Adsorption and Distributio Flashcards
What affects drug absorption?
The physiochemical properties of a drug can determine diffusion and lipid and aqueous solubility: charge, size, polarity
What charge do drugs need to have to cross the lipid bilayer by passive diffusion?
They need to be uncharged or un-ionized. Because most drugs are weak acids and bases there ionization state depends on the ph of the environment
Variation in pH through the GI tract
Mouth: 7.4 acid drug 99.5% ionized basic 0.5 % ionized
Stomach: 1.4 basic drug is 100% ionized
Small intestine : 5.3 acid drug 40% ionized basic is 60% ionized ( most drugs absorbed in small intestine )
Factors that effect the ability of drug to pass membranes and enter the blood vessel lumen
Structure of barriers (epidermal/ mucosal layer, capillary structure)
conc gradient
Surface area
Residence time at membrane
First pass metabolism (broken down in the liver first )
Bioavailability (one way of measuring drug absorption)
Bioavailability (F) is a measure of the extent and rate at which the active ingredient of a drug enters the bloodstream and reaches its site of action.
* It is usually expressed as a percentage or fraction of the drug dose.
* Absolute bioavailability compares the drug’s absorption after oral administration to its absorption when given intravenously (IV), where the drug directly enters the bloodstream.
A higher bioavailability means more of the drug reaches the bloodstream and can be effective, while lower bioavailability might mean less drug reaches its target, potentially requiring higher doses.
tmax and Cmax (second way of measuring drug absorption)
Measure from plasma conc and time course Tmax is time to peak Cmax is maximum concentration
Absorption variation across life span
① newborn gut not mature.
② intestinal transit time short in newborn and long in elderly
③ gastric ph reduced in newborn and elderly
④ not all routes practical e.g. Elderly swallowing pills
Plasma protein binding ( basics what is it)
Plasma proteins such as serum albumin act as carriers for poorly soluble metabolites . Drugs bind to be carried around the body. Binding is reversible. Binding interaction strongly influence pharmacokinetics
How does binding work?
Binding removes drug from free solution, so the drug can no longer diffuse into surrounding tissue. Protiens act like a sink increasing amount of drug in the blood. Aids absorption and transportation and slows elimination. The high affinity can sometimes restrict blood to plasma. Saturation of binding proteins can lead to non linear dosage and competition leads to drug interactions.
How does bound/ free drug is in dynamic
equilibrium exist
Common Binding Site: Drug A and Drug B compete for the same site on plasma protein.
Thermodynamic Motion: Molecules move randomly due to thermal energy, causing chance collisions.
Electrostatic Forces: Electrostatic bindin g can be disrupted by thermal energy (random motion).
Binding Probability: 90% of drug bound means 90% of molecules are bound at any given time, with 10% unbound.
Blood brain barrier
Blood-Brain Barrier (BBB): A selective barrier that protects the brain.
Tight Junctions: Prevent substances from crossing between endothelial cells.
Pericytes & Glial Limitans: Extra layers adding protection.
Lipophilic/Transported Drugs: Only fat-soluble or actively transported drugs can access the brain and cerebrospinal fluid.
Placenta
Placenta and Drug Transfer:
Drug Passage: Drugs must first enter the maternal blood and then cross into the fetal circulation, either by passive diffusion or active transport.
Teratogenic Risk: Drugs may cause harmful effects to the developing fetus, including teratogenic (birth defects) or embryotoxic (toxic to the embryo) effects.
Lipophilic Drugs: Fat-soluble (lipophilic) drugs can easily cross the placenta.
Plasma Protein Binding: Drugs that strongly bind to plasma proteins are less likely to cross the placenta efficiently.
Key Point: The placenta acts as a selective barrier, but many drugs still pass through, potentially affecting fetal development.
Breast milk
Alveolar apical cells form a tight-junction limited lipid barrier between capillaries and alveolar lumen
•Diffusion into milk therefore limited by lipophilicity and size
Adipose tissue (fat)
Located in skin, around organs, breasts, and bone marrow.composed of Adipocyte’s which is cells with large lipid filled vacuoles. lipid soluble drugs accumulate here.
How can drugs be distributed
Drug will be distributed throughout the body in different compartments:
•Extracellular fluid (plasma, interstitial fluid, lymph)
•Intracellular fluid (cell contents)
•Transcellular fluid (CSF, peritoneal, intraocular, synovial etc.)
•Fat
•Bound to protein
Vd volume of distribution
This is the theoretical volume of plasma that would accommodate total amount of drug.
Volumes of fluid compartment
•Plasma fluid≈ 3 litres
•Extracellular fluid ≈ 12 litres
•Total body water ≈ 40 litres
•Vd > 40 litres indicates some storage of drug in tissues
•Vd < 15 litres suggests drug is largely restricted to plasma and interstitial fluid
Variation of distributionacross lifespan
Body composition changes with age
•Higher fat:lean tissue ratio in infants
•Obesity increasing with age
•Relative volume of fluid compartments varies
•Vd tends to be higher in infants
•Pregnancy adds placental and breastmilk compartments
•Plasma protein synthesis in the liver declines with age
•Renal function affects tissue fluid volumes
