Pharm of the Somatic Nervous system III

What is the apparent volume of distribution (Vd)?

The amount of body water that a drug will move into

If you have a Vd of 1L/kg what does that mean?

The drug will get everywhere in the body

What is the calculation to find Vd?

Dose(iv) / C0 (initial drug concentration)

What do we have to remember about our calculations of Vd?

1. It assumes distribution is instantaneous

2. Only approximated w/ IV dose

3. Lots of inter- and intra species variation

4. Doesn't indicate specific locations that the drug goes

What plasma protein do we typically see binding drugs?

Albumin due to nonspecific binding

A drug-protein complex will lead to what?

A bound inactive form of the drug

Only a ____ drug can interact w/ receptors?

Free

Plasma proteins make sure that?

The free concentration of a drug stays constant, (controls concentration gradient)

What MAY reduce protein binding meaning we should decrease the dosage of a drug?

Severe Hypoproteinemia

Combining drugs w/ high protein binding

Why might we have a problem with Combining drugs w/ high protein binding?

There will be more free drug in the system and if it can cause severe side effects it will increase those side effects

Total body water is roughly ____ of body weight?

60% will often be rounded to 1L/kg

Plasma concentration is typically ____ of extracellular fluid?

1/4th

If a drug has a Vd =2 what can we assume?

It is accumulating in a tissue, usually fat

A fat soluble drug like propofol will exist in higher concentrations where in an animal with a low fat content?

Higher concentration in the circulation

What locations do we have a difficult time getting blood to?

CNS

Prostate

Fetal tissue/ placenta

What is clearance?

Capacity of the body to remove a drug

Clearance is NOT a ____ but rather a _____?

NOT a rate,

An amount in a certain time

What two processes does clearance reflect?

Breakdown/metabolism

Excretion

Clearance does not reflect what?

The active breakdown products or loss of activity

Clearance of a drug is the sum of what?

All organs to remove a drug individually

Cl and Vd are the two ______ parameters?

Physiological pharmacokinetics

A 1/2 life is not a component of what?

Physiological pharmacokinetics, it is derived from this

What descries the kinetics of removal of most drugs?

First order elimination

What is first order elimination?

Constant fraction of drug eliminated per unit time (Exponential decay)

What is first order elimination dependent on?

Redistribution from peripheral to central compartemnt

What is half-life?

The time required to change the amount of drug in the body by 50%

Which drug has a shorter half life, Neostigmine, or Pyridostigmine?

Neostigmine

How do you calculate half life?

(0.7 x Vd) / CL

First order elimination tells ____ a drug is eliminated not ____?

How fast, not where or how

What is zero order elimination?

Constant amount of drug eliminated per unit time (linear)

When would we see a zero order elimination?

Usually in usage of high doses, or when a drug has high saturation

Zero order elimination usually gets rid of a drug _____ and doesn't have a ___?

Faster; half-life

Why is knowing the Vd, CL and T1/2 so important?

It determines the best choice of drug for each kind of pathology or condition that may be afflicting a patent

What is dose?

Amount of substance given to an individual

What is dosage?

The standard amount given to a population based on a physical parameter (mostly weight) that has desired effect in a POPULATION

What is toxicity?

The standard amount of substance based on a physical parameter that produces and adverse effect in a population

How many T 1/2 lives need to be done before a drug is eliminated from the body?

5

How many T 1/2 lives need to be done before a drug reaches a steady state?

5

Explain how to reach a steady state in the blood?

-Starting at a dose of 100ug/ml, half life 1 would move down to 50ug/ml.

- second administration of drug at this point would put drug levels at 150ug/ml and half life 2 would move it down now to 75ug/ml

- third administration of drug at would put it to 175 and the half life would be 88ug/ml

and so on until we get to the desired levels in the plasma of 100ug/ml

What does the final blood concentration at the steady state depend on?

Dose not time

What happens if you shorten the dosing interval?

a higher steady state concentration due to waiting less of a half life

What happens if you lengthen the dosing interval?

Taper, lowering the steady state by gradually decreasing the plasma level

What is a loading dose?

initial higher dose of a drug that may be given at the beginning of treatment to RAPIDLY achieve a therapeutic level (after first half life we are already at therapeutic level.