Diphenoxylate Hydrochloride And Atropine Sulfate

Atropine is a potent muscarinic antagonist used to treat symptomatic bradycardia, reduce secretions before surgery, and serve as an antidote for organophosphate poisoning. It belongs to the anticholinergic class of medications.

The dosage of Atropine varies significantly based on the condition being treated. According to ACLS guidelines and FDA labeling:

• Symptomatic Bradycardia: The standard adult dose is 0.5 mg to 1.0 mg administered intravenously every 3 to 5 minutes. The total cumulative dose should generally not exceed 3.0 mg (approximately 0.04 mg/kg), as this dose typically results in full vagal blockade.
• Organophosphate Poisoning: This requires much higher doses. Initial doses of 2 mg to 6 mg IV or IM are common, repeated every 5 to 60 minutes until 'atropinization' occurs (clearing of lung secretions and increased heart rate). In severe cases, continuous infusions may be necessary.
• Preoperative Antisialagogue: The typical dose is 0.4 mg to 0.6 mg administered IM or IV approximately 30 to 60 minutes before the induction of anesthesia.
• Ophthalmic Use: For refraction, 1 drop of 1% solution may be applied to the eye twice daily for 1 to 3 days prior to the procedure.

Pediatric dosing must be calculated with extreme precision, usually based on the child's weight:

• Bradycardia: The typical dose is 0.02 mg/kg IV or IM. The minimum single dose is usually 0.1 mg (to avoid paradoxical bradycardia), and the maximum single dose is 0.5 mg for a child and 1.0 mg for an adolescent.
• Preoperative Use: Doses range from 0.01 mg/kg to 0.02 mg/kg, with a maximum of 0.4 mg to 0.6 mg depending on the child's age and weight.
• Poisoning: Initial doses of 0.05 mg/kg are often used, titrated to effect.

Renal Impairment

Specific dosage adjustments for renal impairment are not formally established in the manufacturer's labeling; however, since a significant portion of Atropine is excreted unchanged by the kidneys, healthcare providers should exercise caution. Prolonged effects may occur in patients with end-stage renal disease.

Hepatic Impairment

Because Atropine is metabolized by the liver, patients with severe hepatic dysfunction may experience slower clearance of the drug. Close monitoring for signs of anticholinergic toxicity is required.

Elderly Patients

Geriatric patients are often more sensitive to the effects of Atropine. Lower initial doses may be considered, particularly because this population is at higher risk for side effects like urinary retention, acute glaucoma, and cognitive impairment (delirium).

Atropine is almost exclusively administered by healthcare professionals in clinical or emergency settings.

• Injection: When given IV, it is usually administered as a rapid bolus. For IM use, it is injected into a large muscle mass.
• Ophthalmic: If using eye drops at home, wash your hands first. Tilt your head back, pull down the lower eyelid, and drop the medication into the pouch. Close your eye and press your finger against the inner corner of the eye (lacrimal sac) for 1-2 minutes to prevent the drug from draining into the nose and throat, which reduces systemic side effects.
• Storage: Store Atropine at room temperature (20°C to 25°C or 68°F to 77°F). Protect the solution from light and do not freeze.

In emergency settings (bradycardia, poisoning), missed doses are not applicable as the drug is given by medical staff as needed. For ophthalmic use at home, if you miss a dose, apply it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and return to your regular schedule. Do not double the dose to catch up.

Atropine overdose can be life-threatening and is characterized by the classic anticholinergic syndrome. Signs include:

• Severe tachycardia (fast heart rate)
• High fever (hyperpyrexia) due to lack of sweating
• Extreme thirst and dry mouth
• Dilated pupils and blurred vision
• Confusion, hallucinations, and seizures
• Urinary retention

In cases of severe overdose, a 'physostigmine' injection may be used as an antidote, as it increases acetylcholine levels to compete with Atropine. Emergency medical attention is required immediately.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop using the medication without direct medical guidance.

Because Atropine blocks the parasympathetic nervous system, its side effects are predictable extensions of its pharmacological action. The most common experiences include:

• Xerostomia (Dry Mouth): This is the most frequent side effect. It can make swallowing or speaking difficult and may persist for several hours after a dose.
• Blurred Vision and Photophobia: Dilation of the pupils (mydriasis) causes sensitivity to light and an inability to focus on near objects (cycloplegia).
• Tachycardia: An increase in heart rate is a primary effect but may feel like 'palpitations' or a racing heart to the patient.
• Dry Skin: Inhibition of sweat glands can lead to dry, flushed skin, especially in warm environments.

