From Physiological Systems To Molecular Drug Targets I

Question 1

Name the 4 major sites of action of drugs

Answer 1

1. Enzymes
2. Transporters
3. Ion channels
4. Receptors

Question 2

What does PNS stand for?

Answer 2

Peripheral Nervous System

Question 3

What is the role of the PNS?

Answer 3

To regulate the body’s internal environment

Question 4

What does the PNS represent?

Answer 4

The output of the CNS

Question 5

What 2 systems does the PNS consist of?

Answer 5

1. ANS = autonomic nervous system
2. SNS = somatic (motor) nervous system

Question 6

How is the ANS controlled?

Answer 6

The ANS is usually outside of voluntary control

Question 7

How is the SNS controlled?

Answer 7

The SNS is under concious control

Question 8

Name the 2 nerves that make up the SNS

Answer 8

Efferent and Afferent

Question 9

What is the role of the efferent nerves?

Answer 9

Control movement by innervating skeletal muscle

Question 10

What is the role of afferent nerves?

Answer 10

Respond to external stimuli e.g. pain-sensing (nociceptive) fibres

Question 11

What is the CNS made up of?

Answer 11

The brain and the spinal cord

Question 12

List 5 processes that the ANS regulates

Answer 12

1. Heart beat
2. Smooth muscle contraction and relaxation
3. All exocrine function
4. Some endocrine function
5. Some steps in intermediate metabolism

Question 13

Name the 3 major systems/divisions of the ANS

Answer 13

1. PNS = Parasympathetic Nervous System
2. SNS = Sympathetic Nervous System
3. ENS = Enteric Nervous System

Question 14

What effect does blocking the noradrenaline receptors have?

Answer 14

Activates the sympathetic system

Question 15

What effect does blocking the muscarinic ACh receptors have?

Answer 15

Blocks the parasympathetic system

Question 16

What effect does activating the muscarinic ACh receptors have?

Answer 16

Activates the parasympathetic system

Question 17

Describe the SNS

Answer 17

The SNS evokes a ‘fight or flight’ response

Question 18

Describe the PNS

Answer 18

The PNS mediates a ‘rest and digest’ state

Question 19

Define: Endocrine gland

Answer 19

A gland which secretes hormones directly into the bloodstream

Question 20

Define: Exocrine gland

Answer 20

A gland which secretes hormones via ducts onto an epithelium rather than directly to the blood

Question 21

List 3 actions of the SNS

Answer 21

1. Pupil dilation (wide)
2. Blood flow directed to the skeletal muscle
3. Bronchodilation (more O2)

Question 22

List 3 actions of the PNS

Answer 22

1. Pupil constriction
2. Blood flow directed to the viscera (organs)
3. Bronchoconstriction

Question 23

What is the role of ACh-esterase?

Answer 23

Convert ACh —> acetate + choline

Question 24

What are ACh-esterase inhibitors also known as?

Answer 24

Anti-cholinesterases

Question 25

What does **blocking ACh-esterase** do?

Answer 25

**Increase** the amount of **ACh** in the **synaptic cleft**

Question 26

**Where** is **ACh broken down** by ACh-esterase?

Answer 26

The **synaptic cleft**

Question 27

Which **receptor** does **atropine block**?

Answer 27

Muscarinic ACh receptor **(mAChR)** Antagonist

Question 28

Which **receptor** does **succinylcholine block**?

Answer 28

Nicotinic ACh receptor **(nAChR)**

Question 29

Name the **substance** that **blocks** the **muscarinic ACh receptor**

Answer 29

Atropine

Question 30

Name the **substances** that **block** the **nicotinic ACh receptor**

Answer 30

**Succinylcholine** and **Tubocurarine**

Question 31

Which **receptor** does **tubocurarine block**?

Answer 31

**Nicotinic ACh** receptor

Question 32

What **effect** does **tubocurarine** have on the **body**?

Answer 32

**Paralyses muscles** By **blocking** the **nicotinic ACh** receptor

Question 33

Name a **condition** that **anticholinesterases** are used to **treat**

Answer 33

**Alzheimer's** Disease

Question 34

What effect does **ACh** have on the **blood pressure**?

