3: Basic Principles III

Question 1

Write the equation for the concentration in plasma of a drug.

Answer 1

Cp = Dose / Vd

Cp is concentration in plasma

Dose = mg or g

Vd = volume of distribution

Question 2

Total body water = _ L

Answer 2

40 L

Question 3

Factors affecting distribution:

1. _______ flow - drugs will distribute first to the more vascular organs with higher blood flow
2. Ability of drug to enter a _______ space - pH, binding, transport, lipid solubility, etc.
3. _______ after administration - equilibrium with various compartments may take a long time to achieve
4. _______ - drug may have to distribute from initial compartments to the target tissue
5. _______ 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

Answer 3

Factors affecting distribution:

1. Blood flow - drugs will distribute first to the more vascular organs with higher blood flow
2. Ability of drug to enter a fluid space - pH, binding, transport, lipid solubility, etc.
3. Time after administration - equilibrium with various compartments may take a long time to achieve
4. Redistribution - drug may have to distribute from initial compartments to the target tissue
5. 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

Question 4

Placenta has no barrier to drugs that are < _______ in molecular weight or _______ soluble. Fetal liver and kidney are immature. See PDR and other references

Answer 4

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

Question 5

_______ is an agent or factor that causes malformation of an embryo.

Answer 5

Teratogen is an agent or factor that causes malformation of an embryo.

Question 6

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.

Answer 6

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.

Question 7

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

Answer 7

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

Question 8

When there is a weak acid overdose we _______ the pH.

When there is a weak base overdose we _______ the pH.

Answer 8

When there is a weak acid overdose we increase the pH.

When there is a weak base overdose we decrease the pH.

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

Plasma = _______ liter

Interstitial fluid = _______ liter

Intracellular fluid = _______ liter

Answer 11

Plasma = 3 liter

Interstitial fluid = 9 liter

Intracellular fluid = 28 liter

Question 12

So extracellular fluid = _L = Plasma _ + Interstitial fluid _L

Answer 12

So extracellular fluid = 12L = Plasma 3 + Interstitial fluid 9L