Drug receptor interactions-pharmacokenitics

Question 0

Pharmacokinetic

Answer 0

Body’s effect on a drug

Question 1

Pharmacodynamic

Answer 1

Drugs effect on body

Question 2

Bioavailability

Answer 2

AUC oral availability/AUC injected availability

AUC injected = 100 % available

Question 3

Covalent therapeutics

Answer 3

Uncommon: irreversible, recovery usually reqs synthesis of new receptors. Typically longer lasting, less specific
Ex: aspirin, alkylators, organophosphates

Question 4

Hydrophobic therapeutics

Answer 4

Most common: weak acids or bases work well as drugs because they can be lipid soluble as neutral elements, or ionized and become water soluble

Question 5

Racemic mixture

Answer 5

Mix of chiral and non-chiral isomers. Extends patent

Question 6

4 things that make a drug therapeutically useful

Answer 6

Able to reach site of action
Can interact with receptor
Acceptably selective for therapeutic and adverse effects
Excreted at reasonable rate

Question 7

G protein couple receptors

Answer 7

7 transmembrane regions
Receptor act-> G protein act -> effector act -> 2nd messenger act
- Effectors: Adenylate cyclase, guanylate cyclase, phoslip C
- examples: glucagon, beta receptors, muscarinic ACh

Question 8

Competitive/non- competitive antagonist

Answer 8

Competitive: reversible, doesn’t change Emax, alters EC50
Non-competetive: irreversible, alters Emax
Both bind active site* note not all antagonist bind receptors

Question 9

EC50/ED50

Answer 9

EC50: concentration reqd to achieve 50% max effect
ED50: dose required to achieve EC50 in 1/2 the population
* Kd is dissoc. Constant. When Kd > EC50, system has spare receptors. Kd is generally a good approximation of EC50

Question 10

Therapeutic window/ index

Answer 10

Index ED50->LD50 (not clinically useful)

Window ED50 -> bottoms of index before lethality curve really begins.

Question 11

Tolerance

Answer 11

PD: drug alters body (receptors) such that drug is less effective i.e. insulin resistance.
PK: body alters drug (increased metabolism/clearance) such that drug is less effective

Question 12

Factors influencing drug absorption

Answer 12

Rate: dissolution, gastric emptying, blood flow, membrane barriers
Extent: dissolution, membrane permeability, efflux transporter substrates

Question 13

Passive diffusion of drugs

Answer 13

Most important/common; lipid soluble via PM, water soluble via aqueous pore channels. [ ] dependent

Question 14

Endocytotic drug absorption

Answer 14

B12 colobamin

Question 15

pH trapping

Answer 15

Lipid Soluble form (electroneutral) passes though PM and is the ionized and trapped as water soluble. Weak acids/bases do this, hence they tend to be ideal drug choices.

Question 16

Routes of administration

Answer 16

Greatest to least bioavailability: IV > IM > enteral

• IV has 100% bioavailability
• transdermal present other issues: formulation and physiological condition of patient make a big difference in administration
• rectal can have first pass or not depending on how high up you go. The vena cava is systemic.

Question 17

Factors affecting absorption

Answer 17

pH of drug, bloodflow, surface area (intestine more efficient that stomach), contact time, food, P-glycoproteins

Question 18

P- glycoprotein

Answer 18

Multi drug resistant transportation pore: kicks drugs out of cell
Selective, saturateable, inhabitable (grapefruit)

Question 19

Bioavailability formula

Answer 19

AUC Oral/AUC IV

Amount of viable drug available after first pass phenomena

Question 20

Cmax/Tmax

Answer 20

Cmax = [max]
Tmax = how long it takes to get to Cmax

Question 21

Vd

Answer 21

Volume of distribution
Vd = total amount of drug(dose given if IV)/plasma [drug]
Or
Vd = dose/Clearance

Question 22

Drug half life

Answer 22

(0.693xVd)/Clearance

Question 23

1st/0th order kinetics

Answer 23

Most drugs are first order
- first order elimination is proportional to concentration of drug perfusing organs. Elimination is only proportional to plasma [ ] at steady state.

Question 24

Steady state

Answer 24

When admin = clearance.

- typically this takes 4-5 half lives

Question 25

Factors effecting distribution

Answer 25

Blood flow to organ, surface area, concentration gradient of plasma protein bound drug, to tissue unbound drug.

Question 26

Peaks and troughs

Answer 26

Peak is dose dependent

Trough is time dependent

Question 27

Orphan receptors

Answer 27

Receptors above the threshold of EC50/Kd ratio

i.e. Kd > EC50

Question 28

Drug half lives N2Ks

Answer 28

1 H/L = 50%
2 H/L = 75%
3 H/L = 87.5%

Question 29

Loading dose

Answer 29

Ldose = (Vd * [desired])/bioavailability

Question 30

Maintenance dose

Answer 30

M dose = (CL * [desired])/bioavailability

Question 31

Endocytosis

Answer 31

Entry method of large molecules like proteins

Question 32

hsp90

Answer 32

Heat shock protein: steroid binding protein that unfolds DNA to initiate TXN. 30 mins -hours

Question 33

Ligand receptors

Answer 33

Growth factors (EGF, IGF, TGF) 
Insulin (Trk)

Question 34

G protein types (3 primary)

Answer 34

Gs - increase cAMP
Gi - decrease cAMP
Gq - increase IP3/DAG via Phospholipase C

Question 35

Potency vs. efficacy

Answer 35

Potency - lower EC50
Efficacy - higher Cmax
* note: make sure you know parameters (pop/pt)

Question 36

PGE function (in general)

Answer 36

Stimulator/activator

• smooth muscle contraction (Airways/uterus)?
• vascular smooth muscle contraction/parturition (+oxy)
• wakefullness
• fever
• immunosuppressive
• oncogenic

Question 37

PGD function (in general)

Answer 37

Opposite PGE

Question 38

Leukotrienes

Answer 38

• Mostly inflammatory (IBD)

- lipoxin a/b coronary vasoconstriction

Question 39

hGR - a

Answer 39

Classic glucocorticoid receptor

- inhibited by HGR - B

Question 40

hGR-B

Answer 40

Inhibits the function of bound hGR-a

Question 41

Cushings disease vs. syndrome

Answer 41

Diseases is in the brain (lots of ACTH and cortisol)

Syndrome is in the adrenals (lots of cortisol with NO ACTH)