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name the four steps of pharmacokinetics
- absorption
- distribution
- metabolism
- excretion
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with pharmacokinetics, which of the four steps take the majority of the time (on a graph)
metabolism and excretion
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where are the largest pores for filtration
Kidney
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What are the two ways drugs are found systemically?
- Free
- bound to plasma proteins (albumin)
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4 methods of membrane penetration for drugs
- 1) aqueous diffusion/filtration
- 2) lipid/passive (simple) diffusion
- 3) Carrier mediated
- 4) Vesicular transport/transocytosis
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What is aqueous diffusion?
movement of particles across channels that are constituitively opened
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What is lipid/passive diffusion?
lipid-soluble molecules pass freely through the membrane via hydrophobic interactions
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What are two examples of carrier mediated transport and their examples?
- 1) Active transport: ATP as energy, utilizing electrochemical gradient (Na,K-ATPase)
- 2) Facilitated transport: down concentration gradient (Na, Glucose, L-Dopa, etc...)
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What are three characteristics of carrier mediated transport?
- Specificity
- Competition
- T-max
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What is vesicular transport?
Phagocytosis (in general)
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What is the ionized and unionized form of Acid?
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What is the ionized and unionized form of Base?
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General rule for ionized/unionized acids?
- weak Acid + Acid = unionized form prevails
- weak Acid + Base = ionized form prevails
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General rule for ionized/unionized bases?
- weak Base + Base = unionized
- weak Base + Acid = ionized
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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
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Which is more soluble, an ionized or unionized particle?
Unionized
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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
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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
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Why is ammonium chloride important to acid/base rxns?
It can be used to acidify the urine so basic drugs are ionized and trapped
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Why is sodium bicarbonate or acetazolamide important?
They can alkalanize the urine so acidic compounds like barbituates and salicylates are ionized and trapped
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What are the three keys to dose dependency?
- Organ function
- Age
- Organ in general
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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/non-ionized)
- Surface area (more is better)
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Which is more bioavailable, IV drug or Oral drug?
IV drug
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Bioavailability formula
[AUCoral/AUCIV] x100
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What organ generally takes care of the first pass effect with oral medications?
Liver (first to metabolize drug)
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What are the 6 parenteral routes if oral medications can't be used?
- Intravenous
- Intramuscular
- Subcutaneous
- Intraperitoneal
- Intraarterial/Intracathecal
- Inhalation
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What are the 5 topical routes for drug use?
- Skin
- Transdermal
- Eye
- Buccal
- Rectal
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What is the volume of distribution formula?
Vd= Total drug in body (DIV) / concentration in plasma (C0)
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What does a drug with a low Vd represent?
Drug that is bound to proteins in plasma and not that free for use
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How much fluid is in the plasma, extracellular compartment, and total body?
- Plasma: 3L
- Extracellular: 12L
- Body water: 41L
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Name the 5 storage methods of drugs?
- Fat
- Tissue
- Bone
- Plasma Proteins
- Transcellular reservoirs (other organs)
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5 areas of drug exclusion in the body (COPEF)
- CSF
- Ocular fluid
- Pleural fluid
- Endolymph fluid
- Fetal fluid
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What is first order elimination of drugs?
Exponential kinetics
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How much drug is eliminated in first order kinetics?
Constant, proportional amount (100-50-25-12.5-6.25 etc...)
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What is the rate limiting factor of first order kinetics?
Concentration
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What is zero order elimination?
saturation achieved and level maintained
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What is the rate limiting principleof zero order kinetics?
Biological system
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How much drug is eliminated in zero order kinetics?
constant amount (100-50-0)
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What type of kinetics does ethanol follow? What is its clearance ratio?
- Ethanol = zero order kinetics
- Clearance ratio = 10g/hr
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Numerical difference b/t a logarithmic graph and a linear graph?
- logarithmic graph: y-axis jumps in log10 functions (.1, 1, 10, 100, 1000, 10000)
- linear graph: jumps in constant ratios (10, 20, 30, 40, 50)
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What do a first-order and a zero-order elimination look like on a logarithmic and a linear graph?
- First order
- Linear:curved line
- Zero order
- Log: curved line
- Linear: straight line
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4 requirements for half life?
- Single compartment
- Size is normal
- equal distribution
- drug in equilibrium
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How many half-lives does it take to find a steady state and to get rid of 50% of drug?
5 1/2ts
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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
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What happens to steady state levels of zero order kinetics if a drug is give in high doses repeatedly?
no steady state level developed
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What happens with saturating kinetics with higher doses than elimination?
Accumulation in body
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What is the rate of elimination formula?
Vd = CL (clearance) x c (concentration)
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What is the natural log Clearance equation?
CL = Vd x 0.693/t1/2
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What is the elimination constant?
Ke = 0.693/t1/2
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How do CL, Vd, (D)ose, and t1/2 all relate to Css (Constant steady state)?
- CL & Vd are inversely proportional to Css
- D & t1/2 are directly proportional to Css
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At what half life do you achieve 90% Css?
3.3 t1/2
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What happens to Css with shortening and lengthening the dosage interval?
- shortening dose interval = higher Css
- Lowering dose interval = lower Css
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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
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What is maintenance dose?
amount of drug eliminated from the body since the last dosing
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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
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What is the formulat for maintenance dose?
Dosage rate ([CL x TC]/F) x Dosing Interval (τ)
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What is loading dose?
The steady state dose administered when you don't have time to wait 5 half-lives to see what the true steady state is
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formula for Loading dose?
loading dose = VdxTC
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What should follow a loading dose?
Proper maintenance dose
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What is normal Creatinine clearance?
120 ml/min
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What is time for onset?
Latency, time for drug to start a response
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What is time to peak effect?
How long it took from latency to reach full effect
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What is duration of action?
time bewteen first effect to last effect
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How long are brand names good for?
Eternity
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How long is a drug formula under copyright?
20 years
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What drugs are exceptions to brand name drugs?
Orphan drugs
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