How Do Respiratory Stimulants Work?

Respiratory stimulants are medications used to stimulate respiration post anesthesia or to treat respiratory conditions such as chronic obstructive pulmonary disease (COPD), respiratory depression/failure, and neonatal apnea. Respiratory stimulants improve the respiratory drive and oxygen inflow as a result.

Respiratory stimulants drive respiration by stimulating the brain’s respiratory center in the medulla oblongata, located at the base of the brain. The medulla senses a rise in carbon dioxide and drop in oxygen levels in the blood and stimulates respiration. Respiratory stimulants work in the following ways:

• Caffeine: Caffeine inhibits the activity of an enzyme known as phosphodiesterase (PDE), which leads to an increase in the intracellular levels of a signaling molecule known as cyclic adenosine monophosphate (cAMP). An increase in medullary cAMP levels enhances its sensitivity to carbon dioxide.
• Doxapram: Doxapram stimulates both central chemoreceptors located in the medulla and peripheral chemoreceptors in the carotid body, a sensory organ in the carotid artery. Chemoreceptors are specialized cells that sense oxygen and carbon dioxide levels in arterial blood and stimulate respiration.

Respiratory stimulants may be administered as:

• Oral tablets, capsules, lozenges, solutions
• Intravenous (IV) injections or infusions, intramuscular (IM) injections

Respiratory stimulants are used in the treatment of the following conditions:

FDA-approved:

• Chronic obstructive pulmonary disease associated with hypercapnia (high carbon dioxide level in the blood)
• Respiratory depression post-anesthesia
• Drug-induced central nervous system depression
• Fatigue and drowsiness
• Respiratory failure
• Neonatal apnea (cessation of breathing in newborn)

Off-label:

• As a stimulant diuretic

Side effects of respiratory stimulants may include the following:

• Pyrexia (fever)
• Flushing
• Sweating
• Pruritus (itching)
• Paresthesia (prickling sensation in the skin)
• Burning/hot sensation especially in the genitals and perineum
• Disorientation
• Hallucinations
• Insomnia
• Irritability
• Nervousness
• Dilation of pupils
• Involuntary movements
• Muscle spasticity (stiffness)
• Muscle fasciculations (twitches)
• Clonus (involuntary muscle contractions)
• Increased deep tendon reflexes
• Bilateral Babinski (a reflex that occurs when the sole is firmly stroked)
• Convulsions
• Restlessness
• Tremor
• Tinnitus (ringing in the ears)
• Dyspnea (shortness of breath)
• Cough
• Hyperventilation/tachypnea (abnormally rapid breathing)
• Rebound hypoventilation (shallow breathing)
• Laryngospasm (spasm of the vocal cords)
• Bronchospasm
• Hiccups
• Phlebitis (inflammation of a vein)
• Variations in heart rate
• Arrhythmia (irregular heartbeat)
• Tachycardia (rapid heartbeat)
• Palpitations
• Lowered T-wave in ECG reading
• Increase in blood pressure
• Urinary bladder stimulation with spontaneous voiding
• Urinary retention 
• Elevation of blood urea nitrogen (BUN)
• Albuminuria (excessive albumin in the urine)
• Hemolysis (destruction of red blood cells) with rapid IV infusion 
• Decrease in hemoglobin, hematocrit, or red blood cell count
• Decrease in white blood cells in patients with leukopenia
• Nausea
• Vomiting
• Diarrhea
• Withdrawal symptoms from caffeine discontinuation include:
  • Anxiety
  • Depression
  • Fatigue
  • Headache
  • Muscle tension
  • Nausea
  • Runny nose

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of respiratory stimulant drugs include:

• Cafcit
• caffeine
• Dopram
• doxapram
• NoDoz
• ReCharge
• Vivarin