LECTURE 5

Question 1

PHARMACODYNAMICS

Answer 1

WHAT DRUG IS DOING W/IN FUNCTIONAL SYSTEM

Question 2

PHARMACOKINETICS

Answer 2

HOW DRUG GETS METABOLIZED W/IN SYSTEM

Question 3

PHARMACOLOGY

Answer 3

STUDY OF PRECISE CONTROL OF BIOLOGICAL FUNCTIONS OF EXOGENOUS APPLICATIONS OF CHEMICALS
CENTRAL PRINCIPLE - FUNCTIONAL RELATIONSHIP BETWEEN DRUG CONCENTRATION AND BIOLOGICAL RESPONSE = THE DOSE RESPONSE FUNCTION

Question 4

LIGAND

Answer 4

BINDS TO A BIOMOLECULE (I.E. PROTEIN RECEPTOR/CHANNEL)

Question 5

BIOMOLECULE

Answer 5

LIPIDS, CARBOHYDRATES, PROTEINS, NUCLEIC ACIDS (RECEPTORS - BIOMOLECULES THAT INITIATE A BIOLOGICAL FUNCTION WHEN A LIGAND BINDS TO IT)

Question 6

AGONIST

Answer 6

(TYPE OF LIGAND) STIMULATES A BIOLOGICAL RESPONSE (CAN BE INHIBITORY OR EXCITATORY)

Question 7

4 MAJOR CATEGORIES OF PROTEIN RECEPTORS

Answer 7

1. ) CELL-SURFACE RECEPTORS
2. ) TRANSPORTERS AND PUMPS
3. ) ENZYMES - CAN INHIBIT OR PROMOTE
4. ) KINASES - REGULATE ACTIVITY OF OTHER PROTEINS IN THE CELL

Question 8

CELL-SURFACE RECEPTORS

Answer 8

(GPCRs, ION CHANNELS) TRANSLATE INFO ON OUTSIDE OF CELL TO BIOLOGICAL MEANINGFUL RESPONSE ON THE INSIDE

Question 9

TRANSPORTERS AND PUMPS

Answer 9

MOVE IONS/MOLECULES ACROSS MEMBRANES (EFFLUX PUMPS)

*PARTICIPATE IN MAINTAINING THE CHEMICAL GRADIENT AND REUPTAKE NEUROTRANSMITTERS IN CLEFT BACK INTO THE CELL

Question 10

ENZYMES

Answer 10

CONVERT STARTING MATERIAL INTO NEW USABLE PRODUCTS

Question 11

KINASES

Answer 11

REGULATE ACTIVITY OF OTHER PROTEINS THROUGHOUT CELL BY PHOSPHORYLATION (REMOVE PHOSPHATE FROM ATP AND RE-LIGATING IT TO A PROTEIN IN NEED)

Question 12

AFFINITY

Answer 12

ABILITY OF A DRUG TO GET TO A RECEPTOR
AT EQUILIBRIUM (BINDS AND DISASSOCIATES), A SPECIFIC AMOUNT OF DRUG WILL OCCUPY A FIXED PERCENTAGE OF RECEPTORS AT ANY GIVEN MOMENT IN TIME
DRUGS THAT ENGAGE W/ A RECEPTOR FOR > PERIODS OF TIME => > AFFINITY
BASED ON THE 3D STRUCTURE OF MOLECULE AND ITS ABILITY TO BIND TO THE ENZYME/RECEPTOR
(Kd) - DRUG CONCENTRATION AT WHICH 50% OF RECEPTORS ARE OCCUPIED
K2/K1 = Kd (RATE OF DISSOCIATION/RATE OF ASSOCIATION)
DRIVES PHARMACOLOGICAL ACTION - IF DRUG CAN’T GET TO RECEPTOR NOTHING WILL HAPPEN

Question 13

AGONIST

Answer 13

BIND TO RECEPTORS VIA A WEAK, REVERSIBLE BOND (A + R –> AR –> EFFECT)
EFFICACY -
EFFECT IS COMPLETELY RELATED TO DOSE
RESPONSE TO AGONIST IS NOT ALWAYS LINEARLY PROPORTIONAL TO THE NUMBER OF RECEPTORS OCCUPIED

BOTH EFFICACY AND AFFINITY ARE BASED ON 3D STRUCTURE

Question 14

EFFECT RESPONSE

Answer 14

SUPERAGONIST/HIGH EFFICACY AGONIST (FEW RECEPTORS OCCUPIED => FULL EFFECT) > PARTIAL AGONIST (100% RECEPTORS OCCUPIED) > ANTAGONISTS (NO INTRINSIC EFFICACY)

