test 1 part 2 Flashcards
Absorption
• The transfer of a drug from the site of administration to the bloodstream
Rate of absorption depends on
- Environment
- Chemical characteristics of drug
- Route of administration
Absorption from the GI tract - oral cavity
- Slightly acidic
- Thin epithelium, high vascularity
- Bypasses hepatic metabolism (skips liver)
Absorption from the GI tract - stomach
• Folds increase surface area
• Very acidic
-some drugs can be absorbed from the stomach but not the main site
Absorption from the GI tract - small intestine
• Deep folds with villi and microvilli
-main site for absorption because of large surface area
Absorption from the GI tract - large intestine
• Little absorption throughout
• Rectum- useful site because bypasses hepatic metabolism - lower part of rectum bypasses liver
-secretes mucous
Passive Diffusion
-most common means for drugs to gain access to the body
• Concentration gradient is driving force
• Does not involve a carrier
• Not saturable
• Low structural specificity
• Major method of drug absorption
• 2 types (Aqueous and Lipid)
Aqueous Diffusion
• Water soluble drugs penetrate the cell membrane through aqueous channels or pores
Fick’s Law
Net diffusion ≈ Area for diffusion x Concentration gradient / Thickness of membrane
Lipid Diffusion
- Lipid soluble drugs readily move across most biologic membranes
- Soluble in the lipid bilayer of membranes
Facilitated Diffusion
- Passage into a cell through transmembrane carrier proteins
- Conformational changes allow passage
- High concentration to low concentration
- Does NOT require energy
- Saturable
- Inhibited by competitors for carrier protein
Active Transport
- Drugs that closely resemble naturally occurring metabolites are transported via carrier proteins in the membrane
- Energy dependent
- Can move against gradient
- Saturable
- Selective
- Competitively inhibited by other cotransported substances
Endocytosis & Exocytosis
- Transport of exceptionally large drugs across membranes
* Engulfment by membrane and transport into or out of cell by pinching off vesicle
Factors Influencing Absorption
- pH
- Blood flow
- Surface area
- Contact time
- P-glycoprotein
If a drug is ionized, why won’t it cross the lipid bilayer?
-an ionized drug forms a hydrophilic polar non-lipophilic molecule with water meaning it will not want to cross the lipid bilayer
the neutral form of a weak acid is
protonated
-weak base is not
acidic drugs are more soluble at what pH
- more acidic pH
- pushes equation to the left (HA)= non-ionized form
a weak base in an acidic environment
-cannot be absorbed
lower the pKa
- more acidic the drug is
- BH+
- HA favored
pH > pKa
B and A- favored
-deprotonated forms predominate
Manipulation of drug excretion by the kidney
- ”Trap” drugs in the urine by ionizing them
- Acidic drugs excreted faster in alkaline urine
- Basic drugs excreted faster in acidic urine
acidic drugs excreted faster in what urine pH
alkaline urine
fluids that can trap drugs
• Stomach • Small intestine • Breast milk • Aqueous humor • Vaginal and prostatic secretions -urine
Blood Flow affecting absorption rate
- Blood flow to absorption site increases absorption
* Intestines receive more flow than stomach so absorption from intestine is favored
Surface Area influencing absorption
- Increase in total surface area for absorption increases efficiency
- Intestines have brush border which increases surface area 1000 fold to that of the stomach
Contact time influencing absorption
- Stomach => Slow emptying = decreased absorption
* Intestine => Slow transit time = enhanced absorption
P-glycoprotein influencing absorption
- Pumps drugs out of the cells => Reduces drug absorption
* Transmembrane transporter protein
Bioavailability
how much drug can be absorbed into your bloodstream after any route of administration
- 100 mg tablet
- 70 mg unchanged
- 70% bioavailability
Determination of Bioavailability
• % Bioavailability= (AUC oral administration / AUC IV administration) X 100
Bioavailability: First-pass Hepatic Metabolism
- Drugs absorbed from GI tract enter portal circulation before entering systemic circulation
- Liver or gut metabolize drug to varying degrees
- Drugs with high first-pass metabolism must be given in doses large enough to ensure enough active drug remains
Bioavailability: Solubility of the Drug
• Hydrophilic drugs poorly absorbed
• Extremely lipophilic drugs poorly absorbed
• IDEAL: largely lipophilic, yet have some solubility in aqueous solutions
-THIS IS WHY MOST DRUGS ARE WEAK ACIDS OR WEAK BASES
Bioavailability: Chemical Instability
- pH of stomach can cause instability
* Degradative enzymes in GI tract
Bioavailability: Nature of Drug Formulation
- Particle size
- Salt form
- Crystal polymorphism
- Enteric coatings
- Binders and dispersing agents
Bioequivalence
• A way to compare two drug formulations
• Comparable
- Bioavailability
- Time to peak blood concentration
Pharmaceutical Equivalence
- Bioequivalent
- Same amount of active drug
- Same dosage
- Same route of administration
Therapeutic Equivalence
• Bioequivalent • Pharmaceutically equivalent • Comparable - Clinical effect - Safety profile GENERIC DRUGS
