Atropine Sulfate in Cardiac Arrhythmias - An Insight

Overview:

Since Atropine sulfate blocks the vagus nerve's effects on the heart, it is frequently used to treat bradycardia, a slow heart rate, and certain types of heart block. Nonetheless, it is not commonly employed for the management of cardiac arrhythmias, particularly those that stem from aberrant electrical impulses within the heart. The United States Food and Drug Administration (USFDA) approved Atropine sulfate for the management of cardiac arrhythmias in 1960.

Drug Group:

The drug group that includes Atropine sulfate is antimuscarinics or anticholinergics. Acetylcholine is a neurotransmitter that acts on the neurological system, and these medications function by inhibiting its action. To minimize salivation and respiratory secretions before surgery, as well as treat organophosphate poisoning and bradycardia (slow heart rate), Atropine sulfate is frequently administered as a premedication.

Dosages:

The available dosages are 0.05 mg/mL (milligrams per milliliter) injection and 0.1 mg/mL injection in Plastic Syringe.

For Patients:

What Are Cardiac Arrhythmias?

Abnormal heart rhythms known as cardiac arrhythmias happen when the electrical impulses that regulate heartbeats malfunction, causing the heart to beat abnormally rapidly, slowly, or irregularly. These erratic heartbeats can impair the heart's capacity to pump blood efficiently, resulting in symptoms including palpitations, lightheadedness, dyspnea, and in extreme situations, even potentially fatal consequences. Arrhythmias can be benign or severe medical disorders that need to be treated.

What Is the Management of Cardiac Arrhythmias?

• Lifestyle Changes: These include staying away from stressors like alcohol, coffee, and cigarettes, keeping a healthy weight, and engaging in regular exercise.

• Medication: To regulate heart rate and rhythm, doctors may prescribe antiarrhythmic drugs. These drugs include sodium channel blockers, calcium channel blockers, and beta-blockers.

• Cardioversion: This process uses medicine or electrical shock to get the heart back to its regular beat.

• Catheter Ablation: In this process, the cardiac tissue regions producing the arrhythmia are destroyed using a catheter.

• Implantable Devices: To help control the heart's rhythm and prevent sudden cardiac death, devices like pacemakers or implantable cardioverter-defibrillators (ICDs) may be installed.

• Lifestyle Modifications: Arrhythmias can be controlled by giving up smoking, controlling stress, and adhering to a balanced diet.

• Surgery: To treat structural heart defects that are the source of the arrhythmias, surgery may be required in some circumstances.

How Does Atropine Sulfate Work?

The main mechanism by which Atropine sulfate acts on the organism is by preventing the neurotransmitter acetylcholine from acting at muscarinic receptors. The suppression of parasympathetic nerve impulses caused by this blockage has a variety of physiological effects, including an increase in heart rate, a relaxation of the smooth muscles in the airways, a decrease in salivary secretion, and dilated pupils.

What Are the Benefits of Using Atropine Sulfate for Cardiac Arrhythmias?

• Elevated Heart Rate: The parasympathetic nervous system, which typically lowers heart rate, is blocked by Atropine sulfate. This raises the heart rate, which is advantageous in cases of bradycardia (low heart rate) or specific kinds of heart block.

• Enhancement of Cardiac Output: Atropine sulfate can improve cardiac output by raising heart rate, which will improve blood supply to important tissues and organs.

• Treatment of Some Arrhythmias: In cases when high vagal tone or elevated vagal activity is the cause of arrhythmia, Atropine sulfate may be used as a short-term treatment to bring the arrhythmia under control.

• Emergency Scenarios: To help restore and maintain an appropriate heart rate and blood pressure until more effective therapy can be given, Atropine sulfate is frequently used in emergency conditions, such as during cardiac arrest or severe bradycardia.

What Must the Patient Inform the Doctor Before Taking Atropine Sulfate?

Patients should disclose to their doctor any pre-existing medical issues before starting Atropine sulfate, particularly if they have a history of the following disorders:

• Myasthenia gravis.

• Glaucoma.

• Heart disease.

• High blood pressure.

• Urinary retention.

• Enlarged prostate.

• To prevent any interactions or negative effects, patients should also declare any allergies they may have to foods, medications, or other substances.

• They should also reveal any current medications, vitamins, or herbal supplements they may be taking.

• To guarantee that patients receiving Atropine sulfate receive safe and efficient treatment, they must provide a thorough medical history.

What Are the Side Effects of Using Atropine Sulfate?

• Dry mouth.

• Blurred vision.

• Dilated pupils.

• Increased heart rate (tachycardia).

• Constipation.

• Urinary retention.

• Flushing of the skin.

• Confusion or hallucinations (especially in elderly patients).

• Difficulty breathing (in high doses).

