Introduction to pharmacology Part 2

Question 1

What is pharmacokinetics and what does it encompass?

Answer 1

The act of what the body does to drugs: This includes:
Absorption
Distribution
Biotransformation
Excretion

Question 2

When is pharmacokinetics important?

Answer 2

When choosing an appropriate route of administration

Question 3

What are the different types of drug entry routes?

Answer 3

Enteral (i.e. the oral route)
Perenteral (i.e non oral route).
Local administration

Question 4

What are examples of different drug entry routes?

Answer 4

oral , intravenous , rectal , percutaneous, intramuscular, etc

Question 5

True or False- Polar drugs are more readily penetrate through cell walls.

Answer 5

False - Non polar drugs more readily penetrate into cell walls.

Question 6

Do most drugs exist as wholly ionised or wholly unionised?

Answer 6

Neither - most drugs are weak acids or bases, which can exist in ionised or unionised forms.

Question 7

How can we calculate how ionised a drug is?

Answer 7

•The degree of ionisation is calculated from the Henderson-Hasselbalch equation:

pH= pKa + log _[A-]_

[HA]

where pka is the measure of how ionised soemthing is.

Question 8

Acids follow an equilibrium equation:

HA A- + H+

thus how does changing conditions shift the side and rate of reaction?

Answer 8

■In an ACID ENVIRONMENT, the reaction will shift to the left, i.e. the un-ionised form

■In an ALKALINE ENVIRONMENT, the reaction will shift towards the right, i.e. the ionised form

■A weak acid in an acid solution will be mainly in its un-ionised form. However, in an alkaline solution it will be trapped in its ionised form. The result is that an acidic drug will be concentrated in a compartment with a high pH.

(acids are proton donors)

Question 9

What equilibrium recation describes the ionisation of a weak base?

Answer 9

Basically the same reaction for weak acids but with B for base and H+ for hydrogen.

BH+ B + H+

•The degree of ionisation is represented by:

pH= pKb + log _[B]_

[BH+]

(basically the same equation for working out ionisation of an acid)

Question 10

How does changing conditions of the ionisation recation of a weak base affect the side of the reaction?

BH+ B + H+

Answer 10

■In an ACID ENVIRONMENT, the above reaction will shift towards the left, i.e. the ionised form

■In an ALKALINE ENVIRONMENT, the reaction will shift towards the right, i.e. un-ionised form

■A basic drug in an alkaline solution will be non-ionised and have a greater ability to cross lipid membranes. However, in an acid environment it will be trapped, as it is ionised. The result is that an alkaline drug will be concentrated in a compartment with a low pH.

Question 11

Why are we so concerned with pka values (a.k.a knowing how ionised a particular drug is)?

Answer 11

Depending on ionisation certain drugs are more likely to be absorbed by certain parts of the body.

■A weak acid e.g. Aspirin pKa= 3.5 is more likely to be absorbed from the stomach

■A weak base e.g. Pethidine pKa= 8.6 is more likely to be absorbed from the small intestine

Question 12

Are conditions in the small intestine more alkali or acidic?

Answer 12

More alkali

Question 13

As well as ionisation what other factor affects absorbtion of drugs through to tissues such as that of the small intestine?

Answer 13

Lipid solubility

Question 14

Why are strong acids and strong bases poorly absorbed by tissues in the intestine?

Answer 14

■Strong bases (pK>10) and strong acids pK<3 are poorly absorbed since they are fully ionised

Question 15

What other factors affect absorption of a drug?

Answer 15

• There are several factors which affect absorption:
• Gut motility
• Splanchnic blood flow (blood flow of the gut)
• Drug Formulation
• Physiochemical factors
• A drug taken after a meal is often more slowly absorbed since progress to the small intestine is delayed
• Drugs can be formulated specifically to delay absorption e.g. capsules, tablets with resistant coatings

Question 16

Typically how long does it take a drug that is orally delivered to be absorbed?

Answer 16

•Typically 75% of an orally administered drug is absorbed within 1-3 hours

Question 17

What is tetracycline and what scernerios is it contraindicated in and why?

Answer 17

It is a type of antibiotic.

It is contraindicated in pregnancy and breastfeeding as it binds to calcium stopping it being absorbed, leading to poor fetal/infant bone development.

It is also reduces the absorption of oral contraceptives ( like most antibiotics).

Question 18

What is bioavailability?

