Do medications begin to get absorbed in the mouth?

Oral Medication Absorption in the Mouth

Yes, certain medications do begin absorption in the mouth, particularly through the sublingual (under the tongue) and buccal (cheek) mucosa, which allows drugs to bypass first-pass hepatic metabolism and enter the systemic circulation rapidly.

Sublingual and Buccal Absorption: Established Routes

The sublingual route is one of the earliest modes of administration for systemic drug delivery, avoiding first-pass metabolism and affording quick drug entry into the systemic circulation 1. This route has been successfully used to deliver various pharmacologically active agents, including cardiovascular drugs, analgesics, and peptides 1.

Key Medications That Utilize Oral Mucosal Absorption

Nitroglycerin is the classic example of sublingual absorption:

• Nitroglycerin is rapidly absorbed following sublingual administration, with mean peak plasma concentrations occurring at approximately 6-7 minutes post-dose 2
• The absolute bioavailability of sublingual nitroglycerin is approximately 40%, though this varies due to factors like sublingual hydration and mucosal metabolism 2
• Onset of vasodilatory effects occurs approximately 1-3 minutes after sublingual administration and reaches maximum by 5 minutes post-dose 2
• Effects persist for at least 25 minutes following administration 2

Aspirin also demonstrates buccal absorption:

• The ACC/AHA guidelines specifically note that "more rapid buccal absorption occurs with non-enteric-coated formulations" of aspirin 3
• This is why patients with suspected acute coronary syndrome are instructed to chew aspirin (162-325 mg) rather than swallow it whole 3
• Chewing aspirin produces rapid clinical antithrombotic effect through immediate and near-total inhibition of thromboxane A2 production 3

Anatomical Basis for Oral Absorption

The sublingual mucosa provides an effective absorption site because it:

• Has rich blood supply that allows direct entry into systemic circulation 1
• Bypasses hepatic first-pass metabolism, which would otherwise degrade many drugs 1
• Offers rapid drug entry compared to gastrointestinal absorption 1

Clinical Implications and Formulation Considerations

Buccal formulations can provide both rapid onset and sustained release:

• Buccal nitroglycerin combines possibilities of short-term treatment and extended prophylaxis 4
• Buccal administration provides rapid introduction directly into systemic circulation while sustained-release properties may confer protection for several hours 4
• Buccal and sublingual nitroglycerin have comparable effects in treating acute anginal attacks, with buccal forms showing advantages for prophylactic use 4, 5

Important formulation distinctions:

• Sustained-release and enteric-coated tablets are specifically designed not to be absorbed in the mouth and should be swallowed whole 3
• Medications in solid dosage forms (tablets) need to undergo disintegration and dissolution in the stomach, duodenum, and proximal jejunum before absorption 3
• Nitroglycerin sublingual tablets are intended for sublingual or buccal administration and should not be swallowed 2

Common Pitfalls

Factors that impair sublingual absorption:

• Tricyclic antidepressants and anticholinergic drugs may cause dry mouth and diminished salivary secretions, making dissolution of sublingual nitroglycerin difficult 2
• Increasing salivation with chewing gum or artificial saliva products may aid dissolution of sublingual medications 2
• Sublingual hydration status affects bioavailability 2

Medications to avoid sublingually:

• Sustained-release and delayed-release medications should be avoided in patients with short bowel syndrome and should not be crushed or dissolved sublingually 3
• Most oral medications are absorbed in the proximal jejunum, not the mouth, and require intact gastrointestinal function 3

Bottom Line

While most oral medications are designed for gastrointestinal absorption, specific formulations—particularly sublingual nitroglycerin and chewed non-enteric-coated aspirin—are intentionally designed to be absorbed through the oral mucosa for rapid systemic effect. This route is clinically significant for emergency cardiovascular medications where rapid onset is critical for patient outcomes.