Basic Principles of Pharmacology

Question 1

What is a drug?

Answer 1

A molecule with a known structure that results in a biological effect but is not a nutrient or dietary supplement

Question 2

What is a medicine?

Answer 2

A drug or combination of drugs that has a therapeutic effect on the body

Question 3

How are drugs classified?

Answer 3

Structure
Mode of action
Therapeutic use

Question 4

How are drugs named?

Answer 4

Chemical name
Generic name
Trade name

Question 5

What are pharmacokinetics?

Answer 5

What the body does to the drug

Question 6

What are pharmacodynamics?

Answer 6

What the drug does to the body

Question 7

What are the four stages of a drug in the body?

Answer 7

Absorption
Delivery
Metabolism
Excretion

Question 8

Which is the only route of administration that offers 100% bioavailability?

Answer 8

Intravenous infusion

Question 9

What is bioavailability?

Answer 9

How much of the drug makes its way into the systemic circulation

Question 10

What are enteral routes of administration?

Answer 10

Any route that involves the gastrointestinal tract

Question 11

What are parenteral routes of administration?

Answer 11

Any route that does not involve the gastrointestinal tract

Question 12

Why is oral best for administration?

Answer 12

Cheap
Easy to dose
Can be done without medical professionals present
Rapid onset

Question 13

What must happen before an oral drug can be absorbed?

Answer 13

It must be dissolved

Question 14

What affect does the dissolution rate have on the drug’s action and how can this be affected?

Answer 14

It is the limiting factor in absorption rate and can be altered by changing the surface area or adding a coating to the tablet to prevent/quicken dissolution

Question 15

Where are oral drugs absorbed?

Answer 15

Anywhere along the GI tract but usually across the small intestine

Question 16

Why is oral routes the most complex for absorption?

Answer 16

The body is designed to prevent absorption of foreign molecules

Question 17

What barriers does the body have against absorption of orally taken drugs?

Answer 17

Gastric acid
Digestive enzymes
Survive and coexist with food
Cope with gut microbiota

Question 18

Explain how the gut microbiota can be used in our favour for drug action

Answer 18

The microbiome can transform the prodrug into it’s active form. This is useful particularly in the colon to make sure the drug gets to the target site

Question 19

How does absorption usually occur?

Answer 19

Transcellular passive diffusion

Question 20

Why are most drugs weak acids or bases?

Answer 20

The drug must be lipophilic to diffuce across the gut epithelium but must dissolve to be able to be absorbed. Weak acids and bases can dissociate into both an ionised form and an unionised form so can both be dissolved in water and diffused across the membrane

Question 21

What are the role of P-glycoproteins

Answer 21

They are a ATP powered drug efflux pump and reduce bioavailability by pumping drugs back out of the epithelial cells

Question 22

Why can L-Dopa pass through the GI tract by a transporter?

Answer 22

It has a very similar structure to tyrosine

Question 23

Describe the first pass effect

Answer 23

The venous drainage from the GI tract goes directly to the liver via the hepatic portal vein. The liver is the main site of metabolism so any drug must survive this stage in order to be truly bioavailable

Question 24

Describe sublingual administration

Answer 24

The drug is placed under the tongue and is absorbed straight into systemic circulation without passing through the liver, however there is a much smaller surface area for absorption

Question 25

Describe rectal administration

Answer 25

The drug is inserted into the GI tract via the anus. Useful when the oral route is compromised due to vomiting or when the drug needs to be used a lot e.g. chronic pain relief and NSAIDs

Question 26

Describe intravenous administration

Answer 26

The drug is placed directly into the systemic circulation to allow rapid onset

Question 27

Describe intramuscular/subcutaneous administration

Answer 27

The drug is injected under the skin or into the muscle and creates a depot of drug that can be slowly released into the systemic circulation

Question 28

Describe inhalation administration

Answer 28

The drug enters the pulmonary circulation via the lungs due to the lung parenchyma permeability and low metabolism

Question 29

Describe intranasal administration

Answer 29

The drug enters into the systemic circulation via the jugular vein

Question 30

Describe topical administration

Answer 30

The drug is applied directly to the site of action for a local affect and generally won't be absorbed by the body

Question 31

Describe transdermal administration

Answer 31

A patch containing the drug creates and external depot of the drug to be slowly absorbed by the skin

Question 32

What is drug distribution?

