Drug Mechanism & Receptor Interactions

Question 1

Pharmacokinetics

Answer 1

what the body does/responds to the drugs - refers to the drugs movement into, through and out of the body

Question 2

Pharmacodynamics

Answer 2

the effects of drugs and their mechanism of action

Question 3

Drug

Answer 3

Chemical substance that interacts with a biological system to produce a physiological effect

Question 4

What are the 4 drug target sites and what are they all?

Answer 4

Receptors
Ion channels
Transport systems
Enzymes

They’re all proteins

Question 5

What is the most common drug target site and its properties?

Answer 5

Receptors - 4 types (Type 1-4)
Usually on CSM (NOT Type 4)
Activated by NT/hormone
Defined via. agonist & antagonist

Question 6

Atropine?

Answer 6

Antagonist
Muscarinic Ach
Competitive & Selective

Question 7

Ach?

Answer 7

Agonist

Question 8

Ion channels?

Answer 8

Drug target site

Selective pores - voltage-sensitive (membrane potential) OR receptor-linked (conformational change)

Question 9

Examples of drugs working on ion channels?

Answer 9

LAs - interact w VSSCs (block it)

Ca2+ channel blockers (if end in -dipine)

Question 10

Transport Systems and examples?

Answer 10

AGAINST [gradient]
Specific for certain species
Require ATP

Examples - Na+/K+ ATPase
NA uptake 1

Question 11

Examples of drugs working on transport systems

Answer 11

TCAs (anti-depressant drugs work on NA uptake proteins)

Cardiac glycosides

Question 12

Enzymes as drug target sites?

Answer 12

Drug can have 3 interactions:
Enzyme inhibitors
False substrates
Prodrugs

Question 13

Explain how enzymes as drug target sites can give rise to unwanted effects

Answer 13

Paracetamol
Becomes saturated in the body, overloading the metabolising enzymes = switches to another enzymes giving rise to toxic by-products = affects liver/kidneys

Question 14

NSDA?

Answer 14

Non-specific drug action

Action produced via. non-protein receptor interactions

Question 15

Examples of NSDAs?

Answer 15

Antacids - addition of base

Osmotic purgatives - laxatives work by drawing H20 into the gut

Question 16

PPB?

Answer 16

Plasma protein binding - acts as reservoir of inactive drugs

Question 17

Agonist

Answer 17

Ligand that stimulates/activates a receptor

e.g. Ach, nicotine

Question 18

Antagonist

Answer 18

Ligand that binds to receptors (Affinity) but does nothing only blocks it (NO efficacy)

Question 19

Full agonist

Answer 19

can stimulate full/maximal response

Question 20

Partial agonist

Answer 20

If given with full agonist, can produce some antagonist activity

Question 21

Selectivity

Answer 21

NOT SPECIFIC as when increase drug dose, can overlap with other receptor populations (giving rise to unwanted side-effects)

Question 22

Drug-receptor structure-activity relationship?

Answer 22

Stringent relationship between the activity of drug & its chemical structure

Can form antagonists from agonists (altering structure)

Question 23

What is required for efficacy?

Answer 23

A transducer!

Could include opening a ion-channel OR linking to an enzyme etc.

Question 24

Dose-response curve for full/partial agonist?

Answer 24

Partial agonist has a LOWER max - this is as it has a reduced efficacy

Question 25

2 types of receptor antagonist

Answer 25

Competitive & Irreversible

Question 26

Competitive?

Answer 26

Competes for same site as agonist Surmountable - can be overcome by higher [agonist] D-R curve shifts to right

Question 27

Examples of competitive?

Answer 27

Atropine | Propranolol - beta1 and 2 (non-selective)

Question 28

Irreversible?

Answer 28

``` Binds tightly to site OR binds to a different site Unsurmountable LONGER duration of action ```

Question 29

Examples of irreversible?

Answer 29

Hexamethonium

Question 30

Effects of antagonist on D-R curve?

Answer 30

Competitive shifts to R as higher [agonist] required for same response Irreversible has a LOWER response as blocking receptors so cannot have the same response as before

Question 31

4 types of drug antagonism?

Answer 31

Receptor blockade Physiological antagonism Chemical antagonism Pharmacokinetic antagonism

Question 32

Drug antagonism?

Answer 32

the way in which drugs can interact to diminish the effect of the other

Question 33

Receptor blockade?

Answer 33

Competitive and irreversible | Can also have 'use-dependency' of ion channel blockers - the more the cell is active, the more it is blocked

Question 34

Physiological antagonism?

Answer 34

Drugs interact w DIFFERENT receptors producing OPPOSITE effects in same tissue e.g. NA and histamine on BP

Question 35

Chemical Antagonism

Answer 35

Interact in solution to antagonise a REACTION (rather than binding to specific receptor) e.g. heavy metal complexed are collated, forming non-toxic clumps that can be excreted

Question 36

Pharmacokinetic antagonism

Answer 36

Agonists that are administered and antagonised by the body itself, reducing [active drug] at site of action Could reduce absorption, increase metabolism & excretion

Question 37

Barbiturates?

Answer 37

pharmacokinetic antagonism If taken for a long time = enzyme-induced so metabolised quickly in the liver which can affect other drugs that are metabolised by same enzyme e.g. Warfarin

Question 38

Drug tolerance?

Answer 38

Gradual decrease in responsiveness to drug with repeated administration

Question 39

5 reason for drug tolerance?

Answer 39

``` Pharmacokinetic factors Loss of receptors Change in receptors Exhaustion of mediator stores Physiological adaption ```

Question 40

Pharmacokinetic Factors

Answer 40

Enzyme-induced | Increased rate of metabolism

Question 41

Loss of receptors?

Answer 41

Receptor 'down-regulation' via. endocytosis | e.g. beta-adrenoceptors

Question 42

Denervation supersensitivity?

Answer 42

Up-regulation of receptors (NOT for drug tolerance)

Question 43

Change in receptors?

Answer 43

Receptor desensitisation - conformational change SO affinity BUT NO efficacy e.g. nAchR at NMJ

Question 44

Exhaustion of mediator stores?

Answer 44

What the name says e.g. amphetamine and NA (less NA so amphetamine cannot work [OneNote!!])

Question 45

Physiological adpation

Answer 45

Body physiologically adapts to the administration of the drug over time e.g. BP dropping drug could cause the activation of RAS

Question 46

Type 1?

Answer 46

``` Ion-channel linked receptor Location is CSM and effector is the channel Direct coupling x4 or 5 domains in subunit e.g. nAchR and GABAa ```

Question 47

Type 2?

Answer 47

``` G-protein coupled receptor Location is CSM and effector can be enzyme or channel G-protein coupling 7-TM structure e.g. mAchR e.g. alpha1/2 and beta1/2 ```

Question 48

Type 3?

Answer 48

``` Kinase-linked receptors Location is CSM and effector is enzymes Direct coupling - protein phosphorylation (tyrosine kinase) Only one subunit - alpha-helix e.g. Insulin/growth receptors ```

Question 49

Type 4?

Answer 49

IC steroid type receptors Located IC and effector is gene transcripts Couple via. DNA NO subunits - have DNA binding domain instead e.g. steroid/thyroid receptors