1.6 General principles of drug action

Question 1

what are the common routes of administration?

Answer 1

oral route (swallow)
IV
cutaneous
sublingual
vaginal/anal

Question 2

1) Why would you want to use the oral route?

2) Why would oral route not be used?

Answer 2

1) – safe
– convenient
– economical

2) – Irritant drugs cause sickness
– Not possible in vomiting patients
– Some drugs destroyed by gut acid/flora
– Intestinal absorption can be erratic

Question 3

In oral route what types of drug are absorbed in the stomach?
2) in the intestine

Answer 3

1) acidic drugs absorbed here, mainly weak acids, small amounts of aspirin , NSAIDS, alcohol
2) • Site of absorption of most exogenous compounds taken orally, Preferentially weak bases (most drugs are)

Question 4

What is the pH of of the duodenum and terminal ileum?

Answer 4

pH ranges from 6 (duodenum) to 7.4 (terminal ileum),

Question 5

What affects the rate of absorption if the drug is to be absorbed in intestines?

Answer 5

1) rate of gastric emptying
2) number and type of transported in enterocytes of epithelium, if drug is hydropholic
3) gut motility
4) gut pH
5) physico-chemical interactions i.e. has it bound to substances in lumen of intestine e.g. tetracycline and Ca, bile-acid-binding resins and other drugs
6) particle size and formulation i.e. how its been prepared pharmaceutical e.g. fast or slow release particles, e,g. resistance coating

Question 6

What is bioavailability (F)?

Answer 6

The fraction of the administered dose which enters the systemic circulation.

Question 7

What is first-pass metabolism?

Answer 7

Occurs in both intestine and liver before drug reaches systemic circulation.

Question 8

How do you calculate F (fraction of drug absorbed)?

2) What is AUC?
3) What does F represent?

Answer 8

AUC (oral) / AUC (IV)

2) the area under the curve where x is time and y concentration in plasma.
3) bioavailability

Question 9

What are the limitations of calculating bio availability

Answer 9

•	Does not consider inter and intra individual variations in;
–	enzyme activity
–	Gastric pH
–	Intestinal motility 
•	Does not consider rate of absorption

Question 10

How do you find

a) Cmax
b) Tmax

Answer 10

read a graph x=time and y=Cp
a) Maximum concentration of compound after administration
– Concentration units (i.e. mg/mL, ng/mL, etc.)
b) Time at which Cmax is reached
– Time units (usually hours)

Question 11

What are the advantages of rectal/vaginal route of aministration?
b) what do blood vessels drain into?

Answer 11

1) • Absorption may be rapid and extensive, but depends on drug and formulation
– pH 7-8

2) bu passes GI/hepatic first pass effects
3) rich blood supply
b) middle and inferior rectal veins, • Superior rectal vein
• Portal (to liver)

Question 12

What are the advantages of sublingual administration?

b) describe drainage

Answer 12

1) Required for fast/rapid response
2) avoids first pass metabolism as …
b) Utilises venous drainage from the mouth to the superior vena cava. going almost directly to the heart through the superior vena cava.

Question 13

When is vaginal/rectal administration useful>

Answer 13

Useful when drug causes nausea and vomiting, or if the patient is already vomiting

e. g. HIV patients , some antiviral drug causes necrosis of tissues so can’t be given IV
b) also avoids 2/3 of first pass metabolism

Question 14

What are the advantages of IV injection?

Answer 14

• predictable, very rapid action,
• alternative route for drugs which are
irritant by (im)
• iv infusion for ill, hospitalised patients

Question 15

What are the disadvantages of IV?

Answer 15

• difficult /painful,
• risk of infection,
• cost and safety,
• immediate adverse effects

Question 16

compare subcantaneous injection with intramuscular:

2) Do subcutaneous injections have systemic or local affect?

Answer 16

1) intramuscular has faster absorbtion (unless deep) than subcutanous due to better blood supply
2) either, subcutanous injection usually systemic, except in dentistry where its a local anaesthetic

Question 17

How can absorbtion of a subcutanous injeciton be increased?

2) how can it be reduced?

