AUTONOMIC DRUGS Flashcards
Bethanechol
Direct Cholinomimetic Agent
Mechanism:
Binds to muscarinic AChR → direct AChR agonism
Activates bowel and bladder smooth muscle
Promote gastric acid secretion by stimulating parietal cell M3 receptors.
No nicotinic agonism
Resistant to AChE
Clinical Use:
Urinary retention
Postoperative ileus
Neurogenic ileus
Carbachol
Direct Cholinomimetic Agent
Mechanism:
Bind to muscarinic/nicotinic AChR → direct AChR agonism
Carbon copy of acetylcholine (but resistant to AChE)
Nicotinic and muscarinic agonism
Increase trabecular outflow through M3 agonism
Clinical Use:
Open-angle and closed-angle glaucoma (alleviates intraocular pressure and causes miosis-
Methacholine
Direct Cholinomimetic Agent
Mechanism:
Bind to muscarinic/nicotinic AChR → direct AChR agonism
Predominantly muscarinic agonism
Can not cross blood-brain barrier (quaternary amine)
Clinical Use:
Diagnosis of bronchial hypersensitivity (activates muscarinic receptors on airway smooth muscle)
Positive test for airway hyperactivity if FEV1 drops by 20% or more with methacholine Not specific Can give positive a postive test: Smoking Respiratory infections Allergic Rhinitis GERD
Pilocarpine
Direct Cholinomimetic Agent
Mechanism:
Bind to muscarinic/nicotinic AChR → direct AChR agonism
Predominantly muscarinic agonism
Resistant to AChE
Can cross blood-brain barrier (tertiary amine)
Clinical Use:
Open-angle and closed-angle glaucoma (↑ contraction of ciliary muscle of the eye, ↑ contraction of pupillary sphincter, opening meshwork into canal of Schlemm)
Xerostomia (e.g., in Sjogren syndrome) (↑ sweat, tears, and saliva production)
Cystic fibrosis sweat test
Cevimeline
Direct Cholinomimetic Agent
Mechanism:
Bind to muscarinic/nicotinic AChR → direct AChR agonism
Predominantly muscarinic agonism
Clinical Use: Keratoconjunctivitis sicca (Sjogren syndrome) (↑ sweat and saliva production)
Donepezil
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Centrallly acting AChE inhibitors
Clinical Use:
Alzheimer disease
Adverse Effects:
Nausea, dizziness, insomnia.
Inhibition of acetylcholinesterase and a consequent reduction in acetylcholine breakdown may improve cognitive function in some patients. However, this mechanism also produces enhanced parasympathetic tone that can lead to adverse effects. Underlying age-related degeneration of the conduction system is common in the elderly, and the effects of acetylcholinesterase inhibition can precipitate bradycardia and atrioventricular block in such patients. These conduction abnormalities lead to reduced cardiac output that may manifest as presyncope (ie, lightheadedness) or syncope.
Contraindications: Cardiac conditions (e.g., conduction abnormalities)
Rivastigmine
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Centrallly acting AChE inhibitors
Clinical Use:
Alzheimer disease
Adverse Effects:
Nausea, dizziness, insomnia.
Inhibition of acetylcholinesterase and a consequent reduction in acetylcholine breakdown may improve cognitive function in some patients. However, this mechanism also produces enhanced parasympathetic tone that can lead to adverse effects. Underlying age-related degeneration of the conduction system is common in the elderly, and the effects of acetylcholinesterase inhibition can precipitate bradycardia and atrioventricular block in such patients. These conduction abnormalities lead to reduced cardiac output that may manifest as presyncope (ie, lightheadedness) or syncope.
Contraindications: Cardiac conditions (e.g., conduction abnormalities)
Galantamine
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Centrallly acting AChE inhibitors
Clinical Use:
Alzheimer disease
Adverse Effects:
Nausea, dizziness, insomnia.
Inhibition of acetylcholinesterase and a consequent reduction in acetylcholine breakdown may improve cognitive function in some patients. However, this mechanism also produces enhanced parasympathetic tone that can lead to adverse effects. Underlying age-related degeneration of the conduction system is common in the elderly, and the effects of acetylcholinesterase inhibition can precipitate bradycardia and atrioventricular block in such patients. These conduction abnormalities lead to reduced cardiac output that may manifest as presyncope (ie, lightheadedness) or syncope.
Contraindications: Cardiac conditions (e.g., conduction abnormalities)
Edrophonium
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Very short duration of action (∼ 10 minutes)
Clinical Use:
Diagnosis of myasthenia gravis (Edrophonium test, Tensilon test)
Exacerbation of myasthenia gravis in a patient treated with long-acting acetylcholinesterase inhibitors (eg, pyridostigmine) occurs due to myasthenic or cholinergic crisis. The edrophonium (Tensilon) test helps to differentiate these 2 conditions. Clinical improvement after edrophonium administration indicates that the patient is undertreated (myasthenic crisis).
Neostigmine
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Can not cross the blood-brain barrier (quaternary amine)
Clinical Use:
Myasthenia gravis
Postoperative and neurogenic ileus and urinary retention (indirect parasympathomimetics can be used in cases of ileus but are contraindicated in cases of bowel obstruction)
Postoperative reversal of neuromuscular blockade
Adverse Effects:
Cause bradycardia if muscarinic antagonist such as glycopyrrolate is not given
Increasing the dose can cause desensitization of nicotinic receptors
Physostigmine
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Lipophilic
Can cross the blood-brain barrier (tertary amine)
Clinical Use:
Atropine, atropa belladonna or Jimson Weed (Datura) overdose (antidote)
Glaucoma
Pyridostigmine
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Can not cross the blood-brain barrier (quaternary amine)
Typically used with glycopyrrolate, hyoscyamine, or propantheline to control side effects
Clinical Use: Myasthenia gravis (longer action compared to neostigmine) (improves muscle strength)
Echothiphate
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Irreversible AChE inhibitor
Long-acting
Increase outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
Clinical Use:
Glaucoma
Adverse Effects:
Miosis (contraction of pupillary sphincter muscles) and cyclospasm (contraction of ciliary muscle)
Distigmine
Indirect Cholinomimetic Agent
Mechanism:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Longer duration of action than pyridostigmine and neostigmine
Clinical Use:
Postoperative ileus and urinary retention
Myasthenia gravis
Pralidoxime
Mechanism:
Regenerates AChE via dephosphorylation (organophosphates bind to the esteratic site of acetylcholinesterase. Oximes cleave this phosphate ester bond and, thereby, reactivate acetylcholinesterase)
Works at both nicotinic and muscarinic sites
Poor blood-brain barrier penetration
Clinical Use:
Initial management of organophosphate toxicity
Should be administered to any patient with neuromuscular dysfunction (eg, weakness, fasciculations).
It should be given only after atropine because can cause transient acetylcholinesterase inhibition, which can momentarily worsen symptoms
Obidoxime
Mechanism:
Regenerates AChE via dephosphorylation (organophosphates bind to the esteratic site of acetylcholinesterase. Oximes cleave this phosphate ester bond and, thereby, reactivate acetylcholinesterase)
Works at both nicotinic and muscarinic sites
Poor blood-brain barrier penetration
Clinical Use:
Initial management of organophosphate toxicity
Should be administered to any patient with neuromuscular dysfunction (eg, weakness, fasciculations).
It should be given only after atropine because can cause transient acetylcholinesterase inhibition, which can momentarily worsen symptoms
Atropine
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
↑ Heart rate (by inhibiting vagal input)
↓ Secretions of exocrine glands
↓ Tone and motility of smooth muscles (i.e., ↓ urgency in cystitis)
↓ Cholinergic overactivity in CNS
Mydriasis and cycloplegia
Clinical Use:
- First drug of choice in unstable (symptomatic) sinus bradycardia (IV)
- Premedication prior to intubation to decrease salivary, respiratory, and gastric secretions
- Uveitis (to prevent and treat anterior and posterior synechiae)
- Urinary urgency, urge incontinence, urinary frequency and/or nocturia (symptoms resulting from, e.g., overactive bladder syndrome) (tolterodine has a more selective effect on the smooth muscle of the bladder and is the preferred drug for treating urinary incontinence)
- Antidote for anticholinesterase poisoning (carbamate insecticides, nerve agents, organophosphate insecticides) (reverses the muscarinic effects of cholinergic poisoning (e.g., bronchoconstriction) but does not reverse the nicotinic effects (e.g., muscle weakness, paralysis)).
