Exam 1: Intro to Pharm Flashcards
Pharmacotherapeutics
Therapeutic (medical) use of a drug
Diagnose, prevent, or treat disease
Six rights
Right drug
Right dose
Right patient
Right route
Right time
Right documentation
FDA Stages for Approval
- Preclinical investigation/testing (all in lab)
- Clinical investigation/testing (longest part)
Clinical investigation
Phase I: Normal (Healthy ) volunteers
Evaluation effects on humans & of drug metabolism
Phase II & III: tested on patients, determine therapeutic effects, dosage ranges, safety
Phase IV: Post marketing surveillance, used for gen. pop., new side effects reporting -> ADRs not found in stage 3
Properties of an Ideal Drug
“Maximum benefit with minimal harm!!”
Effectiveness - Elicits the response it is intended for
Safety - Causes no (or little) harm
Selectivity - Response limited for which it is given
also important:
Reversible action
Predictability
Easy to administer
Few drug interactions
Low cost
Chemically stable
Simple generic name
generic name vs trade/brand name
generic - official name given by manufacturer used in practice, sometimes ending of name can indicate drug classification (-cillin: antibiotic)
trade/brand - most common name, pt might know
generic drug
Tend to be lower cost
Lower cost than “Brand name” drugs …. bc generic is produced after the patent ends for original producer
brand drug vs. generic drug
Both: must have same Active Ingredient
contain same dose of same drug
Concern with generics:
Different binders and fillers
May change absorption-rate and extent
May not work the same
Generic drugs must have FDA approval
Sources of drugs
Plants
Animals or humans: such as Hormones
Minerals or mineral products
Synthetic
Made in the laboratory with same molecular function as natural molecule
Recombinant DNA: fragment of DNA is inserted into DNA of another organisms
Legend
Any drug that requires a prescription
Over-the-counter (nonprescription)
Many Legend drugs are now being approved for OTC sale
Scheduled/ Controlled drugs
Any drug with the potential of being abused
Class I –V
Class I extremely high abuse potential, no accepted medical use (Heroin and LSD)
Class II-V progressively less, have acceptable use but also potential for abuse
1970 Controlled Substance Act
Drug classification
drugs w/ similar characteristics
Treatment: symptoms/illness/disease
(Antiemetic, Analgesic, Antihypertensives)
Similar effect on a body system
(Diuretics, Antacid)
Similar pathophysiology effect
(ACE Inhibitor, Beta Blocker)
Pharmacoceutic Phase
only PO meds
Disintegration (for tablets, capsules are already in solution)
Dissolution - dissolve into the GI fluid before absorption (rate of dissolution dictates rate of absorption)
enteric coatings**
Pharmacokinetic phase
ADME
- absorption
- distribution
- metabolism
- excretion
Three primary ways to cross a cell membranes
- Pass through channels or pores (Only very small ions such as potassium)
2.Pass with the aid of a transport system (Different transport mechanisms- P-Glycoprotein ex.) - Direct penetration of the membrane (Most common)
P-Glycoprotein:
multidrug transporter protein
transports wide variety out of cell so it can be eliminated
present in liver, kidneys, placenta, intestine, and capillaries of the brain
“like dissolves like”
Lipid soluble drugs (lipophilic) can directly penetrate (mostly lipid) cell membranes
Ion transport
Ions (net electric charge) cannot cross membrane
depend on the pH of the environment as to whether the drug is non-ionized and able to cross cell membrane or not
“I(on) can’t get in!” example
Absorption
drug enters the body, gets into blood
Distribution
drug moves from blood to site of action
determined by factors of blood flow to tissues/organs abscesses/tumors ex. of low blood flow
Metabolism
biotransformation
enzymatic alteration of drug structure
most occurs in liver
Normal route is drug absorbed -> goes to liver via portal vein -> just passes through -> then into systemic circ -> after targeted effect -> returns to liver to be metabolized
Excretion
exits and is removed from body
Enteral vs parenteral
enteral - GI - PO & feeding tubes
parenteral - “by injection” IV, SQ, IM
Oral route
multiple preparations - have fillers & binders that allow for better dissolution and absorption
convenient & safe
absorption is variable on GI motility/enzymes & blood flow to GI tract
slower onset & peak times
**must pass through the liver via the portal vein “First pass effect”
enteric-coated drugs
Resist disintegration until in the small intestine
coated to resist pharmacoceutic phase
sustained release drugs
Formulation (actual structure of pill w/ different spheres or matrices) which allows drug to slowly release over time
IV route
parenteral route
less convenient, but immediate absorption (faster absorption and peak times)
Risks: no turning back, fluid overload, infection, etc.
IM/SQ route
large spaces b/t cells - drugs absorb by moving b/t cells, through channels and pores
blood flow impacts absorption - Deltoid = high blood flow
less convenient, complications
Bioavailability
The percentage of the administered drug dose that reaches the systemic circulation (bloodstream) unchanged
Oral never 100%, IV is 100%
oral doses require higher dose
Sublingual/buccal route
quick, self-administrable, economic
bitter taste, irritation of mucosa, not large quantities
Protein binding
drugs bind to proteins in body
albumin (plasma protein) - most drugs bind in some way in bloodstream and dependent on level of attraction
can restrict distribution
“free drug”
the drug that doesn’t bind and can create the action desired
Blood brain barrier
only lipid soluble drugs or drugs w/ a carrier can pass through
capillaries have tight junctions
Fetal-Placental barrier
Not an absolute barrier, lipid soluble & non-ionized agents pass through
Cytochrome P450 Enzymes
most drug metabolism in the liver performed by them
different drugs metabolized by different enzymes
Drug inactivation & accelerated excretion
drugs are inactivated by liver enzymes to become water soluble and be excreted
leads to accelerated renal excretion of drugs bc kidneys can’t excrete lipid solubles
Increased therapeutic action/activation
some transformed into active metabolites w/ increased response (pro drugs)
codeine transforms into morphine after metabolism
pro drugs
no pharmacologic activity UNTIL they are metabolized in the liver
Increased or decreased toxicity
metabolism can change safe drugs (acetaminophen) may become toxic
most drugs are converted to inactive forms to excrete
why is dosing different for infants and malnourished pts?
infants - decreased ability to metabolize drugs
malnourished - deficient hepatic enzymes
First-Pass Effect
Certain drugs are partially or completely inactivated on the first pass through the liver (NOT NORMAL)
Result: drug may have minimal or no therapeutic effect
These are not given PO - think sublingual (nitro ex.)
