Caffeine exerts its effects through multiple pathways:

1. Adenosine Receptor Antagonism:
   • Blocks adenosine A₁ and A_2A receptors in the brain, preventing adenosine-induced sedation and vasodilation (Lippincott).
   • Increases dopamine and norepinephrine release, enhancing alertness and cognitive function (Lange).
2. Phosphodiesterase Inhibition:
   • Inhibits phosphodiesterase enzymes, elevating cyclic AMP (cAMP) levels, though this effect is minimal in humans at typical doses (BNF).
3. Calcium Mobilization:
   • Enhances intracellular calcium release in muscle cells, contributing to mild bronchodilation and cardiac stimulation (Lippincott).

Caffeine is used for:

1. Neonatal Apnea:
   • Caffeine citrate is FDA-approved to treat apnea of prematurity by stimulating respiratory drive (BNF).
2. Analgesic Adjuvant:
   • Enhances the efficacy of pain relievers (e.g., paracetamol, NSAIDs) in migraine and tension headache formulations (Lange).
3. Alertness and Fatigue Reduction:
   • OTC tablets or beverages to combat drowsiness (e.g., shift work, driving).
4. Off-Label Uses:
   • Investigated for cognitive enhancement, asthma (bronchodilation), and weight loss (Lippincott).

Dosage varies by indication and formulation:

Neonatal Apnea (Caffeine Citrate):

• Loading Dose: 20 mg/kg IV or orally.
• Maintenance Dose: 5–10 mg/kg/day (BNF).

Adults (Alertness/Fatigue):

• OTC Tablets: 100–200 mg every 3–4 hours, not exceeding 400 mg/day (Lippincott).

Combination Analgesics:

• Often combined with 100–130 mg caffeine per dose (e.g., Excedrin®).

Caffeine is generally safe in moderation but may cause:

Common:

• Insomnia, restlessness, or anxiety.
• Gastrointestinal upset (nausea, acid reflux).
• Tachycardia or palpitations.

Severe (High Doses):

• Arrhythmias, hypertension, or seizures.
• Caffeine Toxicity: Symptoms include vomiting, hallucinations, and metabolic acidosis (Lange).

Before using caffeine, consider:

• Cardiovascular Conditions: Avoid in uncontrolled hypertension or arrhythmias (BNF).
• Psychiatric Disorders: May exacerbate anxiety or insomnia.
• Pregnancy: Limit to ≤200 mg/day; high doses linked to miscarriage (BNF Category: C).
• Metabolism: CYP1A2 enzyme polymorphisms affect clearance; slow metabolizers are at higher risk of toxicity (Lange).

Caffeine interacts with:

1. Stimulants (e.g., amphetamines):
   • Additive CNS stimulation, increasing arrhythmia risk.
2. MAO Inhibitors (e.g., phenelzine):
   • May cause hypertensive crises (Lippincott).
3. Quinolone Antibiotics (e.g., ciprofloxacin):
   • Inhibit CYP1A2, increasing caffeine levels (BNF).
4. Theophylline:
   • Synergistic toxicity (both are methylxanthines).
5. Oral Contraceptives:
   • Reduce caffeine metabolism, prolonging its effects (Lange).

Generic Names in Pharmacy

• Caffeine (active ingredient)
• Caffeine citrate (used in neonatal apnea)
• Common brand names: NoDoz®, Vivarin®, Cafcit® (IV formulation)