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PMP 102 - Drugs And Medicine > Chemical Kinetics And Drug Metabolism (w9) > Flashcards

Chemical Kinetics And Drug Metabolism (w9) Flashcards

1
Q

What factors effect rate of reaction ?

A
  • Temperature of Reactants
  • Concentrations of Reactants
  • Chemical Nature of Reactants
  • State of Subdivision of the Reactants
  • Presence of a Catalyst
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2
Q

Define ‘order of reaction’ …

A

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

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3
Q

What the generic equation for a unimolecular reaction ?

A

A —> B

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4
Q

What is the generic equation for a bimolecular reaction ?

A

A + B —> C

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5
Q

What is the generic equation for a teramolecular reaction ?

A

A + B + C —> D

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6
Q

What is the differential rate equation ?

A

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

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7
Q

What do the rate equations show ?

A

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

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8
Q

What does the integrated rate equation show ?

A

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

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9
Q

What is exponential decay ?

A

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

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10
Q

Define half life …

A

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

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11
Q

How does half life relate to reactions in first Order ?

A

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.

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12
Q

How does half life relate to second order reactions ?

A

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.

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13
Q

How does half life relate to zero order reactions ?

A

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.

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14
Q

What is the reaction theory ?

A

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

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15
Q

What is the collision theory ?

A

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

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16
Q

What is the transition state theory ?

A

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

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17
Q

Explain the collision theory …

A

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.

18
Q

What is a catalyst ?

A

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.

19
Q

What is a heterogeneous catalysis ?

A

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

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

20
Q

What is a homogeneous catalysis ?

A

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.

21
Q

What are enzymes ?

A

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

22
Q

What are the three phases of drug action ?

A

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.

23
Q

Thinking about pharmacokinetics, what makes a good drug ?

A
  • if it is absorbed well by the body
  • reaches target easily
  • not modified, inactivated or removed from body too quickly
24
Q

Thinking about Pharmacodynamics, what makes a good drug ?

A
  • effective at targeting disease process
  • not toxic
25
Q

What does ADME stand for ?

A
  • 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)
26
Q

What is potency ?

A
  • what dose of drug is required to achieve an effect, usually measured in units of concentration
27
Q

What is efficacy ?

A

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

28
Q

What factors affect drug absorption ?

A

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

29
Q

What factors affect distribution ?

A

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.
30
Q

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

A

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

31
Q

What is the metabolism of drugs necessary for ?

A
  • Designing new drugs which do not form unacceptable metabolites
  • Designing pro-drugs / understanding pre-drug strategy
  • Understanding half-lives and tailoring drug action
32
Q

How are metabolites formed ?

A

When metabolic enzymes attack drug molecules

33
Q

Where are polar drugs excreted from ?

A

The kidney

34
Q

Where do phase I and phase II transformations mainly happen ?

A

In the liver

35
Q

What is the mechanism of drug action in phase I ?

A

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

36
Q

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

A

Glucuronidation (glucuronic acid conjugation)

37
Q

Is sulphate conjugation common and what does it involve ?

A

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

38
Q

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

A

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

39
Q

What is the first pass effect ?

A

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.

40
Q

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

A

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

PMP 102 - Drugs And Medicine (24 decks)

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