Lecture 1: What is Pharmacology?

Question 1

explain the differences between pharmacology and pharmacy

Answer 1

pharmacology = branch of medicine concerned with uses, effects and modes of action of drugs 
pharmacy = how drugs are formulated and dispensed for use as medicines (incl. the law governing medicinal use of drugs)

Question 2

what us therapeutics?

Answer 2

the medicinal use of drugs to treat or relieve the symptoms of disease (not all drugs are medicine)

Question 3

what is toxicology?

Answer 3

the branch of pharmacology that focuses on the harmful effect of chemicals, incl. drugs

Question 4

what is a drug?

Answer 4

a chemical substance of known structure (other than a nutrient/essential dietary ingredient i.e. not vitamins), which when administered to a living organism produces a biological effect

Question 5

how are drugs named?

Answer 5

drugs used therapeutically usually have at least 3 names: (RS)-2-(d-(2-methylpropyl)phenyl)propanoic acid
chemical name e.g.
common name: ibuprofen
proprietary (trade) names e.g. nurofen (names given by pharmaceutical companies)

Question 6

how do drugs produce their effects?

Answer 6

• Drugs are exogenous molecules (come from outside the body) that mimic or block the actions of endogenous molecules (molecules found inside the body)

” A drug will not work unless it is bound” Paul Ehrlich

Question 7

how are drugs grouped?

Answer 7

• they’re usually grouped according to therapeutic use e.g. analgesics, antihypertensives, antibiotics

Or sometimes by mechanism of action e.g. cyclooxygenase inhibitor, beta-blocker

Question 8

propanolol:

1. mechanism of action
2. therapeutic use
3. property name

Answer 8

1. Blocks both beta 1 and beta 2 adrenergic receptors (beta blockers)
2. Treat heart problems, help with anxiety and prevent migranes
3. Inderal

Question 9

salbutamol:
1. mechanism of action
2. therapeutic use
3. property name

Answer 9

1. selective beta2-adrenergic receptor agonist
2. Treat asthma, bronchitis, COPD
3. Ventolin

Question 10

sildenafil

1. mechanism of action
2. therapeutic use
3. property name

Answer 10

1. phosphodiesterase inhibitor
2. Treats erectile dysfunction
3. Revatio/Viagra

Question 11

fexofenadine

1. mechanism of action
2. therapeutic use
3. property name

Answer 11

1. Selective H1-antagonist
2. Symptomatic treatment of seasonal allergic rhinitis & chronic idiopathic urticaria
3. Allegra

Question 12

fluoxetine

1. mechanism of action
2. therapeutic use
3. property name

Answer 12

1. Selective serotonin reuptake inhibitor
2. Treat major depressive disorder, bulimia, OCD etc.
3. Prozac

Question 13

The vast majority of drugs bind to molecular targets that are important proteins within the body. Give examples of some of these target proteins.

Answer 13

• Receptors for neurotransmitters or hormones
• Enzymes
• Ion channels
• Carrier or transport molecules

Question 14

what are “ligands”?

Answer 14

The small drug molecules that bind to large target proteins

note: Modern computer modelling techniques allow drugs to be designed in silico
- Doesn’t tell you how effective the drugs is, only if it will bind to target protein or not

Question 15

How well a drug ‘fits’ into its binding site is governed by what?

Answer 15

• the size and flexibility of the drug (steric factors)

Question 16

How well the drug binds its target protein is determined by what?

Answer 16

• the nature of the chemical bonds that form between the drug molecule and its binding site

Question 17

do drugs bind reversibly or irreversibly to the target protein? and with what kind of bonds?

Answer 17

• Most drugs (ligands) bind reversibly to the target protein through hydrophobic and hydrogen bonds plus weaker van der waals interactions
• some bind irreversibly through covalent interactions

Question 18

what is formed when a drug binds to its target protein?

Answer 18

formation of a ligand-protein complex which’ll alter the activity of the protein in some way

Question 19

what is selectivity in pharmacology and why is it important for drugs to be selective?

Answer 19

• the ability of a drug to affect a particular population
• for drug to be useful therapeutically it must be very selective in its action (e.g. an antihypertensive drug that lowers blood pressure but at same time causes severe GI problems isn’t useful for treating high BP)…shouldn’t cause severe side effects

Question 20

how can high drug selectivity be achieved?