- Scorpion stings (to reduce hypersalivation and bronchoconstriction)
Adverse Effects:
Can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants
Scopolamine (hyoscine)
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Vestibular disturbances (antiemetic)
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Motion sickness
Homatropine
Antimuscarinic Tertiary amine Lipophilic (good oral bioavailability and CNS penetration) Mydriasis Impaired accommodation
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Therapeutic use in patients with uveitis (to prevent synechiae between the iris and the anterior lens capsule)
Diagnostic use (pupillary dilation to allow ocular fundus examination and cycloplegia to allow refractory testing)
Tropicamide
Antimuscarinic Tertiary amine Lipophilic (good oral bioavailability and CNS penetration) Mydriasis Impaired accommodation
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Therapeutic use in patients with uveitis (to prevent synechiae between the iris and the anterior lens capsule)
Diagnostic use (pupillary dilation to allow ocular fundus examination and cycloplegia to allow refractory testing)
Benztropine
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Cholinergic overactivity in CNS
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Antiparkisonian effect (improves tremor and rigidity but has little effect on bradykinesia)
↓ Extrapyramidal symptoms (EPS) caused by antipsychotics
Biperiden
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Cholinergic overactivity in CNS
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Antiparkisonian effect (improves tremor and rigidity but has little effect on bradykinesia)
↓ Extrapyramidal symptoms (EPS) caused by antipsychotics
Trihexyphenidyl
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Cholinergic overactivity in CNS
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Antiparkisonian effect (improves tremor and rigidity but has little effect on bradykinesia)
↓ Extrapyramidal symptoms (EPS) caused by antipsychotics
Oxybutynin
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Tone and motility of smooth muscle cells
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
↓ Bladder spasms and urgency in overactive bladder incontinence
Tolterodine
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Tone and motility of smooth muscle cells
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
↓ Bladder spasms and urgency in overactive bladder incontinence
Solifenacin
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Tone and motility of smooth muscle cells
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
↓ Bladder spasms and urgency in overactive bladder incontinence
Butylscopolamine (hyoscine butylbromide)
Antimuscarinic
Quarternary amine
Hydrophilic (poor oral bioavailability and CNS penetration)
In contrast to scopolamine, butylscopolamine does not cross the blood-brain barrier and thus has no effect on the CNS.
↓ Tone and motility of the gut (antispasmodic effect)
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Antispasmodics for colicky pain (intestinal, biliary or ureteric colic)
Glycopyrrolate
Antimuscarinic
Quarternary amine
Hydrophilic (poor oral bioavailability and CNS penetration)
↓ GI and respiratory secretions
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Preoperative IV use to decrease respiratory secretions
Oral → reduces drooling, peptic ulcer
Ipratropium bromide
Antimuscarinic
Quarternary amine
Hydrophilic (poor oral bioavailability and CNS penetration)
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Bronchodilation (competitive inhibition of muscarinic receptors prevents bronchoconstriction.)
Antimuscarinics cause bronchodilation but actually impair mucociliary clearance and thus cause secretions to remain in the lung; only ipratropium bromide causes bronchodilation without impairing mucociliary clearance.
Clinical Use:
Short duration of action
Treatment of COPD grade I and higher
Acute management of refractory asthma
Tiotropium bromide
Antimuscarinic
Quarternary amine
Hydrophilic (poor oral bioavailability and CNS penetration)
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Bronchodilation (competitive inhibition of muscarinic receptors prevents bronchoconstriction.)
Antimuscarinics cause bronchodilation but actually impair mucociliary clearance and thus cause secretions to remain in the lung; only ipratropium bromide causes bronchodilation without impairing mucociliary clearance.
Clinical Use:
Longer duration of action (LAMA)
Long-term treatment of COPD (grade II and above)
Dicyclomine
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Tone and motility of smooth muscle cells
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Antispasmodics (irritable bowel syndrome)
Hyoscyamine
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Tone and motility of smooth muscle cells
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Antispasmodics (irritable bowel syndrome)
Darifenacin
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↑ Sphincter tone
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
Urinary urgency, urge incontinence, urinary frequency, and/or nocturia (symptoms resulting from, e.g., overactive bladder)
Flavoxate
Antimuscarinic
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
↓ Tone and motility of smooth muscle cells
Mechanism:
Inhibit the effect of acetylcholine on muscarinic receptors
Clinical Use:
↓ Bladder spasms and urgency in overactive bladder incontinence
Albuterol
Short-acting β2 adrenergic agonist
Onset of action → 1-5 minutes
Duration of action → 4-6 hours
A face mask is recommended for children < 4 years on inhalational therapy.
Mechanism:
β2 > β1
Stimulate β2 adrenergic receptors.
Relaxes bronchial smooth muscle
Clinical Use:
Bronchial asthma (used to achieve spasmolysis of the bronchi)
Acute exacerbation (use short-acting selective β2-agonists (e.g., albuterol))
COPD (used to achieve spasmolysis of the bronchi) (Short-acting beta agonist inhalers are often combined with ipratropium bromide)
Hyperkalemia (drive K+ intracellularly)
Adverse Effects:
- Ventricular arrhythmias, vasoconstriction, angina pectoris, tachycardia, and palpitations; may aggravate cardiomyopathy in patients with cardiovascular disease (these effects are due to several processes: 1. β1-mediated cardiac stimulation (no absolute β2 selectivity); 2. reflex tachycardia after β2-mediated vasodilation; and 3. the results of potential hypokalemia)
- Tremor (β2-mediated skeletal muscle stimulation with potential initiation of a tremor)
- Headache, anxiety, and sleep disturbances
- Hyperglycemia (β2-mediated stimulation in the liver → elevated cAMP levels → increased glycogenolysis)
- Hypokalemia (risk of life-threatening arrhythmias) (β2-mediated stimulation of Na+/K+-ATPase → intracellular K+ shift (hyperglycemia also contributes) (increased insulin secretion → activates Na+/K+-ATPase)
- Development of tolerance
- Paradoxical bronchospasm may occur
Use with caution in patients with the following conditions:
Hyperthyroidism
Glaucoma
Diabetes
Hypokalemia
Seizures
Cardiovascular disease (e.g., heart failure, hypertension, arrhythmias, coronary artery disease)
Terbutaline
Short-acting β2 adrenergic agonist
Onset of action → 1-5 minutes
Duration of action → 4-6 hours
A face mask is recommended for children < 4 years on inhalational therapy.
Mechanism:
β2 > β1
Stimulate β2 adrenergic receptors.
Relaxes bronchial smooth muscle
Clinical Use:
Bronchial asthma (used to achieve spasmolysis of the bronchi)
Acute exacerbation (use short-acting)
COPD (used to achieve spasmolysis of the bronchi) (Short-acting beta agonist inhalers are often combined with ipratropium bromide)
Hyperkalemia (drive K+ intracellularly)
Tocolysis (often used to suppress contractions in pregnant women undergoing preterm labor, with pyelonephritis (which can induce preterm labor), or umbilical cord prolapse)
Adverse Effects:
- Ventricular arrhythmias, vasoconstriction, angina pectoris, tachycardia, and palpitations; may aggravate cardiomyopathy in patients with cardiovascular disease (these effects are due to several processes: 1. β1-mediated cardiac stimulation (no absolute β2 selectivity); 2. reflex tachycardia after β2-mediated vasodilation; and 3. the results of potential hypokalemia)
- Tremor (β2-mediated skeletal muscle stimulation with potential initiation of a tremor)
- Headache, anxiety, and sleep disturbances
- Hyperglycemia (β2-mediated stimulation in the liver → elevated cAMP levels → increased glycogenolysis)
- Hypokalemia (risk of life-threatening arrhythmias) (β2-mediated stimulation of Na+/K+-ATPase → intracellular K+ shift (hyperglycemia also contributes) (increased insulin secretion → activates Na+/K+-ATPase)
- Development of tolerance
- Paradoxical bronchospasm may occur
Use with caution in patients with the following conditions:
Hyperthyroidism
Glaucoma
Diabetes
Hypokalemia
Seizures
Cardiovascular disease (e.g., heart failure, hypertension, arrhythmias, coronary artery disease)
Pirbuterol
Short-acting β2 adrenergic agonist
Onset of action → 1-5 minutes
Duration of action → 4-6 hours
A face mask is recommended for children < 4 years on inhalational therapy.
