introduction Flashcards
pharmacology
study of how drugs act on the body and how the body responds to the drugs-includes actions, mechanisms, uses and adverse effects of drugs
pharmokinetics
absorption, distribution, metabolism, and excretion
mechanism of action
the detailed interaction with a specific site in the body to describe how a drug produces an affect in the body
pharmacodynamics
the body’s physiologic response to a drugr
absorption
movement of a drug from its site of administration into the blood-enteral (oral/GI tract) and parenteral (injection) or other routes
distribution
drug movement from the blood to the interstitial space of tissues and from there into cells
distribution is impacted by
blood flow, ability of drug to exit vascular system, and ability of drug to be absorbed by cells
volume of distribution
proportion constant that estimates the total amount of drug in the body to the plasma concentration at any given time
VD=amount of drug in body/plasma concentration of drug
drugs with high VD have greater
extravascular concentrations
metabolism
break down by liver enzymes or other enzymatic processes; metabolites may be the active drug or can be harmful if built up in the body
excretion
primarily refers to renal excretion, but can be fecal, breast milk, sweat, or other means for the drug of active drug metabolites to exit the body
intravenous (IV) absorption pattern
instantaneous
intravenous (IV) advantages
rapid onset –> ideal for emergencies
precise control over drug levels
permits use of large fluid volumes
permits use of irritant drugs
intravenous (IV) disadvantages
irreversible
expensive
inconvenient
difficult to do–>not suitable for self-administration
risk of fluid overload, infection, embolism
drug must be water soluble
intramuscular (IM) barriers to absorption
capillary wall-easy to pass
intravenous (IV) barriers to absorption
none
intramuscular (IM) absorption pattern
rapid with water-soluble drugs
slow with poorly soluble drugs
intramuscular (IM) advantages
permits use of poorly soluble drugs
permits use of depot preparations
intramuscular (IM) disadvantages
possible discomfort
inconvenient
potential for injury
subcutaneous (subQ) barriers to absorption
capillary wall-easy to pass
subcutaneous (subQ) absorption pattern
rapid with water-soluble drugs
slow with poorly soluble drugs
subcutaneous (subQ) advantages
permits use of poorly soluble drugs
permits use of depot preparations
subcutaneous (subQ) disadvantages
possible discomfort
inconvenient
potential for injury
oral (PO) barriers to absorption
epithelial lining of GI tract
capillary wall
oral (PO) absorption pattern
slow and variable
Oral (PO) advantages
easy convenient inexpensive ideal for self-medication potentially reversible-->safer than parenteral routes
oral (PO) disadvantages
variability
possible nausea/vomiting from local irritation
patient must be conscious and cooperative
inactivation of some drugs by gastric acid/digestive enzymes
most metabolism takes place in the
liver
most metabolism is performed by
a group of enzymes called cytochrome P450 system or CYP P450
cytochrome P450 System (CYP P450)
a group of 12 closely related enzyme families
each family is further designated to identify key individual enzymes
what are the 3 CYP families responsible for metabolizing drugs?
CYP1, CYP2, CYP3
metabolism can result in
metabolism can result in
first-pass effect
rapid hepatic inactivation of certain drugs upon oral absorption and “first pass” through the liver
half-life
the amount of time it takes for 50% of the drug to be eliminated (renally, liver metabolism, or other forms of excretion-often a combination)
the 3 big characteristics of the ideal drug
effective
safe-often can be a risk vs. benefit discussion
selectivity-limited side effects/ADRs/ADEs
additional desirable properties of the ideal drug
reversible action predictability ease of administration limited drug interactions low cost reasonable chemical stability
agonist
stimulates a particular receptor
antagonist
blocks a particular receptor
competitive inhibition
the antagonist must have a stronger affinity for the receptor than the agonist
non-competitive inhibition
irreversibly binds
partial agonist
only partially activates the receptor-prevents a ceiling effect
enzyme inhibitor
blocks a particular enzyme crucial in a biologic pathway
dose-response relationship determines
minimum amount of drug to elicit a response
maximum response that can be elicited
dosage to produce desired increase in response
maximal efficacy
maximum response a drug can elicit
potency
the amount of drug we must give to elicit a response
drug interactions
occur when two or more drugs change the therapeutic effect (increase or decrease) OR lead to adverse events
can be a result of multiple drugs that treat the same condition or treating multiple conditions with different drug classes
at times is due to changes in hepatic enzyme activity
CYP 3A4 inducers cause CYP 3A4 enzymes to
metabolize more than usual–>decreases therapeutic effect
CYP 3A4 inhibitors cause CYP 3A4 enzymes to
metabolize less than usual–>increases risk of side effects and increases therapeutic effect, at times to toxicity
minimizing drug interactions
limit the number of drugs a patient is on
obtain a thorough medication history
tailoring specific drug therapy to reduce adverse interactions
tailoring specific drug therapy to reduce adverse interactions
adjust doses in the presence of inducers/inhibitors
adjust timing of administration to minimize interference with absorption
monitoring more closely in additive or known agents that have drug interactions
extra caution when a patient is on a drug with a known narrow therapeutic range
grapefruit juice
CYP 3A4 inhibitor-increases blood level of drugs
adverse drug reactions
any noxious, unintended, and undesired effect that occurs at normal drug doses
allergic reaction/anaphylaxis
more common with some classes of agents-all drugs have a listed ‘contraindication for those allergic to agent or agents similar in structure’
other common ADRs
idiosyncratic carcinogenic teratogenic (birth defect inducing) hepatotoxic nephrotoxic QT interval prolonging drugs
idiosyncratic ADR
uncommon drug response resulting from genetic predisposition
medication guides
FDA approved patient education documents with information on how to minimize harm from potentially dangerous drugs-required for certain drugs (including sample dispensing)
US boxed warnings
strongest safety warning a drug can carry and still remain on the market-vitally important to adhere to and understand
Risk Evaluation and Mitigation Strategies (REMS)
a plan or program to minimize drug induced harm
practical therapeutics
the treatments used to treat or prevent a particular disease
combination of pharmacology, pharmacokinetics, pharmacodynamics, DDIs, ADRs, and individual variation in addition to the clinical literature and the expert clinical guidelines
last-line agents are reserved for patients with specific criteria
significant ADRs, multiple treatment failures, or other extenuating circumstances
