3: Basic Principles III Flashcards
Write the equation for the concentration in plasma of a drug.
Cp = Dose / Vd
Cp is concentration in plasma
Dose = mg or g
Vd = volume of distribution
Total body water = _ L
40 L
Factors affecting distribution:
- _______ flow - drugs will distribute first to the more vascular organs with higher blood flow
- Ability of drug to enter a _______ space - pH, binding, transport, lipid solubility, etc.
- _______ after administration - equilibrium with various compartments may take a long time to achieve
- _______ - drug may have to distribute from initial compartments to the target tissue
- _______ of the patient - Vd can vary with the size of the patient - many drugs are dosed on the basis of weight or body surface area, especially in Pediatrics or chemotherapy
Factors affecting distribution:
- Blood flow - drugs will distribute first to the more vascular organs with higher blood flow
- Ability of drug to enter a fluid space - pH, binding, transport, lipid solubility, etc.
- Time after administration - equilibrium with various compartments may take a long time to achieve
- Redistribution - drug may have to distribute from initial compartments to the target tissue
- Size of the patient - Vd can vary with the size of the patient - many drugs are dosed on the basis of weight or body surface area, especially in Pediatrics or chemotherapy
Placenta has no barrier to drugs that are < _______ in molecular weight or _______ soluble. Fetal liver and kidney are immature. See PDR and other references
Placenta has no barrier to drugs that are < 1,000 in molecular weight or lipid soluble. Fetal liver and kidney are immature. See PDR and other references
_______ is an agent or factor that causes malformation of an embryo.
Teratogen is an agent or factor that causes malformation of an embryo.
Teratogenic effects - especially in _______ trimester, abnormal tissue differentiation Toxic effects - may be chronic or acute:
_______ - addiction, birth weight, specific organ abnormalities
_______ - respiratory depression, hyperbilirubinemia, vascular problems
Avoid unnecessary drugs during pregnancy Use time tested drugs when necessary.
Teratogenic effects - especially in first trimester, abnormal tissue differentiation Toxic effects - may be chronic or acute:
Chronic - addiction, birth weight, specific organ abnormalities
Acute - respiratory depression, hyperbilirubinemia, vascular problems
Avoid unnecessary drugs during pregnancy Use time tested drugs when necessary.
Blood brain barrier - an anatomical protective barrier, created by the existence of “tight junctions” between the capillary _______ cells and also between the choroid plexus cells in the ventricles.
To enter the CNS a drug must be _______ soluble or transported by a _______ mediated mechanism. It prevents drugs from freely entering the brain. Hence only lipid soluble drugs can diffuse from capillary into brain—charged forms _______ enter.
Consequences:
Can affect apparent drug potency
May need to use lipid soluble _______ of the active drug
Will create special problems in treating _______ of lipid soluble or electrolyte drugs
May necessitate the direct _______ of certain drugs into the CNS
Blood brain barrier - an anatomical protective barrier, created by the existence of “tight junctions” between the capillary endothelial cells and also between the choroid plexus cells in the ventricles.
To enter the CNS a drug must be lipid soluble or transported by a carrier mediated mechanism. It prevents drugs from freely entering the brain. Hence only lipid soluble drugs can diffuse from capillary into brain—charged forms cannot enter.
Consequences:
Can affect apparent drug potency
May need to use lipid soluble precursors of the active drug
Will create special problems in treating overdoses of lipid soluble or electrolyte drugs
May necessitate the direct injection of certain drugs into the CNS
When there is a weak acid overdose we _______ the pH.
When there is a weak base overdose we _______ the pH.
When there is a weak acid overdose we increase the pH.
When there is a weak base overdose we decrease the pH.
Protein binding of drugs can change the apparent Vd (remember only free drug interacts with receptor):
_______ if tissue binding occurs
_______ if plasma protein binding occurs
Protein binding of drugs can change the apparent Vd (remember only free drug interacts with receptor):
larger if tissue binding occurs
smaller if plasma protein binding occurs
Drug storage: may need to fill the storage sites before enough free drug is available to interact with receptor - eg: _______ dose.
_______ term - protein binding
_______ term - lipid binding or bone
Drug storage: may need to fill the storage sites before enough free drug is available to interact with receptor - eg: loading dose.
Short term - protein binding
Long term - lipid binding or bone
Plasma = _______ liter
Interstitial fluid = _______ liter
Intracellular fluid = _______ liter
Plasma = 3 liter
Interstitial fluid = 9 liter
Intracellular fluid = 28 liter
So extracellular fluid = _L = Plasma _ + Interstitial fluid _L
So extracellular fluid = 12L = Plasma 3 + Interstitial fluid 9L