Mechanism:
β2 > β1
Stimulate β2 adrenergic receptors.
Relaxes bronchial smooth muscle
Clinical Use: Bronchial asthma (used to achieve spasmolysis of the bronchi) Acute exacerbation (use short-acting) COPD (used to achieve spasmolysis of the bronchi) (short-acting beta agonist inhalers are often combined with ipratropium bromide) Hyperkalemia (drive K+ intracellularly)
Adverse Effects:
- Ventricular arrhythmias, vasoconstriction, angina pectoris, tachycardia, and palpitations; may aggravate cardiomyopathy in patients with cardiovascular disease (these effects are due to several processes: 1. β1-mediated cardiac stimulation (no absolute β2 selectivity); 2. reflex tachycardia after β2-mediated vasodilation; and 3. the results of potential hypokalemia)
- Tremor (β2-mediated skeletal muscle stimulation with potential initiation of a tremor)
- Headache, anxiety, and sleep disturbances
- Hyperglycemia (β2-mediated stimulation in the liver → elevated cAMP levels → increased glycogenolysis)
- Hypokalemia (risk of life-threatening arrhythmias) (β2-mediated stimulation of Na+/K+-ATPase → intracellular K+ shift (hyperglycemia also contributes) (increased insulin secretion → activates Na+/K+-ATPase)
- Development of tolerance
- Paradoxical bronchospasm may occur
Use with caution in patients with the following conditions:
Hyperthyroidism
Glaucoma
Diabetes
Hypokalemia
Seizures
Cardiovascular disease (e.g., heart failure, hypertension, arrhythmias, coronary artery disease)
Levalbuterol
Short-acting β2 adrenergic agonist
Onset of action → 1-5 minutes
Duration of action → 4-8 hours
A face mask is recommended for children < 4 years on inhalational therapy.
Mechanism:
β2 > β1
Stimulate β2 adrenergic receptors.
Relaxes bronchial smooth muscle
Clinical Use: Bronchial asthma (used to achieve spasmolysis of the bronchi) Acute exacerbation (use short-acting) COPD (used to achieve spasmolysis of the bronchi) (short-acting beta agonist inhalers are often combined with ipratropium bromide) Hyperkalemia (drive K+ intracellularly)
Adverse Effects:
- Ventricular arrhythmias, vasoconstriction, angina pectoris, tachycardia, and palpitations; may aggravate cardiomyopathy in patients with cardiovascular disease (these effects are due to several processes: 1. β1-mediated cardiac stimulation (no absolute β2 selectivity); 2. reflex tachycardia after β2-mediated vasodilation; and 3. the results of potential hypokalemia)
- Tremor (β2-mediated skeletal muscle stimulation with potential initiation of a tremor)
- Headache, anxiety, and sleep disturbances
- Hyperglycemia (β2-mediated stimulation in the liver → elevated cAMP levels → increased glycogenolysis)
- Hypokalemia (risk of life-threatening arrhythmias) (β2-mediated stimulation of Na+/K+-ATPase → intracellular K+ shift (hyperglycemia also contributes) (increased insulin secretion → activates Na+/K+-ATPase)
- Development of tolerance
- Paradoxical bronchospasm may occur
Use with caution in patients with the following conditions:
Hyperthyroidism
Glaucoma
Diabetes
Hypokalemia
Seizures
Cardiovascular disease (e.g., heart failure, hypertension, arrhythmias, coronary artery disease)
Formoterol
Long-acting β2 adrenergic agonist
Onset of action → 1-5 minutes
Duration of action → > 12 hours
A face mask is recommended for children < 4 years on inhalational therapy.
Mechanism:
β2 > β1
Stimulate β2 adrenergic receptors.
Relaxes bronchial smooth muscle
Clinical Use: Bronchial asthma (used to achieve spasmolysis of the bronchi) Prophylaxis (in chronic disease) use long-acting selective β2-agonists (e.g., salmeterol) COPD (used to achieve spasmolysis of the bronchi) (short-acting beta agonist inhalers are often combined with ipratropium bromide) Hyperkalemia (drive K+ intracellularly)
Adverse Effects:
- Ventricular arrhythmias, vasoconstriction, angina pectoris, tachycardia, and palpitations; may aggravate cardiomyopathy in patients with cardiovascular disease (these effects are due to several processes: 1. β1-mediated cardiac stimulation (no absolute β2 selectivity); 2. reflex tachycardia after β2-mediated vasodilation; and 3. the results of potential hypokalemia)
- Tremor (β2-mediated skeletal muscle stimulation with potential initiation of a tremor)
- Headache, anxiety, and sleep disturbances
- Hyperglycemia (β2-mediated stimulation in the liver → elevated cAMP levels → increased glycogenolysis)
- Hypokalemia (risk of life-threatening arrhythmias) (β2-mediated stimulation of Na+/K+-ATPase → intracellular K+ shift (hyperglycemia also contributes) (increased insulin secretion → activates Na+/K+-ATPase)
- Development of tolerance
- Paradoxical bronchospasm may occur
Use with caution in patients with the following conditions:
Hyperthyroidism
Glaucoma
Diabetes
Hypokalemia
Seizures
Cardiovascular disease (e.g., heart failure, hypertension, arrhythmias, coronary artery disease)
Salmeterol
Long-acting β2 adrenergic agonist
Onset of action → 30-45 minutes
Duration of action → >12 hours
A face mask is recommended for children < 4 years on inhalational therapy.
Mechanism:
β2 > β1
Stimulate β2 adrenergic receptors.
Relaxes bronchial smooth muscle
Clinical Use: Bronchial asthma (used to achieve spasmolysis of the bronchi) Prophylaxis (in chronic disease) use long-acting selective β2-agonists (e.g., salmeterol) COPD (used to achieve spasmolysis of the bronchi) (short-acting beta agonist inhalers are often combined with ipratropium bromide) Hyperkalemia (drive K+ intracellularly)
Adverse Effects:
- Ventricular arrhythmias, vasoconstriction, angina pectoris, tachycardia, and palpitations; may aggravate cardiomyopathy in patients with cardiovascular disease (these effects are due to several processes: 1. β1-mediated cardiac stimulation (no absolute β2 selectivity); 2. reflex tachycardia after β2-mediated vasodilation; and 3. the results of potential hypokalemia)
- Tremor (β2-mediated skeletal muscle stimulation with potential initiation of a tremor)
- Headache, anxiety, and sleep disturbances
- Hyperglycemia (β2-mediated stimulation in the liver → elevated cAMP levels → increased glycogenolysis)
- Hypokalemia (risk of life-threatening arrhythmias) (β2-mediated stimulation of Na+/K+-ATPase → intracellular K+ shift (hyperglycemia also contributes) (increased insulin secretion → activates Na+/K+-ATPase)
- Development of tolerance
- Paradoxical bronchospasm may occur
Use with caution in patients with the following conditions:
Hyperthyroidism
Glaucoma
Diabetes
Hypokalemia
Seizures
Cardiovascular disease (e.g., heart failure, hypertension, arrhythmias, coronary artery disease)
Clonidine
Sympatholytic drug
Mechanism:
α2 agonist
Stimulates α2-receptors in the brainstem, decreasing peripheral vascular resistance and lowering blood pressure (BP)
Clinical Use: ADHD Tourette syndrome Hypertensive urgency (limited situations) Symptom control in opioid withdrawal
Adverse Effects: Orthostatic hypotension Sedation and CNS depression Rebound hypertension caused by abrupt discontinuation of medication Respiratory depression Miosis Dry mouth Rash Bradycardia
Guanfacine
Sympatholytic drug
Mechanism:
α2 agonist
Stimulates α2-receptors in the brainstem, decreasing peripheral vascular resistance and lowering blood pressure (BP)
Clinical Use: ADHD Tourette syndrome Drug withdrawal Hypertensive urgency (limited situations) Symptom control in opioid withdrawal
Adverse Effects: Orthostatic hypotension Sedation and CNS depression Rebound hypertension caused by abrupt discontinuation of medication Respiratory depression Miosis Dry mouth Rash Bradycardia
Dobutamine
Direct sympathomimetic drug
Mechanism: β1 > β2, α Inotropic effects > chronotropic effects No change or mild decrease in BP Raises HR, cardiac output (CO)
Clinical Use:
Heart failure (At high doses, acts as a β-agonist. Therefore, in patients with heart failure, high-dose dobutamine is useful because it increases CO (due to an increase in heart rate as well as contractility by β1 agonism) and decreases cardiac afterload (due to peripheral vasodilation by β2 agonism))
Cardiogenic shock
Cardiac stress testing
Adverse Effects:
Tachycardia and arrhythmias
Can precipitate angina or myocardial infarction in patients with coronary artery disease
Dopamine
Direct sympathomimetic drug
Mechanism: D1 = D2 > β > α Chronotropic effects at lower doses (β effect) Vasoconstriction at high doses (α effect) Raises BP (at high doses), HR, CO
Clinical Use:
Heart failure
Cardiogenic shock
Unstable bradycardia
Epinephrine
Direct sympathomimetic drug
Mechanism: β > α (at high doses the α effect is predominant) Stronger β2-receptor effect than norepinephrine Raises BP (at high doses), HR, CO
Clinical Use: Anaphylaxis Cardiac arrest (IV epinephrine is used if the patient is hemodynamically unstable and requires cardiopulmonary resuscitation) Septic shock Postbypass hypotension Asthma Open-angle glaucoma
Fenoldopam
Direct sympathomimetic drug
Mechanism: D1 Vasodilates coronary and peripheral vessels Promotes natriuresis Raises CO, HR Lowers BP (through vasodilatation)
Clinical Use:
Hypertensive crisis
Postoperative hypertension
Isoproterenol
Direct sympathomimetic drug
Mechanism: β1 = β2 Marginal α effect Raises CO, HR Lowers BP (through vasodilatation)
Clinical Use:
Bradycardia or heart block
It may worsen ischemia.
