Introduction to Pharmacology Flashcards
Pharmacology
the study of medications and their effects on living systems
Pharmacotherapeutics
use of medications for therapeutic reasons
Pharmacodynamics
how the drug affects the system
Pharmacokinetics
how the body affects the drug
- absorption
- distribution
- elimination
Toxicology
study of the adverse affects from medications
Adverse Drug Reactions (ADRs)
severe side effects of drugs
Specificity of drugs/receptors
only effects specific receptors
Endogenous ligand
- a substance that is naturally occuring in the body and can be effected by a drug/a drug can mimic the affect of the substance
Downregulation of receptors
decrease in available number of receptors
upregulation of receptors
increase in available number of receptors
Receptor principles
- quantitative relationship
- drug selectivity
- activation/inhibition
- quantitative relationship between dose/concentration and the effects
- drug selectivity: based on the shape and type of receptors (alpha/beta) that they stimulate
- activation/inhibition of receptor causes different clinical effects
Types of graded dose response of drugs
- Linear relationships between concentration and effect that produce a hyperbolic curve
- logarithmic relationships between the concentration and effect gives a sigmoidal curve
Emax in a graded dose response of drugs
- max effect where doses greater do not produce added benefit
minimal effective dose
- concentration below which there are not any clinical benefits
What is a quantal dose response
- when the minimium dose required to produce an intended magnitude of response is evaluated for a population
- can give a therapeutic index which can measure how safe a drug it
Therapeutic window
- is the dosage range between the minimum effective dose and the minimum toxic dose
Therapeutic index
- calculated by median toxic dose or median lethal dose by the median effective dose
- generally the larger the range the more safe the drug is
- (have a very high toxic dose but a small effective dose)
What doses can be found from a quantal dose response curve
- median effective dose: needed to obtain a response
- median toxic dose: dose at which it is toxic to the biological system
- median lethal dose: where it is lethal to the system
Drug potency
- the amount of drug needed to produce a desired effect
- a drug is more potent if you need to take less amount to get desired response
durg efficacy
- the drugs ability to reach the max effect/ a measureable response
Full agonist
- a drug or endogenous ligand that is capable of fully activating the effector system upon binding to the receptor
Partial agonist
- a drug or endogenous ligand that binds to the receptor but achieves a lower maximal effect when with full occupancy due to lower maximal efficacy
- in the presence of a full agonist the partial agonist can act as inhibitor
Allosteric response
does not bind directly to the receptor’s active site but influences the affinity of the receptor
- can be an activator or inhibitor
Competitive antagonist
- a drug that binds to or very close to an agonist receptor site in a reversible way but does not activate the effector system
- with a competitive agonist the ED (effective dose) shifts to higher doses
noncompetitive antagonist
- causes a downward shift of the maximum response with no shift on the dose axis
- binds to the receptor site
- their binding is nearly irreversible or irreversible
-effects of a noncompetitive antagonist can not be over come with increase in dose
What are the trans membrane signalling mechanisms
- transmembrane diffusion
- transmembrane enzyme receptors
- transmembrane receptor
- transmembrane channels
- g protein-coupled receptors
transmembrane diffusion/intracellular recepotr
- diffuse into the cell and bind to an intracellular receptor
- bind to lipid soluble agonists
transmembrane enzyme receptors/transmembrane receptor
- binds outside and causes an effect inside
- or activates cytoplasmic tyrosine kinase molecules
- have enzymatic activity on the inside
transmembrane channels
- when the agonist or ligand binds it will open the channel to allow ions/substances to flow into the cell
- drugs that mimic these will help to regulate the flow into the cell
g protein-coupled receptors
- increase intracellular concentrations of secondary messengers such as cAMP
- 3 components
1. extracellular ligand binds to specific surface receptor
2. receptor binding triggers activation of G protein located in the cytoplasmic face of plasma membrane
3. activated G protein then changes activity of an element usually an enzyme of ion channel
What are factors that influence concentration of a drug
- rate of absorption
- distribution to the tissues
- elimination from the body
- parameters: volume of distribution and clearance
- bioavailability: how much is actually available after being broken down
What affects the rate of absorption of a drug
- physical and chemical properties of the drug
- route of administration
What are the routes of administration
- enteral
- parenteral
Enteral administration
going through the GI tract
- oral, sublingual, buccal, rectal
- 1st pass effect: loss of potency due to being metabolized by the liver and GI system
- no do much with sublingual and buccal since there is some direct absorption
Parenteral administration
- vascular (intravenous= direct/dangerous and intra-arterial= targets a specific organ)
- intramuscular
- subcutaneous
- inhalation
