LECTURE 5-8: PHARMACOKINETICS

Question 1

life cycle of a drug

Answer 1

Administration -> absorption -> distribution -> action -> metabolism -> elimination

Question 2

Drug given by oral route is given the abbreviation

Answer 2

PO (per oral)

Question 3

two main routes of administration

Answer 3

1. oral
2. parenteral

Question 4

parenteral administration abbreviations

Answer 4

1. IV
2. IM
3. SC, SQ

Question 5

Bolus dosing

Answer 5

single dose, all at once

Question 6

IV constant rate infusions (CRI)

Answer 6

medication continuously administered to a patient and is used to maintain consistent plasma levels of that medication

Question 7

Absorption

Answer 7

• Getting the drug from the site of administration into the blood

Question 8

does IV have absorption phase

Answer 8

No

Question 9

bioavailability

Answer 9

The fraction of drug that gets into the blood

Question 10

What’s in a tablet or an injection besides the drug?

Answer 10

excipient / bulk / carrier

Question 11

excipient

Answer 11

inactive substance used to carry an active substance

Question 12

examples of excipients

Answer 12

– Salts
– Inactive substances such as talcum, lactose
– Solubilising liquids e.g. alcohol, propylene glycol

Question 13

why add excipient

Answer 13

– to make the drug work better
– sometimes to make the drug easier to work with

Question 14

what is the rate limiting steps of absorption

Answer 14

solubilisation of the drug into the aqueous environment of the gut

Question 15

how are majority of drugs absorbed

Answer 15

passive diffusion

Question 16

factors affecting absorption

Answer 16

1. lipophilicity/hydrophilicity
2. surface area
3. first-pass metabolism
4. vascularity / disease process

Question 17

what is bioavailability compared against, what gives 100% bioavailability

Answer 17

IV

Question 18

Drug distribution

Answer 18

• Moving the blood from the body to the extravascular space (i.e. the tissues)

Question 19

pattern of drug distribution

Answer 19

• Where drugs go around the body

Question 20

volume of distribution

Answer 20

• the propensity that a drug has for leaving the blood and entering the tissues is calculated by the pharmacokinetic term volume of distribution (Vd)

Question 21

drug distribution depends upon

Answer 21

1. regional blood flow
   - rapid distribution to organs with high CO
2. ability to cross lipid membranes
   - lipophilicity/ hydrophilicity
   - pH partition effect
   - extent that drug binds to tissue and fluid constituents (protein binding)

Question 22

pH partition effect

Answer 22

o Unionised drug readily diffuses across lipid membranes.
o Acidic drugs are more unionised in acidic environments and alkaline drugs are more unionised in alkaline environments “like likes like”
o Plasma is slightly more basic than tissues.
o Therefore weak bases tend to distribute out of plasma and into tissues. In the relatively more acidic environment of the tissues the basic drugs become “trapped”.

Question 23

most drugs are ___ acids or bases

Answer 23

weak

Question 24

proteins in blood and tissues have ___ charges

Answer 24

weak

Question 25

NSAIDs examples

Answer 25

ibuprofen

Question 26

why do NSAIDs accumulate at site of inflammation despite their low Vd's (and why they have a low Vd)

Answer 26

- they are highly bound to plasma proteins (e.g. albumin) and so there is little unbound (= free) drug available for distribution, so NSAIDs have low Vd’s - but during inflammation (when the drug is most needed) it will follow the blood protein into the inflamed area

Question 27

Do NSAIDs have high or low Vd

Answer 27

low

Question 28

Vd =

Answer 28

drug amount in body / blood concentration

Question 29

Metabolism

Answer 29

- The biotransformation of a lipophilic compound into a more hydrophilic compound in order to facilitate elimination

Question 30

Why needs to be hydrophilic for elimination?

Answer 30

Kidney can do it easier

Question 31

phase 1 metabolism

Answer 31

- substance is converted to a more polar metabolite - oxidation, reduction and hydrolysis - often involves cytochrome p450 enzyme system

Question 32

Phase II metabolism

Answer 32

- following or independent of phase I - involves conjugation with an endogenous hydrophilic compound - this phase makes it more hydrophilic - gluccurondination is most common

Question 33

where does phase II occur

Answer 33

liver!! but sometimes kidney and intestine

Question 34

hepatic enzymes can be induced by

Answer 34

some older anticonvulsant drugs

Question 35

hepatic enzymes can be inhibited by

Answer 35

omeprazole

Question 36

sequelae to metabolism

Answer 36

- excretion of the water-soluble metabolite - conversion of prodrugs -> active molecule - enterohepatic cycling

Question 37

enterohepatic cycling

Answer 37

Drug absorbed from gut straight into hepatic circulation, metabolised and eliminated in the gut, reabsorbed from the gut into hepatic...

Question 38

Elimination

Answer 38

removal of drug form body

Question 39

elimination can be accelerated by

Answer 39

diuresis

Question 40

elimination can be slowed by

Answer 40

kidney disease or heart disease

Question 41

Metabolism and elimination is quantified by

Answer 41

drug clearance

Question 42

Major modes of elimination

Answer 42

- Hepatic excretion – passed in faeces via bile - Renal excretion – passed in urine - Combination of hepatic AND renal - Miscellaneous e.g. exhalation, sweat, milk etc

Question 43

Renal drug removal vie

Answer 43

- Glomerular filtration - Tubular secretion

Question 44

renal drug reabsorption by

Answer 44

- Tubular reabsorption

Question 45

what kind of drugs may be reabsorbed from kidney

Answer 45

highly lipophilic drugs

Question 46

what is the upper MW limit of filtration through glomerulus

Answer 46

20,000

Question 47

what affects renal elimination

Answer 47

pH of drug and environment effects drug lipophilicity / hydrophilicty which effect renal elimination

Question 48

If someone had an entire packet of weak acid drug - how could elimination be hastened

Answer 48

alkalinise their urine - will make drug more ionised meaning less reabsorbed and faster elimination

Question 49

Drug clearance

Answer 49

- The volume of blood from which a drug is removed per unit time - Usually expressed in mL/min/kg (alternatively L/hr/kg)

Question 50

M and E together are quantified by

Answer 50

drug clearance

Question 51

ratio between the proportion of unioinsed to ionised is determined by

Answer 51

pH of drug relevant to pH of the environment