Cardiac arrest from heart block when pacemaker therapy is unavailable
Electrophysiologic evaluation of tachyarrhythmias.
Methyldopa
Direct sympathomimetic drug
Mechanism:
α2
Lowers BP
Clinical Use:
HTN, especially in pregnancy
Adverse Effects:
Direct Coombs ⊕ hemolysis, drug-induced lupus, hyperprolactinemia, peripheral edema
Midodrine
Direct sympathomimetic drug
Mechanism: α1 Raises BP (through vasoconstriction) Lowers HR No change or decrease in CO
Clinical Use:
Autonomic insufficiency and symptomatic orthostatic hypotension
Adverse Effects:
May exacerbate supine hypertension.
Hypertension (due to peripheral vasoconstriction) and reflex bradycardia
Urinary retention
Ischemia and necrosis, especially of the fingers or toes
Piloerection
Mirabegron
Direct sympathomimetic drug
Mechanism:
β3
Raises BP
Clinical Use:
Urinary urge incontinence or overactive bladder
Norepinephrine
Direct sympathomimetic drug
Mechanism: α1 > α2 > β1 Raises BP (through vasoconstriction) Lowers HR (reflex bradycardia) as a response to the increased mean arterial pressure (MAP), which counteracts chronotropic effects No change or increase in CO
Clinical Use:
Septic shock (used in attempts to increase peripheral vascular resistance. Dobutamine and vasopressin can also be administered in cases of reduced cardiac contractility and septic shock. Norepinephrine has a weaker β2 effect than epinephrine)
Neurogenic shock (preferred agent because α agonism increases peripheral vascular resistance (to counteract hypotension from loss of sympathetic tone) and β agonism increases heart rate (to counteract bradycardia from unopposed parasympathetic vagal tone))
Hypotension
Oxymetazoline
Direct sympathomimetic drug
Mechanism:
α1 > α2
May raise BP
Clinical Use:
Epistaxis
Rhinitis, sinusitis (topical decongestant)
Rosacea
Phenylephrine
Direct sympathomimetic drug
Mechanism: α1 > α2 Raises BP (through vasoconstriction) Lowers HR No change or decrease in CO
Clinical Use:
Hypotension
Rhinitis, obstructed Eustachian tubes
Phenylephrine acts as a nasal decongestant by reducing hyperemia and mucosal edema
Allergic conjunctivitis
Open-angle glaucoma (has a mydriatic effect without causing cycloplegia)
Ischemic priapism (high-dose intracavernosal phenylephrine injection)
Cocaine
Indirect sympathomimetic drug
Mechanism:
Increase the synaptic activity of endogenous catecholamines by inhibiting reuptake
Clinical Use:
Local anesthesia
Vasoconstriction
Causes mydriasis in eyes with intact sympathetic innervation –> fused to confirm Horner syndrome.
Amphetamine
Indirect sympathomimetic drug
Mechanism:
Increase the synaptic activity of endogenous catecholamines by increasing presynaptic release and inhibiting reuptake
Clinical Use:
ADHD
Narcolepsy
Obesity
Ephedrine
Indirect sympathomimetic drug
Mechanism:
Increase the synaptic activity of endogenous catecholamines by increasing presynaptic release
Clinical Use:
Anesthesia-induced hypotension
Urinary incontinence (to improve urinary continuity through activation of α-receptors within the bladder)
Nasal congestion (pseudoephedrine) (reduces hyperemia and edema and opens nasal meatus and Eustachian tubes)
Adverse Effects: Hypertension Reflex bradycardia (due to hypertension) or tachycardia Dizziness Nausea, vomiting
Tizanidine
Sympatholytic drug
Mechanism:
α2 agonist
Clinical Use: Muscle spasticity ALS Multiple sclerosis Cerebral palsy
Adverse Effects:
Hypotension
Weakness
Xerostomia
Phenoxybenzamine
Sympatholytic drugs
Mechanism:
Nonselective α receptor antagonists
Irreversible blockade can only be overcome by synthesis of new alpha adrenergic receptors, which can take up to 3 days or even longer.