Question 15

ANTAGONISTS

Answer 15

BLOCK RECEPTORS TO PREVENT AGONSTS FROM BINDING
PRODUCE NO EFFECT
BLOCK ACTION OF AGONIST - ONLY HAVE TO BLOCK/ALTER OPENING TO FUNCTION
DOSE RELATED EFFECTS
ANTAGONISTS ARE EITHER COMPETITIVE OR NON-COMPETITIVE
BIND VIA WEAK, REVERSIBLE CHEMICAL BONDS

Question 16

EC50

Answer 16

EFFECTIVE DRUG CONCENTRATION AT 50% EFFECTIVE = USED TO COMPARE POTENCY
AFFINITY OF PARTIAL AGONIST/FULL AGONIST = SAME; HOWEVER, EFFICACY IS DIFFERENT
HIGH POTENCY = HIGH EFFICACY

Question 17

NON-COMPETITIVE ANTAGONIST

Answer 17

BIND TO ALTERNATIVE SITE ON RECEPTORS WHICH CHANGES THE 3D SHAPE OF AGONST-BINDING SITE
DIFFERENT PHARMACOLOGICAL RESPONSE THAN COMPETITIVE ANTAGONIST
FULL EFFECT OF AGONIST IS NOT ACHIEVED
AGONIST CONCENTRATION DOES NOT MATTER B/C IT IS NOT COMPETING W/ THE SAME SITE
CAN’T COMPARE THE EC50 OF AGONIST

Question 18

COMPETITIVE ANTAGONIST

Answer 18

BIND TO THE SAME SITE AS AGONIST

Question 19

IC50

Answer 19

WHAT CONCENTRATION OF ANTAGONIST => 50% BLOCKADE

Question 20

PHARMACOKINETICS (ADME)

Answer 20

ABSORPTION - ACHIEVING SIGNIFICANT BLOOD CONCENTRATION OF A DRUG W/ A SPECIFIC ADMINISTRATION
DISTRIBUTION - GETTING DRUG TO THE TARGET
METABOLISM - PROCESSING OF THE DRUG ONCE IN THE BODY
ELIMINATION - GETTING RID OF THE DRUG
DRUG CONCENTRATION AT TARGET DETERMINED BY THESE FACTORS

Question 21

GRAPHING DRUG CONCENTRATION TO TIME

Answer 21

INCREASED DOSE TO CMAX = ABSORPTION
TMAX = TIME REQUIRED TO REACH MAX BLOOD CONCENTRATION FOR A SPECIFIC DOSE
CMAX = MAX BLOOD CONCENTRATION FOR A SPECIFIC DOSE
T1/2 = HALF LIFE OF A DRUG - IMPORTANT FOR DOSING A DRUG TO MAKE SURE THAT THE BODY ISN’T COMPLETELY DEPLETED OF A DRUG

ADME HELPS W/ DOSING

Question 22

BIOAVAILABILITY

Answer 22

AMOUNT OF A DRUG AVAILABLE FOR THERAPEUTIC ACTIVITY
IV = 100% > INTRAMUSCULAR > SUBCUTANEOUS > INHALATION > TRANSDERMAL > RECTAL (PARTIALLY BYPASSES 1ST PASS EFFECT (AS DOES IV ADMIN.)) > SUBLINGUAL > SPINAL/BRAIN > ORAL
IM/SC DELIVERY REQUIRES A LIPOPHILIC DRUG => LONG ONSET

IV = 100% JUST MEANS THAT 100% OF THE DRUG IS IN THE BLOOD DOESN’T MEAN AMOUNT AVAILABLE FOR ACTION

Question 23

ORAL ADMINISTRATION

Answer 23

ORAL = SUBJECT TO 1ST PASS EFFECT WHERE MOST DRUGS GET ABSORBED IN THE STOMACH/SM. INTESTINE

• WHATEVER IS ABSORBED HERE –> LIVER => METABOLIZED DRUGS
• METABOLIZED IN THE LIVER OR LUNGS (CYTOCHROME P450) => MORE HYDROPHILIC METABOLITE (FAVORS EXCRETION)

Question 24

TRANSDERMAL ADMINISTRATION

Answer 24

TD = GOOD FOR PPL W/ GI ISSUES (DRUG PERMEATES SC LAYER)

