Pharmacokinetics Flashcards
Vd equation
amount of drug/desired plasma concentration
Volume distribution assumes (2 things)
the drug distributes completely all at once, does not undergo any biotransformation or elimination
If a drug is lipophilic/hyrdophilic, it requires a ____/____ amount to achieve a plasma concentration
lipophilic=higher
hydrophilic=lower
How do you calculate a loading dose of an IV med
IV dose= Vd x plasma concentration/ bioavailability -which is 1
An acid ____ a H+
donates
A base ___ a OH+
accepts
What is ionization?
The process of when a molecule gains a positive or negative charge
Ionized or nonionized is more water soluble?
Ionized
Explain the following for nonionized molecules: Solubility Active or nonactive? Hepatic biotransformation? Renal elimination? Diffuses across lipid barrier?
Solubility-lipophilic Active or nonactive-active Hepatic biotransformation? yes Renal elimination? no Diffuses across lipid barrier? yes
Explain the following for ionized molecules: Solubility Active or nonactive? Hepatic biotransformation? Renal elimination? Diffuses across lipid barrier?
Solubility-hydrophilic Active or nonactive-nonactive Hepatic biotransformation? no Renal elimination? yes Diffuses across lipid barrier? no
What happens when you put a weak acid into a weak base?
It will become ionized. The acid wants to donate it’s protons and the base wants to accept it.
What happens when you put a weak acid into an acid?
It will be nonionized. Both acids want to donate their protons so they both retain them.
Name the 3 key plasma proteins
Albumin, AAG (alpha-1 acid glycoprotein), beta-globulin
Do the following bind to acid or bases? Albumin, AAG, beta-globulin
Albumin-acids, AAG & beta-globulin-bases
Which conditions decrease albumin?
Liver disease, renal disease, old age, malnutrition, pregnancy
Which conditions increase a1-acid glycoprotein?
surgical stress, MI, Rheumatoid arthritis, chronic pain, advanced age
Which conditions decrease a1-acid glycoprotein?
pregnancy, neonate
Are protein binding and plasma concentration inversely or directly proportional?
inversely. As protein building increases, plasma concentration decreases.
What are phase 1 reactions?
Oxidation, reduction, hydrolysis
What is oxidation?
Adds an oxygen molecule to a compound. Involves loss of electrons.
What is reduction?
Adds electrons to a compound.
What is hydrolysis?
Adds water to a compound to split into 2 parts
What is a phase 2 reaction? What happens?
Conjugation, adds an endogenous, highly polar, water substrate to make it inactive and water soluble.
What are CP 450 inducers? What happens?
They break down drugs FASTER. Increased clearance, decreased plasma concentration, re-dosing may be needed.
Smoking, barbituates, ethanol, phenytoin, carbamazepine, rifampin
What are CP 450 inhibitors? What happens?
They SLOW metabolism of drugs. Decreased clearance, increased plasma concentration, may have to decrease dose. Grapefruit Cimetidine Omeprazole Isoniazid SSRI's Erythromycin Ketoconazole
What is pharmacokinetics?
What the body does to the drug
What is pharmacodynamics?
What the drug does to the body
What does ADME mean in pharmacokinetics?
A-absorption, D-distribution, M-metabolism, E-elimination
Conditions that affect site of absorption
Blood flow, surface area, membrane thickness, metabolism, GI motility, pH, presence of other substance
Rate of diffusion equation
Concentraion gradient x SA x diffusion coefficient/ membrane thickness
The rate of diffusion is directly proportional to what?
Concentration gradient and SA
The rate of diffusion is inversely related proportionally to what?
Membrane thickness
What is the definition of bioavailability?
Fraction of unchanged drug that reaches the systemic circulation following administration
Aqueous Diffusion: Flow (with or against) a concentration gradient.
concentration, with
Lipid Diffusion: goes from (greater/less) to (greater/less) concentration.
greater to less
Active transport diffusion
uses ATP (Na/K pump)
Facilitated Diffusion
Passive action without the use of ATP, (glucose and insulin)
Endocytosis diffusion
the wall of the membrane engulfs the molecule. (Phagocytosis, Pinocytosis)
Protein binding can affect:
Distribution of drugs, potency, elimination
Hepatic microsomal enzymes are mainly found in the ______ of the _____. Examples:
endoplasmic reticulum, liver. Ex: Cytochrome P-450, Acetyl CoA, Transferases
CYP-2D6 inducers.
Phenytoin, Carbamazepine, dexamethasone
CYP-2D6 Inhibitors
Isoniazid, SSRI’s, Quinidine
What is absolute bioavailability?
the amount of drug that reaches the systemic circulation from an IV dose
What is relative bioavailability?
the amount of drug that reaches the systemic circulation from a non-IV form
Name fastest to slowest routes to reach peak plasma concentration:
(I) (T)hink (I) (C)an (P)lease (E)veryone (B)ut (S)usie & (S)ally
IV, tracheal, Intercostal, Caudal, Paracervical, Epidural, Brachial Plexus, Sciatic/Subarachnoid, Subcutaneous
Ion trapping is:
a build-up of a higher concentration across a cell membrane due to the pKa value and difference in pH across the membrane.
Define clearance
volume of plasma that is cleared of drug per unit time
What are the major clearing organs
liver, kidney
Define steady state
occurs when the amount of drug entering the body is equivalent to the amount of drug being eliminated from the body.
Clearance is directly proportional to:
blood flow to clearing organ, extraction ratio, drug dose
Clearance is inversely proportional to:
half life, drug concentration in the central compartment
How many half-times must elapse to achieve steady state?
5
Renal excretion of drugs involves__ (3 things)
glomerular filtration, active tubular secretion, passive tubular secretion
Renal clearance is inversely correlated with:
age and creatinine clearance
The distribution phase of elimination or the ___ phase is:
alpha; redistribution of drug from the plasma and vessel rich group to the less perfused tissues of the peripheral compartment
The elimination phase or ____ phase:
after distribution slows, get slow continuous elimination from the central compartment
Weak acids combine with salts to make ____ charged ions
positively. Ex sodium thiopental, sodium nitroprusside
Weak bases combine with salts to make ____ charged ions
negatively. Ex: morphine sulfate, lidocaine hydrochloride
The higher the pka, the _____ the amount of drug in the nonionized form
greater
What is the drug class that doesn’t fall into an acid or base?
NMBDs
CYP-2D6 deficient individuals have less response to ____
codeine
CYP-2D6 inducer individuals have decreased response to ____
Zofran