Clinical Use:
Pheochromocytoma
Adverse Effects: Reflex tachycardia (Caused by antagonism of cardiac α-2 receptors. Normally, these receptors trigger a negative feedback loop after activation of the sympathetic nervous system) Orthostatic hypotension
Phentolamine
Sympatholytic drugs
Mechanism:
Competitive and reversible α receptor antagonists
Clinical Use:
Hypertensive emergencies
Tyramine ingestion in patients on MAO inhibitors
Cocaine-induced hypertension (second-line) (should only be given to patients who do not fully respond to benzodiazepines, nitroglycerin, or calcium channel blockers)
Pheochromocytoma
Vasopressor extravasation
Adverse Effects: Reflex tachycardia (Caused by antagonism of cardiac α-2 receptors. Normally, these receptors trigger a negative feedback loop after activation of the sympathetic nervous system) Orthostatic hypotension
Prazosin
Sympatholytic drugs
Mechanism:
α1-antagonist
Clinical Use:
Urinary symptoms of BPH (produce symptomatic improvement in patients with BPH by their action on smooth muscles present in prostate and bladder base. Patients with smooth muscle predominance best respond to treatment with alpha-1 blockers)
Hypertension
PTSD-related nightmares
Adverse Effects:
Orthostatic hypotension (contraction of veins and arterioles helps maintain blood pressure when standing up and is prevented by α-1 antagonism)
Retrograde ejaculation (muscles of the bladder neck are relaxed and cannot prevent retrograde ejaculation)
Dizziness, headache
Peripheral edema
Nausea, constipation
Intraoperative floppy iris syndrome (IFIS) (omplication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constriction. May lead to retinal detachment and endophthalmitis)
Urinary frequency
Terazosin
Sympatholytic drugs
Mechanism:
α1-antagonist
Clinical Use:
Benign prostatic hyperplasia
Arterial hypertension
Adverse Effects:
Orthostatic hypotension (contraction of veins and arterioles helps maintain blood pressure when standing up and is prevented by α-1 antagonism)
Retrograde ejaculation (muscles of the bladder neck are relaxed and cannot prevent retrograde ejaculation)
Dizziness, headache
Peripheral edema
Nausea, constipation
Intraoperative floppy iris syndrome (IFIS) (omplication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constriction. May lead to retinal detachment and endophthalmitis)
Urinary frequency
Doxazosin
Sympatholytic drugs
Mechanism:
α1-antagonist
Clinical Use:
Benign prostatic hyperplasia
Arterial hypertension
Adverse Effects:
Orthostatic hypotension (contraction of veins and arterioles helps maintain blood pressure when standing up and is prevented by α-1 antagonism)
Retrograde ejaculation (muscles of the bladder neck are relaxed and cannot prevent retrograde ejaculation)
Dizziness, headache
Peripheral edema
Nausea, constipation
Intraoperative floppy iris syndrome (IFIS) (omplication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constriction. May lead to retinal detachment and endophthalmitis)
Urinary frequency
Tamsulosin
Sympatholytic drugs
Mechanism:
α1-antagonist
Blocks alpha-1A/D (found on prostate) > alpha-1B receptors
Clinical Use:
Benign prostatic hyperplasia
Adverse Effects:
Orthostatic hypotension (contraction of veins and arterioles helps maintain blood pressure when standing up and is prevented by α-1 antagonism)
Retrograde ejaculation (muscles of the bladder neck are relaxed and cannot prevent retrograde ejaculation)
Dizziness, headache
Peripheral edema
Nausea, constipation
Intraoperative floppy iris syndrome (IFIS) (omplication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constriction. May lead to retinal detachment and endophthalmitis)
Urinary frequency
Acebutolol
Direct sympathomimetic drug with intrinsic sympathomimetic activity (ISA)
Mechanism:
Partial β-agonists
Selectively bind to and block β1 receptors, which are primarily found in the heart
Decrease the heart rate, contractility, and AVN conductivity
Clinical Use:
Coronary heart disease
Compensated heart failure
Cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT)
Adverse Effects:
Bradycardia
Bradyarrhythmia
Cardioselectivity is dose-dependent: β2 receptor blocking activity increases with higher doses (in high doses, cardioselective beta blockers lose their selectivity and can block β2 receptors as well, resulting in β2 receptor blockade-mediated adverse effect)
Generally do not cause bronchoconstriction or vasoconstriction
Generally do not interfere with glycogenolysis; safe in diabetic patients
Atenolol
Cardioselective beta blockers (β1 selective) without intrinsic sympathomimetic activity (ISA)
Has low potential to penetrate the blood-brain barrier
Mechanism:
Selectively bind to and block β1 receptors, which are primarily found in the heart
Decrease the heart rate, contractility, and AVN conductivity
Clinical Use:
Coronary heart disease
Compensated heart failure
Cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT)
Adverse Effects:
Bradycardia
Bradyarrhythmia
Cardioselectivity is dose-dependent: β2 receptor blocking activity increases with higher doses (in high doses, cardioselective beta blockers lose their selectivity and can block β2 receptors as well, resulting in β2 receptor blockade-mediated adverse effect)
Generally do not cause bronchoconstriction or vasoconstriction
Generally do not interfere with glycogenolysis; safe in diabetic patients
Bisoprolol
Cardioselective beta blockers (β1 selective) without intrinsic sympathomimetic activity (ISA)
Mechanism:
Selectively bind to and block β1 receptors, which are primarily found in the heart
Decrease the heart rate, contractility, and AVN conductivity
Clinical Use:
Coronary heart disease
Compensated heart failure
Cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT)
Adverse Effects:
Bradycardia
Bradyarrhythmia
Cardioselectivity is dose-dependent: β2 receptor blocking activity increases with higher doses (in high doses, cardioselective beta blockers lose their selectivity and can block β2 receptors as well, resulting in β2 receptor blockade-mediated adverse effect)
Generally do not cause bronchoconstriction or vasoconstriction
Generally do not interfere with glycogenolysis; safe in diabetic patients
Carvedilol
Nonselective beta blockers (β1, β2, and β3 receptors) with additional α-blocking action
In addition to its α- and β-blocking action, also has antioxidant properties, which helps in the treatment of heart failure by decreasing disease progression and aiding ventricular remodeling.
Mechanism:
Potent vasodilators because of their α-blocking action (vasodilation → ↓ peripheral vascular resistance, ↓ preload, ↓ afterload, and ↑ renal blood flow; reduce portal hypertension and pressure gradient in hepatic venous)
Improve endothelial function and vascular remodeling (this may make them useful in the management of ischemic stroke.
Clinical Use:
Esophageal variceal bleeding (prophylactic use)
Adverse Effects:
Bronchoconstriction (may exacerbate asthma/COPD)
Vasoconstriction (avoid in patients with peripheral vascular disease)
Hypoglycemia and hyperglycemia
Bradycardia and syncope
Orthostatic hypotension
Esmolol
Cardioselective beta blockers (β1 selective) without intrinsic sympathomimetic activity (ISA)
Rapidly acting, short-duration
Mechanism:
Selectively bind to and block β1 receptors, which are primarily found in the heart
Decrease the heart rate, contractility, and AVN conductivity
Clinical Use: Coronary heart disease Compensated heart failure Cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT) Aortic dissection
Adverse Effects:
Bradycardia
Bradyarrhythmia
Cardioselectivity is dose-dependent: β2 receptor blocking activity increases with higher doses (in high doses, cardioselective beta blockers lose their selectivity and can block β2 receptors as well, resulting in β2 receptor blockade-mediated adverse effect)
Generally do not cause bronchoconstriction or vasoconstriction
Generally do not interfere with glycogenolysis; safe in diabetic patients
Labetalol
Nonselective beta blockers (β1, β2, and β3 receptors) with additional α-blocking action
Mechanism:
Potent vasodilators because of their α-blocking action (vasodilation → ↓ peripheral vascular resistance, ↓ preload, ↓ afterload, and ↑ renal blood flow; reduce portal hypertension and pressure gradient in hepatic venous)
Improve endothelial function and vascular remodeling (this may make them useful in the management of ischemic stroke.
Clinical Use:
Pregnancy-induced hypertension (e.g, labetalol)
Esophageal variceal bleeding (prophylactic use)
Adverse Effects:
Bronchoconstriction (may exacerbate asthma/COPD)
Vasoconstriction (avoid in patients with peripheral vascular disease)
Hypoglycemia and hyperglycemia
Bradycardia and syncope
Orthostatic hypotension
Metoprolol
Cardioselective beta blockers (β1 selective) without intrinsic sympathomimetic activity (ISA)
Mechanism:
Selectively bind to and block β1 receptors, which are primarily found in the heart
Decrease the heart rate, contractility, and AVN conductivity
Clinical Use:
Coronary heart disease
Compensated heart failure
Cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT)
Adverse Effects:
Bradycardia
Bradyarrhythmia
Dyslipidemia
Cardioselectivity is dose-dependent: β2 receptor blocking activity increases with higher doses (in high doses, cardioselective beta blockers lose their selectivity and can block β2 receptors as well, resulting in β2 receptor blockade-mediated adverse effect)
Generally do not cause bronchoconstriction or vasoconstriction
Generally do not interfere with glycogenolysis; safe in diabetic patients
Nadolol
Nonselective beta blockers (β1, β2, and β3 receptors) without intrinsic sympathomimetic activity (ISA)
Mechanism:
Block β1, β2, and β3 receptors
Clinical Use:
Alternative to cardioselective beta blockers
Nonbleeding esophageal varices.
Adverse Effects:
Bronchoconstriction (may exacerbate asthma/COPD)
Vasoconstriction (avoid in patients with peripheral vascular disease)
Hypoglycemia and hyperglycemia
Bradycardia and syncope
Nebivolol
Cardioselective beta blockers (β1 selective) without intrinsic sympathomimetic activity (ISA)
Mechanism:
Selectively bind to and block β1 receptors, which are primarily found in the heart
Decrease the heart rate, contractility, and AVN conductivity
The only beta blocker that causes NO-mediated vasodilation: it decreases vascular resistance by stimulating β3 receptors and activating NO synthase in the vasculature. The drug has the advantages of a beta blocker with additional alpha-blocking properties. It is a long-acting drug requiring once-daily dosing.
