Dose respose relationship

1. Assist Prof Dragana Drakul
Dose response relationship

2. Agonist and antagonist
 Agonist
 Antagonist
 Afinity
 Efficacy

3. Dose response relationship
 Full description of drug effect in the function of dose
[E=f(D)]
 Dose response line: dose is ploted on X-axe and the
effect is ploted on Y-axe

4. Dose response relationshhip
Graded relationship Quantal relationship
 describes a drug
effect which increases
in proportion to
increasing drug dose
• describes a drug
effect which is binary
(either present or
absent).
• A quantal response to
a drug is observed in
a population, and is
either present or
absent in any single
individual

8. THERAPEUTIC INDEX, SAFETY
FACTOR, THERAPEUTIC RANGE
 TI is the ratio of median lethal dose and median
effective dose (LD50:ED50)
 Safety factor is the range between maximal
therapeutic dose (ED99) and minimal lethal dose
(LD1).
 Therapeutic range is the range between minimal
toxic dose and minimal therapeutic dose.

11. PARAMETERS
1. Potency is correlated with affinity of drug to
receptor
2. Maximal effect represents activity (efficacy) of
drug
3. Minimal effect (treshold effect) is the minimal
measurable effect, the effect of minimal
therapeutic dose
4. Biological variability–patients could have
significantly different responses to the same
dose of drug
5. Slope is dependent on mechanism of action

12. Different doses
 Physiological  without measurable effect,
 Therapeutical (minimal, median i maximal)
 Daily (sum of all individual doses during a day),
 Toxic (induces toxic effect),
 Lethal (death)

13. Experimental part
 Experimental model– isolated guinea pig ileum
 Ileal segment 3 cm long – placed in the organ
bath.
 Guinea pig ileum is consisted of smoot muscle
cells that are involved in peristaltic movements of
GIT.
 Dilatation of ileum– activation of nuerons in
enteric nervous system – nervous impulses from
myenteric plexus and parasimpatic neurones
induces smooth muscle cells in the intestine wall-
synchronized rithmic movements toward anus.

14. Experimental part
 AcH – excitatory neurotransmiter in enteric n.s.
 AcH activates M1 i M3 receptors
 Effect?
 Organ bath for isolated organs
 Guinea pig ileum
 AIM:
 Relationship of AcH doses (increasing doses)
 And the effect (contraction or shortening of ileal
segment)

15. Organ bath

16. Ileum

17. Experimental design
Time (min:sec) Action
0:00 Printer starts
0:30 Agonist (AcH)
1:00 Printer stops, washing with fresh Tyrod solution
2:00 Washing with fresh Tyrod solution
2:30 Printer starts
3:00 Agonist (AcH)
1. Incubation (30 min)
2. Stretching to physiological tonus (1g)
3. Administration of submaximal dose (repetition)
4. Administration of increasing doses of AcH
5. Processing the result
6. Dose effect curve

18. 3. Submaximal dose

19. 4. Increasing doses Ach

20. 5. Processing the results
AcH
Dose (mcg) Log (10) Effect (mm) Effect (g) Effect (%)
0,025 -1,60206 0,45 0,45 8,5
0,05 -1,30103 1,2 1,2 22,6
0,1 -1 2 2 37,7
0,2 -0,69897 3,1 3,1 58,5
0,4 -0,39794 4,6 4,6 86,8
0,8 -0,09691 2,45 4,9 92,5
1,6 0,20412 2,4 4,8 90,6
3,2 0,50515 2,52 5,04 95,1
32 1,50515 2,65 5,3 100,0

21. 5. Dose effect curve
0.0
25.0
50.0
75.0
100.0
125.0
0 10 20 30 40
efekat
(%)
Ach mcg
Arithmetic scale
0.0
25.0
50.0
75.0
100.0
125.0
0.01 0.1 1 10 100
Efekat
(%)
Log (Ach mcg)
Logarithmic scale

22. Thank you for your attention
 knowledge = f (effort made)