3.4
Absorção de Medicamentos: Fatores que Afetam a Absorção Gastrointestinal
O processo de absorção oral de medicamentos pode ser influenciado por vários fatores. Medicamentos fracamente ácidos tendem a ser absorvidos mais faci…
A absorção de um medicamento administrado por via oral é influenciada por vários fatores.
Drogas fracamente ácidas são mais propensas a serem absorvidas pelo estômago, onde são predominantemente não ionizadas.
Em comparação, a absorção do intestino superior, que contém drogas ionizadas, pode ser baixa.
Na realidade, a camada mucosa do estômago dificulta a difusão. Sua área de superfície menor em comparação com o intestino reduz ainda mais a taxa de absorção do estômago.
As vilosidades intestinais fornecem uma área de superfície maior, o que, juntamente com um maior fluxo sanguíneo, leva a uma maior absorção do medicamento.
Se o alimento estiver no estômago, os medicamentos podem ser mal absorvidos, pois formam complexos com os constituintes dos alimentos.
Os alimentos também retardam o esvaziamento gástrico, ou seja, o movimento dos medicamentos para o intestino delgado, o que retarda a absorção intestinal.
O movimento rápido do conteúdo intestinal durante a diarreia retarda ainda mais a absorção do medicamento.
Além disso, o epitélio intestinal composto pelos transportadores de glicoproteína P geralmente bombeia as drogas de volta para o lúmen intestinal. Isso reduz a absorção do medicamento no sangue.
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Q1: Why is the small intestine a better site for drug absorption than the stomach?
The small intestine provides superior drug absorption due to its larger surface area created by intestinal villi, combined with higher blood flow. In contrast, the stomach has a smaller surface area and a thick mucous layer that hinders diffusion. These anatomical and physiological features make the intestine the primary site for drug absorption.
Q2: How does food in the stomach affect oral drug absorption?
Food interferes with drug absorption through two mechanisms: drugs form complexes with food constituents, reducing their bioavailability, and food delays gastric emptying, slowing the movement of drugs into the small intestine. This delayed transit further reduces the rate of intestinal absorption, ultimately decreasing overall drug absorption.
Q3: What role do P-glycoprotein transporters play in drug absorption?
P-glycoprotein transporters in the gut epithelium actively pump drugs back into the gut lumen, reducing their absorption into the bloodstream. This efflux mechanism acts as a barrier to drug absorption, limiting the amount of drug that enters systemic circulation from the gastrointestinal tract.
Q4: Why are weakly acidic drugs absorbed more readily from the stomach?
Weakly acidic drugs are predominantly nonionized in the stomach's acidic environment, allowing them to cross the stomach lining more easily through passive diffusion. In contrast, drugs in the upper intestine are often ionized, making them less able to penetrate the intestinal epithelium, resulting in lower absorption rates.
Q5: How does diarrhea impact drug absorption from the gastrointestinal tract?
Diarrhea accelerates the movement of gut contents through the gastrointestinal tract, reducing the time available for drug absorption. This rapid transit limits drug contact with the intestinal epithelium, resulting in decreased absorption and lower drug bioavailability in the bloodstream overall.
Q6: What is the relationship between surface area and drug absorption in the GI tract?
Surface area directly influences absorption rates: the intestine's larger surface area, enhanced by villi, supports greater drug absorption compared to the stomach's smaller surface. Combined with higher intestinal blood flow, this increased surface area facilitates more efficient drug uptake into systemic circulation.
Q7: How do ionization states of drugs affect their absorption at different GI sites?
Drug ionization state determines absorption efficiency at specific GI locations. Nonionized drugs, like weakly acidic drugs in the acidic stomach, cross membranes readily. Ionized drugs in the upper intestine have reduced membrane permeability, though the intestine's superior surface area and blood flow often compensate for lower ionization-based absorption.