Disease affects Drug absorption Flashcards
Drug absorption can be influenced by changes in…
Gastric + intestinal motility
Surface area available for absorption
Altered physical + chemical properties of the intestinal luminal content
What contributes to the development of Crohn’s?
Immunological causes + genetics
Crohn’s can spread across entire intestine. Common for terminal ileum to be involved
Diarrhoea, abdominal pain, fever + weight loss
How does Crohn’s affect drug absorption?
The thickened bowel wall and strictures may significantly alter the bowel motility
Mucosal lesions may lead to changes in intestinal permeability
Involvement of specific intestinal areas (e.g., terminal ileum) may cause bile acid malabsorption and subsequent fat maldigestion
Coeliac disease is _____ of the _____
Caused by _______
What does coeliac impair in terms of absorption?
Atrophy
Small intestinal mucosa
Hypersensitivity to gluten
Impairs absorption of ALL nutrients, plus fat.
Because of fat impairment, lymphatic transport will be affected.
Elimination of wheat will restore everythig to normal.
_____ and a _____ frequently occurs as part of _____
The cause is accompanying infections and/or the AIDS virus itself that can damage the _____
Intestinal permeability in patients with AIDS enteropathy is _____ similar to coeliac disease
Despite _____ permeability, _____ total drug exposure (including anti-HIV drugs) is frequent in patients with AIDS
Diarrhoea + general wasting syndrome
AIDS
Intestinal
Increased
Intestinal
Reduced
Systemic diseases can alter intestinal absorption of drugs.
Give an example of a systemic disease that impairs drug absorption
Other than diabetes, name other diseases which can impair drug absorption
What can extensive intestinal resection cause? And how does this affect drug absorption?
Short bowel syndrome
Surgical removal of up to about 50% of the small intestine can be well tolerated (if treated correctly post-op) because remaining intestine can adapt and to absorb more nutrients
Resection of more than 70% of the small intestine results in severe malabsorption.
What are the 3 factors responsible for malabsorption in small-bowel resection?
Marked reduction of the absorptive surface
Gastric acid hypersecretion, resulting in pancreatic lipase inactivation and fat maldigestion
Reduction of bile acid pool below the amounts necessary for critical micellar concentration
What is altered absorption be due to?
Altered gastric pH
Chelation
Adsorption
Altered gastric emptying
Altered intestinal motility
Altered intestinal blood flow
Altered activity of epithelial transporters (will be discussed on the example of P-glycoprotein)
Altered intestinal CYP450 activity (will be discussed after metabolism-related interactions section)
How can altered absorption be due to altered pH?
Compounds that create an environment with specific pH may affect solubility + permeability of co-administered drugs
Effect of formulation: Didanosine is an antiretroviral compound that is acid labile and requires neutral to basic pH for absorption, therefore the formulation is buffered. Co-administered compounds that require acidic pH for dissolution (ketoconazole, itraconazole) will have reduced absorption
Effect of active compounds: Antacids, H2-antagonist and proton pump inhibitors all increase gastric pH. As a result dissolution of weak bases could be decreased and their absorption could be reduced: certain azoles, β-lactam antibiotics
How can absorption be altered due to chelation?
Drugs may form insoluble complexes in the GIT by chelation
Chelation involves formation of a ring structure between a metal ion and an organic molecule
This reduces absorption
How can absorption be altered due to adsorption?
Adsorption is a process of ion binding or hydrogen binding.
This interaction mostly occurs with drugs that are designed as adsorbents (such as cholestyramine that is designed to adsorb bile acids)
Cholestyramine reduce absorption of antibiotics. They should not be used together.
How can absorption be altered due to gastric emptying + intestinal motility?
Because the primary location of drug absorption is in the small intestine, changes in gastric emptying and intestinal motility may have significant effects on the rate and extent of the absorption
High fat meal or lipid-based formulation cause a delayed gastric emptying
Prolonged gastric retention can cause degradation of acid-labile compounds e.g. penicillin + erythromycin
How can absorption be altered due to gastric emptying + intestinal motility?
Intestinal blood flow can be modulated by vasoactive agents (agents that constrict or dilate blood vessels).
However, there is no evidence to date that this results in clinically significant drug interactions