Clinical Use:
Coronary heart disease
Compensated heart failure
Cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT)
Adverse Effects:
Bradycardia
Bradyarrhythmia
Cardioselectivity is dose-dependent: β2 receptor blocking activity increases with higher doses (in high doses, cardioselective beta blockers lose their selectivity and can block β2 receptors as well, resulting in β2 receptor blockade-mediated adverse effect)
Generally do not cause bronchoconstriction or vasoconstriction
Generally do not interfere with glycogenolysis; safe in diabetic patients
Pindolol
Nonselective beta blockers (β1, β2, and β3 receptors) with intrinsic sympathomimetic activity (ISA)
Mechanism:
Partial β-agonists
Block β1, β2, and β3 receptors
Clinical Use:
Alternative to cardioselective beta blockers
Adverse Effects:
Bronchoconstriction (may exacerbate asthma/COPD)
Vasoconstriction (avoid in patients with peripheral vascular disease)
Hypoglycemia and hyperglycemia
Bradycardia and syncope
Propranolol
Nonselective beta blockers (β1, β2, and β3 receptors) without intrinsic sympathomimetic activity (ISA)
Mechanism:
Block β1, β2, and β3 receptors
Does not significantly lower blood pressure
Clinical Use: Alternative to cardioselective beta blockers Essential tremor Migraine prophylaxis Portal hypertension Hyperthyroidism and thyroid storm Infantile hemangioma Akathisia
Adverse Effects:
Bronchoconstriction (may exacerbate asthma/COPD)
Vasoconstriction (avoid in patients with peripheral vascular disease)
Hypoglycemia and hyperglycemia
Bradycardia and syncope
Timolol
Nonselective beta blockers (β1, β2, and β3 receptors) without intrinsic sympathomimetic activity (ISA)
Mechanism:
Block β1, β2, and β3 receptors
Clinical Use:
Alternative to cardioselective beta blockers
Glaucoma
Migraine prophylaxis
Adverse Effects:
Bronchoconstriction (may exacerbate asthma/COPD)
Vasoconstriction (avoid in patients with peripheral vascular disease)
Hypoglycemia and hyperglycemia
Bradycardia and syncope
Apraclonidine
Direct sympathomimetic drug
Mechanism:
α2-agonist
Decrease aqueous humor synthesis
Clinical Use:
Glaucoma
Adverse Effects:
Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritus
Brimonidine
Direct sympathomimetic drug
Mechanism:
α2 adrenergic agonist.
Decreases the production of aqueous humor
Induce vasoconstriction (topical)
Clinical Use:
Open-angle glaucoma and ocular hypertension.
Rosacea-associated erythema.
Adverse Effects:
Do not use in closed-angle glaucoma
Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritus
Pseudoephedrine
Direct sympathomimetic drug
Mechanism:
α1 >α2
Constricts blood vessels in the nose and thereby reduces edema, hyperemia, and congestion. Also some stimulation of β2-adrenergic receptors causing smooth muscle tissue in respiratory bronchioles to dilate.
Clinical Use: Nasal congestion (pseudoephedrine) (reduces hyperemia and edema and opens nasal meatus and Eustachian tubes)
Adverse Effects:
Hypertension
Reflex bradycardia (due to hypertension) or tachycardia
Dizziness
Nausea, vomiting
Rebound congestion (when used > 4–6 days)
Anxiety and/or ↑ CNS stimulation (e.g., alertness, nervousness, insomnia)
Tachyphylaxis
Dexmedetomidine
Sympatholytic drug
Mechanism:
α2 agonist
Clinical Use:
Sedation
Adverse Effects: Agitation Orthostatic hypotension Bradycardia Hypertension Constipation Nausea Sedation
Alfuzosin
Sympatholytic drugs
Mechanism:
α1-antagonist
Clinical Use:
Benign prostatic hyperplasia
Adverse Effects:
Orthostatic hypotension (contraction of veins and arterioles helps maintain blood pressure when standing up and is prevented by α-1 antagonism)
Retrograde ejaculation (muscles of the bladder neck are relaxed and cannot prevent retrograde ejaculation)
Dizziness, headache
Peripheral edema
Nausea, constipation
Intraoperative floppy iris syndrome (IFIS) (omplication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constriction. May lead to retinal detachment and endophthalmitis)
Urinary frequency
Silodosin
Sympatholytic drugs
Mechanism:
α1-antagonist
Clinical Use:
Benign prostatic hyperplasia
Adverse Effects:
Orthostatic hypotension (contraction of veins and arterioles helps maintain blood pressure when standing up and is prevented by α-1 antagonism)
Retrograde ejaculation (muscles of the bladder neck are relaxed and cannot prevent retrograde ejaculation)
Dizziness, headache
Peripheral edema
Nausea, constipation
Intraoperative floppy iris syndrome (IFIS) (omplication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constriction. May lead to retinal detachment and endophthalmitis)
Urinary frequency
Mirtazapine
Sympatholytic drugs
Mechanism:
α2-antagonist
Also inhibits 5-HT2, 5-HT3 receptors, and H1-receptors.
Clinical Use:
Depression
Adverse Effects:
↑ Sedation
↑ Appetite and weight
Hypercholesterolemia
Tetrabenazine
Monoamine-depleting agent
Mechanism:
Reversible inhibition of vesicular monoamine transporter-2 (VMAT-2) → impaired packaging of monoamines (dopamine, serotonin, and norepinephrine) into presynaptic vesicles → ↓ dopamine release
Clinical Use: Hyperkinetic disorders (chorea associated with Huntington disease, Tourette syndrome, Tardive dyskinesia, Hemiballismus)
Adverse Effects: Parkinson-like syndrome Depression Suicidal ideation Sedation Akathisia Fatigue
Reserpine
Monoamine-depleting agent
Mechanism:
Reversible inhibition of vesicular monoamine transporter-2 (VMAT-2) → impaired packaging of monoamines (dopamine, serotonin, and norepinephrine) into presynaptic vesicles → ↓ dopamine release
Clinical Use:
Tardive dyskinesia
Psychiatric disorders
Hypertension
Adverse Effects: Parkinson-like syndrome Depression Angina Bradycardia Peripheral edema Nasal obstruction Diarrhea
Celiprolol
Selective β1 blocker with intrinsic sympathomimetic activity (ISA)
Mechanism:
Selectively bind to and block β1 receptors, which are primarily found in the heart
Decrease the heart rate, contractility, and AVN conductivity
Clinical Use:
Coronary heart disease
Compensated heart failure
Cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT)
Adverse Effects:
Bradycardia
Bradyarrhythmia
Cardioselectivity is dose-dependent (β2 receptor blocking activity increases with higher doses)
Generally do not cause bronchoconstriction or vasoconstriction
Generally do not interfere with glycogenolysis; safe in diabetic patients
Bucindolol
Nonselective beta blockers (β1, β2, and β3 receptors) with additional α-blocking action
Mechanism:
Potent vasodilators because of their α-blocking action (vasodilation → ↓ peripheral vascular resistance, ↓ preload, ↓ afterload, and ↑ renal blood flow; reduce portal hypertension and pressure gradient in hepatic venous)
Improve endothelial function and vascular remodeling (this may make them useful in the management of ischemic stroke.
