Pharmacokinetics Flashcards
what is the definition of pharmacokinetics?
a study of how the drug moves throughout the body
what dictates a drugs activity at the receptor site and why?
certain enantiomers have higher affinity
what is an example of medication that contains both L and D isomers?
amphetamines given as ‘mixed salts’
for patients with hypothyroidism what isomer of thyroid hormone is given?
L-isomer
what is captopril used for and what is its trade name?
- ACE inhibitor used in treatments for hypertension
- Capoten
what does ADME stand for and what can influence them ?
- Absorption
- Distribution
- Metabolism
- Excretion
age, ethnicity and disease state
how is absorption influenced?
route of administration and how it distributes within the body
what are the two routes a drug may be administered and what are examples?
enteral
- mouth (50% bypass first-pass effect)
- rectal (100% bypass first-pass effect)
- sublingual
parenteral (bypass first-pass effect)
- intravenous
- intramuscular
- subcutaneous
- transdermal
what does extensive first-pass effects mean?
- drugs taken orally will deposite into the hepatic portal system
what is the quickest way to make 100% bioavailability ?
IV
what factors influence absorption?
- Concentration of drug given
- route of administration
- Surface area of the cell membrane
- Lipophilicity
- Lower the thickness of the membrane, the greater the absorption
- Lower the molecular weight of the drug the greater the absorption
- The greater the regional blood flow to the target tissue, the greater the absorption.
- drugs given orally, the rate of gastric emptying is important
what determines the hydrophobicity or hydrophilicity of a drug?
partition coefficient
what is Fick’s Principle equation?
Diffusion = (C1-C2) X Surface area of membrane X Permeability Coefficient/
Thickness of membrane
how does passive vs active transport effect the rate of absorption?
any drug that uses a transporter (active) will have a cap of effectiveness even if the dose is increased
what are the 4 processes that absorption can perform?
- aqueous diffusion
- passive diffusion
- carrier mediated
- active transport
what drugs can cross the placenta? what are some examples?
Nonionized drugs and drugs with high lipophilicity typically will have a higher advantage in crossing the placenta
- opioids
- benzodiazepines
- atropine
- beta-blockers
- local anesthetics
what are two important mechanisms for receptor cycling and release of neurotransmitters?
- exocytosis
- endocytosis
the absorption of weak acids and weak bases are influenced by?
ionization state
what are the normal pH’s of the stomach, small intestines and colon and how does the pH effect absorption?
- 2-2.5
- 6-8
- 5.5-7
drugs where their pKa is closest to the pH absorb better
what is an effective way to eliminate weak bases through the kidneys ?
ion trapping
explain what ion trapping is?
ion trapping occurs when a drug becomes ionized in a specific environment, preventing it from crossing membranes and leading to its accumulation in that compartment.
what is bioavailability and what factors influence it?
-the fraction (f) of unchanged drug reaching the systemic circulation following administration by any route
* Foods or certain types of drugs can influence the bioavailability.
what can influence drug distribution to various parts of the body?
plasma proteins such as albumin and alpha-1-glycoprotein
what does Volume Distribution tell us and what is the formula?
- what compartment the drug enters
- VD = Amount of Drug in the body / PC
PC = plasma concentration in the body
how does the volume of distribution influence drug elimination?
- For drugs that have a high volume of distribution, the body needs a longer time to
eliminate the drug. - For drugs with a low volume of distribution, then these drugs will be eliminated quickly.
what are the three main determinants for volume of distribution?
- Properties of the drug
- Size of the extra-vascular space (children vs adults, lean vs obese)
- Any disease state that influences the plasma protein concentrations (theory)
what is enterohepatic recycling?
lipid solubility can cause binding to bile salts and allowing reentry the systemic circulation causing the drugs to stay in the systemic circulation for a longer period of time
what are examples of drugs that undergo enterohepatic recylcing?
- Diazepam (benzodiazepine)
- Valproic acid (mood stabilizer)
- Oral contraceptives
- Warfarin (anti-coagulant)
- Morphine (analgesic)
what is necessary for activation of some drugs and to help remove them from the systemic circulation?
metabolism or biotransformation
what are Xenobiotics?
wide variety of foreign substances that the body needs to metabolize and eliminate
what are prodrugs?
drugs that need to undergo metabolism to become active (codeine, heroin, L-dopa)
what are phase I reactions and phase II reactions?
- Phase I reactions make the drug more polar by adding a functional
group, such as –OH, -NH 2, and –SH. - Sometimes Phase I reactions cannot cause a drug to be excreted, so a Phase II reaction is required which adds another functional group, such
as glucuronic acid, sulfuric acid, or acetic acid
how does Cytochrome P450 metabolize drugs in the liver?
- NADPH and flavoprotein reduce iron to become an acceptor
- CYP (P450) requires carbon monoxide on iron before becoming an acceptor of O2
- H2O is then utilized to cause hydrolysis and addition of –OH group to the drug.
what are three examples of non-cytochrome P450 Phase I reactions?
- xanthine oxidase
- alchohol dehydrogenase
- microbiome
what is enzyme induction and what are some examples of inducers?
certain drugs or substances increase the production (expression) or activity of metabolic enzymes, usually in the liver
- Phenytoin (anti-epileptic)
- Rifampin (antibiotic)
- St. John’s wort (anti-depressant)
what is Enzyme inhibition and what are some examples of inhibitors?
when two drugs compete as substrates for the drug metabolizing enzyme (drug-drug interactions)
- Chlorpromazine (anti-psychotic)
- Cimetidine (anti-histamine)
-Grapefruit juice
what can enzyme inhibition cause?
- can increase the amount of active drug in the systemic
circulation, thus increasing the drug effect (PD) - can result in the inhibition of metabolism of the drug and thus decrease the ability to eliminate the drug (PD/PK)
what are the factors that influence metabolism?
- Rate of blood flow to the liver
- Rate of entry into the liver (bioavailability)
- P450 Enzyme induction/inhibition
- Individual differences (e.g., metabolism, sex, genetics, age)
- Diet and environmental factors
what are the three ways excretion occurs?
through the bile , feces or urine
what is clearance and what could give the best indication in a clinical setting?
- Clearance is the volume of plasma from which a certain amount of drug is removed per unit time
- glomerular filtration rate (GFR)
what is the formula for clearance?
CL = Rate of elimination / Pc
- Rate of elimination is the amount of substance
removed per unit time
- PC = plasma concentration of the drug
for first order kinetics, the rate of drug elimination is proportional to?
the drug concentration
- As the concentration increases, the elimination rate increases.
for zero order kinetics, the rate of drug elimination is ?
constant, regardless of the drug concentration
- This typically happens when the body’s metabolic enzymes are saturated.
what are the 3 processes that can occur when a drug is in the process of being excreted?
- Glomerular filtration
- Tubular secretion
- Passive reabsorption
what are the factors that can influence excretion?
- Age
- Environmental factors (e.g., toxins)
- Disease (e.g., renal insufficiency, renal failure)
- Sex
- Drug-drug interactions
- Genomics
