
name the four steps of pharmacokinetics
 absorption
 distribution
 metabolism
 excretion

with pharmacokinetics, which of the four steps take the majority of the time (on a graph)
metabolism and excretion

where are the largest pores for filtration
Kidney

What are the two ways drugs are found systemically?
 Free
 bound to plasma proteins (albumin)

4 methods of membrane penetration for drugs
 1) aqueous diffusion/filtration
 2) lipid/passive (simple) diffusion
 3) Carrier mediated
 4) Vesicular transport/transocytosis

What is aqueous diffusion?
movement of particles across channels that are constituitively opened

What is lipid/passive diffusion?
lipidsoluble molecules pass freely through the membrane via hydrophobic interactions

What are two examples of carrier mediated transport and their examples?
 1) Active transport: ATP as energy, utilizing electrochemical gradient (Na,KATPase)
 2) Facilitated transport: down concentration gradient (Na, Glucose, LDopa, etc...)

What are three characteristics of carrier mediated transport?
 Specificity
 Competition
 Tmax

What is vesicular transport?
Phagocytosis (in general)

What is the ionized and unionized form of Acid?

What is the ionized and unionized form of Base?

General rule for ionized/unionized acids?
 weak Acid + Acid = unionized form prevails
 weak Acid + Base = ionized form prevails

General rule for ionized/unionized bases?
 weak Base + Base = unionized
 weak Base + Acid = ionized


If pKa = 9, which is acid/basic and why? pH 10 or pH 8?
 Acidic: pH 8 b/c it is lower than the pKa
 Basic: pH 10 b/c it is higher than the pKa

Which is more soluble, an ionized or unionized particle?
Unionized

what is ion trapping?
 When either a weak base or a weak acid is in the opposite environment and becomes ionized
 ** ionization = can't absorb b/c not lipid soluble

Why are strong acids difficult to absorb?
They are always ionized in the body and therefore are not lipid soluble and can't go through passive diffusion

Why is ammonium chloride important to acid/base rxns?
It can be used to acidify the urine so basic drugs are ionized and trapped

Why is sodium bicarbonate or acetazolamide important?
They can alkalanize the urine so acidic compounds like barbituates and salicylates are ionized and trapped

What are the three keys to dose dependency?
 Organ function
 Age
 Organ in general

What are the seven factors that modify absorption?
 Solubility (aqueous is best)
 Dissolution (pill or liquid)
 Concentration (high is better)
 Blood flow (fast is better)
 Contact time (more is better)
 pH (ion/nonionized)
 Surface area (more is better)

Which is more bioavailable, IV drug or Oral drug?
IV drug

Bioavailability formula
[AUC_{oral}/AUC_{IV}] x100

What organ generally takes care of the first pass effect with oral medications?
Liver (first to metabolize drug)

What are the 6 parenteral routes if oral medications can't be used?
 Intravenous
 Intramuscular
 Subcutaneous
 Intraperitoneal
 Intraarterial/Intracathecal
 Inhalation

What are the 5 topical routes for drug use?
 Skin
 Transdermal
 Eye
 Buccal
 Rectal

What is the volume of distribution formula?
V_{d}= Total drug in body (D_{IV}) / concentration in plasma (C_{0})

What does a drug with a low V_{d} represent?
Drug that is bound to proteins in plasma and not that free for use

How much fluid is in the plasma, extracellular compartment, and total body?
 Plasma: 3L
 Extracellular: 12L
 Body water: 41L

Name the 5 storage methods of drugs?
 Fat
 Tissue
 Bone
 Plasma Proteins
 Transcellular reservoirs (other organs)

5 areas of drug exclusion in the body (COPEF)
 CSF
 Ocular fluid
 Pleural fluid
 Endolymph fluid
 Fetal fluid

What is first order elimination of drugs?
Exponential kinetics

How much drug is eliminated in first order kinetics?
Constant, proportional amount (100502512.56.25 etc...)

What is the rate limiting factor of first order kinetics?
Concentration

What is zero order elimination?
saturation achieved and level maintained

What is the rate limiting principleof zero order kinetics?
Biological system

How much drug is eliminated in zero order kinetics?
constant amount (100500)

What type of kinetics does ethanol follow? What is its clearance ratio?
 Ethanol = zero order kinetics
 Clearance ratio = 10g/hr

Numerical difference b/t a logarithmic graph and a linear graph?
 logarithmic graph: yaxis jumps in log10 functions (.1, 1, 10, 100, 1000, 10000)
 linear graph: jumps in constant ratios (10, 20, 30, 40, 50)

What do a firstorder and a zeroorder elimination look like on a logarithmic and a linear graph?
 First order
 Log: linear line
 Linear:curved line
 Zero order
 Log: curved line
 Linear: straight line

4 requirements for half life?
 Single compartment
 Size is normal
 equal distribution
 drug in equilibrium

How many halflives does it take to find a steady state and to get rid of 50% of drug?
5 1/2ts

If a person needs to be tested for drug effectiveness and the half life of the drug is 6 days, when should they go to see their physician? Why?
 30 days (1 month)
 ** because you need to pass at least 5 half lives to find the steady state of the drug in a person's body

What happens to steady state levels of zero order kinetics if a drug is give in high doses repeatedly?
no steady state level developed

What happens with saturating kinetics with higher doses than elimination?
Accumulation in body

What is the rate of elimination formula?
V_{d} = CL (clearance) x c (concentration)

What is the natural log Clearance equation?
CL = V_{d} x 0.693/t^{1/2}

What is the elimination constant?
K_{e} = 0.693/t^{1/2}

How do CL, V_{d}, (D)ose, and t^{1/2} all relate to C_{ss} (Constant steady state)?
 CL & V_{d} are inversely proportional to C_{ss}
 D & t^{1/2} are directly proportional to C_{ss}

At what half life do you achieve 90% C_{ss}?
3.3 t^{1/2}

What happens to C_{ss} with shortening and lengthening the dosage interval?
 shortening dose interval = higher C_{ss}
 Lowering dose interval = lower C_{ss}

T/F: The time to reach steady state levels is related to the size of dose?
F, time to reach steady state is NOT related to size of dose, just half life. Dose will only affect the amount of steady state

What is maintenance dose?
amount of drug eliminated from the body since the last dosing

What is the elimination rate (dosing rate) formula for Maintenance dose?
 Elimination rate = [CL x TC]/F
 CL = clearance
 TC = desired concentration
 F = bioavailability if not given IV

What is the formulat for maintenance dose?
Dosage rate ([CL x TC]/F) x Dosing Interval (τ)

What is loading dose?
The steady state dose administered when you don't have time to wait 5 halflives to see what the true steady state is

formula for Loading dose?
loading dose = V_{d}xTC

What should follow a loading dose?
Proper maintenance dose

What is normal Creatinine clearance?
120 ml/min

What is time for onset?
Latency, time for drug to start a response

What is time to peak effect?
How long it took from latency to reach full effect

What is duration of action?
time bewteen first effect to last effect

How long are brand names good for?
Eternity

How long is a drug formula under copyright?
20 years

What drugs are exceptions to brand name drugs?
Orphan drugs