Answer 34

ACh **decreases the blood pressure** More ACh = greater decrease in BP

Question 35

What **substance** does **atropine block** the **effects of**?

Answer 35

**ACh**

Question 36

What substance **blocks the effects** of **ACh**?

Answer 36

**Atropine**

Question 37

**How** does **atropine block** the effects of **ACh**?

Answer 37

By **blocking** (antagonist) the **muscarinic ACh receptor**

Question 38

Name the **receptor** that causes an **increase in BP** when **bound to ACh** (as atropine has blocked the muscarinic receptor)

Answer 38

**Nicotinic** receptor

Question 39

How many **subtypes** of **muscarinic receptor** exist?

Answer 39

**5**: M₁, M₂, M₃, M₄, M₅

Question 40

What **type of receptor** do **muscarinic receptors** exist as?

Answer 40

**G protein-coupled receptors**

Question 41

What **response** do **M1, M3 and M5** (odd numbers) **cause**?

Answer 41

They cause an **increase in IP3**

Question 42

What **type of G protein** are **M1, M3 and M5**?

Answer 42

**Gα_q**

Question 43

What **type of G protein** are **M2 and M4**?

Answer 43

**Gα_i/o**

Question 44

What **response** do **M2 and M4** (even numbers) cause?

Answer 44

**Decrease in cAMP**

Question 45

Why is it not recommended to target **agonist drugs** at the **mAChR subtypes**?

Answer 45

The **agonists** are **non-selective** - could target any/all of the subtype receptors = **unpredictable effects**

Question 46

Why is it preferable to target **mAChR subtype receptors** with **antagonist drugs**

Answer 46

Drugs that are **antagonists** are **more selective** so they have a more **predictable** effect, only targeted **at 1 receptor**

Question 47

What are the **benefits** of having a **more selective drug**?

Answer 47

* More likely to be **safe** * More likely to be **potent/efficacious**

Question 48

What is the **role of Gα_q**? (M1/M3/M5)

Answer 48

**Activates phospholipase C** (which converts PIP2 into IP3 + DAG)

Question 49

What is the **role** of **phospholipase C**?

Answer 49

It converts **PIP2** into **IP3 + DAG**

Question 50

What **effect** does **IP3 + DAG** have on the cell?

Answer 50

Increases **intracellular calcium:** * Secretion * Contraction * Vasodilation

Question 51

List **3 effects** of an **increase** in **intracellular calcium**

Answer 51

1. **S**ecretion 2. **C**ontraction 3. **V**asodilation

Question 52

Name the **enzyme** that is **inhibited by Gαi/o** (M2/M4)

Answer 52

**Adenylate cyclase** (so ATP can't be converted to cAMP)

Question 53

What **enzyme** do **M2/M4** **inhibit**?

Answer 53

**Adenylate cyclase** (so ATP can't be converted to cAMP)

Question 54

What is the **role** of **adenylate cyclase**?

Answer 54

Convert **ATP** to **cAMP**

Question 55

Name a **physiological effect** of a **reduction in cAMP**

Answer 55

**Bradycardia** = reduced heart rate

Question 56

Define: **Cholinergic**

Answer 56

Relating to **nerve cells** in which **ACh** acts as a **neurotransmitter**

Question 57

The **actions** of **mAChRs mimic** which **nervous system**?

Answer 57

**Parasympathetic** nervous system

Question 58

List **4 parasympathetic effects** caused by the **actions of mAChRs**

Answer 58

1. **Bradycardia** 2. **Vasoconstriction** 3. Increased **secretion** 4. Increased **gut motility**

Question 59

List 4 **physiological effects** of the **actions of atropine** (blocking mAChRs)

Answer 59

1. **Tachycardia** (increased heart rate) 2. Pupillary **dilation** 3. Block **secretion** 4. Inhibits **gut motility**

Question 60

Name **3 indications** of **atropine**

Answer 60

1. **Smooth muscle relaxants** (e.g. IBS) 2. **Cardiovascular** (e.g. to treat bradycardia after heart attack) 3. **Anaesthesia** (to prevent vagal inhibition of the heart)

Question 61

What is the **mechanism** of action of **atropine**?

Answer 61

* **Antagonist** * Blocks at **muscarinic ACh receptors** * **Non-selective** * Doesn't block **nicotinic receptors**