- transdermal
distribution of a drug
- permeation: movement between biological compartments
- volume of distribution = distribution is no homogeneous throughout the body it can be sequestered into different tissues/physical compartments
Elimination
- removes biological active compounds through metabolism and excretion
- expressed as clearance: rate of drug elimination/plasmaconcentration
- major clearn organs: kidney, lung, liver, and GI tract
Elimination kinetics 1st order
- rate of elimination is proportional to concentration
- ex more concentration = clearance is faster
- constant clearance and half life
Elimination kinetics: zero order
- same amount is eliminated each time
half life
- determined by drugs volume of distribution and clearnace
- how long does it take for 1/2 of the concentration to be gone
half life
- determined by drugs volume of distribution and clearance
- how long does it take for 1/2 of the concentration to be gone
What is the aim of a dosing regimen
results in the achievement of therapeutic levels of the drug in the blood while staying within the therapeutic window
Loading dose
maintenance dose
- loading dose = (Vd x desired plasma concentration)/bioavailability
- maintenance: the goal is to keep the concentrations within the therapeutic window
how does half life affect steady state
- patients who take medications for a period of time will respond better If the medication remains at a therapeutic dose
- this dose can be achieved by continuous administration or small frequent doses
- can be achieved to some degree of using half life
How can you use half life to determine dosage
- to achieve steady state, want to minimize fluctuations between peak plasma levels and lowest level before the next dose
- can dose at the half life of the drug
- after about 5 half lives the drug should ready steady state
Drug elimination (how long does it take to be eliminated)
- usually takes 5 half lives for a drug to be completely eliminated from the body
- drug interactions should be considered when switching meds
What are factors that can affect half-life
- drug metabolism, elimination and storage
- drug interactions
- pharmacogenomics
- these all change/increase the risk of adverse drug reactions
describe the metabolism of drugs
- primarily occurs in the liver – more medications means the liver must work harder which can lead to damage
- some metabolism can occur in the heart and kidneys which can affect the organ especially If they have an issue with that organ
- biotransformation: most common is conversion into water soluble compounds by microsomal enzymes in the liver and allows for excretion by the kidney
(transforms the drug to help with elimination from the body)
Describe elimination by the kidneys
- glomerular filtration: the drug is taken out of the bloodstream
- tubular secretion
- reabsorption of some drugs: goes back into the bloodstream
(consider how much will be excreted/reabsorbed when making a drug)
What are problems that can arise with drugs and kidney dysfunction
- reduced elimination of drugs affects the 1/2 life
- increased risk of adverse effects
- more likely to have drug interactions
- ex: people with kidney disease and older adults (systems slows down)
What are some other ways of elimination
kidneys are the main one others include
- lungs
- feces
- sweat
- salvia
- breast milk
Other factors that can affect metabolism and excretion
- disease
- age
- gender
- diet
- activity
Medication storage in adipose tissue
- can store lipid soluble drugs
- most of the drug is eliminated
- if more of the drug is stored in tissue:
~ slower release
~ decreased bioavailability (ability to be used for the rest of the body) - some can be stored for a long period of time
- more adipose tissue = more medication can be stored
What are other tissues that store medications
- bone: lead which can affect cognitive development
- muscle: antimalarial drugs
- organs (liver, kidney, heart): can cause damage in the organ
(some antibiotics are stored in the kidney)
what does drug interactions mean
- metabolism of one drug, food, or substance can promote, enhance, or reduce the metabolism of another drug
Drug interactions that reduce metabolism
increase the risk of adverse effects
- ex: grapefruit and statins for cholesterol causes risk of statin myopathy due to the grapefruit having an enzyme that does not allow the breakdown of statin
drug interactions that increase metabolism
decreases the effectiveness
- the drug will move through the system too quickly
- alcohol and acetaminophen
Describe pharmacogenomics
- genetic differrneces may affect pharmacokinetics
- variations in cytochrome expression can increase or decrease drug metabolism
- overtime differences can occur such as epigenetic changes
EX: codeine, placid, warfarin
- rapid conversion of codeine to morphine
- increased or decreased platelet aggregation
- decreased clotting
Drug tolerance
- related to enzyme induction: can produce more or the enzymes stay active longer
- body adjusts to drug and breaks it down more quickly
- more enzymes are produced
- enzymes are degraded slower
What does off label uses mean
- used for a function other than what it was FDA-approved for
- EX:
1. Neurontin: seizure medication that is also used for nerve pain
2. fluoxetine (prozac): depression but also used for bulimia and premature ejaculation
Other risk factors for adverse drug reaction
- age
- dose
- prolonged use of medication
- multiple medications
