Cholinergic Handout

Question 1

What are cholinergic drugs?

Answer 1

Medications that produce the same effects as parasympathetic nervous system.

Question 2

[True/False] Cholinergic drugs are available OTC?

Answer 2

False. They are prescription only.

Question 3

What are 4 therapeutic uses of cholinergic drugs?

Answer 3

Myasthenia Gravis
Glaucoma
Alzheimer’s Disease
Atropine/OP poisoning

Question 4

A disease that causes severe muscle cramping?

Answer 4

Myasthenia Gravis

Question 5

A disease that is caused by increased pressure inside the eye.

Answer 5

Glaucoma

Question 6

The most common form of dementia among older people.

Answer 6

Alzheimer’s Disease

Question 7

It accelerates the heart rate, constricts the blood vessels, and raises blood pressure.

Answer 7

Sympathetic Nervous System

Question 8

It serves to slow the heart rate, increase the intestinal and gland activity, and relax the sphincter muscles.

Answer 8

Parasympathetic Nervous System

Question 9

Primary neurotransmitter of the PNS?

Answer 9

ACh

Question 10

What are the two types of ACh receptors?

Answer 10

Nicotinic and Muscarinic

Question 11

What two substrates make ACh?

Answer 11

Choline and Acetyl CoA

Question 12

When ACh is broken down by AChE, what is produced?

Answer 12

Choline and Acetate

Question 13

What are the two main forms of cholinesterases in the body?

Answer 13

Acetylcholinesterase

Butylcholinesterase

Question 14

What residue does AChE and BChE both contain?

Answer 14

Serine

Question 15

What two ways can you find AChE and BChE?

Answer 15

Bound to a cell membrane or in a soluble form.

Question 16

Soluble ____ is very important in keeping plasma _____ low.

Answer 16

BChE; [AChE]

Question 17

In regards to BChE, what causes different elimination rates of some drugs?

Answer 17

Genetic Variation

Question 18

What are 3 ways drugs may be designed to influence cholinergic transmission?

Answer 18

Acting on ACh receptors

Affecting the availability of compounds involved in the synthesis, release, and uptake of ACh.

Affecting the biochemical pathways and enzymes involved in the synthesis, packaging, release, hydrolysis, and re-uptake of ACh

Question 19

What are two ways cholinergic drugs can act?

Answer 19

As an agonist (mimic the effect of ACh)

Antagonist (to block the effect of ACh.

Question 20

How do muscarinic aginsts bind?

Answer 20

Heterogeneously to receptors in the brain and peripheral nervous system.

Question 21

What cholinesterase inhibitor that is used to treat Alzheimer’s does not inhibit BChE?

Answer 21

Galantamine

Question 22

What drug was approved for the treatment of moderate-severe AD?

Answer 22

Memantine (binds to NMDA receptors)

Question 23

What did the first drug used to treat AD have complexed with it?

Answer 23

tacrine

Question 24

The rate of hydrolytic regeneration of the phosphorylated enzyme is much slower than that of the carbamylate enzyme.

Answer 24

Irreversible Inhibitors (forms a phosphorylated enzyme)

Question 25

Pyridostigmine and Neostigmine are ______ acetylcholine esterase inhibitors.?

Answer 25

Reversible.

Question 26

Tabun Nerve Gas, Sarin Gas, and VX Nerve gas are ________ acetylcholin esterase inhibitors.

Answer 26

Irreversible

Question 27

What are the antidotes for OP poisoning called?

Answer 27

Oximes

Question 28

What are 3 HIV enzymes that are potential site for therapeutic drugs?

Answer 28

Reverse transcriptase Protease Integrase

Question 29

How does HIV get the proteins it needs to work?

Answer 29

It uses HIV Protease to splice up larger proteins.

Question 30

What family of proteases does HIV protease belong to?

Answer 30

Apartyl proteases.

Question 31

What are 3 requirements to design an HIV protease therapeutic agent?

Answer 31

They must have a Ki value in nanomolar or subnanomolar range Must not target mammalian aspartyl proteases Adequate bioavailability

Question 32

What do they base the structure of HIV protease therapeutic agents off of?

Answer 32

Physiological peptide substrate

Question 33

How do you increase the stability of HIV protease therapeutic agents?

Answer 33

You replace the amide bonds.

Question 34

Most HIV protease inhibitors have a replacement of the peptide bond by a simple _____ _____.

Answer 34

Secondary alcohol

Question 35

What is the lead HIV protease inhibitor?

Answer 35

Viracept

Question 36

What is the approach used for the development of Viracept?

Answer 36

Crystal structure of target enzyme Computational analysis and ligand design Organic synthesis of designed ligand Biochemical evaluation of the ligand

Question 37

_____-based drug design is an integral part of drug discovery today.

Answer 37

Structure

Question 38

Why is there drug resistance in HIV?

Answer 38

The high mutation rate of HIV due to infidelity of RT.

Question 39

How do you treat HIV drug resistance?

Answer 39

Use combination therapy.

Question 40

Are the combination RT and protease therapeutic drugs on the market effective?

Answer 40

No, because of HIV's mutation rate.

Question 41

Where does Maraviroc bind?

Answer 41

CCR5 instead of CXCR4

Question 42

What is a new possible therapeutic agent found in green tea and binds to CD4?

Answer 42

EGCG

Question 43

How does EGCG work?

Answer 43

It prevents the interaction between gp120 and CD4, which could be useful in combination therapy

Question 44

What other disease can EGCG be useful against besides HIV?

Answer 44

Cancer