Pharmacokinetics

Question 1

What is pharmacology ?

Answer 1

The study of how chemical substances interact with living systems

Question 2

What is a drug?

Answer 2

A potentially toxic substance that alters a physiological process

Question 3

What is pharmacokinetics ?

Answer 3

Time course of the drug concentration in the body, i.e. what the body does to the drug.

Question 4

What is pharmacodynamics?

Answer 4

This is the study of the relationship between drug concentration to pharmacologic effects, i.e. what the drug does to the body

Question 5

What is meant by the term bioavailability?

Answer 5

The fraction of drug absorbed into systemic circulation. I.e. the amount of drug that makes it into the blood stream

Question 6

What are the different routes that we can administer a drug? 9

Answer 6

1. Parenteral (administered or occurring elsewhere in the body other than the mouth or alimentary canal) IV 2. Parenteral IM 3. Parenteral SC 4. Transdermal 5. Topical 6. Oral 7. Sublingual 8. Buccal 9. Inhaled

Question 7

What methods of drug administration cause the most immediate effects?

Answer 7

1. IV 2. Inhalation (oral or nasal) 3. Sublingual

Question 8

How long can orally administered drugs take to provide relief?

Answer 8

It can take up to 30 minutes.

Question 9

Meals can retard the absorption of certain drugs.

Answer 9

Drugs interact

Question 10

Liquids or powders dissolved in water will act more quickly than tablets of capsules

Answer 10

K

Question 11

What is first pass metabolism?

Answer 11

1st pass metabolism refers to the elimination (of a drug) that occurs when it is first absorbed by the small intestine and passes through the liver via the portal system.

Question 12

Explain how a drug is eliminated by first pass metabolism.

Answer 12

When a drug is administered orally, it must pass through the digestive tract before it enters systemic circulation. En route, the drug will pass through the hepatic portal vein and enter then liver. The liver will metabolise some of the drug. Whats left of the drug will then enter systemic circulation

Question 13

When a drug is administered orally, what factors play a role? 3

Answer 13

1. Gut metabolism 2. Food 3. Liver metabolism and blood flow

Question 14

How does parenteral IV differ from oral administration in terms of bioavailability?

Answer 14

When a drug is administered through parenteral IV it is delivered directly into the systemic circulation. Therefore, 100% of the drug is present. Whereas, when the drug is taken orally, it can interact with food, the gut and liver. This results is metabolism and elimination of the drug prior to reaching systemic circulation. Therefore, the bioavailability will be less than 100%

Question 15

What are the 4 pharmacokinetic practices?

Answer 15

1. Absorption: how is the drug absorbed2
2. Distribution: how is the medicine spread throughout the body
3. Metabolism/Biotransformation: is the drug converted into other chemicals in the body
4. 4. Excretion: how is the drug eliminated from the body

Question 16

In order for a drug to produce a therapeutic effect, what must first occur?

Answer 16

For a drug to produce a therapeutic effect, it must be absorbed into the blood stream and distributed into circulation.

Question 17

Once the drug is in circulation, how does it cross the plasma membrane?

Answer 17

There are four ways in which the drug can cross the plasma membrane, namely: 1. Passive diffusion 2. Facilitated passive diffusion 3. Active transport 4. Pinocytosis

Question 18

What is passive diffusion?

Answer 18

Passive diffusion is the movement of water, water soluble molecules and small lipids from an area of high concentration to an area of low concentration. This process is: 1. The most common and most important mechanism of drug absorption. 2. No energy is required 3. Not saturable 4. Non-selective 5. A non ionized drug is lipid soluble and will diffuse easily

Question 19

What is facilitated passive diffusion?

Answer 19

Facilitated passive diffusion is similar to passive diffusion but is mediated by carrier proteins. Transport against the concentration can’t occur. Energy is not required.

Question 20

What is pinocytosis ?

Answer 20

Pinocytosis is the physical engulfment of a substance by the cell. It has a small role in drug transport. Fat soluble vitamins such as vitamin KADE are absorbed this way.

Question 21

What is active transport?

Answer 21

Active transport is the movement of a substance against a concentration gradient with the use of energy. This process is: 1. Relatively unusual 2. Selective, e.g. iodide, amino acids, sugars, vitamins 3. Competition for transport can occur 4. Drugs resembling natural substrates can be transported 5. Requires energy 6. Can occur against the concentration gradient.

Question 22

What is pKA?

Answer 22

1. pKa is a method used to indicate the strength of an acid 2. A lower pKa, indicates that acid is stronger. The lower the value the more dissociation will occur. 3. Remember we want to keep drugs in their uncharged form for absorption, so weaker acids are required.

Question 23

Explain the role the environment plays on a drugs absorption.

Answer 23

For a drug to be absorbed across the the cell membrane, we require it to be in its uncharged form. Therefore, a weak acid requires a acidic environment which will keep the drug in its non-ionized form facilitating easy movement across the lipid-bilayer. These acidic conditions are found in the stomach. Conversely, a weak base requires a strongly basic environment. Conditions like this are present in the small intestine

Question 24

What does distribution of the drug depend on? 6

Answer 24

Distribution depends on: 1. Physiochemical properties of the drug 2. Tissue permeability; lipid solubility 3. Cardiac output and blood flow 4. Perfusion rate of the tissue 5. Transmembrane pH 6. Binding of plasma and tissue proteins

Question 25

True or false a bound drug has an effect?