Answer 20

• design drugs that bind w a high degree of specificity to their target protein. Ideally they will bind ONLY to their target protein & no others

NO drug binds with complete specificity – no drug is free from unwanted side effects

Question 21

explain the difference between selectivity and specificity in pharmacology

Answer 21

SELECTIVITY – the degree to which a drug acts on a given site relative to other sites

SPECIFICITY – the capacity of a drug to cause a particular action in a population

Question 22

what is pharmacodynamics (PD)?

Answer 22

defined as “what the drug does to the body” i.e consequence of drug’s actions at a molecular level on the physiology of an organism

Question 23

what is pharmacokinetics (PK)?

Answer 23

defined as “what the body does to the drug” I.e. how the drug is “handled” by the organism e.g. how it gets to its site of action, how it is metabolised or how its distributed to the different organs

Question 24

what are the four critical elements of pharmokinetics?

Answer 24

Absorption

Distribution

Metabolism

Excretion

(ADME)

Question 25

ADME is influenced by

Answer 25

- by the properties of the drug e.g. is the drug in a stable acid environment? - the characteristics of the person taking the drug e.g. a person who suffers from liver damage will not metabolise a drug as well as a person with a healthy liver

Question 26

what does ADME stand for?

Answer 26

Absorption Distribution Metabolism Excretion

Question 27

Importance of absorption in pharmacokinetics?

Answer 27

determines how much and how quickly the drug enters the blood

Question 28

What influences absorption in pharmacokinetics?

Answer 28

the chemical properties of the drug: - Its molecular size - Its lipid solubility, in turn influenced by its ionization (highly charged drugs won't be dissolved in lipids and s won't be absorbed across the gut) - Its chemical stability. Some drugs can't be taken orally because they aren’t stable in acid environment e.g. of stomach

Question 29

Importance of distribution in pharmacokinetics?

Answer 29

important to know: where does the drug go after it has been absorbed?

Question 30

describe distribution in pharmacokinetics

Answer 30

- Usually drugs are distributed around body by circulating in blood plasma and diffusing through tissues dissolved in ECF - the ability of a drug to dissolve in plasma or ECF is determined by its water (aqueous) solubility note: when studying drug action we usually measure its concentration in blood plasma, the assumption being that the conc in blood plasma will be related to the conc of drug at its site of action

Question 31

what are some factors that can interfere with how well a drug is distributed within the body?

Answer 31

Does the patient have adequate circulation? Does the drug bind to proteins in blood plasma, in particular albumin, drug bound to albumin is "trapped" in the blood (cant leave blood to enter ECF to produce effect) Does the drug "partition" into body fat stores, drug dissolved in body fat is not active Can the drug gain access to the organ it acts on e.g. brain is protected by blood brain barrier (BBB) - many drugs struggle to cross BBB - to quantify impact of these factors we need to measure volume of distribution

Question 32

what is the volume of distribution?

Answer 32

- volume the drug would occupy if the total amount administered was dissolved in solution at same conc as that found in blood plasma

Question 33

A drug that acts throughout the body is said to have...what?

Answer 33

"systemic" actions

Question 34

Give two examples of using knowledge of pharmacokinetics to minimise systemic side effects:

Answer 34

1. Local anaesthetics 2. non-sedating antihistamines e.g. cetirizine – these drugs relieve hay fever symptoms (e.g. by acting on airways) but don’t cause drowsiness because they're designed to not cross the BBB

Question 35

Importance of metabolism and excretion in pharmacokinetics?

Answer 35

These two factors determine how long the effects of a drug last Drugs are usually metabolised (broken down) in the liver to metabolites which are then excreted by the kidneys

Question 36

Things in terms of metabolism and excretion in pharmacokinetics?

Answer 36

Does patient have a healthy liver? How effective are the liver enzymes e.g. genetic differences between patients Are the metabolites active e.g. codeine is metabolised to morphine Are the metabolites toxic e.g. paracetamol toxicity is due to a harmful metabolite, not paracetamol itself

Question 37

Different ways drugs are excreted

Answer 37

most drugs (or at least their metabolites) are excreted in the urine, other routes of excretion include the faeces, sweat, bile and breath

Question 38

define a drug's half-life

Answer 38

the time it takes for the amount of a drug's active substance in your body to reduce by half (in plasma conc)

Question 39

what is clearance?

Answer 39

the volume of blood plasma cleared of drug in unit time (e.g. ml of plasma per minute)