Cirrhosis or hepatitis
risks for drug toxicity due to inability to metabolize
prolonged half-life
AST & ALT
liver enzymes that we check if drug can be hard on liver
Renal drug excretion
Glomerular filtration (protein bound drugs will not filter)
Passive reabsorption (lipid soluble drugs can’t be excreted)
Active transport- P-glycoprotein pumps certain agents into urine
Urine pH
affects drug excretion
acidic urine -> weak base drugs and vice versa
b/c they ionize the drug and make it no longer lipid soluble and won’t reabsorb back into the body
**important to help treat overdoses and improve excretion rate
Renal disease
drug elimination slowed or impaired
can lead to drug accumulation
half-life prolonged
Plasma half-life
1st: Time it takes for a medication to decrease concentration in the plasma by 50% after administration
2nd: time it takes for the second half of the drug concentration to be reduced by half again
takes about 4 half lives for any drug to be “almost” out of the blood stream
Pharmacodynamic phase
drug’s effects on the body
Primary - therapeutic
Secondary - adverse
Cellular receptors
Most drugs work because they bind to a particular “receptor” to create a response or to block a response
“Lock and Key” theory
selectivity (beta-blockers) and affinity (naloxone) are important
Occupancy Theory
The intensity of the response to the drug is proportional to the number of receptors occupied.
Agonist
Mimics the action of the endogenous molecule
Activates or “turns on” the receptor
Antagonist
Blocks action of endogenous molecules
Prevent or shut down activation of the receptor
Partial agonist
Mimics action like an agonist but with less intensity
Low affinity
Maximal Efficacy
Largest effect that a drug can produce
Relative Potency
Amount of drug we must give to elicit a response
Highly potent drugs require smaller doses
Plasma drug levels
ED
Average effective dose in 50% of the population
May be referred to as the Minimum effective concentration (MEC)
LD
Average lethal dose
Lethal to 50% of animals during testing
May be referred to as the Toxic concentration (MTC)
Onset of Action
Period of time it takes after the drug is given to create a response
Peak Action
Time it takes for a drug to reach it’s highest concentration
Duration of action
Length of time during which the drug is present in a concentration great enough to produce a response
Therapeutic Index
“therapeutic range” or “therapeutic window”
Estimates the margin of safety of a drug
“low” or “narrow” therapeutic index
have a “narrow margin” of safety
serum drug levels monitored
ex - Digoxin, anticonvulsants, Gentamycin
“high” therapeutic index
have a wide margin of safety
Less danger
Peak serum level
Highest plasma concentration
Peak time will vary depending on drug and route
Drug guide will tell you the proposed peak time
Blood sample is drawn at the proposed peak time
Trough serum level
Lowest plasma concentration
Blood is drawn before the next dose is due
Side Effect
Predictable “secondary effect”
Sometimes harmless and beneficial
Sometimes causes injury
Toxic Effect:
When a drug accumulates in the blood above a therapeutic level
Idiosyncratic Reaction
Unpredictable.
Client overreacts or underreacts to a drug
Allergic Reaction
Unpredictable immune response
May be mild or severe
Carcinogenic
Ability of medications, environment and chemicals to cause cancer
Teratogenic
Drug induced birth defect from a teratogen
highly dependent on when given in pregnancy
Physical Dependence
Patient’s body has adapted to drug due to prolonged exposure – will experience withdrawal symptoms if drug is discontinued
Drug interactions
An altered effect of a drug as a result of an interaction with another drug, nutrient or plasma/electrolyte levels
Pharmacokinetic Drug Interactions
Changes that occur in the absorption, distribution, metabolism or elimination
Pharmacodynamic Drug Interactions
Changes that occur in the drug’s effect on the body
Include Additive, Synergistic, or Antagonistic effects
Enzyme Inducers
will increase the metabolic rate of other drugs
Increase in metabolism will likely cause rapid drug excretion and a decrease in drug concentration in the blood
“Enzyme Inhibitors”
Drugs that inhibit the CYP Enzymes are “inhibitors”
Example : Cimetidine
Enzyme Inhibitors will decrease the metabolic rate of other drugs
If metabolism is decreased, the plasma concentrations of the other drugs will be increased
Toxicity is likely
Additive Effect
When two drugs with similar action are administered
Can be desirable or undesirable
Example: Codeine and Acetaminophen
Synergistic Effect
One drug potentiates the other
Clinical effect is substantially greater than the combined effect of the two
The effect can be desirable or undesirable
Example: Alcohol and a Narcotic
Drug- nutrient interactions
Foods/nutrients can bind with drugs, causing less or slower drug absorption
ex. tetracycline w/ dairy
theophylline w/ caffeine
Drug/lab considerations
Abnormal plasma or serum electrolyte concentrations can affect certain drug therapies
Example:
Patient with a decreased serum potassium level or an increase in serum calcium level will be more prone to Digoxin Toxicity