Atropine is a high-alert medication. It must be used with extreme caution in patients with certain underlying conditions. Because it affects the autonomic nervous system, it can impact nearly every organ system in the body. Patients and caregivers should be aware that Atropine can impair the body's ability to regulate temperature; therefore, exposure to high temperatures while under the influence of Atropine can lead to heatstroke.

No FDA black box warnings for Atropine. While it is a potent and potentially dangerous drug if misused, it does not currently have a mandated boxed warning on its labeling.

• Cardiovascular Risks: While used to treat slow heart rate, Atropine can cause paradoxical bradycardia if administered in doses lower than 0.5 mg. It can also induce tachycardia, which may worsen angina (chest pain) or increase the size of a myocardial infarction (heart attack) by increasing the heart's oxygen demand.

Certain drugs should never be used concurrently with Atropine due to the risk of severe, life-threatening interactions:

• Pramlintide: This medication slows gastric emptying. When combined with Atropine, the effect on the GI tract can be so severe that it leads to complete intestinal paralysis.
• Potassium Chloride (Solid Oral Forms): Atropine slows GI transit time, which can cause solid potassium supplements to sit in one spot in the esophagus or stomach for too long, leading to severe ulcers or perforation.

• Other Anticholinergics: Drugs like benztropine, trihexyphenidyl, or high-dose antihistamines (diphenhydramine) have additive effects. This can lead to 'anticholinergic toxicity,' characterized by delirium, severe tachycardia, and dangerous hyperthermia.

Atropine must NEVER be used in the following conditions because the risks far outweigh any potential benefits:

• Narrow-Angle Glaucoma: Atropine causes the iris to block the drainage angle of the eye, which can lead to a sudden, catastrophic rise in eye pressure and permanent blindness.
• Obstructive Uropathy: In patients with bladder neck obstruction (often due to severe prostate enlargement), Atropine can cause acute, painful urinary retention.
• Obstructive GI Disease: Conditions such as achalasia, pyloric stenosis, or paralytic ileus are worsened by Atropine's ability to stop muscular contractions in the gut.
• Severe Ulcerative Colitis: Atropine can inhibit bowel motility to the point where the colon dilates dangerously, a condition known as toxic megacolon.

Atropine is classified as FDA Pregnancy Category C. This means that animal reproduction studies have shown an adverse effect on the fetus, or there are no adequate and well-controlled studies in humans. Atropine readily crosses the placenta. While it is not known to cause specific birth defects, it can cause tachycardia (fast heart rate) in the fetus. It should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, such as in life-threatening maternal bradycardia or poisoning.

Atropine is excreted in human breast milk. Long-term use may lead to anticholinergic effects in the nursing infant, such as constipation or irritability. More importantly, Atropine and other anticholinergics are known to suppress lactation by inhibiting the hormone prolactin and reducing fluid secretions. Breastfeeding is generally not recommended if a mother requires repeated doses of Atropine.

Atropine is used in children for bradycardia, as a preoperative medication, and as an antidote. However, infants and young children are particularly susceptible to the toxic effects of Atropine. 'Atropine fever' (hyperpyrexia) is a significant risk in children because they have a higher surface-area-to-volume ratio and their temperature regulation is easily disrupted by the suppression of sweating. Dosing must be strictly weight-based.

Atropine is a competitive, reversible antagonist of the muscarinic acetylcholine receptors. It has equal affinity for the M1, M2, M3, M4, and M5 receptor subtypes. By occupying the receptor site, it prevents the neurotransmitter acetylcholine from binding. This effectively 'turns off' the parasympathetic nervous system's influence on target organs. It does not have significant activity at nicotinic receptors (those found at the neuromuscular junction) at standard clinical doses, which is why it does not cause muscle paralysis.

The onset of action for IV Atropine is 2-4 minutes for heart rate effects. The duration of effect on the heart is typically 1-2 hours, but the effects on the pupils and salivary glands can last much longer (up to 24 hours systemically, or several days when applied topically to the eye). Tolerance does not typically develop with acute use, but sensitivity can vary widely between individuals.

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