For Doctors:

Description:

Atropine sulfate injection is a sterile, nonpyrogenic solution containing Atropine sulfate monohydrate dissolved in water for injection, with added sodium chloride to ensure isotonicity. It can be administered via subcutaneous, intramuscular, or intravenous injection. Each milliliter (mL) contains either 0.1 mg (adult strength) or 0.05 mg (pediatric strength) of Atropine sulfate monohydrate, equivalent to 0.083 mg (adult strength) or 0.042 mg (pediatric strength) of Atropine, along with 9 mg of sodium chloride. The solution may be adjusted for pH with sodium hydroxide or sulfuric acid. It has an osmolality of 0.308 mOsmol/mL (calc.), with a pH ranging from 4.2 (3.0 to 6.5). The added sodium chloride does not affect serum electrolyte balance.

The solution does not contain any bacteriostat, antimicrobial agent, or additional buffer (except for pH adjustment). It is designed solely for single-dose injection use. Any leftover portion from smaller doses should be discarded. Atropine Sulfate, USP, is chemically identified as 1α H, 5α H-Tropan-3-α-ol (±)-tropate (ester), sulfate (2:1) (salt) monohydrate, with the formula (C17H23NO3)2 · H2SO4 · H2O. It exists as colorless crystals or white crystalline powder and is highly soluble in water.

Atropine, derived from the belladonna plant, comprises equal parts of d- and l-hyoscyamine, with the latter responsible for its activity. Sodium Chloride, known as NaCl, is a white crystalline powder easily soluble in water. The syringe is made from a special polypropylene formulation. Although water permeates slowly from inside the container, it minimally affects solution concentration over its shelf life. While solutions may extract trace amounts of chemical components from the plastic, biological testing confirms the safety of the syringe material.

Therapeutic Uses of Atropine Sulfate:

• Bradycardia: By inhibiting the parasympathetic nervous system and raising heart rate, Atropine sulfate is used to treat bradycardia or slow heart rate.

• Antidote for Poisoning: By preventing the effects of too much acetylcholine, it can be used as an antidote for poisoning caused by some cholinergic agents, such as nerve agents or organophosphate pesticides.

• Antispasmodic: By preventing acetylcholine's actions on smooth muscle, Atropine sulfate relieves spasms in the bladder and gastrointestinal tract.

• Uses in Ophthalmology: It is used to paralyze the ciliary muscle and dilate the pupil (mydriasis), which aids in eye examinations and some eye procedures.

• Reduced Secretions: Atropine sulfate can lessen salivary and respiratory secretions, which is useful in situations when excessive secretions are an issue or during some medical procedures.

Dosage Forms and Strengths:

The available dosages are 0.05 mg/mL injection and 0.1 mg/mL injection in Plastic Syringe.

Dosage and Administration:

Before administering parenteral drug products, visually inspect them for particulate matter and discoloration, if the solution and container allow. Only administer if the solution is clear and the seal is intact. Any unused portion should be discarded. While intravenous administration is generally favored, subcutaneous, intramuscular, and endotracheal routes are also viable. For endotracheal tube administration, dilute one to two milligrams in a maximum of 10 mL(milliliters) of sterile water or normal saline. Adjust dosage based on heart rate, PR interval, blood pressure, and symptoms.

Indications:

• Bradycardia: When bradycardia symptoms arise, Atropine sulfate is used to elevate heart rate.

• Antispasmodic: It relieves colic and other gastrointestinal spasms.

• Antidote: Organophosphate poisoning is one kind of poisoning for which Atropine sulfate is used as an antidote.

• Use in Ophthalmology: During eye exams or surgeries, it is used to dilate the pupil and relax the eye muscles.

• Preanesthetic: Before surgery, Atropine sulfate is occasionally given as a pre-anesthetic to lessen respiratory tract secretions.

Contraindications:

• Glaucoma: Atropine sulfate can potentially exacerbate glaucoma by raising intraocular pressure.

• Myasthenia Gravis: It can make the neuromuscular disorder's sufferers more tired and feeble in their muscles.

• Urine Retention: Because of its anticholinergic properties, Atropine sulfate may exacerbate urine retention.

• Disorders of the Obstructive Digestive System: It can exacerbate problems such as pyloric stenosis and paralytic ileus.

• Severe Ulcerative Colitis: Atropine sulfate can exacerbate the symptoms and lengthen the course of severe ulcerative colitis.

• Hypersensitivity to Atropine: Avoid using Atropine or its derivatives if the individuals have a known sensitivity to it.

• Serious Tachycardia: Atropine sulfate may make tachycardia worse in certain situations.

Warnings and Precautions:

When the recurrent administration of Atropine becomes necessary for patients with coronary artery disease, it is advised to limit the total dose to two to three milligrams (maximum 0.03 to 0.04 mg/kg) to prevent the adverse effects of Atropine-induced tachycardia on myocardial oxygen demand. Atropine can cause complete urine retention in patients with prostatic hypertrophy, induce acute glaucoma, cause partial organic pyloric stenosis to become a complete obstruction, and cause bronchial secretions inspissation and viscid plugs to form in patients with chronic lung disease.

What Are the Adverse Reactions of Atropine Sulfate?

• Bigger, dilated, or enlarged pupils.

• Blindness.

• Chest pain, discomfort, or tightness.

• Decreased vision.

• Decrease in urine volume.

• Decrease in frequency of urination.

• Difficulty in passing urine.

• Eye pain.

• Tremor.

• Ataxia.

• Coma.

