Basic Principles VI Flashcards
drug administration
-absorption and elimination can occur simultaneously
steady state
- drug enters a compartment at a constant rate and is eliminated in a manner proportional to the concentration in the Vd
- eventually the elimination increases to equal the rate of entry and steady state is achieved
- stable plasma levels result in a stable patient dose
- continuous infusions
- ct vs number of half lives
- usually takes 4 half lives to get there
- time required to reach ss is independent of dose
- concentration at ss is directly proportional to dose, and inversely proportional to clearance
half life
- 0.693/ ke
- time required to reach Css only depends on half life
steady state 2
- Ra =Re
- absorption= clearance
individual variation
-some people have higher clearance, reach ss after two half lives or more than 4, just need to adjust dose because that changes concentration at ss in order to get desired therapeutic limit.
repeated administration
- IV or other route
- repeated administration of a fixed dose of a drug at a fixed tim interval
- first order absorption plus first order elimination
- plasma concentration reaches steady state level
achievement of a steady state
- single doses
- when dose interval is much greater than t1/2
- antibiotics, diuretic
- peaks and falls
achievement of a steady state with repeat individual doses
- when dose interval is approx equal to t1/2 or less a steady state can be achieved
- antihypertensives
- rises over min effective concentration and rises and falls within a therapeutic range
- Css = Cav
- amount of fluctuation depends on the dose and time interval
dose per unit time
- determines Css average- not route of administration
- the same dose per unit time even if given different ways results in same Css
- may have wide swings or constant rise
- wide swings may not be tolerable due to tox or subtherapeutic
achievement of steady state relationship to t1/2
- if elimination is 1st order then approach to steady state is also first order and depends on the Ke of elimination process
- it takes approx 4 times t1.2 to achieve steady state
- dose does not affect time, only concentration
- fast elimination rate= fast to SS, short half life
Css
- 2 x Cp at 1st half life
- see graph
loading doses
- rapid attainment of therapeutic plasma level (not SS)
- used to change the SS concentration
- loading dose followed by maintenance doses
- doesn’t shorted tim to SS in the plasma, just ups the concentration for immediate need
- sometimes loading dose starts to decrease before maintenance dose gets enough concentration, symptoms might come back- might need incremental loading dose
drug tox
- lots of factors
- route, time, disease, drug hx- absorption
- age, weight, sex, route- distribution
- age, sex, species, genetics, route, time, disease, drug hx- biotransformation
- age, disease, drug hx- excretion
- emotional factors
- all lead to pharmacological response
- bell curve- freq of response vs dose required- sensitive people, normal people, resistant people
iatrogenic
- may be predictable, not dose dependent
- chemo, nitro
spontaneous
- not predictable, not dose dependent
- allergy-immunolgically mediated- reproducible in same patient
- idiosyncratic- not immunologic- not necessarily reproducible
tolerance
- decreased response to continued admin
- decrease receptors
- increased metabolism
resistance
-refractoriness to the drug effect- bacteria, receptors
side effects
- secondary effects
- may be toxic, innocuous or beneficial
- secondary receptors or actions
cumulation
- drug administered faster than it can be eliminated
- increase in plasma levels- toxicity possible
drug dependence/ addiction
- tolerance
- homeostasis
- physical withdrawal syndromes
therapeutic index
- toxic dose/ therapeutic dose
- TD50/ ED50
- ideal clinical is TD1/ED99
- plotted as log dose curves and decide upper limit of therapeutic window to get most response in most people, less than 10% toxic
- TI from 50 on toxic curve over 50 from normal curve- 15/5= 3
- see graph
margin of safety
-TD50- ED50
drug interactions
- direct molecular-antacids combine with gastric acids, antibiotics and Ca
- change absorption-charcoal binds molecules
- protein binding and displacement- can create tox for old drug
- receptor effects- competitive/ non competitive inhibition
- change metabolism- induction or inhibition
- change excretion- active transport inhibitors or simple competition for a transporter
- change pH or other electrolytes- alter excretion or protein binding
unique features of newborn phys
- increased extracellular fluid
- immature enzyme systems
- decreased renal function
- constant alteration of fluid composition with age
- redistribution of circulation with shunting