Question 25

LIVER METABOLISM

Answer 25

50% OF ALL DRUGS METABOLIZED BY CYP-3A (DRUG COMBINATIONS CAN EXCITE OR INHIBIT CYP-3A ACTIVITY) SMOKING INHIBITS CYP-3A ENZYMATIC ABILITY - DOSE OF DRUG DECREASES DRUG:DRUG INTERACTIONS

Question 26

FACTORS THAT MODIFY DRUG METABOLISM

Answer 26

GENETIC POLYMORPHISM DOSE OVERLOAD OF ENZYME CAPACITY AGE - ENZYME MAKEUP - OLD AND YOUNG AT RISK FOR DRUG METABOLISM ISSUES DISEASE (DOSE-ADJUSTMENT COMMON) - I.E. LIVER DISEASE, RENAL DISEASE SEX - M/F SEX DIFFERENCES SMOKING DIET - VEGANS HAVE LESS ENZYMES

Question 27

SPECIAL PROPERTIES OF A DRUG TO PAY ATTENTION TO:

Answer 27

1. ) TARGET 2. ) WHAT ENZYMES METABOLIZE IT 3. ) EXCRETION

Question 28

ENZYME-INDUCED DRUG

Answer 28

DRUG:DRUG INTERACTION - WHEN A DRUG IS ONBOARD, METABOLISM OF WHATEVER IS BEING BROKEN DOWN BY PARTICULAR ENZYME WILL INCREASE (CYP2D6) ASPIRIN = ENZYME-INDUCED (CAUSES AN INCREASE IN METABOLISM OF THE DRUG IN COMBINATION - GRAPE FRUIT JUICE AS WELL) INCREASED METABOLISM => DECREASED EFFICACY/POTENCY

Question 29

ENZYME-INHIBITING DRUG

Answer 29

DRUG:DRUG INTERACTION - WHEN A DRUG IS ONBOARD, METABOLISM OF WHATEVER IS BEING BROKEN DOWN BY PARTICULAR ENZYMES WILL DECREASE (CYP2D6) INCREASED POTENCY AND POSSIBILITY OF OVERDOSING

Question 30

POLYMORPHISMS IN LIVER

Answer 30

CAUSE DIFFERENTIATION BETWEEN PEOPLE AND THEIR METABOLISM OF THE SAME DRUG (PHARMACOGENOMICS) PERSON:DRUG INTERACTIONS RAPID METABOLIZERS - DECREASED DRUG POTENCY/EFFICACY SLOW METABOLIZERS - INCREASED DRUG POTENCY/EFFICACY (CAUSES TOXICITY)

Question 31

DOSE RESPONSE CURVE

Answer 31

``` CONCENTRATION = EXOGENEOUS FLUID (MG/ML) DOSE = EXOGENEOUS FLUID ADMINISTERED TO A PATIENT (MGML^-1KG^-1) ``` SHOWS EFFICACY AND AFFINITY AFFINITY AND POTENCY ARE VERY CLOSELY RELATED COMPARE DRUGS @ EC50 W/ ADDED ANTAGONIST, AGONIST CURVE WILL SHOW PARALLEL SHIFTS TO THE RIGHT (COMPETITIVE - DOESN'T MATTER FOR NON-COMPETITIVE) - CAN OVERWHELM ANTAGONIST W/ HIGHER CONCENTRATIONS OF AGONIST W/NON-COMPETITIVE ANTAGONIST - SHIFT = TO THE RIGHT AND DOWN B/C AGONIST CAN NEVER GET TO FULL EFFECT B/C IT CAN'T BIND

Question 32

NON-SURMOUNTABLE ANTAGONIST

Answer 32

BINDS JUST LIKE THE COMPETITIVE ANTAGONIST AND DOESN'T DISASSOCIATE - SEE THE SAME PATTERN OF ANTAGONISM AS A NON-COMPETITIVE ANTAGONIST

Question 33

PORTAL SYSTEM

Answer 33

UPPER 1/3 OF INTESTINE SYSTEM THAT ABSORBS THE MEDICINE TO THE LIVER SOME METABOLISM OCCURS IN LUNGS AS WELL

Question 34

METABOLITES

Answer 34

WHEN METABOLIZED - PARENT DRUG BREAKS DOWN INTO METABOLITES LESS POTENT B/C THEY ARE MORE HYDROPHILIC AND THIS PROMOTES EXCRETION THEY ARE LESS ACTIVE THAN PARENT DRUG - EXCEPT PRO-DRUGS