What Are the Pharmacological Aspects of Atropine Sulfate?

Mechanism of Action:

Atropine acts as an antimuscarinic agent by counteracting the muscarine-like effects of acetylcholine and other choline esters. Smooth muscles that are responsive to acetylcholine but are not directly innervated, as well as structures innervated by postganglionic cholinergic nerves, are blocked from experiencing the muscarinic effects of acetylcholine. Like other antimuscarinic agents, Atropine primarily works through competitive antagonism, which can be overridden by increasing acetylcholine concentration at receptor sites through the use of anticholinesterase agents. Atropine antagonizes receptors found in peripheral structures affected by muscarine, such as exocrine glands and smooth and cardiac muscle. While responses to postganglionic cholinergic nerve stimulation can also be inhibited by Atropine, this occurs less readily compared to responses to injected choline esters.

Pharmacodynamics:

Atropine-induced inhibition of the parasympathetic system may initially stimulate certain functions, particularly affecting the heart where it initially slows the rate before causing tachycardia due to vagal control paralysis. Atropine has a stronger and longer-lasting effect on the heart, intestines, and bronchial muscles compared to Scopolamine. However, its impact on the iris, ciliary body, and certain glands is weaker than that of Scopolamine. Unlike Scopolamine, Atropine may stimulate the medulla and higher cerebral centers but does not depress the central nervous system when utilized in clinical dosages. While mild vagal excitation occurs, the increased respiratory rate and depth likely result from bronchiolar dilatation. Large or repeated doses of Atropine may cause respiration to become more labored and unreliable.

Adequate doses of Atropine eliminate various types of reflex vagal cardiac slowing or asystole. It also prevents or eliminates bradycardia or asystole caused by choline esters, anticholinesterase agents, or other parasympathomimetic drugs, as well as cardiac arrest induced by vagus stimulation. Atropine may reduce partial heart block severity when vagal activity is a factor. In some cases of complete heart block, Atropine may accelerate the idioventricular rate or stabilize it. Occasionally, a large dose may cause atrioventricular (A-V) block and nodal rhythm.

Atropine sulfate Injection, USP counteracts the peripheral dilatation and sudden blood pressure drops caused by choline esters. However, when given alone, blood pressure and blood vessels are not always impacted by Atropine. Significant postural hypotension may result from systemic dosages, which marginally increase systolic and decrease diastolic pressures. Moreover, these dosages marginally raise cardiac output and lower central venous pressure. Therapeutic amounts occasionally cause cutaneous blood vessels, especially in the "blush" area, to widen. In infants and young children, this can result in an Atropine "fever" since sweat gland function is suppressed.

Atropine administered intravenously (rapid, continuous infusion over three minutes) has effects on heart rate (highest heart rate) and saliva flow (minimum flow), although these effects take seven to eight minutes to manifest. The amount of drug in the peripheral compartment has a non-linear relationship with both effects. Following intramuscular injection (0.5 to 4 mg dosages), alterations in plasma Atropine levels closely correspond with alterations in heart rate.

Pharmacokinetics:

Following injection, Atropine quickly exits the bloodstream and disperses throughout the body. Exercise, both before and after intramuscular Atropine administration, enhances its absorption due to increased blood flow in the muscles and reduces its clearance. The pharmacokinetics of Atropine become nonlinear when administered intravenously at doses ranging from 0.5 to 4 mg. Atropine binds to plasma proteins by approximately 44 percent, and this binding becomes saturated within the concentration range of two to 20 μg/mL (microgram per milliliter). It easily crosses the placental barrier into the fetal circulation but is not detected in the amniotic fluid. Enzymatic hydrolysis, especially in the liver, breaks down much of the drug, with 13 to 50 percent excreted unchanged in the urine. Traces are detected in various secretions, including milk. Noratropine, atropin-n-oxide, tropine, and tropic acid are the principal metabolites of Atropine. The metabolism of Atropine is hindered by organophosphate pesticides. In specific populations, the elimination half-life of Atropine is over twice as long in children under two years old and the elderly (>65 years old) compared to other age groups. Gender does not affect the pharmacokinetics and pharmacodynamics (heart rate changes) of Atropine.

What Are the Drug Interactions?

The administration of Atropine sulfate Injection slowed down the absorption rate of Mexiletine but did not change its oral bioavailability. However, when Atropine was combined with intravenous Metoclopramide as pretreatment for anesthesia, the delayed absorption of Mexiletine was reversed.

Use in Specific Populations:

• Pregnant Women: Pregnancy Category C is assigned to Atropine as there have been no animal reproduction studies conducted. It remains unclear whether Atropine poses risks to fetal development in pregnant women or affects reproductive capacity.

• Nursing Mothers: Regarding nursing mothers, trace amounts of Atropine have been detected in breast milk, but the clinical implications are not yet understood.

• Geriatrics: After reviewing the current literature, no clinical evidence has been found to distinguish response variations between elderly and younger patients. Typically, when prescribing for elderly patients, caution is advised in dose selection, with initial dosages usually set at the lower end of the range. This approach accounts for the higher likelihood of reduced hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other medication therapies.