Detajmium, featuring a 4-(3'-diethylamino-2'-hydroxypropyl) substitution, exhibits prolonged blockade with frequency-dependent kinetics, offering an alternative for sustained antiarrhythmic activity. These modifications highlight targeted chemical alterations to overcome ajmaline's inherent pharmacokinetic challenges without altering its core pharmacological mechanism.

Biosynthesis

Natural Pathway

Ajmaline is a monoterpenoid indole alkaloid (MIA) biosynthesized primarily in species of the Rauwolfia genus, such as Rauvolfia serpentina, through a complex enzymatic pathway that assembles the molecule from amino acid and terpenoid precursors. This natural pathway, one of the most thoroughly characterized MIA routes in the Apocynaceae family, involves 12 enzymatic steps and occurs predominantly in root tissues where alkaloid accumulation is highest. The process begins with the decarboxylation of the amino acid L-tryptophan to form tryptamine, catalyzed by the enzyme tryptophan decarboxylase (TDC), which provides the indole moiety essential for the alkaloid scaffold. Concurrently, secologanin—a monoterpenoid glucoside derived from the methylerythritol phosphate (MEP) pathway—is synthesized in parallel. The core of the pathway initiates with the condensation of and secologanin to produce strictosidine, the universal precursor for most MIAs, mediated by strictosidine (STR). Strictosidine undergoes deglycosylation by strictosidine (SGD) to yield a reactive aglycone, which is then cyclized and rearranged through a series of oxidations, reductions, and acetylations involving enzymes such as geissoschizine (GS), sarpagan bridge (SBE), polyneuridine (PNAE), vinorine (VS), and vinorine hydroxylase (VH). These steps lead to key intermediates like polyneuridine , vinorine, and vomilenine, ultimately forming 17-O-acetylnorajmaline after successive reductions by vomilenine reductase (VR) and 1,2-dihydrovomilenine reductase (DHVR). Hydrolysis of the acetyl group by 17-O-acetylnorajmaline (AAE) produces norajmaline, setting the stage for the terminal modification. The final step in ajmaline formation involves N-methylation of norajmaline at the nitrogen, catalyzed by norajmaline N-methyltransferase (NAMT, also known as NNMT), which utilizes S-adenosyl-L-methionine as the methyl donor to yield ajmaline. This , part of a γ-tocopherol C-methyltransferase-derived specific to , exhibits high substrate specificity for ajmalan-type intermediates and is highly expressed in Rauwolfia roots, correlating with ajmaline accumulation. The entire pathway highlights the intricate orchestration of compartmentalized enzymes in plant cells, ensuring efficient production of this pharmacologically significant .

Synthetic Production

The synthetic production of ajmaline presents significant challenges due to its complex pentacyclic structure, which features 12 enzymatic steps in its biosynthetic pathway and nine chiral centers, making total laborious and inefficient for large-scale manufacturing. Early efforts in , such as those employing Pictet-Spengler cyclizations and glycol cleavage strategies, have achieved but remain limited by low yields and multiple stereoselective steps required to establish the correct configuration at the chiral centers. Recent advances in have enabled de novo biosynthesis of ajmaline in engineered microorganisms, bypassing the need for plant extraction by reconstructing the pathway from simple precursors like and secologanin. In a 2024 study, researchers engineered () to produce ajmaline through an 11-step pathway starting from strictosidine aglycone, incorporating enzymes such as geissoschizine synthase (GS), and downstream reductases including vomilenine reductase (VR, identified as RsCAD2) and its dehydrogenase (DHVR, RsRR4). This microbial system achieved de novo titers of approximately 57 ng/L after 96 hours, with yields improving to 128 μg/L when supplemented with the intermediate vomilenine, demonstrating proof-of-concept for pathway functionality despite rate-limiting reductions at the vomilenine-to-17-O-acetylnorajmaline step. Similar approaches using plant cell cultures, such as hairy roots of species, have been explored for semi-synthetic production, yielding ajmaline alongside related alkaloids like , though these rely on endogenous enzymes rather than fully reconstructed pathways. Key challenges in these biotechnological methods include the instability of reactive intermediates like polyneuridine aldehyde and the need for precise stereocontrol in multi-step cascades, which can lead to side products and low overall efficiency in hosts. Despite these hurdles, synthetic production offers advantages over traditional extraction from roots, including greater scalability through optimization, consistent purity without environmental contaminants, and reduced dependence on slow-growing , potentially enabling sustainable pharmaceutical supply. Ongoing refinements, such as enzyme engineering and pathway modularization, aim to boost titers to industrially viable levels.

