Principles of Pharmacology 1

Question 1

In simple terms, what is meant by pharmacodynamics?

Answer 1

What a drug does to the body

Question 2

In simple terms, what is meant by pharmacokinetics?

Answer 2

What the body does to a drug

Question 3

What 3 questions do we ask when analysing the pharmacodynamics of a drug?

Answer 3

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

Question 4

Where is the euphoric effect of cocaine produced?

Answer 4

Dopaminergic neurons in the nucleus accumbens in the brain

Question 5

What is the target site of cocaine?

Answer 5

The dopamine reuptake protein on the pre-synaptic terminal

Question 6

What is the effect of cocaine after it interacts with its target site?

Answer 6

It blocks the reuptake protein so dopamine remains in the synapse for longer

Question 7

What are the 4 target sites for drugs? Give an example drug for each

Answer 7

Receptors (eg nicotine)
Transport protein (prozac)
Enzyme (asprin)
Ion channel (anaesthesia)

Question 8

What is selectivity?

Answer 8

How closely a drug binds to its target site

Question 9

How is dose related to selectivity?

Answer 9

Drugs can bind to multiple targets but usually have higher selectivity for one target over others. Increasing dosage can cause it to bind to other unwanted targets and produce side effects

Question 10

What are the 4 types of drug- receptor interactions?

Answer 10

Electrostatic interactions - this is the most common mechanism and includes hydrogen bonds and Van der Waals forces.
Hydrophobic interactions - this is important for lipid soluble drugs.
Covalent bonds - these are the least common as the interactions tend to be irreversible
Stereospecific interactions - a great many drugs exist as stereoisomers and interact stereospecifically with receptors.

Question 11

What is an angonist?

Answer 11

Something that binds to a receptor and activates/opens the function

Question 12

What is an antagonist?

Answer 12

Something that binds to a receptor and blocks the channel/function of it

Question 13

What does affinity mean?

Answer 13

The strength of a drug receptor interaction

Question 14

What does efficacy mean?

Answer 14

The ability of an individual drug molecule to produce an effect once bound to a receptor

Question 15

Describe levels of affinity and efficacy in full agonists

Answer 15

They have high affinity and efficacy

Question 16

What is potency?

Answer 16

The concentration or dose of a drug required to produce a defined effect

Question 17

How is potency measured?

Answer 17

ED50- estimated half maximal dose

EC50- estimated half concentration

Question 18

Out of potency and efficacy which is related to dose?

Answer 18

Potency

Question 19

In pharmacokinetics, what does absorption mean?

Answer 19

The passage of a drug from administration to entering the blood plasma

Question 20

What is bioavailability?

Answer 20

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

Question 21

What method of drug administration results in 100% bioavailability?

Answer 21

Intravenous injection

Question 22

What are the 2 ways by which drugs travel around the body?

Answer 22

Bulk flow- in the bloodstream

Diffusional transfer- diffusion of individual molecules across a lipid membrane

Question 23

What are the 4 mechanisms by which drugs can diffuse across plasma membranes?

Answer 23

Simple diffusion
Diffusion through an aqueous pore
Carrier mediated diffusion
Diffusion down an electrochemical gradient

Question 24

Are drugs usually more water or lipid soluble?

Answer 24

Water

Question 25

Describe how lipid solubility works with drugs? Are they more lipid soluble when ionised or unionised?

Answer 25

It is not an all or nothing concept | Drugs are either weak acids (donate H+) or weak bases (accept H+), they are more lipid soluble when they are unionised

Question 26

What 2 factors determine if the drug is ionised or unionised?

Answer 26

The pKa | The pH in the part of the body

Question 27

Describe ionisation/unionisation of a drug when the pKa and pH change

Answer 27

When the pKa of the drug and pH are equal the drug is 50% ionised and 50% unionised If a drug is a weak acid, as the pH rises the ionised form will dominate If a drug is a weak base, as the pH drops the ionised form will dominate

Question 28

Where are most drugs absorbed and why not in the stomach?

Answer 28

Weak bases will be ionised in the stomach and so will be difficult to absorb, weak acids may be absorbed but will become ionised at the physiological pH Most drugs are therefore absorbed by the transport proteins in the renal tubule, biliary tract, GI tract, blood brain barrier

Question 29

What are the 4 factors that effect drug distribution?

Answer 29

Regional blood flow Plasma protein binding Tissue localisation Capillary permeability

Question 30

How will regional blood flow affect drug distribution?

Answer 30

Certain tissues eg the liver and the brain receive more blood than others so will receive a higher proportion of the total drugs in the bloodstream

Question 31

How will capillary permeability affect drug distribution?

Answer 31

Some capillaries eg at the blood brain barrier are continuous and have no gap junctions, making it more difficult for drugs t o diffuse across as they transport proteins

Question 32

How will plasma protein binding affect drug distribution?

Answer 32

Some drugs circulate bound to plasma proteins which will affect their distribution depending on: Conc of plasma protein in blood Affinity of drug to bind to plasma protein Free drug conc

Question 33

How will tissue localisation affect drug distribution?

Answer 33

If a certain drug has an equilibrium that favors a fat high environment (eg because its highly fat soluble) compared to an aqueous environment it will be localised to fat high tissues eg the brain

Question 34

What is the main way drugs are manipulated so they can be metabolised?

Answer 34

The aim is to make them less lipid soluble so they remain in the blood and can be carried to the site of excretion

Question 35

What is the first step in drug metabolisation?

Answer 35

Introduce a reactive (polar) group to the drug via oxidation, reduction or thiolysis

Question 36

What enzyme is commonly used in step 1 of drug metabolisation?

Answer 36

Cytochrome P450 (for oxidation)

Question 37

What is a pro drug?

Answer 37

A drug thats inactive until its metabolised

Question 38

What is the second step in drug metabolisation?

Answer 38

Add a conjugate to the reactive group that makes the drug less lipid soluble

Question 39

What is first pass (presystemic) metabolisation?

Answer 39

A lot of drugs are absorbed in the GI tract and and enter hepatic circulation so are metabolised before they even enter systemic circulation

Question 40

How is first pass (presystemic) metabolisation solved? How does this lead to side effects?

Answer 40

Give higher doses of drug so some make it past the liver without being metabolised and enter systemic circulation. Different concs will make it into systemic circulation for different people when dose is increased, leading to different levels of side effects

Question 41

What are the areas of drug excretion? Which 2 are the main ones?

Answer 41

Mainly in the kidney (in urine) and via liver (in bile) | Also can be via breast milk or via lungs

Question 42

What are the routes for drug excretion in the kidney? Describe them

Answer 42

Glomerular filtration- 20% of plasma is filtered into the glomerulus Secretion into the PCT- 80% of the remaining plasma, there are transporters for weakly acidic and basic drugs that can move them opposite to the gradient Reabsorbtion in the DCT- lipid soluble drugs can be reabsorbed into the bloodstream here

Question 43

How is reabsorption in the DCT affected?

Answer 43

Has the drug been past the second stage of metabolisation?- it will be a lot less lipid soluble if so so more likely to be excreted that reabsorbed Urine pH- if urine pH is more basic then a weakly acidic drug will be less likely to be reabsorbed and will be excreted

Question 44

How does biliary excretion work?

Answer 44

Drugs are removed from the plasma into the bile in the liver

Question 45

What is enterohepatic recycling?

Answer 45

A glucuronide metabolite is transported into bile Its excreted into the small intestine The enzymes hydrolyse it and remove the glucuronide conjugate The drug is a lot more lipid soluble It returns to the liver and re-enters systemic circulation The drug ends up having a really prolonged effect