Group 8/21/19 Flashcards
(134 cards)
Learning objectives
- Pharmacokinetics: the dynamics of drug metabolism, excretion, and clearance (finished Goodman and Gilman’s Ch2)
- Anatomy of the upper limb and chest (muscles, tendons, nerves, bone)
- Anatomy of brachial plexus
what polarity class must drugs be before elimination and why?
drugs must be metabolized into more hydrophilic metabolites in order to be eliminated from the renal system; lipophilic elements will not pass readily into the urine
Drug-metabolizing reactions generally transform the drugs into polar, inactive metabolites before they’re excreted
what are the phase 1 reactions of biotransformation that can happen in the liver?*
oxidation, reduction, or hydrolytic reactions with cytochrome P-450. Usually yield slightly polar, water-soluble metabolites, that are often still active.
Geriatric patients will lose this phase first.
what are the phase 2 reactions of biotransformation that can happen in the liver?*
conjugations (Methylation, Glucuronidation, Acetylation, Sulfation) of the phase 1 product with a second molecule. Usually yields very polar, inactive metabolites (renally excreted)
Geriatric patients have More GAS, more phase 2 reactions
Patients who are slow acetylators have increased side effects from drugs because their metabolism is lower
prodrugs definition
pharmacologically inactive compounds that are converted to their active forms by metabolism. Usually requires an ester hydrolysis reaction or amide linkage.
what is the most important organ for excreting drugs and their metabolites?
kidneys
what are the 3 processes of excretion of drugs and metabolites in the urine?
glomerular filtration, active tubular secretion, and passive tubular resorption
where do drugs enter during glomerular filtration, what influences how quickly they are filtered?
- drug enters the tubular lumen to be filtered
- only unbound drug is filtered, so filtration rate depends on extent of plasma binding of drug and glomerular filtration rate
where do drugs enter during active tubular secretion, what happens in this process?
- drug enters proximal renal tubule
- adds the drug to the tubular fluid from the peritubular network
what happens during passive tubular resorption?
- drugs from tubular lumen are resorbed back into systemic circuation
- nonionized forms (more permeable) of weak acids and bases undergo passive resorption, especially on distal tubule
how does the pH of the tubular urine influence excretion of the drugs?
when tubular urine is basic, weak acids are ionized and excreted faster
when tubular urine is acidic, less weak acids are ionized and less acids are excreted
opposite effect for basic drugs (basic drugs excreted slow with basic urine; fast with acidic urine)
what is enterohepatic recycling, and what is its effect?
transporters in the hepatocyte will secrete drugs and metabolites into bile, released into GI tract, reabsorbed into body
can prolong the effects of a drug or toxin
excretion by other routes
drugs can be excreted into sweat, saliva, and tears
how does the pH of milk influence what kind of drugs congregate in it?
milk is more acidic than plasma
basic compounds are more congregated there, does not influence entry of nonelectrolytes
excretion/elimination definition
elimination is a measurement of the amount of a substance removed from systemic circulation per unit time (e.g., mg/min, μg/min, etc.).
clearance definition
clearance is the volume of plasma in systemic circulation from which a substance is completely removed per unit time, measured in L/h or mL/min
equation rate of elimination/C takes into account the concentration of unbound drug
hepatic clearance
drug has a near unity extraction ratio from the liver to the bile, and it has a low concentration.
Elimination rate is limited by the rate the drug can be transported by blood in liver.
how does the drug metabolizing capacity of an eliminating organ relate to how quickly it extracts a drug?
If the organ can metabolize the drug quickly, clearance relates to the organ’s blood flow. If the drug is metabolized slowly, it’s cleared proportionally to the unbound fraction of the drug in the blood and the drug’s intrinsic clearance
renal clearance and factors that affect it
extracts the drug to the urine. Filtration rate of the drug depends on volume of fluid passing through, unbound drug concentration, drug’s intrinsic clearance. Reabsorption depends on protein binding, blood flow, and the state of the nephrons
rates of distribution
the drug starts in the central volume, which includes plasma and tissue reservoirs
These are in equilibrium, and the drug distributes to a final volume
concentrations in the plasma decrease in a log-linear fashion
if blood flow to an organ is affected, it affects the rate of distribution to that organ
compartments in the multicompartment model of drug disposition
central compartment includes highly perfused lean organs like heart, brain, liver, lung, kidneys
final compartment are slowly perfused tissues such as muscle, skin, fat and bone
terminal half life
can occur in drugs that have had prolonged dose or have a high concentration
drug goes beyond the central compartment to deep compartments, and equilibrate slowly from there. Once drug from central compartment gets cleared, then this will start to equilibrate and diffuse out, prolonging half life
what are nonlinear pharmacokinetics and what are they caused by?
nonlinear caused by changes in the parameters, like the clearance, volume of distribution, or half life, depending on the dose or concentration of the drug
can be caused by saturation of protein binding, hepatic metabolism, or active renal transport of the drug
saturable protein binding, and how organs with a low vs high clearance-extraction ratio are affected
drug concentration may increase so that binding sites are occupied and unbound drug concentration increases
organs with low clearance-extraction ratio (eg liver) will cause V and CL to increase as drug concentration increases
organs with high clearance-extraction ratio will increase V and therefore increase the half life