Pharmacology

Mechanism of Action

Ajmaline primarily exerts its effects by blocking voltage-gated sodium channels, particularly the cardiac isoform Nav1.5 encoded by the gene, which is responsible for the rapid influx of sodium ions during the phase of the . This blockade occurs at multiple receptor sites on the Nav1.5 channel, preferentially targeting the open state of the channel and reducing the sodium current (I_Na). As a result, the rate of rise and amplitude of phase 0 of the action potential are diminished, leading to slowed conduction in cardiac tissues. In addition to its sodium channel effects, ajmaline inhibits hERG potassium channels (encoded by KCNH2), which mediate the rapid delayed rectifier current (I_Kr) essential for cardiac . This inhibition is state-dependent, binding to the open channel conformation at key residues such as Tyr-652 and Phe-656 in the inner cavity, thereby reducing outward potassium currents. The consequent prolongation of the action potential duration manifests electrocardiographically as prolongation and can contribute to by slowing the process in ventricular myocytes. The use-dependent nature of ajmaline's blockade enhances its selectivity for rapidly firing cardiac tissues, such as those involved in tachyarrhythmias. At therapeutic concentrations, the drug accumulates in the channel during repeated depolarizations, resulting in a more pronounced inhibition of sodium and currents at higher heart rates compared to slower rhythms. This property underlies its antiarrhythmic efficacy by stabilizing excitable membranes and suppressing abnormal impulse propagation without excessively affecting normal .

Pharmacokinetics

Ajmaline is administered primarily via the intravenous route due to its poor oral . After intravenous administration, ajmaline demonstrates biphasic characterized by a rapid distribution of approximately 6 minutes and an elimination of about 95 minutes. The drug is highly bound to plasma proteins, with binding rates around 75-76%, primarily to alpha-1-acid . Metabolism occurs predominantly in the liver through enzymes, notably , involving processes such as mono- and di-hydroxylation of the ring, O-methylation, reduction at C-21, oxidation at C-17 and C-21, and N-oxidation, resulting in multiple conjugated metabolites. Excretion is mainly renal, with only a small fraction (about 5%) eliminated unchanged in , and the overall process is minimally impacted by renal impairment in terms of intravenous clearance, though renal has been shown to increase the rate of oral absorption in experimental settings.

Clinical Applications

Diagnosis of Brugada Syndrome

The Ajmaline challenge test serves as a key diagnostic tool to unmask the type 1 Brugada electrocardiographic (ECG) pattern in patients suspected of Brugada syndrome with a normal or equivocal baseline ECG. The protocol involves intravenous infusion of ajmaline at a dose of 1 mg/kg body weight (maximum 100 mg), administered over 5 to 10 minutes via syringe pump, with continuous 12-lead ECG monitoring, preferably using high right precordial leads (V1-V3 positioned in the 2nd, 3rd, and 4th intercostal spaces). Infusion is fractionated in some protocols (e.g., 10 mg every 2 minutes) and halted upon emergence of the diagnostic pattern, QRS widening exceeding 30% of baseline, or ventricular ectopy. A positive test is defined by the provocation of a type 1 ST-segment in at least one right precordial lead, featuring a coved morphology with J-point of ≥2 mm descending into a negative T-wave. This confirms the Brugada pattern when combined with clinical features such as unexplained syncope or family history of sudden death. The test's high sensitivity, reaching up to 80% in detecting genetic carriers of mutations associated with , surpasses that of alternatives like , which yields positive results in only about 4% of cases compared to 26% with ajmaline ( 8.76). Ajmaline's brief duration of action enables rapid offset and reversal of effects, typically within minutes, minimizing prolonged monitoring needs. Safety is paramount, as the test carries a small risk (approximately 1.3%) of inducing symptomatic ; it must therefore be conducted exclusively in specialized centers with immediate access to external defibrillators, personnel, and (ECMO) for managing potential hemodynamic collapse. This sodium channel blockade by ajmaline provokes the pattern by accentuating the underlying abnormalities in susceptible individuals.