Answer 32

The reversible movement of drugs from systemic circulation into cells & interstitium

Question 33

How do drug enter the tissues from capillaries?

Answer 33

Paracellular passive diffusion

Question 34

Why is drug distribution not uniform?

Answer 34

Perfusion rates vary between different organs

Question 35

What determines distribution of lipophilic drugs?

Answer 35

Perfusion rates

Question 36

How does the anaesthetic thiopental stop working?

Answer 36

The drug diffuses back across the blood brain barrier to the periphery where it has no effect

Question 37

How can the blood brain barrier be used to our advantage?

Answer 37

It is very impermeable so we can use this to prevent drugs that we don't want in the brain from getting in

Question 38

Describe why L-Dopa is used to treat Parkinson's but not dopamine

Answer 38

Dopamine cannot cross the blood brain barrier but L-dopa can

Question 39

Why is L-Dopa taken with carbidopa?

Answer 39

Carbidopa inhibits dopa decarboxylase but cannot cross the blood brain barrier. This means that L-Dopa will be converted to dopamine in the brain where it's needed but not in the periphery where it will cause damage

Question 40

Where are P-glycoproteins present?

Answer 40

GI epithelium Blood brain barrier Placenta

Question 41

What can affect bioavailability from the systemic circulation

Answer 41

The drug's affinity with plasma proteins

Question 42

Describe the drug-drug interaction between aspirin and warfarin

Answer 42

Warfarin binds readily to albumin however aspirin has a higher affinity so displaces the warfarin and will increase the bioavailability

Question 43

What is drug sequestration?

Answer 43

The accumulation of drugs in a tissue to the point at which the concentration in the tissues becomes higher.

Question 44

What is drug metabolism?

Answer 44

The chemical modification of xenobiotics

Question 45

What is the main site of metabolism?

Answer 45

The liver

Question 46

What is phase 1 metabolism?

Answer 46

Oxidation, reduction or hydrolysis by cytochrome P450

Question 47

What is phase 2 metabolism?

Answer 47

Conjugation

Question 48

Describe the metabolism of paracetamol

Answer 48

Phase 1 - Oxidation to NAPQI | Phase 2 - Conjugation with GSH

Question 49

Describe the metabolism of tamoxifen

Answer 49

Metabolised to endoxifen by reduction. Endoxifen is the active drug which binds to oestrogen receptors

Question 50

Describe the metabolism of aspirin

Answer 50

Hydrolysed into salicylic acid and acetic acid

Question 51

How can we alter a drug's metabolism?

Answer 51

Adding different bonds that are metabolised faster or slower

Question 52

What are three types of phase 2 metabolism?

Answer 52

Glucuronidation, sulphation and acetylation

Question 53

Describe enzyme induction

Answer 53

The drug induces cytochrome P450 which reduces availability of other drugs

Question 54

Describe enzyme inhibition

Answer 54

Metabolic enzymes are inhibited by the drug which increases availability of other drugs

Question 55

What can affect drug metabolism?

Answer 55

Age | Illness

Question 56

What routes can drugs be excreted by?

Answer 56

Faeces, lungs, saliva, sweat, tears, breastmilk, urine

Question 57

How is renal excretion calculated?

Answer 57

(filtration + secretion) - reabsorption

Question 58

What drugs can pass through the Bowman's capsule?

Answer 58

Any drug not bound to plasma proteins

Question 59

What affect does glucuronidation have on renal secretion?

Answer 59

It make the drug a substrate of organic anion transporters in the PCT so they can be taken into the tubule

Question 60

What affect does probenecid have when taking drugs that are naturally substrates of OATs

Answer 60

Probenecid blocks OATs to prevent transport

Question 61

How can reabsorption be manipulated?

Answer 61

Altering the pH of the urine - changes the position of the dissociation equilbrium so more/less of the drug is in the charged form which is more easily excreted

Question 62

What affect does SGLT2 inhibition have?

Answer 62

Prevents glucose reabsorption independently of beta cell function and insulin

Question 63

Describe enterohepatic cycling

Answer 63

The drug is glucuronidised, then enters the bile caniculi and entered back into the GI tract. Some will then have their glucuronic group removed so it is reabsorbed into the systemic circulation