Pharmacodynamics and pharmacokinetics

Question 1

What are the three questions to ask when considering how a drug exerts its effects on the body?

Answer 1

Where is the effect produced?
What is the target for the drug?
What is the response that is produced after an interaction with this target?

Question 2

What must happen for a drug to produce a measurable effect?

Answer 2

It must bind to a specific target in the body and it must reach the relevant tissue in specific concentrations.

Question 3

What are the majority of drug targets in the body?

Answer 3

Proteins

Question 4

What are the four classes of drug target proteins?

Answer 4

Receptors. Enzymes. Ion channels. Transport proteins

Question 5

What are the two basic mechanisms in which drugs work?

Answer 5

Can either act on targets to enhanced activation or they prevent activation of the target

Question 6

What must be true for a drug to be an effective therapeutic agent?

Answer 6

Must show a high degree of selectivity for a particular drug target

Question 7

What are the 4 main chemical interactions that drugs interact with receptors via?

Answer 7

Electrostatic - the most common mechanism and includes hydrogen bonding/ VdWs forces.
Hydrophobic interactions - lipid soluble drugs
Covalent bonding - least common and tend to be irreversible
Stereospecific interactions - many drugs exist as stereoisomers and interact stereospecifically with receptors

Question 8

In terms of drug interactions with receptors, how are drugs divided into two categories?

Answer 8

Agonists and antagonists

Question 9

What differentiates the way in which agonistic and antagonistic drugs work?

Answer 9

Only agonists can bind and activate receptors

Question 10

What does the affinity of a drug determine?

Answer 10

The strength of the binding of the drug to the receptor

Question 11

What is efficacy?

Answer 11

The ability of an individual drug molecule to produce an effect once bound to a receptor. When a drug occupies a receptor it does not necessarily produce one standard unit of response

Question 12

What is drug potency?

Answer 12

The concentration or dose of a drug required to produce a 50% tissue response. EC50

Question 13

In terms of pharmacokinetics how is absorption defined?

Answer 13

The passage of a drug from the site of administration into the plasma

Question 14

In terms of pharmacokinetics what is bioavailability?

Answer 14

The fraction of the initial dose that gains access to the systemic circulation

Question 15

In terms of pharmacokinetics what is the difference between absorption and bioavailability?

Answer 15

Absorption deals with the process for drug transfer into the systemic circulation whereas bioavailability deals with the outcome of the drug transfer (how much)

Question 16

In what two ways do most drugs move across membranes?

Answer 16

Diffusion across lipid membranes or by carrier mediated transport

Question 17

Most drugs are either weak acids or weak bases, what does this mean about those drugs?

Answer 17

They will exist in two forms, ionised or unionised

Question 18

What two things determine wether or not a drug is ionised?

Answer 18

The dissociation constant (pKa) for that drug and the pH in the particular part of the body it will enter the venous circulation

Question 19

What will the composition of a drug be in terms of ionisation if the pKa and pH of the tissue are equal?

Answer 19

The drug will be equally dissociated between the two forms, 50% ionised 50% unionised

Question 20

If the pKa of a drug is low (e.g 3.5) what will happen as the pH increases?

Answer 20

The ionised form starts to dominate

Question 21

What are the 4 locations in pharmacokinetics where the most important carrier systems relating to drug action are found?

Answer 21

Renal tube. Biliary tract. Blood brain barrier. Gastrointestinal tract

Question 22

What are the four factors which will influence how different tissues are exposed to amounts of drug?

Answer 22

Regional blood flow, plasma protein binding, capillary permeability, tissue localisation

Question 23

How does regional blood flow affect how much drug a tissue receives?

Answer 23

Different tissues receive different amounts of cardiac output, more drug will be distributed to tissues that receive most blood flow

Question 24

In terms of plasma protein binding what determines the amount of drug that is bound?

Answer 24

The free drug concentration, the affinity for the protein binding sites, the plasma protein concentration

Question 25

What is the most important plasma protein for binding drugs and which drugs is it particularly good at binding?

Answer 25

Albumin, particularly good at binding acidic drugs

Question 26

True or false, a drug that is bound to a plasma protein can leave the blood?

Answer 26

False, the drug must dissociate from the protein, only free drug is able to diffuse out of the blood

Question 27

What happens to drugs during metabolism to make them easier to excrete?

Answer 27

Conversion of drugs to metabolites that are as water soluble as possible

Question 28

in the liver what is the main cytochrome responsible for drug metabolism?

Answer 28

P450

Question 29

What are the two kinds of biochemical reaction involved in drug metabolism? How do both stages act together?

Answer 29

Phase 1 - introduce a reactive group to the drug
Phase 2 - add a conjugate to the reactive group.
Both stages together act to decrease lipid solubility which then aids excretion and elimination

Question 30

What are the three ways by which a phase 1 drug metabolism reaction can occur?

Answer 30

Oxidation, reduction and hydrolysis

Question 31

In terms of drug metabolism how do all oxidation reactions start? What is the aim of this?

Answer 31

With a hydroxylation step using the cytochrome P450 system to incorporate oxygen into non-activated hydrocarbons

Question 32

What is the end result of phase 1 metabolism?

Answer 32

Production of metabolites with functional groups that serve as a point of attack for the conjugating systems of phase 2

Question 33

What are pro-drugs?

Answer 33

Where the parent drug has no activity of its own and will only produce an effect once it has been metabolised to the respective metabolite.

Question 34

What is the result of phase 2 drug metabolism?

Answer 34

Attachment of a substituent group to a metabolite, and the resulting metabolite is nearly always inactive and less lipid soluble, aiding excretion.

Question 35

What are the majority of the phase 2 drug metabolism enzymes?

Answer 35

Transferases

Question 36

What problems arise from first pass (presystemic) metabolism?

Answer 36

Other than drugs that are pro-drug, little active drug will reach the systemic circulation

Question 37

What is first pass (presystemic) metabolism?

Answer 37

Orally administered drugs are predominantly absorbed from the small intestine and enter the hepatic portal blood supply where they can be heavily metabolised.

Question 38

What is the solution to first pass (presystemic) metabolism but what new problems can this cause?

Answer 38

Administer a larger dose of the drug to ensure enough reaches the systemic circulation. However the extent of first pass metabolism differs amongst individuals as a result the drug effects and side effects are hard to predict

Question 39

What are the two most important routes of drug excretion?

Answer 39

Via the kidney in urine or via the liver in bile

Question 40

What are the three major routes for drug excretion via the kidney?

Answer 40

Glomerular filtration. Active tubular secretion. Passive diffusion across the tubular epithelium

Question 41

What drugs are able to diffuse through the glomerular filtrate?

Answer 41

Drug molecules with a molecular weight of less than 20,000, these will have a quicker excretion rate

Question 42

What is the most important method for drug excretion in the kidney?

Answer 42

Active tubular secretion