Exam 3- Pharam - Section 1 Flashcards
Study of drug movement of drugs in the body across biological membranes from the time of absorption until elimination
Drug deposition
4 stages of drug deposition
1) Absorption
2) Distribution
3) Biotransformation (Metabolism)
4) Excretion
Factors affecting the deposition of drugs:
- biological cell membranes
- concentration gradient
- pump mechanism
- site of admin
- total body water
- plasma protein binding
- disease
Properties of a cell membrane:
- phospholipid bilateral
- membrane proteins
- cell junctions (gap, tight)
- aqueous pores
4 Mechanisms of transport across a membrane
1) Passive diffusion
2) Facilitated diffusion
3) Active Transport
4) Pinocytosis
Mechanism:
- moves down conc. Gradient
- NO energy required
- most common form
Passive Diffusion
3 Mechanisms of passive diffusion
- Transmembrane
- Paracellular
- Simple
Transmembrane passive diffusion
-movement by passive diffusion through aqueous protein channels in the cell membrane
Paracellular mechanism of passive diffusion
- movement via filtration through intracellular aqueous pores
- tissues that have barrier mechanism have tight intracellular junctions
Simple mechanism of Passive diffusion
- movement through lipid membrane
- majority of drugs move through the body via this route
Mechanism:
- moves down concentration gradient
- requires a carrier
- NO energy required
- Saturable
Facilitated diffusion
Example of facilitated diffusion
Glucose transport in muscle
Mechanism:
- Moves uphill Low-High
- Requires energy (ATP)
- requires a carrier
- selectivity
- saturable
- competitive inhibitions by co-transported compounds
Active transport
2 classifications of active transport
- Primary
- Secondary
Primary Active Transport
- Na+/ K+ ATPase
- transport pump
- Most abundant active transport pump in the body
Secondary Active Transport
- Na+ dependent glucose transporter in renal tubules
- Na+ transported, glucose is hitch hiker
- Glucose sized keyhole next to Na+ port
Pinocytosis
- endocytosis or “cell drinking”
- drug dissolved in water
- can be toxic
Example of Pinocytosis
Sequestration of aminoglycoside antibiotics (amikacin, gentamicin) in renal tubules
**can cause renal damage and can be renal toxins
Factors affecting Simple Diffusion
1) concentration gradient
2) lipid solubility
3) degree of ionization
Drugs move across membranes from high to low “down hill”
Concentration gradient
Lipid solubility
- lipid membrane limits diffusion
- need to be lipophilic to enter lipid portion
- **higher lipid solubility of the drug= faster crossing cell membranes
- non-lipid solvable drugs are more dependent on molecular size
Degree of Ionization
- drugs cross bio membrane in non-ionized form (more lipid solvable form)
- Rate of diffusion depends on degree of ionization
What does the degree of ionization depends on?
- pH of the drug
- pKa of the drug
- ph of the environment in vivo
______ is the pH of a drug at which 50% of the drug is ionized and 50% is non-ionized
pKa
Weak acids are more ionized in __________ solutions.
Alkaline
Weak bases are more ionized in ________ solutions
Acidic
_________ is a proton donor, and contributes h+ to a solution
Acid
_______is a proton acceptor and binds or buffers H+ in a solution
Base
What is the most abundant and most important buffer system?
Bicarbonate - carbonic acid buffer system
CO2 + H2O H2CO3 HCO3- + H+
The Ubiquitous Equation
Non-carbonate buffers
- Proteins
- Phosphates
- Ammonia
The buffer system for Intracellular fluid (ICF)
Phosphate + Protein (mostly Hgb) > carbonic acid
The buffer system for Interstitium fluid?
Carbonic acid > protein > phosphate
What is the buffer system for Cerebrospinal (CSF) ?
Carbonic acid
What is the buffer system for Renal tubular filtrate?
Carbonic acid > phosphate > Ammonia
The buffer system for plasma (intravascular) fluid?
Carbonic acid > phosphate > protein