Clinical Use:
Esophageal variceal bleeding (prophylactic use)
Adverse Effects:
Bronchoconstriction (may exacerbate asthma/COPD)
Vasoconstriction (avoid in patients with peripheral vascular disease)
Hypoglycemia and hyperglycemia
Bradycardia and syncope
Orthostatic hypotension
α1-agonists Adverse Effects
- Hypertension (due to peripheral vasoconstriction) and reflex bradycardia
- Urinary retention (α1 agonists are responsible for the contraction of the bladder neck)
- Ischemia and necrosis, especially of the fingers or toes (caused by the vasoconstrictive effects of α1 agonists. Patients with hypovolemia are at the highest risk of this side effect)
- Rebound congestion (with nasal decongestants used > 4–6 days)
- Piloerection
α2-agonists Adverse Effects
Mainly due to their sympatholytic effects
- CNS depression (e.g., sedation)
- Respiratory depression
- Bradycardia and hypotension
- Miosis
- Rebound hypertension after sudden interruption (can occur up to 20 hours after cessation of the α2-agonist)
- Dry mouth (typically seen with clonidine; the mechanism by which clonidine causes this side effect is not completely understood)
β1-agonists Adverse Effects
Tachycardia and arrhythmias
Can precipitate angina or myocardial infarction in patients with coronary artery disease
β2-agonists Adverse Effects
Tremor (most common side effect), agitation, insomnia, diaphoresis
Hypotension (due to peripheral vasodilation) and reflex tachycardia
Metabolic disturbances (hyperglycemia, hypokalemia)
β Blockers Absolute Contraindications
- Symptomatic bradycardia (<50 bpm)
- Cardiogenic shock and hypotension (systolic blood pressure below 90 mm Hg)
- Pheochromocytoma (administration of beta blockers before alpha blockers → unopposed α-adrenoceptor mediated vasoconstriction → hypertensive crisis (except nonselective beta blockers with α-antagonism, such as carvedilol and labetalol))
- Decompensated heart failure
- Combination with calcium channel blockers (diltiazem or verapamil) because can precipitate AV block (both groups of drugs have a negative dromotropic effect (delayed AV transmission))
- Sick sinus syndrome (without a pacemaker); heart block greater than first-degree
Nonspecific phosphodiesterase inhibitors
inhibitors of PDE3, 4, and 5
Theophylline (methylxanthines)
Mechanism:
Nonspecific PDE inhibition → ↓ hydrolysis of cAMP → ↑ cAMP levels
Adenosine receptor blockade
Inhibition of proinflammatory mediators
Deceleration of fibrotic changes in the lung
Relaxation of the bronchial musculature → bronchodilation
Clinical Use:
COPD (severe and refractory cases)
Asthma
Adverse Effects:
Usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity)
Metabolized by cytochrome P-450.
Nausea, vomiting, arrhythmias and seizures
Seizures are the major cause of morbidity and mortality in theophylline intoxication.
Theophylline (methylxanthines)
Nonspecific phosphodiesterase inhibitors
(inhibitors of PDE3, 4, and 5)
Mechanism:
Nonspecific PDE inhibition → ↓ hydrolysis of cAMP → ↑ cAMP levels
Adenosine receptor blockade
Inhibition of proinflammatory mediators
Deceleration of fibrotic changes in the lung
Relaxation of the bronchial musculature → bronchodilation
Clinical Use:
COPD (severe and refractory cases)
Asthma
Adverse Effects:
Usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity) (adenosine receptor block seems to be mainly responsible for severe cardiac and neurological side effects)
Metabolized by cytochrome P-450.
Nausea, vomiting, arrhythmias and seizures
Seizures are the major cause of morbidity and mortality in theophylline intoxication.
Sildenafil
Phosphodiesterase type 5 inhibitor (PDE5 inhibitor)
Mechanism:
PDE5 inhibition → ↓ breakdown of cGMP → ↑ cGMP → ↑ smooth muscle relaxation in reaction to nitrous oxide activation → pulmonary vasodilation, penile smooth muscle relaxation, and increased blood flow
Decrease in pulmonary vascular resistance
↑ Blood flow in the corpus cavernosum → increase in penis size during an erection
Inhibition of proinflammatory mediators
Deceleration of fibrotic changes in the lung
Relaxation of the bronchial musculature
Clinical Use:
Erectile dysfunction
Pulmonary hypertension
Adverse Effects:
Headaches, cutaneous flushing (due to vasodilation)
Lightheadedness
Runny nose, nasal congestion
Exanthema
Dyspepsia
Hypotension in patients taking nitrates and alpha blockers
Cyanopia (blue- tinted vision) via inhibition of PDE-6 in retina (only sildenafil)
Rarely → myocardial infarction, stroke, hearing loss, optic neuropathy
Tadalafil
Phosphodiesterase type 5 inhibitor (PDE5 inhibitor)
Mechanism:
PDE5 inhibition → ↓ breakdown of cGMP → ↑ cGMP → ↑ smooth muscle relaxation in reaction to nitrous oxide activation → pulmonary vasodilation, penile smooth muscle relaxation, and increased blood flow
Clinical Use:
Erectile dysfunction
Pulmonary hypertension
BPH (only tadalafil)
Adverse Effects:
Headaches, cutaneous flushing (due to vasodilation)
Lightheadedness
Runny nose, nasal congestion
Exanthema
Dyspepsia
Hypotension in patients taking nitrates and alpha blockers
Rarely → myocardial infarction, stroke, hearing loss, optic neuropathy
Roflumilast
Phosphodiesterase type 4 inhibitor (PDE4 inhibitor)
Mechanism:
PDE4 inhibition → ↑ cAMP in bronchial epithelium, granulocytes, and neutrophils
Inhibition of proinflammatory mediators
Deceleration of fibrotic changes in the lung
Relaxation of the bronchial musculature
Clinical Use:
Severe COPD
Adverse Effects:
GI upset (nausea, abdominal pain)
Weight loss
Mental disorders (sleep disturbances, anxiety, depression)
Milrinone
Phosphodiesterase type 3 inhibitor (PDE3 inhibitor)
Mechanism:
PDE3 inhibition → ↑ cAMP
-In the myocardium → ↑ cAMP → activation of calcium channels → cardiostimulatory effects → ↑ inotropy and ↑ chronotropy
-In peripheral vessels → ↑ cAMP → inhibition of myosin light chain kinase → smooth muscle relaxation → vasodilation with reduced cardiovascular preload and afterload
-In platelets → ↑ cAMP → inhibited platelet aggregation
-Increase cardiac contractility acutely in cardiac failure
-Vasodilation and antiplatelet action in intermittent claudication
-Inhibition of platelet aggregation for angina prophylaxis, TIA/stroke prevention, and deceleration of restenosis in coronary stents
Clinical Use:
Acute treatment of decompensated cardiac failure with cardiogenic shock (usually in combination with other drugs (e.g., ACE inhibitors, diuretics))
Adverse Effects: Tachycardia, ventricular arrhythmias (most common and severe side effect, so not recommended for chronic use) (the severity of this side effect is the reason why PDE3 inhibitors are not recommended for patients with acute heart failure) Headaches, nausea Hypotension Gastrointestinal upset Facial flushing
Contraindications:
Severe obstructive cardiomyopathy or ventricular aneurysm
Hypovolemia
Tachycardia
Amrinone
Phosphodiesterase type 3 inhibitor (PDE3 inhibitor)
Mechanism:
PDE3 inhibition → ↑ cAMP
-In the myocardium → ↑ cAMP → activation of calcium channels → cardiostimulatory effects → ↑ inotropy and ↑ chronotropy
-In peripheral vessels → ↑ cAMP → inhibition of myosin light chain kinase → smooth muscle relaxation → vasodilation with reduced cardiovascular preload and afterload
-In platelets → ↑ cAMP → inhibited platelet aggregation
-Increase cardiac contractility acutely in cardiac failure
-Vasodilation and antiplatelet action in intermittent claudication
-Inhibition of platelet aggregation for angina prophylaxis, TIA/stroke prevention, and deceleration of restenosis in coronary stents
Clinical Use:
Acute treatment of decompensated cardiac failure with cardiogenic shock (usually in combination with other drugs (e.g., ACE inhibitors, diuretics))
Adverse Effects: Tachycardia, ventricular arrhythmias (most common and severe side effect, so not recommended for chronic use) (the severity of this side effect is the reason why PDE3 inhibitors are not recommended for patients with acute heart failure) Headaches, nausea Hypotension Gastrointestinal upset Facial flushing
Contraindications:
Severe obstructive cardiomyopathy or ventricular aneurysm
Hypovolemia
Tachycardia
