Chemical Kinetics And Drug Metabolism (w9)

Question 1

What factors effect rate of reaction ?

Answer 1

• Temperature of Reactants
• Concentrations of Reactants
• Chemical Nature of Reactants
• State of Subdivision of the Reactants
• Presence of a Catalyst

Question 2

Define ‘order of reaction’ …

Answer 2

Order of Reaction: The power to which the concentration of reactants must be raised to give a rate equation that describes the experimental data

Question 3

What the generic equation for a unimolecular reaction ?

Answer 3

A —> B

Question 4

What is the generic equation for a bimolecular reaction ?

Answer 4

A + B —> C

Question 5

What is the generic equation for a teramolecular reaction ?

Answer 5

A + B + C —> D

Question 6

What is the differential rate equation ?

Answer 6

Differential Rate Equation: A rate equation where the rate of consumption of a reactant / formation of a product is written as a differential

Question 7

What do the rate equations show ?

Answer 7

Rate Equations: Show the rate of the reaction at a particular instant during the reaction – Rates of reaction cannot be measured directly

Question 8

What does the integrated rate equation show ?

Answer 8

Integrated Rate Equation: Shows how the concentration varies with time. It is derived from the differential rate equation. It is an expression linking concentration of reactant A at a particular time [A]t compared to the concentration of A at the start of the reaction [A]0 and the rate constant k

Question 9

What is exponential decay ?

Answer 9

The concentration of the reactants decays as long as a logarithmic exponent with time
- a constant fraction of the drug reacts per unit of time

Question 10

Define half life …

Answer 10

The half life of a reactant is the time taken for its concentration to fall to half of the initial value

Question 11

How does half life relate to reactions in first Order ?

Answer 11

Half life of a reactant in a first order reaction is independent of its initial concentration, so t1/2 is constant through the course of the reaction.

Question 12

How does half life relate to second order reactions ?

Answer 12

Half life of a reactant in a second order reaction is inversely proportional to the initial concentration and to the rate constant so t1/2 is bigger if [A]0 is lower in concentration. It is not constant.

Question 13

How does half life relate to zero order reactions ?

Answer 13

The half life of a reactant in a zero order reaction is proportional to the initial concentration and inversely proportional to the rate constant. It is not constant.

Question 14

What is the reaction theory ?

Answer 14

A theory based on a model of how a reaction occurs at a molecular level - collision theory and transition state theory

Question 15

What is the collision theory ?

Answer 15

Reactant molecules behave like hard spheres, collisions between these spheres may result in a reaction.

Question 16

What is the transition state theory ?

Answer 16

It assumes the reactants form a transition state at the maximum on the energy profile - more sophisticated theory

Question 17

Explain the collision theory …

Answer 17

For a reaction to occur, two molecules must collide in the correct orientation with a particular minimum amount of kinetic energy. This is to overcome the energy required to break the existing bonds.

Question 18

What is a catalyst ?

Answer 18

A substance that changes the rate of a reaction without being consumed in the reaction.

Provides an alternative pathway for the reaction with a lower Gibbs activation energy for the rate-determining step.

Question 19

What is a heterogeneous catalysis ?

Answer 19

A catalysis which is in a different physical state than the reactants.

Products and any unreacted starting materials are easily separated from the catalyst.

Question 20

What is a homogeneous catalysis ?

Answer 20

A catalysis in the same physical state as the reactants.
It is more difficult to recover the catalyst.
Enzyme catalyses reactions in cells takes place in aqueous solution and involve homogeneous catalysis.

Question 21

What are enzymes ?

Answer 21

Protein molecules that catalyse a specific reaction and remain unchanged by the reactions they catalyse

Question 22

What are the three phases of drug action ?

Answer 22

1) Pharmaceutical Phase: Disintegration of the pill / capsule in gastrointestinal tract (GI), release of the drug, dissolution of drug

2) Pharmacokinetic Phase: Absorption from GI tract into bloodstream and what the body does to the drug

3) Pharmacodynamic Phase: Mechanism by which the drug interacts with the molecular target. What the drug does to the body.

Question 23

Thinking about pharmacokinetics, what makes a good drug ?

Answer 23

• if it is absorbed well by the body
• reaches target easily
• not modified, inactivated or removed from body too quickly

Question 24

Thinking about Pharmacodynamics, what makes a good drug ?

Answer 24

• effective at targeting disease process
• not toxic

Question 25

What does ADME stand for ?

Answer 25

- Absorption: Process of drug entering the body and therapeutic agent entering the blood - Distribution: Drug may reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids of various compartments in the body - Metabolism: Biotransformation / chemical conversion of drug molecules. - Elimination: Clearance of drugs and metabolites from the body (urine, bile, faeces)

Question 26

What is potency ?

Answer 26

- what dose of drug is required to achieve an effect, usually measured in units of concentration

Question 27

What is efficacy ?

Answer 27

The maximal effect of a drug, this is measured as a response usually in percentage

Question 28

What factors affect drug absorption ?

Answer 28

Factors Affecting Drug Absorption - Solubility: Drugs need to be water-soluble to pass into the blood for distribution -Ionisation: Drugs need to be close to neutral to pass through membranes - Stability: Drugs need to be chemically stable until they reach their site of action

Question 29

What factors affect distribution ?

Answer 29

Factors Affecting Distribution: - Plasma solubility: Including binding to plasma proteins (bind and release) - Lipophilicity: Balance between water and fat solubility. Influences drug levels in blood, muscles, adipose tissue, and organs - Perfusion: Level of blood flow to a tissue. Major organs (heart, liver . . .) well perfused, but brain is a special case – blood-brain barrier.

Question 30

What is it called when a drought is removed without metabolism ?

Answer 30

Excretion - major routes = urine (renal) or faeces (biliary) - minor routed =exhalation (lungs) or sweat

Question 31

What is the metabolism of drugs necessary for ?

Answer 31

- Designing new drugs which do not form unacceptable metabolites - Designing pro-drugs / understanding pre-drug strategy - Understanding half-lives and tailoring drug action

Question 32

How are metabolites formed ?

Answer 32

When metabolic enzymes attack drug molecules

Question 33

Where are polar drugs excreted from ?

Answer 33

The kidney

Question 34

Where do phase I and phase II transformations mainly happen ?

Answer 34

In the liver

Question 35

What is the mechanism of drug action in phase I ?

Answer 35

Mechanism of action: Split molecular oxygen so one of the oxygen atoms is introduced into the drug, the other ends up in water

Question 36

What type of conjugation reaction is most common in phase II ?

Answer 36

Glucuronidation (glucuronic acid conjugation)

Question 37

Is sulphate conjugation common and what does it involve ?

Answer 37

Less common and only involves phenols, alcohols, arylamines, N-hydroxy compounds

Question 38

Will drugs with amide groups have a shorter or longer half life than drugs containing esters ?

Answer 38

Drugs containing amide groups will have longer half life as they are more stable than drug as containing esters.

Question 39

What is the first pass effect ?

Answer 39

The effect that occurs when orally administered drugs pass directly to the liver once they enter the blood supply, this means they are exposed to metabolism before they are distributed to the rest of the body. This mean a certain percentage of this drug will be transformed before it reaches its target.

Question 40

How do drugs administered via injection or inhalation avoid the first pass effect ?

Answer 40

They are distributed around the body before they reach the liver where they are metabolized.