Pharm 3. Flashcards by Abbey Phelps

What volume is the plasma approximately?

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What volume is the interstitial fluid approximately?

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If a drug can cross the capillary membrane, what is the total volume it is in?

12L

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What volume is the intracellular fluid?

28L

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If a drug can cross the cells membrane, what is the total volume it is in?

40L

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What is the equation for volume of distribution of a drug?

Vd = dose / Cp (concentration in plasma)

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If the volume of distribution is large, what does that say about the drug?

It is dissolved over more body fluid

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How can you find the volume of distribution using liters and kg?

Vd = L / Kg

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How are doses for average adults determined?

established in volunteer trials - standard doses vs. weight based vs BSA

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How are doses for pediatrics determined?

weight based dosing (mg/Kg)

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What is the effect of protein binding a drug?

can be stuck in plasma - may need a loading dose Vd = 3L

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What is the effect of high degree of tissue binding

High apparent Vd > 40L

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plasma volume

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total Vd

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What are the factors affecting distribution?

blood flow (distribute first to vascular organs), ability of drug to enter fluid space (pH, binding, transport, lipid, etc), time after administration, redistribution, size of patient

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What is the special consideration for distribution with the placenta?

placenta has no barrier to drugs that are

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blood brain barrier

anatomical protective barrier - created by existence of tight junctions between capillary endothelial cells and the choroid plexus cells in ventricles

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How does a drug enter the CNS?

lipid soluble or transported by a carrier mediated mechanism

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What are the consequences of the BBB?

can affect apparent drug potency, may need lipid soluble precursors of active drug (dopa-dopamine), will create special problems in treating overdoses, may necessitate the direct injection of certain drugs into CNS

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What will increasing the plasma pH produce in the brain?

shift of weak acid drug from brain to plasma

What will decreasing the plasma pH produce in the brain?

shift of weak base drug from brain to plasma

What effect does protein binding have on apparent Vd?

becomes larger if tissue binding occurs and smaller if plasma protein binding occurs

What effect does protein binding have on the physiologic system?

can result in unexpected drug toxicity - because act as reservoirs of active drugs - if a second drug is introduced that has a higher affinity for the same plasma protein than the first drug, this will cause toxicity of the first drug

loading dose

may need to fill the storage sites before enough free drug is available to interact with receptor

short term drug storage

protein binding

long term drug storage

lipid binding or bone

drug displacement = ?

more free drug at receptor = greater pharmacologic response

What are the purposes of biotransformation?

1. drug detoxification 2. prepare drug for excretion

How is a drug prepared for excretion?

1. make drug larger 2. add positive or negative charges 3. make drug more water soluble

What are the sites of biotransformation?

liver esp. smooth ER, cytoplasm, and mitochondria. can happen anywhere else in the body as well

induction

increase metabolism of the primary drug or other drugs - might be observed as an increase in first pass metabolism

inhibition

use a drug to block the metabolism of another drug or endogenous compound

What is the most common metabolic transformation? Example?

drug oxidation (ex. ethanol -> acetaldehyde)

What are the components of hepatic mixed function oxidase system? (i don’t think this is important……)

1. NADPH (reducing agent) 2. cytochrome P450 reductase (lends electrons) 3. cytochrome P450 4. Mg++ 5. phospholipid 6. O2

What does the hepatic mixed function oxidase system usually metabolize?

lipid soluble drugs

What are P450 characteristics?

1. 12 P450 groups in humans both for toxic drugs and endogenous compounds 2. low specificity 3. large genetic variations 4. catalyze primarily oxidations but also some reductions

Why is the diversity of P450s important?

reduce the chance of inhibition

What is the P450 system influenced by?

disease factors (liver), age, sex, multiple drugs using same enzyme

drug reductions

add hydrogen or change the proportion of hydrogen in the molecule

drug hydrolysis

cleave a molecule by the addition of a water molecule

What are phase I reactions?

activities of drugs vs activities of metabolites - may be sufficient for excretion or may prepare the drug molecule for phase II

What are phase II reactions?

liver - conjugation - synthesize a new molecule by combining the drug or metabolic product of phase I with a molecule provided by the cell. resulting molecule is larger, charged, water soluble, inactive

What do hepatic microsomal enzymes do?

induction (increase metabolism), inhibition (decrease metabolism), saturation

What do non-microsomal enzymes do?

inhibition ONLY, saturation

When do enzyme systems have a rate limiting step in the clearance of drug from plasma?

1. when metabolism is more important than renal elimination 2. “rate limiting step” for clearance when enzyme is relatively slow

What is the equation for the velocity of metabolism?

V = Vmax [D] / Km + [D] D = drug concentration

If D

efficient enzyme systems = first order ( a proportion of drug is being metabolized per unit of time no matter concentration

If D >> Km in the velocity of metabolism equation then……

inefficient enzyme systems (V = Vmax) - zero order - system is saturated, overwhelmed. only metabolizing an amount as opposed to a proportion