Answer 25

False. A bound protein has no effect.

Question 26

What are the 3 things that drug binding depends on?

Answer 26

The amount of bound drug depends on: 1. Free drug concentration 2. The protein concentration 3. Affinity for binding sites.

Question 27

List and explain 3plasma proteins that bind drugs.

Answer 27

1. Albumin: binds many acidic and a few basic drugs 2. Beta-globulin and an alpha1 acid glycoprotein have also been found to be in certain basic drugs .

Question 28

List 5 things that have an fact on plasma protein binding :

Answer 28

1. Renal failure 2. Inflammation 3. Fasting 4. Malnutrition 5. Competition from other drugs can also affect the percentage of drugs bound

Question 29

What will allow the drugs to have a broader distribution?

Answer 29

Drugs with a high lipid solubility can easily penetrate fat stores and cross membrane barriers. This allows the drug to have a broader distribution.

Question 30

What drugs are more easily eliminated from the body?

Answer 30

Water soluble or charged drugs are more easily eliminated from the body. Whereas fat soluble drugs can be stored in the body, providing longer lasting effects.

Question 31

Which two barriers prevent free distribution of drugs?

Answer 31

1. The blood brain barrier 2. Placenta

Question 32

What is metabolism of drugs?

Answer 32

Drug metabolism is the chemical conversion of medication inside the body into metabolites.

Question 33

What is the purpose of drug metabolism?

Answer 33

Drug metabolism is a clearing process that breaks down substances into their water soluble or charge form which is required for easy excretion.

Question 34

What is the primary site of drug metabolism?

Answer 34

The primary site of drug metabolism is the liver. However, this process may also occur in the kidneys, GI tract and the lungs.

Question 35

Metabolism is the chemical conversion of drugs into metabolites. Explain what metabolized drugs may be?

Answer 35

Metabolised drugs maybe: 1. Inactive 2. Less active 3. More active 4. More toxic 5. Similar activity to a parent compound

Question 36

What is phase 1 drug metabolism?

Answer 36

Phase 1 drug metabolism is the metabolic modification of the drug. This includes: 1. Oxidation 2. Reduction 3. Hydrolysis Phase 1 drug metabolism is made possible by the cytochrome P-450 enzymes.

Question 37

What is phase II drug metabolism?

Answer 37

Phase II drug metabolism is the synthesis or conjugation phase. Adding a polar group to facilitate drug elimination.

Question 38

Cytochrome p 450 enzymes are involved in phase 1 drug metabolism. What substances induce cytochrome p 450 enzyme activity? 5

Answer 38

1. Ethanol (alcohol) 2. Phenobarbitone (epileptic drug) 3. Rifampacin (anti-bacterial drug used to treat TB, leprosy and Legionnaires disease). 4. Phenytoin (anti-seizure medication) 5. Smoking (nicotine) The presence of any of these substances results in activation of tea cytochrome p 450 enzymes. This results in an increased conversion of drugs into their water-soluble or charged states. Therefore, any increased activation of these enzymes will result in increased elimination of a drug.

Question 39

Cytochrome p 450 enzymes are involved in phase 1 drug metabolism. What substances inhibit cytochrome p 450 enzyme activity? 5

Answer 39

1. Cimetidine (proton pump inhibitor) 2. Erythromycin (anti-bacterial used for resp tract infections, chlamydia, syphilis and pelvic inflammatory disease) 3. Grapefruit juice (furancoumarins in the juice block enzyme activity). 4. Ketoconazole (anti-fungal medication) 5. Quinidine (anti-arrhythmic medication)

Question 40

List the different routes of drug elimination. 7

Answer 40

Drugs can be eliminated in the following ways: 1. Urine 2. Lungs 3. Sweat 4. Milk 5. Saliva 6. Faeces 7. Bile

Question 41

Is drug elimination dependent on route of administration?

Answer 41

No, drug elimination is independent of route of administration. I.e. drugs are eliminated the same regardless of how they get into the body.

Question 42

Name the 3 processes involved in renal elimination.

Answer 42

1. Active tubular secretion 2. Glomerular filtration 3. Tubular reabsorbtion

Question 43

Describe the process of active tubular secretion.

Answer 43

Active tubular secretion: - occurs in the proximal convoluted tubule - weak acids such as probencid, penicillins and salicylic acid -weak bases such as amphetamine, quinine and imipramine

Question 44

Describe the process of glomerular filtration. 3

Answer 44

1. Molecules smaller than 20 kDa pass into filtrate. 2. Drug must be free and not protein bound. 3. Drugs with high lipid solubility are reabsorbed passively and are therefore, slowly excreted.

Question 45

Describe the process of tubular reabsorption.

Answer 45

Tubular reabsorption can be : 1. Active or passive 2. Reabsorption id governed by the pH of the tubular fluid and the pKa of the drug. 3. Acids are best eliminated in alkaline urine 4. Bases are best eliminated in acidic urine

Question 46

What is tubular reabsorption governed by?

Answer 46

Tubular reabsorption is governed by the pH of the tubular fluid and the pKa of the drug.

Question 47

How is an acidic drug best eliminated?

Answer 47

Acidic drugs are best eliminated in basic urine.

Question 48

How are basic drugs best eliminated?

Answer 48

Basic drugs are best eliminated in acid urine.