unit 2 Flashcards
bioavailability
the amount of drug in the blood that is free to bind at specific target sites to elicit drug action
bioavailability depends on:
route of administration, absorption and distribution, binding, inactivation (metabolism), excretion
oral delivery
advantages - relatively safe, convenient, economical
disadvantages - irritation, nausea, possible destruction by acid or enzymes, complexes with substances in GI tract, relatively slow onset for emergency use, cannot be used in unconscious or uncooperative patient, possible “first-pass” effect, absorption is often irregular and incomplete
sublingual delivery
advantages - eliminates “first pass” effect, polypeptides are absorbed
disadvantages - drug can be irritating or have bad taste
rectal delivery
advantages - can be used in an unconscious patient, can be used in vomiting patient, relatively rapid absorption, eliminates first pass effect, convenient for administering drugs to neonates and young children
disadvantages - lack of compliance
intravenous delivery
advantages - complete dose enters the blood, rapid onset of action, controllable rate of absorption, sterile conditions are needed
disadvantages - not easy for self medication, drug must be water soluble, can be painful
subcutaneous delivery
advantages - by altering the vehicle, the duration of action of many drugs can be prolonged, pellets can be used
disadvantages - irritating drugs cannot be used, absorption cannot usually be controlled
intramuscular delivery
advantages - rapid absorption of drugs in aqueous solutions, can use depot forms and thereby prolong the duration of action of many drugs
disadvantages - irritation is a slight problem, possible injection into blood vessel
intraperitoneal delivery
advantages - rapid absorption
disadvantages - infection and adhesions
intra-arterial delivery
advantages - high concentration in a particular organ or area
disadvantages - difficult access, danger of hemorrhage
intraspinal delivery
advantages - ensure entry into CNS
disadvantages - difficult technique
inhalation delivery
advantages - very rapid absorption
disadvantages - best for gaseous and volatile liquids, must use aerosol of very fine particle size if drug is not volatile; hard to control the amount of dose absorbed, irritation
topical delivery
advantages - usually produces a local effect without systemic effects, but can also be used for producing systemic effects
disadvantages - possibility of the absorption of a large amount of drug into blood, drug must not be irritating
intracranial delivery
advantages - primarily for experimental use, parenchymal, intraventricular
absorption of drugs
molecules cross membranes by:
- simple diffusion
- facilitated diffusion
- active transport
-gated channels
- pinocytosis/exocytosis
factors that determine the passage of molecules across membranes
solubility, size, polarization, ionization
drugs tightly bound to plasma proteins
have a limited distribution to tissues
tissues involved in metabolisms and excretion
tend to concentrate drugs and or drug metabolites
amine drugs
amphetamine, imipramine are usually found in high concentrations in tissues
acidic drugs
often highly bound to plasma proteins and are not found in very high concentration in tissues
the highest concentrations of a drug are not necessarily
found in those tissues in which it exerts its action(s)
the degree of distribution depends on
the delivery of the drug by the circulatory system, the ease of the drug crosses membrane barriers and the extent the drug is bound to plasma proteins
many drugs bind _____ to albumin and certain globulins in the plasma
reversibliy
many drugs that are highly bound to plasma protein
may compete with or displace one another from binding sites. this may be the mechanism of dangerous drug interactions when two or more highly bound drugs are in the blood at the same time
plasma protein binding sites
may become saturated so that marked increases in the plasma concentrations of the free drug may result after further administration of the drug
blood brain barrier
primarily composed of endothelial cells of brain capillaries. it functionally acts as a lipid barrier with pores. there are tight junctions between the endothelial cells, and this also restricts the movement of soleus out of the capillaries. lipid soluble drugs pass the blood brain barriers much more readily than do more water soluble compounds.
therapeutic range definition
the relationship between plasma levels and the therapeutic response, high enough that the drug is effective but not too excessive that it cant be excreted
advantages of establishing the therapeutic range
patient adherence, avoid toxicity, reduce costs of therapy
drug metabolism
metabolism converts drug to more hydrophilic compounds - mostly excreted as urine
biotransformation reactions phase 1
introduce or unmask a chemically functional group - the part of the drug that is reactive
biotransformation reactions phase 2
combines a functional group with an endogenous substance - something that is made in the body is attached to the functional group
- the liver is pivotal in these phases
sites of drug metabolism
liver, first pass effect, cellular location is the endoplasmic reticulum, cytochrome
enzyme induction
can be induced so there are more enzymes available, as there are more enzymes present it can be metabolized quicker - this can lead to build up a tolerance to the drug
drugs often cross reaction
alcohol might induce enzymes in an alcoholic that has an impact on a specific drug that they take
prodrugs
not active in the form that they are given, they need to be metabolized before they are active
drug excretion
important for terminating drug action, various routes, but kidney is primary
renal excretion
filtration, diffusion, active transport
renal excretion can be increased by:
increasing urine volume, changing the pH of urine, increasing blood flow to kidneys
other routes of excretion
liver, GI tract, lungs, mammary glands, salivary glands, sweat glands
pharmacodynamics
how the drug interacts at a cellular level
receptor theory
the application of receptor models to explain drug behavior
- concept of a receptor was introdued in the early 1900s
ligand
a molecule that binds to a receptor with some selecitivty
receptor agonist
a molecule that binds to a receptor to produce a biological response
receptor antagonist
a molecule that binds to a receptor and blocks or dampens a biological response
concept of a receptor
receptors largely determine the quantitative relations between does or concentrations of drug and pharmacologic effects, receptors are responsible for selectivity of drug action - the confirmation, the shape of the drug is important
- receptors mediate the actions of pharmacological antagonists
dose response
therapeutic index = lethal dose 50/effective does 50
mechanisms of producing desired and toxic effects
beneficial and toxic effects mediated by same receptors in the same tissues, beneficial and toxic effects mediated by identical receptors but in different tissues or by different effector pathways, mediated by different types of receptors
idiosyncratic drug response
a genetically determined abnormal response to a chemical
hyporeactive
resistance to respond to a drug
hyperreactive
response to a very low dose (innate)
hypersensitivity
allergic or immunologic response
tolerance
decreased responsiveness that is acquired
sensitization
acquired enhanced responsivess to a drug
supersensitivity
results from denervation or antagonist treatment
tachyphylasic
decreased responsiveness that is acquired rapidly
cross tolerance
tolerance to one drug that results in tolerance to another
sex differences and drug action
related to basal metabolism rate, differences in relative amounts of different tissues, women on oral contraceptives metabolize drugs at a slower rate
active transport
the movement of ions or molecules across a cell membrane into a region of higher concentration, assisted by enzymes and requiring energy
agonist
a drug or substance that binds to a receptor inside a cell or on its surface and causes the same action as the substance that normally binds to the receptor
