Lecture 1 Flashcards
what are the usage of these types of drugs:
- therapeutic
- diagnostic
- prophylactic
- thera=to treat certain conditions
- diag=to assess current state of health
- prophylactic=to prevent disease state
what are pharmacodynamics
-2 things
entails the biochemical and physiological effects of drugs (what a drug does) AND their mechanism of action (how the drug has an effect and the correlation of drug action w/ their chem structure)
what are the 6 drug targets
- receptors
- ion channels
- enzymes
- transporters (symporters/antiporters)
- nucleic acids
- idiosyncratic targets
- ions, GI contents, etc
what is an agonist? what are the 2 types
activates the target
full=mimics response of natural ligant
partial=lower efficacy than full agonist
what is an antagonist?
how can it bind
neutral: prevents the target from signalling
- can bind competivielty (to active site) or non competivetly (somewhere to prevent active site being accessed)
what is an inverse agonist
reduces basal receptor activity below baseline
what does the dose responsive curve (DR) give information about
potency and efficacy
-exsists both for therapeutic and side effects of a drug
what is potency
what is efficacy
potent=the more potent the less drug you need
-related to concentration of a mg, NO EFFECT
efficacy=the more efficacious, the greater the maximal effect
-related to maximal therapeutic effects
what is ED50?
what is LD50?
ED50=dose needed to be effective in 50% of indiv
LD50(TD50)= dose needed to kill 50% of subjects, T=toxic
what is the therapeutic index
what is the ideal number for this
LD50/ED50
ideally want this ratio to be infinite
wnat ED50 < < < < < < LD 50
what is the therapeutic window
concentration range wehre drug is effective w/o side effects
-large TI is good and means
what does a large therapeutic index mean
a much greater dosage is required for toxic or lethal effects compared to the dosage for therapeutic benefits
what is pharmacokinetics
examines the processes affecting the fate of drugs in the body
what are the steps to pharmakokinetics
absorption
distribution
metabolism
elimination
what are route of administration of drugs
oral parenteral (IV, IM, SC) sublingual (under tonue) inhalation topical/transdermal patch rectal
what are the advantages and disadvantages to oral delivery
advantages -easy -high compliance disadvangtage -first pass metabolism -may be modified by digestive enzymes or stomach acid
what is bioavailability
amount of administered drug that actually enters the circulation
what affects bioavailabilty
absorption
first-pass metabolism
what are the key factors of drug distribution
- chemical structure of drug (ease of transport through membrane)
- blood flo w
- plasma protein binding (albumin)
what cna albumin affect
distribution
metabolism
elimination
what is aparent volume of distrubution
dose/ [drug]
what kind of avd does blood only have?
blood+tissues?
fat?
blood only=low AVD
blood+tissues=high AVD
fat=very high AVD
wehre does most metabolism happen
liver
what is the first pass effect
most oral drugs undergo processing/metabolism in the liver prior to having access to its target
what is phase 1 and phase 2 or metabolism
phase 1: oxidation by CYP450 enzymes
-results in active metabolite
phase 2: conjugation
drug=> phase 1=> derivative=> phase 2
how does elimination happen
- kidney=> urine through glomerular filtratoin ( bile=> feces
- sweat
- respiration
what is elimination kinetics affected by
metabolism and elimination rate
what is first order elimination kinetics
what is zero order
first: constant t half life, takes 4-5 half lives to remove drug from body
- plasma [drug] decreases exponentially w/ time
- most drugs
zero: no half life, rate of elimination constant
- constant amount of drug metabolized per unit of time
- eliminate faster
- larger dosage=longer time
what is clearance
the volume of blood or plasma filtered per unit of time to account for the drop of drug concentration
how can clearance be measured
not measured directly, determined by drop in concentration with time
when do you need to take special care when prescribing medication
- patient is infant/child
- pregnant women
- elderly (renal health main consideration)
what is an infants change in ADME
A: skin more permeable
-high gastric pH, slower emptying, lack of flora
D: infants are high % water => AVD changes
M: CYP450 enzymes are poorly expressed initially
-conjunction takes months to develop
E: glomerular filtration requires 2 wks to mature
-tubular secretion takes several months
what does bilirubin do in infants
binds albumin to blood
in infants, the drug can compete w/ bilirubin for albumin binding sites which lead to what
increase in bilirubin =>kernicterus
what happens in kernicterus
neurological deficits, seizures, abnormal reflees and eye movements
if the patient is pregnant what changes can occur
changes in AVD
chaignes in CYP450 levels
will it cross into the fetus?
-placenta not a great barrier, can alter/met drugs
what are the infectious agents
Toxoplasmosis Other (ex syphillis) Rubell a Cytomegalovirus Herpex Simplex
is absorption affected by age
not significantly bc indiv changes in absorption cancel net change
- increased gastric pH
- decreased gastric emptying
- slowed GI motility
- thinning of Gi tract
- reduced splanchnic flow (blood flow around GI tract)
what avd chnages occur when old
increase in fat%
decrease in water%
decrease in protein binding (more free drug, slightly compensating by increase in metabolism)
what are the changes in metabolism/exretion whne old
- phase 1 rxns are impaired (cyp expression decreased_
- phase 2 unaffected
- decrease in kidney function w/ age (GFR substantially decreases)
