Anagrelide hydrochloride and Atropine Sulfate

• Generic Name: anagrelide
• Dosage Forms: n.a.
• Other Brand Names: Agrylin

Reduction of elevated platelet counts and associated risk of thromboembolic and hemorrhagic events in patients with thrombocythemia secondary to essential thrombocythemia (ET) and other myeloproliferative disorders. Has been designated an orphan drug by FDA for the treatment of ET.

Management of ET generally based on a risk-stratification approach. Treatment with a cytoreductive agent (e.g., anagrelide, hydroxyurea) usually reserved for patients at high risk (i.e., age >60 years, previous history of thrombosis, and/or platelet count ≥1,500,000/mm3) of developing thromboembolic and/or hemorrhagic complications. Some clinicians also recommend cytoreductive therapy in intermediate-risk ET patients (e.g., 40–60 years of age, platelet count >1,000,000/mm3, and cardiovascular risk factor [smoking, arterial hypertension, hypercholesterolemia, or diabetes mellitus] or familial thrombophilia).

Hydroxyurea (often combined with low-dose aspirin) generally considered drug of choice in high-risk patients with ET because of proven efficacy and infrequent acute toxicity. However, because of potential leukemogenic effects with hydroxyurea when used long term or sequentially with other cytotoxic drugs, anagrelide or interferon alfa suggested as alternative therapy in high-risk patients, particularly younger patients (<40–60 years of age), and in those who do not respond to or cannot tolerate hydroxyurea. Consider cautious use of low-dose aspirin concomitantly with anagrelide based on relative risks of thrombosis and arterial hemorrhage in individual patients. (See Specific Drugs or Foods under Interactions.)

• Generic Name: atropine
• Dosage Forms: n.a.
• Other Brand Names:

  Sal-Tropine, AtroPen, Atreza

Used as a preoperative medication to inhibit salivation and excessive secretions of the respiratory tract (antisialagogue). However, current surgical practice (e.g., using general anesthetics that do not stimulate salivary and tracheobronchial secretions) has reduced the need to control excessive respiratory secretions during surgery.

Used to prevent other cholinergic effects during surgery (e.g., cardiac arrhythmias, hypotension, bradycardia) secondary to excessive vagal stimulation, carotid sinus stimulation, or pharmacologic effect of drugs (e.g., succinylcholine).

Used to block adverse muscarinic effects of anticholinesterase agents (e.g., neostigmine, pyridostigmine) that are used after surgery to reverse the effects of neuromuscular blocking agents.

Used as a premedication for bradycardia during emergency pediatric intubation. Not routinely recommended because of lack of supporting evidence, but may be considered in situations where there is an increased risk of bradycardia (e.g., when succinylcholine is used to facilitate intubation).

Ineffective for preventing acid-aspiration pneumonitis during surgery.

Used in ACLS for management of symptomatic bradycardia. Reverses cholinergically mediated decreases in heart rate, systemic vascular resistance, and BP.

Considered initial drug of choice in adults with unstable bradycardia (e.g., that accompanied by altered mental status, cardiac ischemia, acute heart failure, hypotension, or other signs of shock).

In pediatric advanced life support (PALS), used for treatment of bradycardia secondary to increased vagal activity or primary AV block when bradycardia persists despite adequate oxygenation, ventilation, and CPR (if indicated).

Previously included in ACLS guidelines for treatment of asystole or pulseless electrical activity (PEA) during CPR; however, routine use during cardiac arrest no longer recommended because of lack of evidence demonstrating benefit.

May be beneficial for treatment of AV nodal block. However, not likely to be effective in patients with type II second-degree or third-degree AV block, including third-degree AV block accompanied by a new wide QRS complex where location of block is at or below the His-Purkinje level; transcutaneous pacing or rate-accelerating β-adrenergic drugs (e.g., dopamine or epinephrine) preferred in these patients until transvenous pacing can be performed.

Used in patients with MI who develop symptomatic or hemodynamically unstable sinus bradycardia. Other uses in MI setting include treatment of sustained bradycardia and hypotension associated with nitroglycerin use, and treatment of nausea and vomiting associated with morphine use.

Use cautiously in the presence of acute myocardial ischemia or MI because heart rate is a major determinant of myocardial oxygen requirements.

May be ineffective in patients who have undergone cardiac transplantation due to lack of vagal innervation in transplanted heart. Risk of paradoxical slowing of the heart rate and high-degree AV block in patients receiving atropine after cardiac transplantation.

Used concomitantly with a cholinesterase reactivator (pralidoxime chloride) to reverse muscarinic effects associated with toxic exposure to organophosphate anticholinesterase pesticides.

Used to reverse muscarinic effects associated with toxic exposure to carbamate anticholinesterase pesticides. Concomitant cholinesterase reactivator (pralidoxime chloride) therapy may not be necessary.

A challenge (test) dose of atropine may be useful in diagnosing cholinergic poisoning. Failure of the challenge dose to elicit typical antimuscarinic effects (e.g., mydriasis, tachycardia, dry mucous membranes) strongly suggests the presence of organophosphate or carbamate poisoning.

Use atropine in conjunction with other protective measures (e.g., decontamination, immediate evacuation, specialized masks and clothing) and treatments (e.g., anticonvulsant for seizures).

Used concomitantly with a cholinesterase reactivator (pralidoxime chloride) to reverse muscarinic effects associated with toxic exposure to organophosphate anticholinesterase nerve agents (e.g., sarin, soman, tabun, VX [methylphosphonothioic acid]) in the context of chemical warfare or terrorism.

Initial management of nerve agent poisoning includes aggressive airway control and ventilation (administration of nebulized β-adrenergic agonist [e.g., albuterol] and antimuscarinics [e.g., ipratropium bromide] may be necessary), and administration of atropine and pralidoxime chloride; diazepam may be needed for seizure control.

Treatment of muscarinic effects associated with toxic ingestion of mushrooms containing muscarine (e.g., certain members of the Clitocybe and Inocybe genera). However, substantial toxicity is uncommon, and supportive symptomatic care (e.g., atropine) rarely is necessary.

Has been used to facilitate hypotonic duodenography or contrast examination of the colon; however, glucagon appears to be more effective and generally is preferred in these examinations.

Has been used to increase visualization of the urinary tract in excretion urography.

Has been used by oral inhalation as a bronchodilator for short-term treatment of bronchospasm associated with bronchial asthma, bronchitis, and COPD; however, a solution for oral inhalation no longer commercially available in the US.

Has been used as an adjunct in the treatment of peptic ulcer disease; however, no conclusive data that the drug promotes healing, decreases rate of recurrence, or prevents complications of peptic ulcers.

With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition.

Has been used in the treatment of functional disturbances of GI motility such as irritable bowel syndrome; however, efficacy is limited. Use only if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit.

Has been used as adjunctive therapy in the management of hypermotility disorders of the lower urinary tract. May provide symptomatic relief, but the underlying cause should be determined and specifically treated.

With the exception of uninhibited or reflex neurogenic bladder, there is generally little evidence to support the use of antimuscarinics in the treatment of various GU disorders.

Has been used in conjunction with morphine or other opiates for symptomatic relief of biliary or renal colic; however, only exerts weak biliary antispasmodic action.

Has been used to reduce pain and hypersecretions in acute pancreatitis, but little evidence of benefit.