Treatment of Arrhythmias

Ajmaline, a class Ia , is employed in the acute management of select cardiac arrhythmias through its blocking properties, which prolong the action potential duration and refractory period in cardiac tissue. Unlike its role in diagnostic provocation, therapeutic application focuses on suppressing ongoing abnormal rhythms to restore normal or control ventricular rates. Key indications for ajmaline include (JET), particularly in postoperative or congenital settings where rapid suppression of the ectopic focus is required. It is also indicated for symptomatic (SVT), such as atrioventricular nodal reentrant tachycardia, where it effectively terminates episodes by slowing conduction through the AV node and accessory pathways. As an adjunct therapy, ajmaline supports the management of (VT), especially monomorphic forms refractory to first-line agents, by reducing arrhythmia burden in refractory patients. Additionally, it is used for acute control of in Wolff-Parkinson-White (WPW) syndrome, where rapid anterograde block in the accessory pathway prevents dangerously high ventricular rates. Dosing for acute arrhythmia management typically involves intravenous administration to achieve rapid onset, with a standard regimen of 1 mg/kg body weight infused over 5 minutes, not exceeding 100 mg total, or as repeated boluses of 10-50 mg every 2-5 minutes under continuous ECG monitoring. For sustained control, a continuous at 10-50 mg/h may follow initial boluses, adjusted based on response and plasma levels targeting 0.4-2.0 μg/ml for antiarrhythmic efficacy. Oral dosing, at 50-100 mg every 6-8 hours, is reserved for maintenance in stable patients but is less common due to variable . The efficacy of ajmaline in these indications stems from its blockade of voltage-gated sodium channels (Nav1.5), which is particularly pronounced in accessory pathways and ectopic foci, thereby interrupting reentrant circuits and suppressing abnormal . In SVT and WPW-related , intravenous ajmaline has demonstrated anterograde block in over 50% of accessory pathways, rapidly converting arrhythmias to without significant hemodynamic compromise in most cases. For VT, suppression is observed at therapeutic plasma concentrations. It is used for (JET), particularly in postoperative or congenital settings, but requires cautious use due to potential proarrhythmic effects. Pharmacokinetic considerations, such as its short of 10-15 minutes, support intravenous use for precise titration in acute settings.

Safety Profile

Adverse Effects

Ajmaline, a class Ia , is associated with a range of adverse effects, primarily cardiovascular, though other systems may be affected. These effects are generally dose-dependent and more pronounced during provocative testing, such as for diagnosis, where the drug is administered intravenously. While most side effects are transient and resolve upon discontinuation, serious complications can occur, particularly in predisposed individuals, with an overall incidence of severe events reported as low but not negligible. Cardiovascular adverse effects represent the most critical risks, including life-threatening ventricular arrhythmias such as sustained or fibrillation, occurring in approximately 1.8% of patients during ajmaline challenges. and are common due to the drug's blockade, which slows conduction and can exacerbate underlying rhythm disturbances. QT interval prolongation has also been documented, potentially leading to in susceptible cases. In severe instances of refractory ventricular arrhythmias, (ECMO) may be required for circulatory support. Gastrointestinal disturbances, including , , and , are frequently reported and typically mild to moderate in severity, often resolving shortly after infusion cessation. Neurological symptoms such as , , and sensations of warmth or flushing are common during administration, with rarer manifestations including or cranial nerve palsies. Hypersensitivity reactions are uncommon but can include or, in isolated cases, immune-mediated . Hepatic effects, such as cholestatic or elevated liver enzymes indicative of , have been observed, sometimes persisting for months after a single dose. , potentially immune-mediated, is a recognized serious that limits long-term use of ajmaline. Respiratory issues, including or , are rare and often secondary to cardiovascular compromise rather than direct pulmonary . Overall, adverse effects are more frequent in pediatric patients and those with genetic predispositions, underscoring the need for careful monitoring during use.

Contraindications and Precautions

Ajmaline is contraindicated in patients with known to the drug or its components, as this can lead to severe allergic reactions. It is also absolutely contraindicated in individuals with complete , severe , sick sinus syndrome, or with a below 50 beats per minute, due to the risk of exacerbating conduction disturbances and potentially causing life-threatening arrhythmias. Additionally, ajmaline should not be used in cases of overdosage, as it may worsen toxicity and cardiac instability. Relative contraindications include , where ajmaline should be used only if the potential benefits outweigh the risks, particularly avoiding administration in the first trimester due to limited data on fetal effects. It is contraindicated during , as excretion into is unknown and could pose risks to the . Caution is advised in patients with renal or hepatic impairment, as renal dysfunction can increase ajmaline's through reduced hepatic extraction, potentially leading to higher plasma levels and , while hepatic issues may heighten the risk of cholestatic . Precautions for safe administration include continuous electrocardiographic (ECG) monitoring throughout the to detect any conduction abnormalities or arrhythmias promptly. Ajmaline should be administered only in controlled clinical settings, such as a unit equipped with facilities, to manage potential cardiac complications. Drug interactions that increase toxicity risk must be considered; for example, concurrent use with can enhance arrhythmogenic effects due to additive impacts on cardiac conduction. Other precautions involve avoiding use in uncompensated or incomplete unless benefits are deemed essential, with close monitoring for hemodynamic changes.

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  53. https://medtigo.com/drug/ajmaline/
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  56. https://medinfogalway.ie/ivguides/ajmaline-intravenous-adults
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