Test 1 part III Flashcards
what are the 2 categories of selectivity
- beneficial/therapeutic effects
- toxic/adverse effects
due to drug selectivity you should administer the ______________ dose that produces an acceptable benefit
lowest
due to selectivity of drugs you should consider attacking receptors in different parts of the body to ________________ and ____________
achieve a more therapeutic effect; less toxic benefit
what are the 5 basic mechanisms for transmembrane signaling
- lipid soluble chemical signal (ligand) passively diffuses through the membrane and acts on intracellular receptor
- signal binds to extracellular portion of transmembrane protein and activates enzyme activity on the cytoplasmic side
- signal binds to extracellular portion of a transmembrane receptor that is bound to a separate protein (cytoplasmic side) –> signal
- signal binds to and directly opens an ion channel d/t ion shift
- signal binds to a cell surface receptor linked to an effector enzyme by a G-protein
transmembrane signaling that is done through signal binding extracellularly to transmembrane protein and activates enzymatic activity on the cytoplasmic side is often limited by _______________
down-regulation
what are the common 2ndary messengers used with G-protein signal transduction
cAMP
IP3
cGMP
what is the function of the secondary messenger in signal tranduction of G-coupled protein being IP3 (inositol -1,4,5-triphosphate)
Ca2 release
can work with or against cAMP
what is the function of cAMP as the secondary messenger in signal transduction with G protein
- mobilization of stored energy
- conservation of water
- Ca2+ homeostasis
- increased HR and contraction of the heart
- regulates the production of adrenal and sex steroids
- relaxation of smooth muscle`
what is the function of cGMP as the seondary messenger in signal tranduction with Gprotein
relaxation of VASCULAR smooth muscle
what are the two principle functions of secondary messengers in signal transduction
- amplification
- flexible regulation
________________ is the attachment of a phosphoryl group to an amino acid during signal transduction (from a secondary messenger) that powerfully enhances the signal by recording a molecular memory that the pathway has been activated
amplification
_________________ is the part of signal transduction where 2ndary messengers use the presence or absence of particular kinases or kinase substrates to produce different effects in different cell types
flexible regulation
_______________ is also called cytosol or cytoplasmic mixture
intracellular volume
intracellular volume accounts for _________ of total body water; and extracellular fluid accounts for ___________ of total body water
2/3; 1/3
_________________ accounts for 60-65% of total body water
intracellular volume
what are the components of extracellular fluid volume
plasma volume and interstitial volume
__________________ is your intravascular fluid that is 95% water.
plasma volume
what are the contents of plasma volume
95% water
also contains dissolved proteins, gluocse, clotting factors, electrolytes, hormones, and CO2
_________________ is described as the fluid around the tissue cells
interstitial volume
fluid that accumulates in interstitial spaces = ________________
edema
drugs administered IV are distributed to the __________________ compartment then redistributed to the __________________ compartment; then to the ______________________ compartment for elimination
central; peripheral; central
what is the formula for volume of distribution
Vd = amount of drug in body at equilibrium before elimination starts / plasma concentration of drug
____________ relates the amount of drug in the body to the concentration of drug in the blood
volume of distribution
what are the characteristics/properties of drugs with a small volume of distribution (Vd)
- bind to plasma binding proteins
- poor lipid solubility (hydrophillic)
- highly ionized
- faster elimination
properties of drugs with large volume of distribution (Vd)
- unbound
- highly lipid soluble (lipophillic)
- non-ionized
- drug diffuses into tissues (low plasma concentration)
- long terminal half life
what are the mechanisms of tissue permeation (i.e. drug absorption)
- aqueous diffusion
- lipid diffusion
- active and facilitated transport
- endo/exocytosis
what characteristics must a drug possess to permeate to the tissues via aqueous diffusion
small molecule, unbound, neutrally charged, and hydrophillic
tissue permeation through aqueous diffusion is drive by the ________________, but the process is governed by __________________
concentration gradient; Fick’s law of diffusion
tissue permeation through the cell via passive diffusion down the concentration gradient describes which mechanism
lipid diffusion
which method/mechanism of tissue permeation utilizes special carriers fixed in the cell to move the drug molecules against the concentration gradient
active transport
which method/mechanism of tissue permeation utilizes special carriers fixed in the cell to move the drug molecule through the cell with the concentration gradient
facilitated diffusion
which method/mechanism of tissue permeation utilizes transport proteins to move the drug molecule through the cell
endocytosis/exocytosis
the larger (via molecular weight) a drug molecule is, the ________________ it is absorbed
slower
the more lipid soluble a drug is the ___________ it is absorbed
faster
as molecular weight of different insulin preparations increases, their ___________ also increases
onset
a drug needs a molecular weight of at least ______________ for good receptor binding; but a MW > ____________, does not diffuse easily through the body
100; 1000
ionization = lipid _________________
INsolubility
a drug in its lipid soluble form will be significantly ________________ via passive diffusion during passage down the renal tubule. Thus, the drug will NOT be ________________
reabsorbed; eliminated
under normal urine pH conditions of 6.0, what drug would be more easily EXCRETED, a weak acid or a weak base ?
weak base
weak acids are hydrogen ________________ ,and weak bases are hydrogen ____________
donors; acceptors
muscle relaxants are a quaternary amine (4 C + 1 H), this makes them permanently charged (i.e. ionized), meaning they are lipid ______________
insoluble
what is the single most important factor for determining drug concentrations
clearance
the higher the therapeutic index, the ______________ the drug
safer
the clinically acceptable risk of toxicity (from a drug) depends on what factor?
the severity of the dz
__________________ theoretical volume of plasma that is 100% cleared of a drug in a given unit of time
clearance
what are the units clearance is measured in
mL/min
most drugs are eliminated via _______________________
first order kinetics
_______________ is a constant fraction of the drug eliminated per unit of time
first order kinetics
_______________ is a constant amount of drug eliminated per unit of time
zero order kinetics
clearance is influenced by what factors?
drug dose
organ blood flow
liver and kidney function
