Absorption Flashcards
(32 cards)
What is parenteral administration?
Parenteral administration is the medical term used to describe the administration of medications by injection/infusion.
What routes are included in parenteral administration?
- Intradermal
- Subcutaneous
- Intramuscular
- Intravenous
- Intrathecal
- Intra-arterial
What is extravascular administration?
- Drugs that are NOT administered via the parenteral routes, but administered by other routes. They have to cross several biological barriers to enter the systemic circulation. Including: Oral, rectal, transdermal,
- Inhaled, buccal, sublingual intranasal.
How is the stomach absorbed in absorption
What role and properties does the stomach have to aid absorption?
The stomach is the preparation for absorption and the site of disintegration and dissolution. Properties include:
o Protective mucous barrier – minimal absorption
o Acidic pH – as required for digestion
o Hydrolysis of “acid-labile” drugs
o Favours dissolution of weak bases
What role and properties does the colon have in absorption
The colon is a site for slower absorption
o Mucous lining
o No villi (lower surface area)
o Important for extent of absorption for some drugs
What role and properties does the small intestine have in absorption?
The small intestine is the primary site of absorption, some disintegration and dissolution (particularly enteric coated tablets).
o Large surface area
o Villi and microvilli
o No mucous barrier
o Highly vascularised organ
o pH 6.6. on average
o fluctuates between 6 to 7.5 along the small intestine
What is passive diffusion? what drugs does passive diffusion facour?
- Passive diffusion refers to the diffusion of drug from a region of high concentration (gastrointestinal tract) to one of low concentration (blood). This process does not require energy.
- Most common mechanism of absorption
- Favours small and lipophilic drugs
What is facilitated diffusion?
- Diffusion of drug molecules moving across a concentration gradient (from high concentration to low concentration). Involves specific carrier proteins on the cell membrane that form reversible associations with the drug molecules aiding their passage into the cell.
- Applies to drugs that have low lipid solubility and larger in size
- Operates without energy and does not transport against the concentration gradient.
What is active transport?
- Active transport involves using energy to move molecules against a concentration gradient into the blood from an area of low concentration to high concentration.
- Favours drugs that are structurally similar to endogenous substances and usually in the small intestine.
What is pinocytosis?
- This process involves large drug molecules that are engulfed by a cell via an endocytic process called pinocytosis. It invaginates the fluid and solutes, then fuses again to form a vesicle that transports the drug across the cell.
- This process involves energy
- Mainly used for large proteins and certain vitamins
What does the rate and extent of drug absorption depend on?
Its ability to dissolve in gastrointestinal fluid and its ability to move across the GI lining.
What is the rate-limiting step?
The rate limiting step is the slowest of the 2 properties that the rate and extent of drug absorption depend on.
What happens to weak acids and bases when they dissolve in the Gi tract?
When weak acids or bases dissolve in the GI tract, they dissociate and establish an equilibrium between their ionised (charged) and unionised form.
Which species of the drug is more water soluble? Ionised or unionised?
The ionised species of a drug is more water soluble than the unionised species which is more lipid soluble.
What is the extent of ionisation dependent on?
Extent of ionisation is dependent on the pKa of a drug and the pH of the medium in which the drug is dissolved.
How do weak acids act in acidic and less acidic enviroments?
- In acidic environments (e.g. the stomach (pH 1.2)), weak acids exist predominantly in their unionised form (more lipid soluble) and are able to cross the cell membrane more easily.
- In less acidic environments (e.g. the colon (pH 5.5-7)), the extent of ionisation of weak acids increases and less unionised drug is available to cross the cell membrane.
How do week bases act in acidic and less acidic environments?
- In less acidic environments (e.g. the colon (pH5.5-7)), the extent of ionisation of weak bases is reduced and more unionised drug is available to cross the cell membrane.
- In acidic environments (e.g. the stomach (pH 1.2), the extent of ionisation of weak bases increases and less unionised drug is available to cross the cell membrane.
How does food affect blood flow to splanchnic circulation?
A large network of capillaries and lymphatic vessels perfuse the duodenum and peritoneum, with the splanchnic circulation receiving approximately 28% of the cardiac output, which is increased after meals.
How does blood flow affect absorption?
A high degree of blood flow helps to maintain a concentration gradient (high concentration in gastrointestinal tract - > low concentration in plasma) to facilitate rapid passive diffusion.
What conditions decrease mesenteric blood flow, as well as absorption of drugs rectally and transdermally?
- Congestive heart failure, and shock states will decrease the rate that drugs are moved into systemic circulation, thereby decreasing the concentration gradient and rate of drug absorption.
How does total surface area affect absorption?
Increased total surface area helps to increase absorption of medications. Therefore most oral drugs are absorbed from the small intestine (particularly the duodenum) due to its unique anatomy that provide a huge area for drugs to passively diffuse.
What are the three mechanisms that increase the surface area of the small intestine?
- Folds of Kerckring: valve-like folds I the mucous membrane
- Vili: small projections from the folds
- Microvilli: even smaller projections that form a brush border
Which conditions can damage the villi and microvilli to decrease surface area and consequently absorption.
- Inflammatory bowel disease, coeliac disease, and gastroenteritis