Enoximone
Phosphodiesterase type 3 inhibitor (PDE3 inhibitor)
Mechanism:
PDE3 inhibition → ↑ cAMP
-In the myocardium → ↑ cAMP → activation of calcium channels → cardiostimulatory effects → ↑ inotropy and ↑ chronotropy
-In peripheral vessels → ↑ cAMP → inhibition of myosin light chain kinase → smooth muscle relaxation → vasodilation with reduced cardiovascular preload and afterload
-In platelets → ↑ cAMP → inhibited platelet aggregation
-Increase cardiac contractility acutely in cardiac failure
-Vasodilation and antiplatelet action in intermittent claudication
-Inhibition of platelet aggregation for angina prophylaxis, TIA/stroke prevention, and deceleration of restenosis in coronary stents
Clinical Use:
Acute treatment of decompensated cardiac failure with cardiogenic shock (usually in combination with other drugs (e.g., ACE inhibitors, diuretics))
Adverse Effects: Tachycardia, ventricular arrhythmias (most common and severe side effect, so not recommended for chronic use) (the severity of this side effect is the reason why PDE3 inhibitors are not recommended for patients with acute heart failure) Headaches, nausea Hypotension Gastrointestinal upset Facial flushing
Contraindications:
Severe obstructive cardiomyopathy or ventricular aneurysm
Hypovolemia
Tachycardia
Cilostazol
Nonspecific phosphodiesterase inhibitor
Mechanism:
PDE3 inhibition → ↑ cAMP
-In the myocardium → ↑ cAMP → activation of calcium channels → cardiostimulatory effects → ↑ inotropy and ↑ chronotropy
-In peripheral vessels → ↑ cAMP → inhibition of myosin light chain kinase → smooth muscle relaxation → vasodilation with reduced cardiovascular preload and afterload
-In platelets → ↑ cAMP → inhibited platelet aggregation
-Vasodilation and antiplatelet action in intermittent claudication (especially cilostazol, which has weaker cardiac inotropic effects)
-Inhibition of platelet aggregation for angina prophylaxis, TIA/stroke prevention, and deceleration of restenosis in coronary stents
Clinical Use:
Intermittent vascular claudication
Antiplatelet (antianginal, TIA/stroke prevention) (with aspirin)
Coronary stent restenosis prophylaxis
Adverse Effects:
Nausea, headache, facial flushing, hypotension, abdominal pain
Dipyridamole
Phosphodiesterase type 3 inhibitor (PDE3 inhibitor)
Mechanism:
PDE3 inhibition → ↑ cAMP
-In the myocardium → ↑ cAMP → activation of calcium channels → cardiostimulatory effects → ↑ inotropy and ↑ chronotropy
-In peripheral vessels → ↑ cAMP → inhibition of myosin light chain kinase → smooth muscle relaxation → vasodilation with reduced cardiovascular preload and afterload
-In platelets → ↑ cAMP → inhibited platelet aggregation; ↓ Adenosine reuptake → ↑ extracellular adenosine concentration → vasodilation (dipyridamole)
-Increase cardiac contractility acutely in cardiac failure (with the exception of cilostazol)
-Vasodilation and antiplatelet action in intermittent claudication (especially cilostazol, which has weaker cardiac inotropic effects)
-Inhibition of platelet aggregation for angina prophylaxis, TIA/stroke prevention, and deceleration of restenosis in coronary stents
-Dipyridamole dilates the coronary arteries and can therefore be used in cardiac stress testing
Clinical Use:
Cardiac stress testing (dipyridamole only, due to coronary vasodilation)
Intermittent vascular claudication
Antiplatelet (antianginal, TIA/stroke prevention) (with aspirin)
Coronary stent restenosis prophylaxis
Adverse Effects:
Nausea, headache, facial flushing, hypotension, abdominal pain
Amphetamines Toxicity Antidote/Management
Enhance sympathetic effect → serotonin syndrome
Benzodiazepines (sedation and control of seizures) Ammonium chloride (acidifies urine, which results in increased excretion of basic amphetamines)
Antimuscarinic/anticholinergic agents (e.g., atropine, medications with anticholinergic effects, jimson weed, deadly nightshade) Poisoning Antidote/Management
Physostigmine (crosses blood brain barrier)
Barbiturates Toxicity Antidote/Management
Sodium bicarbonate (alkalizes urine, which results in increased excretion of acidic barbiturates)
Benzodiazepines Toxicity Antidote/Management
Flumazenil
Digitalis Toxicity Antidote/Management
Inhibits Na+/K+-ATPase → cardiac arrhythmias, xanthopsia
Digoxin-specific antibody
Dabigatran Toxicity Antidote/Management
Renal elimination → supratherapeutic levels → excessive bleeding, acute renal failure
Idarucizumab
Heparin Toxicity Antidote/Management
Increases activity of antithrombin → excessive bleeding
Protamine sulfate
Opioids Toxicity Antidote/Management
Naloxone
Salicylates Toxicity Antidote/Management
Salicylate metabolites accumulate in liver → hepatic failure and metabolic acidosis
Sodium bicarbonate (alkalinize urine) Activated charcoal Dialysis
Thrombolytic agents (e.g., recombinant tPA) Toxicity Antidote/Management
Catalyze conversion of plasminogen to plasmin → excessive bleeding
Aminocaproic acid
Tricyclic antidepressants Toxicity Antidote/Management
Muscarinic ACh receptor inhibition → anticholinergic syndrome
Sodium bicarbonate (to stabilize cardiac cell membrane) Benzodiazepines for control of seizures Activated charcoal
Warfarin Toxicity Antidote/Management
Vitamin K antagonism (γ-carboxylation of clotting factors) → excessive bleeding
Fresh frozen plasma (immediate effect) and/or prothrombin complex concentrate (immediate antidote) Vitamin K (delayed antidote)
Carbon dioxide Toxicity Antidote/Management
↑ CO2 decreases O2 concentration → headaches, cardiac arrhythmias, respiratory depression, coma
Normal or high concentration oxygen depending on severity
Arsenic Toxicity Antidote/Management
Dimercaprol
Succimer
Carbon monoxide Toxicity Antidote/Management
Formation of carboxyhemoglobin → tissue hypoxia → cherry-red skin tone with bullous skin lesions, somnolence, agitation, headache, vomiting, coma
100% high-flow oxygen
Consider HBOT
Cyanide Toxicity Antidote/Management
Blocks electron transport chain → anion gap metabolic lactic acidosis, bitter almond breath, altered mental status
Hydroxycobalamin
Methemoglobin-forming agents (e.g.,amyl nitrite, sodium nitrite, 4-DMAP)
Sodium thiosulfate
Gold Toxicity Antidote/Management
Dimercaprol
Succimer
Penicillamine
Lead Toxicity Antidote/Management
Dimercaprol
Succimer
Penicillamine
EDTA
Mercury Toxicity Antidote/Management
Dimercaprol
Succimer
Copper Toxicity Antidote/Management
Penicillamine
Trientine
Iron Toxicity Antidote/Management
Deferoxamine
Deferasirox
Deferiprone
Methanol Toxicity Antidote/Management
Formation of toxic metabolites in the liver → anion gap metabolic acidosis, seizures, dyspnea
Fomepizole
Ethanol (less effective than fomepizole)
Dialysis
Ethylene glycol (antifreeze) Toxicity Antidote/Management
Formation of toxic metabolites in the liver → anion gap metabolic acidosis, seizures, dyspnea
Fomepizole
Ethanol (less effective than fomepizole)
Dialysis
Ethylene glycol (antifreeze) Toxicity Antidote/Management
Formation of toxic metabolites in the liver → anion gap metabolic acidosis, seizures, dyspnea
Fomepizole
Ethanol (less effective than fomepizole)
Dialysis
Methemoglobin Toxicity Antidote/Management
Cannot bind oxygen → cyanosis, coma, brown blood (see methemoglobinemia)
Methylene blue Vitamin C (weak reducing agent)
Cytochrome P-450 Inhibitors
Sodium valproate Isoniazid (weak inhibitor) Cimetidine Ketoconazole Fluconazole Acute alcohol overuse Chloramphenicol Erythromycin/clarithromycin Sulfonamides Ciprofloxacin Omeprazole Metronidazole Amiodarone Ritonavir Grapefruit juice Gingko biloba
Cytochrome P-450 Substrates
Theophylline
OCPs
Anti-epileptics
Statins (except pravastatin)
Lansoprazole Carbamazepine Haloperidol Cyclosporin Tacrolimus Benzodiazepine Ca+2 channel blockers
Cytochrome P-450 Inducers
St. John’s wort Griseofulvin Carbamazepine Chronic alcohol overuse Rifampin Modafinil Nevirapine Phenytoin Phenobarbital Primidone Glucocorticoids
Sulfa Drugs
Sulfonamide antibiotics Sulfasalazine Probenecid Furosemide Acetazolamide Celecoxib Thiazides Sulfonylureas
Platinum agent (eg, cisplatin, carboplatin and oxaliplatin) Toxicity
Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis.