Answer 17

1) enzyme hyaluronidase

2) co-injection with vasoconstritor e.g. epinephrine (adrenaline), this is done in dentistry

Question 18

enteral vs parenteral

Answer 18

enteral uses GI tract, parenteral doesn’t

Question 19

Give 4 enteral routes of administration:

Answer 19

oral, sublingual, rectal, vaginal

Question 20

Give 5 parenteral routes of administration:

Answer 20

• Intravenous
• Intramuscular
• Subcutaneous
• Transdermal
• Inhaled

Question 21

Which administration method is absorbtion not releavant to ?

Answer 21

IV injection

Question 22

What are the ways can drugs cross a cell membrane?

Answer 22

• passive diffusion through lipid
• diffusion through aqueous channel
• carrier mediated transport
• Membrane engulfment
• Pinocytosis: rare form of absorption however.

Question 23

What factor about the drug determines rate of absorbtion if drug diffueses through lipid?

Answer 23

lipid solubility, effected by pKa of drug, so if the drug is ionised (due to being an acid in alkali or vice verse) not absorbed as well

Question 24

How do you find percentage ionisation/ un-ionised?

Answer 24

pH-pKA
eg. Warfarin= pKa=5
pH is 5
5-5=0
Therefore, using table it shows ionisation is 50%. You must use table to find it.
Remember to match up heading and units of the table with blank space
e.g. if pH is 3, then it will be 1% ionised and 99% un-ionised.

Question 25

What is the term guven to when acids accumulate in basic fluid compartment and vise versa

Answer 25

pH partitioning

Question 26

What affects how much a drug is distributed to other tissues?

Answer 26

– Its ability to cross cell membranes (based on physiochemical properties) – Blood flow to individual tissues – Extent of its plasma protein binding

Question 27

What is drug distribution?

Answer 27

reversible transfer of drug from one location to another within the body either blood plasma, intersticial fluid or intracellular

Question 28

What are the 2 things drugs bind to plasma?

Answer 28

1. albumin | 2. – Alpha 1 acid glycoprotein (AAG)

Question 29

Where is Alpha 1 acid glycoprotein (AAG) synthesised? 2) What does it bind to? 3) What effects it conc. in blood? 4) what is the normal range?

Answer 29

liver • Binds mostly basic and some neutral drugs • Acute phase protein, elevated in some diseases (cancer), inflammation • Normal range: 0.4 - 1.1 mg/mL

Question 30

Where is albumin synthesised? 2) what does it bind to? 3) What causes its conc to be reduced? 4) What is the normal range?

Answer 30

1) liver 2) Binds mostly acidic and some neutral drugs 3) Decreased in malnutrition and cirrhosis 4) Normal range: 3.5 – 5 g/dL

Question 31

What form of drug is not active or absorbed in blood? | 2) Which form is?

Answer 31

1) plasma protein bound | 2) free drug

Question 32

How do you calculate volume of distribution? | 2) describe the units

Answer 32

total amount of drug in body/ drug blood plasma | 2) units of volume (usually L or mL), sometimes per unit of weight (i.e. L/kg)

Question 33

will Vd value be big or small if.. 1) drug is confined to plasma compartment 2) accumulate outside plasma

Answer 33

1) small | 2) big

Question 34

Another calculation of Vd is.... (involves a plus sign)

Answer 34

``` Vp+ Vt(fu/fUt) Vp= plasma volume of drug Vt=tissue volume of drug fu= fraction unbound in plasma fut= fraction unbound in tissue ```

Question 35

Give volume in : a) total body water b) intracellular c) extracellular volume - d)intersitial volume - e) plasma volume

Answer 35

a) 42 litres b) 28 litres c) 14 litres - d) 10 litres - e) 4 litres

Question 36

What sort of drug is distributed throughout body water?

Answer 36

lipid soluble drugs

Question 37

What sort of drug is distributed throughout extracellular compartment?

Answer 37

low lipid solibility so cannot easily enter cells

Question 38

What sort of drugs accumulate in plasma compartment?

Answer 38

are too large to cross capillary wall easily or bound to plasma proteins