Rates and Orders of Reactions

Question 1

What is pharmacokinetics?

Answer 1

Pharmacokinetics is the study of the rate at which drug reactions
occur. It is a mathematical way to understand the way Absorption,
Distribution, Metabolism and Excretion of drugs happen.

Question 2

What is the order of a reaction?

Answer 2

The power dependence of the rate on the concentration of each reactant

Question 3

What is the rate constant?

Answer 3

Rate constant is a proportionality constant that appears in a rate law.

Question 4

What is a Zero-order reaction?

Answer 4

It is a reaction in which the rate of reaction is not dependent on the concentration of the reactants.

Question 5

Provide the formulas for K and t1/2 for a zero-order reaction

Answer 5

1. [A] = -kt + [A]o
2. t1/2 = [A]0 / 2k

Unit of K is Conc per second

Question 6

Give 2 examples of zero-order reactions.

Answer 6

i. Conversion of vitamin A acetate to anhydrous vitamin A
ii. Photolysis of cefotaxime
iii. Loss of colour in multi sulfa drugs
iv. Release of drugs from IV infusion and transdermal drug delivery systems.

Question 7

What is a First-order reaction?

Answer 7

It is a reaction in which the rate of reaction depends on the first power of a single reactant

Question 8

Give 2 examples of first-order reactions.

Answer 8

i. Absorption, distribution and elimination rates
ii. Microbial death kinetics

Question 9

Provide the formulas for K and t1/2 for a first-order reaction

Answer 9

1. In[A] - In[A]o = -kt
2. t1/2 = 0.693/k

Unit is per second.

Question 10

What is a second order reaction?

Answer 10

It is a reaction in which the rate of reaction depends on the second power of a single reactant or first power two reactants.

Question 11

Provide the formulas for K and t1/2 for a second-order reaction

Answer 11

1. 1/[A]t - 1/[A]0 = kt
2. t1/2 = 1/[A]0K

Unit is per conc per second

Question 12

Give an example of a pseudo-zero-order reaction.

Answer 12

A suspension with excess solid drug

Question 13

Describe how suspended drugs degrade in zero order.

Answer 13

In a suspension, the drug in solution maintains a constant concentration due to the drug’s solubility. As the drug in solution decomposes, more drug is released from the suspended particles, keeping the concentration stable.
The solid drug in suspension acts as a reservoir, replenishing the drug in solution and ensuring a constant concentration, thus following zero-order kinetics.
The constant concentration in the solution is dictated by the drug’s equilibrium solubility in the given solvent at a specific temperature.

Once all the suspended solid drug has dissolved, the system transitions to first-order kinetics, where the drug concentration in solution starts to decrease.

Question 14

What is a pseudo-first order reaction?

Answer 14

It is a case where a second order reaction is made to act as a first-order reaction.

This is found in the case in which one reacting material is present in great excess or is maintained at constant concentration as compared with other substance.

Question 15

Give 2 examples of a pseudo-first order reaction.

Answer 15

i. Decomposition of ascorbic acid tablet.
ii. Aspirin hydrolysis

Question 16

Give 3 examples of complex reactions.

Answer 16

i. Opposing reaction (A<>B): Both reactions are first order or the forward is first order while the backward reaction is second order. e.g. epimerization of tetracycline

ii. Consecutive reactions (A>B>C): Simplest is one where both the orders of reaction is first order. If K(BC) > K(AB) then B can be considered as unstable intermediate and rate-determining step for overall reaction would be conversion of A to B.
e.g. Degradation of chlorbenzodiazepine by hydrolysis to lactam and further to benzophenone.

iii. Parallel reactions: reactions in which a substance reacts or decomposes in more than one way, producing two or more products
e.g. Purified insulin degrades by two mechanisms- deamidation and
polymerization

Question 17

What are the methods of determining the order of reaction?

Answer 17

1. Substitution method: substitute data into the formulas for various orders as see which produces a consistent k value.
2. Data plotting method:
   zero order: conc vs. time is linear
   first order: InC vs. time is linear
   second order: 1/C vs. time is linear
3. Initial rate method: Graphs are plotted of concentration against time and the initial rate is determined from the gradient at t = 0
   - If it is a straight line the reaction is first order.
   - If a curve is obtained then we can say it is second order reaction.
   - A straight horizontal line is zero order.
4. Determination of half-life method: The relationship in general between half-life of a reaction in which the concentrations of all reactants are identical, is
   t1/2 ∞ 1/an-1
   *Where n is the order of reaction.