PK

Question 1

Describe pathway for drug absorption extravascularly vs intravascularly

Answer 1

Extravascular - from mouth to stomach where drug dissolves, then small intestine where most absorption occurs bc of large surface area and then into the liver through the portal bein

Intravascular - from IV into blood stream and then to the liver

the drugs move to the liver and get metabolized (first pass metabolism- where they are no longer able to exert their therapeutic effect, e.g lidocaine or we have to increase the dose a lot e.g. propranolol) or go through enterohepatic recycling (when the liver excretes drugs into the bile for reabsorption)

Question 2

Pharmacokinetics is

Answer 2

what the body does to the drug
ADME

Question 3

passive diffusion

Answer 3

movement of drug concentration from high to low (requires no energy) ex: from gut to blood

Question 4

active diffusion

Answer 4

movement of concentration from low to high (requires energy to go against gradient) ex: when drugs require transport proteins to cross the gut wall

Question 5

which dosage forms enter the blood stream

Answer 5

IV, Intra-arterial (intravascular)

Some extravascular:
PO, SL, buccal, IM, Subcutaneous

eye meds, topical meds, nasal meds, dermal meds, are all local

Question 6

define disintegration vs dissolve/dissolution

Answer 6

disintegrate is when ex: drug breaks down into its smaller pieces

dissolve/dissolution: when the active ingredient is released from the dosage form. only dissolved drug is absorbed into the blood stream. its how well something can be absorbed into the blood

Question 7

What is the Noyes whitney equation and how can it be increased

Answer 7

describes the dissolution rate, increased when particle sizes are smaller (SA is increased)

Hydrophillic drugs are more soluble

The dissolution rate is also dependent on the inactive ingredients used to make the dosage form. ex: polymers are used to make extended release formulations so they have a slower time to dissolve, enteric coating as well (dulcolax, entocort)

Question 8

List the rate of absorption from fastest to slowest for dosage forms

Answer 8

IV, SL, ODT, Immediate release tab, Extended release tab

Question 9

Bioavailability meaning

Answer 9

percentage of drug absorbed from extravascular administration relative to intravascular

Low F/poor absorption = < 10%
High F/good absorption = >70%

ex: we give 100 mg dose, but only 20 mg shows up in systemic circulation so the F is 20%

This allows us to understand how to dose drugs and how to interchange drugs from IV to PO ex: linezolid and levofloxacin have a 100% bioavailability , so we know the IV to PO conversions are 1:1

Question 10

F =

Answer 10

Remember 100 and AUC and Dose “ex ex (aka PO), in in (aka IV)”

F= 100 x AUC ex/AUC iv x Dose iv/Dose ex

Question 11

how do you calculate equivalent dose of a drug if dosage form is changed

Answer 11

= amount absorbed from CURRENT dosage form/Bioavailability (F) from NEW dosage form

Question 12

What properties effect the distribution of a drug

Answer 12

MW (lower the better)
Lipophilicity (lipid like is better to cross membranes)
Ionization status (non charged is better)
Protein binding– mainly albumin, (unbound is better) – for protein bound drugs (phenyoin and unionized calcium), we need to use correction formulas when pts have a low albumin (<3.5)

*we dont need to do correction for ionized calcium and free phenytoin

Question 13

Why do we use correction formulas for phenytoin and calcium when albumin is < 3.5

Answer 13

because the serum value of the drug is likely high because many of the molecules are unbound to protein . the formula helps us understand what the value would be if the concentration of albumin was normal so we can assess then if we need to do anything with the drug therapy. Usually the corrected level is higher than the serum level and the patient has a greater percentage of UNBOUND phenytoin.

Question 14

What is the desired therapeutic range for phenytoin?

Answer 14

10-20 mcg/mL

if albumin is low, we expect serum phenytoin to be low. if albumin is high, we expect phenytoin to be high

Question 15

What is the Vd

Answer 15

an apparent volume of how large of an area the drug has distributed to in the body

Vd (L) = amount of drug in body /concentration of drug in plasma

Its determined from the amount of drug in the body immediately after an IV drug is given. the smaller it is, the less the drug is distributing. If it’s larger, that means it very widely distributes to tissues

Question 16

Metabolism

Answer 16

conversion of original structure to other chemical forms or “metabolites”

the gut and liver are the primary sites because they have a lot of metabolic enzymes in the tissues.

