Lecture 1

Question 1

what are the usage of these types of drugs:

1. therapeutic
2. diagnostic
3. prophylactic

Answer 1

1. thera=to treat certain conditions
2. diag=to assess current state of health
3. prophylactic=to prevent disease state

Question 2

what are pharmacodynamics

-2 things

Answer 2

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)

Question 3

what are the 6 drug targets

Answer 3

1. receptors
2. ion channels
3. enzymes
4. transporters (symporters/antiporters)
5. nucleic acids
6. idiosyncratic targets
   - ions, GI contents, etc

Question 4

what is an agonist? what are the 2 types

Answer 4

activates the target
full=mimics response of natural ligant
partial=lower efficacy than full agonist

Question 5

what is an antagonist?

how can it bind

Answer 5

neutral: prevents the target from signalling

- can bind competivielty (to active site) or non competivetly (somewhere to prevent active site being accessed)

Question 6

what is an inverse agonist

Answer 6

reduces basal receptor activity below baseline

Question 7

what does the dose responsive curve (DR) give information about

Answer 7

potency and efficacy

-exsists both for therapeutic and side effects of a drug

Question 8

what is potency

what is efficacy

Answer 8

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

Question 9

what is ED50?

what is LD50?

Answer 9

ED50=dose needed to be effective in 50% of indiv

LD50(TD50)= dose needed to kill 50% of subjects, T=toxic

Question 10

what is the therapeutic index

what is the ideal number for this

Answer 10

LD50/ED50
ideally want this ratio to be infinite
wnat ED50 < < < < < < LD 50

Question 11

what is the therapeutic window

Answer 11

concentration range wehre drug is effective w/o side effects
-large TI is good and means

Question 12

what does a large therapeutic index mean

Answer 12

a much greater dosage is required for toxic or lethal effects compared to the dosage for therapeutic benefits

Question 13

what is pharmacokinetics

Answer 13

examines the processes affecting the fate of drugs in the body

Question 14

what are the steps to pharmakokinetics

Answer 14

absorption
distribution
metabolism
elimination

Question 15

what are route of administration of drugs

Answer 15

oral 
parenteral (IV, IM, SC) 
sublingual (under tonue) 
inhalation 
topical/transdermal patch 
rectal

Question 16

what are the advantages and disadvantages to oral delivery

Answer 16

advantages 
-easy 
-high compliance
disadvangtage 
-first pass metabolism 
-may be modified by digestive enzymes or stomach acid

Question 17

what is bioavailability

Answer 17

amount of administered drug that actually enters the circulation

Question 18

what affects bioavailabilty

Answer 18

absorption

first-pass metabolism

Question 19

what are the key factors of drug distribution

Answer 19

• chemical structure of drug (ease of transport through membrane)
• blood flo w
• plasma protein binding (albumin)

Question 20

what cna albumin affect

Answer 20

distribution
metabolism
elimination

Question 21

what is aparent volume of distrubution

Answer 21

dose/ [drug]

Question 22

what kind of avd does blood only have?
blood+tissues?
fat?

Answer 22

blood only=low AVD
blood+tissues=high AVD
fat=very high AVD

Question 23

wehre does most metabolism happen

Answer 23

liver

Question 24

what is the first pass effect

Answer 24

most oral drugs undergo processing/metabolism in the liver prior to having access to its target

Question 25

what is phase 1 and phase 2 or metabolism

Answer 25

phase 1: oxidation by CYP450 enzymes
-results in active metabolite
phase 2: conjugation

drug=> phase 1=> derivative=> phase 2

Question 26

how does elimination happen

Answer 26

1. kidney=> urine through glomerular filtratoin ( bile=> feces
2. sweat
3. respiration

Question 27

what is elimination kinetics affected by

Answer 27

metabolism and elimination rate

Question 28

what is first order elimination kinetics

what is zero order

Answer 28

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

Question 29

what is clearance

Answer 29

the volume of blood or plasma filtered per unit of time to account for the drop of drug concentration

Question 30

how can clearance be measured

Answer 30

not measured directly, determined by drop in concentration with time

Question 31

when do you need to take special care when prescribing medication

Answer 31

1. patient is infant/child
2. pregnant women
3. elderly (renal health main consideration)

Question 32

what is an infants change in ADME

Answer 32

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

Question 33

what does bilirubin do in infants

Answer 33

binds albumin to blood

Question 34

in infants, the drug can compete w/ bilirubin for albumin binding sites which lead to what

Answer 34

increase in bilirubin =>kernicterus

Question 35

what happens in kernicterus

Answer 35

neurological deficits, seizures, abnormal reflees and eye movements

Question 36

if the patient is pregnant what changes can occur

Answer 36

changes in AVD
chaignes in CYP450 levels
will it cross into the fetus?
-placenta not a great barrier, can alter/met drugs

Question 37

what are the infectious agents

Answer 37

Toxoplasmosis 
Other (ex syphillis) 
Rubell a
Cytomegalovirus 
Herpex Simplex

Question 38

is absorption affected by age

Answer 38

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)

Question 39

what avd chnages occur when old

Answer 39

increase in fat%
decrease in water%
decrease in protein binding (more free drug, slightly compensating by increase in metabolism)

Question 40

what are the changes in metabolism/exretion whne old

Answer 40

• phase 1 rxns are impaired (cyp expression decreased_
• phase 2 unaffected
• decrease in kidney function w/ age (GFR substantially decreases)