Pharmacology

Question 1

What is Pharmacokinetics?

Answer 1

Time course of drug concentration in the body. The processes that determine time course are: A - absorption D - distribution M - metabolism E - excretion

Question 2

Oral vs Parenteral dosing?

Answer 2

I.V. drug maximal concentration straight away maximal, then slopes down as clearance begins Oral drug starts at 0 concentration and rises up to maximal as it is absorbed via gut and passes through liver, then slopes down as clearance begins

Question 3

Dose = …

Answer 3

Dose = concentration x volume

Question 4

What are the 3 ways drugs cross cell membrane?

Answer 4

1. Diffusion (through lipid bi-layer) 2. Diffusion through aqueous channel 3. Via protein carrier (transporter) (active or facilitated)

Question 5

Describe pathway of oral drugs?

Answer 5

1. ingested
2. STOMACH
3. disintegration
4. disolved in gastric fluids
5. absorbed in SMALL INTESTINE
6. enters portal vein in blood
7. LIVER
8. variable drug removed (metabolised)
9. drug distributed through systemic circulation
10. excreted (unbound drug & metabolites) by KIDNEY

Question 6

Bioavailability formula?

Answer 6

F = f_g x f_H

f_{g =} proportion of dose absorbed from gut proportion of f_{H =} dose absorbed from hepatic

Question 7

Bioavailability…?

Answer 7

Proportion of administered dose which reaches the systemic circulation intact.

F = f_g x f_H

Question 8

f_H = …?

Answer 8

f_H = 1 - E_H

E_H is the extraction ratio from liver.

E_H = CL_H/Q_H

CL_H = hepatic clearance

Q_H = hepatic blood flow 90L/hr

Question 9

Volume of Distribution definition?

Answer 9

A theoretical value of the fluid volume that would be required to contain all the drug (uniformly distributed) in the body at the same concentration measured in the blood.

Question 10

Volume of distribution formula:

V_D = …

Answer 10

V_D = t_otal amount of drug in body_
blood/plasma concentration

Question 11

What are the functions of drug metabolism (4)?

Answer 11

• Detoxification / termination of activity
  in most cases the products of metabolism have less biological activity than the parent drug
• Clearance
  by concerting the drug to another compound, metabolism clears the parent drug
• Enhances elimination
  products of metabolism are more readily excreted by the kidney
• Minimising oral exposure
  First pass metabolism is a protective barrier against exposure to toxic orally ingested chemicals.

Question 12

What are the main types of drug metabolism reactions?

Answer 12

1. Functionalization (phase 1) reactions
   Cytochrome P450 enzymes
2. Conjugation (pahase 2) reactions
   enzymes are transferases - UDPGs

Question 13

What ways does Renal Elimination involve?

Answer 13

1. Filtration
2. ~Active secretion
3. ~Passive reabsorption

Question 14

What is the GFR?

Answer 14

Glomerula filtration rate

~120ml/min

Question 15

Renal clearance formula…?

Answer 15

CL_R = (CL_GF + CL_secretion) x (1 - FR)

CL_GF = cleareance by glomerula filtration

CL_se = clearance by renal tubular secretion

FR = fraction reabsorbed in renal

Question 16

Renal clearance - fraction unbound…

Answer 16

CL_GF = GFR x f_u

f_u = fraction of drug unbound in the blood that can enter urine

Question 17

Systemic clearance of drug…?

Answer 17

CL_systemic = CL_renal + CL_hepatic

CL_renal = CL_s x f_e

f_e - fraction of dose excreted in urine unchanged

Question 18

Hepatic clearance…?

Answer 18

CL_H = Q_H x E_H

Q_H = hepatic blood flow rate 90L/hr

E_H = hepatic extraction ratio
E_{H =} (C_in - C_out) / C_in

Question 19

Intrinsic Clearance: CL_int

Answer 19

CL_int = V_max / K_m

intrinsic clearance is the clearance at the enzymatic level.

V_max = the capacity of enzyme to catalyse a reaction

Question 20

High hepatic clearance…

Answer 20

Hepatic enzymes have excess capacity to clear the drug from the blood

High hepatic clearance E_H > 0.67

*large effect on bioavailability

Question 21

Low hepatic clearance…

Answer 21

Capacity of hepatic enzymes to clear the drug from the blood is rate limiting.

Low hepatic clearance E_H < 0.2

Question 22

Half-life…?

Answer 22

Time taken for the blood/plasma concentration to be reduced by one half (50%)

t_1/2 = 0.693 x Vd
CL_s