Answer 18

■bioavailability refers to the fraction of the dose that proceeds unaltered from the site of administration and becomes available at the site of action

• basically percentage of drug that actually reaches the target site in the form you want it in.

Question 19

What is bioavailability largely dependant on?

Answer 19

■Bioavailability is to a large extent dependent on the rate of absorption

Question 20

As well as rate of absorption what other factors affect bioavailability?

Answer 20

First pass metabolism

Question 21

What is first past metabolism?

Answer 21

■First pass metabolism represents the breakdown of a drug by biotransformation via enzymes this can be within the gut wall or liver before it reaches the plasma compartment.

Basically the start point at which drugs start to be broken down or acted upon

Question 22

What factors affect distribution of a drug?

Answer 22

■Following absorption, distribution of a drug is frequently not uniform, due to:

■physicochemical properties of the drug

■differences in blood flow between tissues - i.e. if a tissue is more vascular it will recieve more of the drug through the blood supply

■degree of “leakiness’ of the blood vessels within a particular tissue

■A drug may have an affinity for a particular tissue component e.g. melanin or fat.

■Plasma protein binding is another important variable

Question 23

Why does plasma protein binding affect drug distribution?

Answer 23

Essnetially whist the drug is travelling around in the blood it starts binding to the proetin in the blood lasma, reducing bioavailability as the drug is getting caught up with the protein rather than reaching the intended target site.

Question 24

Does plasma proetin binding also affect drug elimination?

Answer 24

Yes

Question 25

What are the protein components of blood plasma?

Answer 25

Albumin, beta-globin and alpha acid glycoprotein

Question 26

Which type of drugs does albumin typically bind to hindering its distribution?

Answer 26

Albumin binds to mainly acidic drugs e.g. warfarin and non-steroidal anti-inflammatory drugs (NSAID).

Question 27

Which type of drugs does beta-globin and alpha glycoprotein typically bind to hindering its distribution?

Answer 27

■ß-globin and a acid glycoprotein, bind mainly basic drugs e.g. propanolol

Question 28

Why are non polar drugs poorly eliminated from the kidney?

Answer 28

They tend to get reabsorbed by cells in the tubules whilst being eliminated

Question 29

How does elimination of drugs from the body occur?

Answer 29

■The elimination of drugs from the body occurs by metabolism ( also known as biotransformation) and excretion

Question 30

What is metabolism of drugs?

Answer 30

■Metabolism involves the enzymatic conversion of the drug into another chemical entity

Question 31

What are the two stages of drug metabolism called and what is the point of them?

Answer 31

■Drug metabolism (occurring predominantly in the liver) involves two types of chemical transformation, which are termed phase I and phase II reactions

■The purpose is to make the drug more polar (hydrophilic) to hasten its secretion by the kidneys

Phase I reactions involve adding or unmasking a functional group e.g. –OH, -NH2, -SH.

■Phase II processes (often termed conjungation) involve the attachment of a substituent group e.g. glucuronyl, acetyl, methyl or sulphate. These reactions make the drug more polar so that it can be excreted by the kidneys

Question 32

What are examples of routes of excretion of a drug?

Answer 32

■Most drugs leave the body in the urine either unchanged or as polar metabolites

■Other drugs are secreted into bile via the liver followed by loss of the drug via the faeces

Question 33

What affects the rate of excretion of drugs?

Answer 33

■The rate of renal clearance is variable: some drugs are lost in a single transit whilst others are cleared more slowly

Question 34

Why do we need to be careful about prescribing drugs that do not undergo biotransformation and for whom do we need to be more careful?

Answer 34

■For those drugs that are excreted without biotransformation, drug action can only be terminated by renal elimination. These drugs therefore need to be prescribed with special care in the elderly and in those with altered renal function

Question 35

What factors affect drug metabolism?

Answer 35

■Some drugs increase the activity of drug metabolizing enzymes e.g. barbiturates

■Other drugs inhibit drug metabolizing enzymes e.g. erythromycin, ethanol

^ thus we need to be careful of different drugs interacting with eachother.

■Genetic polymorphisms lead to inter-individual variation in drug metabolism a.k.a everyone is different and the way their bodies absorb drugs is different

■Age: neonates may have an immature drug metabolizing mechanism. The elderly may have impaired hepatic metabolism of drugs and also show an impaired glomerular filtration rate reducing renal clearance.

Question 36

What is the intrathecal administration of drugs?

Answer 36

Adinistration into the spinal chord