T2 - Drug Absorption E2 Flashcards
Define drug absorption
Mass transfer that involves the movement of unchanged drug molecules from the site of absorption to the blood stream
How is the rate of absorption quantified?
Measured by rate and time parameters
Ka (absorption rate constant)
Tmax (time for the drug concentration to reach max in plasma
What is tlag?
The time it take for a drug to show signs of concentration after being administered
What is a formulation?
Drug and excipients become a drug in a dosage forms
What are the fates of dosage forms?
- Drug is not absorbed
- Drug release and dissolutes
What are the fates of drug release and dissolution?
- Drug decomposes, metabolized, bound, or excreted
- Drug is absorbed into systemic circulation
What is the critical step of drug absorption?
Drug molecules will cross the cell membrane by simple diffusion
What is the rate-limiting step of drug absorption?
Crossing epithelia or endothelia
What is absorption t1/2?
Time for 50% of the administered dose is absorbed
What is bioavailability?
The extent of absorption that is related to the magnitude of the drug reaching to systemic circulation
What are the factors that influence drug absorption?
- Type of dosage form formulation
- Physiochemical properties of the drug
- Physioanatomic condition of the host patient
- Pathologic conditions of the host patient
What are the types of dosage form that are used for absorption?
- Tablets
- Capsules
- Powders
- Suspensions
- Emulsions
- Solutions
What are physiochemical properties that affect drug absorption?
- Aqueous solubility
- Permeability (logP)
- Molecular weight
- Ionization constant (pKa)
- Solid state form
- Particle size
What is the physio-anatomic condition of the stomach that affects absorption?
- pH
- Emptying time
- Motility
- Degradation
What is the physio-anatomic condition of the intestine that affects absorption?
- pH
- Blood flow
- Degradation by enzymes and microflora
- Secretion by efflux transporter proteins
What are the pathologic condition of the patient that affect drug absorption?
- GI disease
- CV disease
- Hepatic disease
What factors of drug absorption that are linked to drug and product?
- Type of dosage formulation used
- Physicochemical properties of the drug
What factors of drug absorption that are linked to the patient?
- Physio-anatomic condition of the host patient
- Pathologic conditions of the host patient
How can excipients influence the drug release from its dosage form?
- Type and quality of excipients
- Manufacturing processes such as granulation method or compression force used for tablets can affect drug absorption
What dosage form must a drug be in order to be absorbed?
Solution at the site
Rank the order of drug forms rate of absorption from slowest to fastest?
Sustained release products → Enteric coated tablets → Coated tablets → Tablets → Capsules → Suspension → Emulsions → Solutions
Illustrate the type of forms and how they make their way in the blood
What is the most important physicochemical parameter for drug absorption?
Solubility
Describe the solubility differences between polar and nonpolar solutes?
Polar is more soluble in water
Describe the solubility differences between ionized and un
Ionized are more soluble in water
What happens if a drug has low aqueous solubility?
Poor oral absorption
What factor effects the solubility of weak acids and bases?
pH and pKa of drug
Why are small particles more soluble?
- Greater surface area
- Dissolve rapidly
- Faster absorption
Describe the solubility differences between amorphous and crystalline forms?
Amorphous dissolves faster being more favorable
Why are crystal polymorphs with greater absorption more favorable?
- Contain different dissolution rates
- Differences in absorption
Describe the differences between good aqueous solubility and good lipophilicity
Solubility has a faster dissolution rate
Lipophilicity has good permeation across the membrane
What makes lipophilicity permeable to cell membranes?
Biological membranes are lipoidal on nature and more permeable to lipid-soluble drugs
Describe the relationship between hydrophilicity and lipophilicity?
Log P increase, increases the rate of absorption
What are the exceptions of the log P rule?
Non-ionized form of a drug has a greater log P value than the ionized form; therefore, the non-ionized form in solution penetrates lipid membranes more rapidly than the ionized form.
What is gastric emptying?
The progression of the gastric contents toward the duodenum
How can gastric emptying rate be modified?
- Light physical activity stimulates emptying, vigorous exercise delays it
- Type, volume, viscosity, temperature of ingested food (liquid leaves faster than semisolids)
- Concurrent drug therapy with cholinergic drugs increase the rate of gastric emptying
How does controlling gastric emptying control the rate of drug absorption in the small intestine?
The stomach has a smaller membrane surface area relative to small intestine, the rate of drug absorption can be influenced by the rate at which the drug arrives at the small intestine
How can delays in gastric emptying affect the extent of drug absorption?
Increase, decrease, or ineffective
What processes in the GIT can reduce the extent of drug absorption after oral route administration?
- Gut wall metabolism of drugs by metabolizing enzymes
- Drug secretion by efflux transporters in the GI
- Drug degradation in the GI
What happened when drugs enter the GIT?
Suffer metabolism in the GI mucosal cells
What is the importance of enterocytes?
Located in the upper segment of the small intestine they express CYP-450 (CYP3A4) that limits the availability of drug molecules for absorption
What is an important role of drug metabolism in the small intestine?
Drug oxidation and conjunction mediated by CYP
What happens to a drug once it penetrates the intestinal membrane into the enterocyte’s cytoplasm?
Drug is subjected to a secretion process mediated by a transported that moves the drug back into the intestinal lumen
What mediates drug secretion into the intestinal lumen?
An active carrier-mediated efflux transporter proteins such as P-glycoprotein or multidrug resistance
What is the function P-glycoprotein?
- Limits drug absorption
- Expressed constitutively in the luminal membrane of small intestine enterocytes
What is microflora drug degradation?
Microorganisms are capable of carrying out drug degradations through enzyme-mediated metabolism (lyases, hydrolases, proteases, glycosidases, sulfatases)
What macromolecules are susceptible to degradation in the GI?
- Polypeptides
- Nicleotides
- Fatty acids
Describe the blood flow of the GIT?
GIT is supplied with networks of blood vessels and the rate of blood flow to GIT is 30% of the total cardiac output
What is aclorhydria?
The reduced gastric acid discharge and the simultaneous rise in gastric pH
What occurs when there is a pathological change in stomach emptying and GI permeability?
Abnormalities associated with celiac diseases, constipation, diarrhea, and vomiting
What is steatorrhea?
Impaired secretion of bile causing decreased lipophilic drug absorption resulting in fatty stool
How can pathologic conditions of a patient be altered?
- The population of intestinal drug metabolizing enzymes by enzyme induction or inhibition
- pH of the intestine
- Normal GI flora by using antibiotics
- Secretion of digestive enzymes
- Intestinal blood flow
- Hepatic diseases such as liver cirrhosis
How can cardiovascular diseases affect intestinal blood flow?
Pathological changes associated with CHF → decreased blood flow to GIT and gastric emptying rate and altered GI pH