Question 17

Why is lidocaine never given PO

Answer 17

because it goes through extensive first pass metabolism. It goes into the liver and then gets metabolized and the F is reduced so much before it even has a chance to have an effect.

Some drugs that go through first pass metabolism can be given orally but at really high doses (ex: propranolol)

Question 18

excretion occurs through

Answer 18

skin /sweat
urine /kidney **
gut/feces**
lungs/air
liver/bile

depends on dosage form

Question 19

Clearance

Answer 19

volume of blood from which drug is removed per unit of time

rate of elimination (mg/time of collecting urine )/concentration = Cl OR
F x Dose/(AUC) = Cl

clearance stays constant with changing drug concentrations in first order kinetics because the rate of the kidneys doesn’t speed up or slow down.

IF GIVING DRUG IV, F=1!!!! because IV is 100% bioavailable

Question 20

first vs zero order kinetics vs michealis-mentin kinetics

Answer 20

most drugs go through first order kinetics: where a constant percent of drug is removed per unit of time (ex: if we give double dose at steady state, we expect concentration to increase too)

zero order: when a constant amount of drug is removed per unit of time

Michaelis-mentin kinetics relates to enzymes being saturable aka non linear or mixed kinetics. there is a maximal rate of metabolism (Vmax) that can occur, and if drug amounts increase when enzymes are saturated, it leads to toxicity and these are typically narrow therapeutic index drugs because at higher concentrations (past the Km) the drugs concentration will more than double (phenytoin, theophylline, voriconazole). The Km (michaelis-mentin constant) is the concentration at half of the vmax. increasing the dose can lead to disproportionate amount of drug so we have to use special equations to avoid toxicity

Question 21

what dose adjustment should you make for a patient on phenytoin with a serum conc. of >7 mcg/mL

Answer 21

We must avoid doubling the dose, we should always increase in small increments of 30-50 mg in order to avoid oversaturating the enzymes and causing higher concentrations/toxicity.

it follows michaelis-mentin kinetics and its metabolism can be saturated at higher doses

Question 22

elimination rate constant formula (Ke)

Answer 22

Ke = Cl/Vd

or if needed to predict the concentration of drug at anytime after the dose (t), we can use

Ke = [ln (C1/C2)]/t
C1 is first or higher drug concentration (the peak) , C2 is the second or lower drug concentration at time (t). if you need to find the trough or peak using the Ke formula, use Ke = ln (c1/c2)/t OR C1x e^(-ke * t) = C2

Question 23

half life equation and definition

Answer 23

t1/2 = .695/ke

remember, ke = ln(c1/c2)/t

the time it takes for the drug concentration to drop by 50%

half life can show up in days too for example if the Ke is in days , not just hours!

Question 24

what is steady state and how many half lives does it take to reach steady state for drugs using first order kinetics

Answer 24

where the rate of drug intake equals the rate of elimination

Takes 5 half lives to reach steady state for drugs that use first order kinetics in a one compartment model (drug is rapidly and evenly distributed throughout the body) and assuming no loading dose

Question 25

How many half lives does it take for 95% of the drug to be eliminated if no additional doses are given

Answer 25

5 half lives

Question 26

when is a loading dose required

Answer 26

when we need to rapidly achieve therapeutic concentrations of a drug.
helpful when half life is long relative to frequency of admin

Question 26

when is a loading dose required and what is the formula

Answer 26

when we need to rapidly achieve therapeutic concentrations of a drug.
helpful when half life is long relative to frequency of admin. ex: a patient is in afib an their digoxin PO dose wont reach steady state until 14 days.
chai. no bueno. we should give a loading dose so they can reach ss faster

(Desired concentration x Vd)/F (decimal)

Question 27

when are peaks and troughs drawn and what changes can affect these

Answer 27

peak: 30 minutes after the end of an infusion to allow for distribution to occur. (ex: aminoglycosides). the highest concentration in the blood the drug will reach (before it starts getting metabolized). changing the dose will affect the peak

trough: 30 minutes or immediately before the next dose is due: the lowest concentration reached by the drug. changing interval/frequency affects the trough