Drug Administration and Distribution

Question 1

what type of forms can be absorbed across lipid membranes?

Answer 1

Non-ionised forms

Question 2

What is the ratio of ionised to non-ionised drug dependent on?

Answer 2

pH and pKa value of drug

Question 3

What does the ratio of ionised to non-ionised drug affect?

Answer 3

Whether the drug is absorbed and where is the GI tract it happens

Question 4

What are examples of molecules that can be absorbed across lipid membranes?

Answer 4

Gases (e.g. CO2, O2)
Hydrophobic molecules (e.g. benzene)
Small polar molecules (e.g. H20 and ethanol)

Question 5

What are examples of molecules that cannot be absorbed across lipid membranes?

Answer 5

Large polar molecules (e.g. glucose)
Charged molecules (e.g. Amino acids, H+ ions, Na+ ions)

Question 6

What are drugs?

Answer 6

Weak electrolytes i.e. acids of bases

Question 7

What form do drugs exist in?

Answer 7

Equilibrium of charged and uncharged forms

Question 8

What is the equilibrium equation for bases?

Answer 8

RNH2 + H+ RNH3+

Question 9

What is the equilibrium equation for acids?

Answer 9

RCOOH RCOO- + H+

Question 10

What is pKa?

Answer 10

Dissociation consant (pH at which drug is 50% ionised and 50% unionised, i.e. ratio of 1:1)

Question 11

What is pH?

Answer 11

pKa + log ([RCOO-]/ [RCOOH])
Since log (1/1)= log (1)= 0

Question 12

What is the equation when pH and pKa are equal?

Answer 12

RCOO- = RCOOH

Question 13

What happens to weak acids when the pH of the environment increases?

Answer 13

Ionisation increases

likely to be absorbed

Question 14

What happens to weak bases when the pH of the environment increases?

Answer 14

Ionisation decreases

unlikely to be absorbed

Question 15

What changes for each pH unit?

Answer 15

10-fold change

Question 16

What is the pH of the plasma?

Answer 16

7.35-7.45

Question 17

What is the pH of the buccal cavity?

Answer 17

6.2-7.2

Question 18

What is the pH of the stomach?

Answer 18

1.0-3.0

Question 19

What is the pH of the duodenum?

Answer 19

4.8-8.2

Question 20

What is the pH of the jejunum and ileum?

Answer 20

7.5-8.0

Question 21

What is the pH of the colon?

Answer 21

7.0-7.5

Question 22

What happens in the stomach with a pKa of 4?

Answer 22

RCOOH RCOOH
Drug absorption
In the stomach, low pH, push equal towards protanation (uncharged)
In stomach weak acid, largerly protonated, largely uncharged so absorption may occur

Question 23

What happens in the intestine with a pKa of 4?

Answer 23

H+ + RCOO-
No drug absorption
As you get into the intestine, pH rises, molecule will split into two, have charged form of drug and very little absorption

Question 24

What happens for basic drugs in the intestine?

Answer 24

RNH2 RNH2

Drug absorption

Question 25

What happens for basic drugs in the stomach?

Answer 25

H+ + RNH3 | No drug absorption

Question 26

What are acidic drugs?

Answer 26

E.g. aspirin- mainly non-ionised in stomach- readily absorbed

Question 27

What are basic drugs?

Answer 27

E.g. amphetamine- mainly ionised in stomach- poorly absorbed

Question 28

What are neutral drugs?

Answer 28

E.g. alcohol, readily abosrbed

Question 29

What are the routes of drug administration?

Answer 29

Oral Sublingual/buccal Rectal- avoids first class metabolism Epithelial- topical (skin), corneal, nasal Inhalation Injection- intravenous, sub-cutaneous, intramuscular, intrathecal (into CNS epidural ,for speed of onset of action)

Question 30

What are the advantages of the oral route?

Answer 30

Administration easy and convenient No skilled personnel required Drug preparation need not be sterile

Question 31

What are the disadvantages of the oral route?

Answer 31

Effects are slow | Absorption may be incomplete

Question 32

Why can some drugs no be given orally?

Answer 32

Ionised throughout pH range of gut (tubocurarine) Too large to be absorbed (insulin) Destroyed in the gut by acids, enzymes or bacteria (proteins) Destroyed in the liver after absorption (GTN)

Question 33

What is the inhalation route useful for?

Answer 33

Large surface area of alveoli in lungs | Good pulmonary blood supply

Question 34

What effects can inhalation drugs have?

Answer 34

Local effects on the lung (e.g. for asthma, salbutamol) | Systemic effects e.g. GAs

Question 35

What do injected drugs bypass?

Answer 35

Difficulties of absorption in the gut

Question 36

What must injected drugs be?

Answer 36

Sterile Drugs can only be given by skilled staff Exact dose of drug given is known

Question 37

What are the advantages of the intravenous route?

Answer 37

Rapid effect Large volumes can be used Irritant drug solutions can be used

Question 38

What are the disadvantages of the intravenous route?

Answer 38

Rapid delivery to heart, CNS- side effects | Cannot recall drug

Question 39

What are the advantages of the intramuscular and sub-cutaneous routes?

Answer 39

Control onset with drug vehicle Aqueous- rapid effect Oily- slow effect

Question 40

What are the disadvantages of the of the intramuscular and sub-cutaneous routes?

Answer 40

Damage at injection site | Limited to small volumes

Question 41

What does distribution of drugs involve?

Answer 41

Drugs getting to the site of action

Question 42

What do drugs need to do?

Answer 42

Get out of plasma and into tissues

Question 43

What allows drugs to move easily into interstitial fluid?

Answer 43

Capillaries which are leaky (large pores), therefore drugs can move easily around tissues and interact with target cells

Question 44

How do drugs travel around in the bloodstream?

Answer 44

Bound to plasma proteins

Question 45

What does bound drug-plasma protein complex mean?

Answer 45

Bound fraction retained in plasma Only unbound fraction can diffuse into tissues Only unbound fraction is active

Question 46

How are capillaries in the CNS different?

Answer 46

No pores | Only lipophillic drugs can cross capillary membrane into CNS ionised drugs excluded

Question 47

What kind of drugs can pass across the placenta?

Answer 47

Only lipophilic drugs

Question 48

How will effect of drugs be terminated?

Answer 48

Distribution of drugs away from their site of action