Lecture 2: Drug Targets Flashcards Preview

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Flashcards in Lecture 2: Drug Targets Deck (39):
1

T or F

When a GPCR is activated the affinity of its G-protein alpha subunit for GDP is decreased

 

True

2

The receptors for a group of signaling molecules known as GFs are often:

A) Ligand-gated ion channels

B) GPCRs

C) Nuclear receptors

D) Membrane transporters

E) Receptor tyrosine kinases

E. Receptor tyrosine kinases

3

What are 3 targets of targeted anticancer drugs?

1) Monoclonal antibodies to GF receptors

2) Monoclonal antibodies to ligands of GF receptors

3) Multikinase inhibitors

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4

What is inhibited by targeted anticancer drugs?

Upregulated GF signaling

5

Spironolactone is what type of drug?

Used to treat what?

- Aldosterone receptor antagonist

- Tx for chronic HTN and alleviates chronic heart failure

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6

What is the MOA of the drug Verapamil?

- Blocks L-type calcium channels = Calcium antagonist

- Used to tx atrial and supraventricular arrythmia, angina pectoris, and HTN

 

7

What is an adverse effect of Verapamil?

Constipation

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8

What is the MOA of Digoxin?

Inhibits Na+/K+-ATPase --> enhances cardiac contractility

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9

Which pathology is Digoxin used to treat?

CHF

10

What do TF's regulate the recruitment of?

Either promote (activators) or inhibit (repressors) the recruitment of RNA polymerase to specific genes

11

What are 5 GPCR ligands?

1) Biogenic amines

2) Peptides/proteins

3) AAs

4) Lipids

5) Nucleotides

12

What are the classes of GPCRs and their functions?

- Gs: activates adenylyl cyclase and Src tyrosine kinase

Gi: inhibits adenylyl cyclase but activates Src tyrosine kinase

Gq: activates phospholipase C

13

What specific DNA sequence do TF's bind to?

Response element

14

What is unique about insulin and IGF RTKs?

Contain polypeptide chains, α and β, linked by disulfide bond 

*Most RTKs possess a single polypeptide chain

15

List 5 hormones/cytokines that utilize a JAK-STAT pathway for signaling?

1) GH (somatotropin)

2) Erythropoietin

3) Leptin

4) Interferons

5) IL-2 to 10, and 15

16

IGF-1, VEGF, EGF, NGF, and PDGF are able to assert their actions through the use of which type of receptor?

Receptors with tyrosine kinase activity (RTK)

17

What is the defining feature of a TF?

Presence of the DNA-binding domain

18

What is unique about the effects of nuclear receptor drugs?

Effects can persist after the agonist concentraton has been reduce to zero

19

Describe the mechanism of a steroid hormone activating its receptor?

How is the receptor inactivated?

- In absence of hormone, hsp90 is bound and prevents folding into active conformation

- Binding of a hormone ligand (steroid) dissociates hsp90 and permits conversion to active configuration

20

What 3 types of drugs are inhibitors of voltage-gated Na+ channels?

1) Local anesthetics

2) Antiarrythmia drugs

3) Epilepsy drugs

21

Activation of a Nicotinic acetylcholine receptor induces influx of?

Causes?

- Na+

- Membrane depolarization

22

Nicotinic acetylcholine receptors are pentameric receptor found in what 2 locations?

1) Skeletal muscle

2) Neuronal cells

23

What is the differene between the actions of excitatory and inhibitory NTs in terms of channels they open?

Excitatory (ACh and Glutamate) open cation channels --> depolarization --> APs

Inhibitory (GABA and Glycine) open anion channels --> hyperpolarization --> prevent APs

24

GABA-A receptors are what type of channels and cause the influx of what?

Affects membrane potential how?

Anionic channels causing inward Cl- influx and hyperpolarization

25

What 4 things are GABA-A receptors a target for?

1) Inhalation anesthetics

2) IV anesthetics

3) Ethanol

4) Hypnotic and anti-anxiety benzodiazepine drugs

26

Propofol and neurosteroids modulate which subunit of GABA-A channels?

β subunit

27

Ethanol and volatile anesthetics modulate which subunit of GABA-A channels?

α subunit

28

Benzodiazepines modulate which subunit of GABA-A channels?

γ-subunit

29

Point mutations in Ras are found in 90% of what type of cancer?

Pancreatic adenocarcinomas

30

Point mutations in Raf are found in 70% of what type of cancers?

Melanomas

31

Spironolactone targets which ion channels?

Leads to?

- ENaC and Na+, K+ ATPase

- Decreases reabsorption of Na+, decreasing BP, and helps to alleviate heart failure

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32

What is the effect of Verapamil on the SA and AV node; used therapeutically for what?

- SA node = decreased HR

- AV node = decreased AV contractility

- Tx for atrial and supra-ventricular arrhythmia

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33

What is the effect of Verapamil on cardiomyocytes; used therapeutically for what?

- Decreased contractility and O2 demand

- Tx for Angina pectoris

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34

What is the effect of Verapamil on vascular smooth muscle; used therapeutically for what?

- Vascular smooth muscle relaxation

- Tx for HTN

35

What is the effect of Digoxin on GI smooth muscle, brain nuclei and the SA and AV nodes?

Producing what side effects?

- GI smooth muscle: increased contractility --> vomiting and diarrhea

- Brain nuclei: enhanced neuronal activity and increased vagal activity --> vomiting, diarrhea, disorientation, confusion, visual disturbances, bradycardia, and slowed AV conductivity

- SA and AV node: bradycardia and slowed AV conductivity

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36

What is the MOA of Etoposide?

Topoisomerase type II inhibitor --> DNA damage --> induction of p53 --> triggers apoptosis of cancer cells

37

How does Etoposide work?

What are its therapeutic uses?

- Causes DNA damage as a topoisomerase inhibitor leading to activation of p53

- p53 induces expression of proteins causing release of proapoptotic proteins from mitochondria into cytosol

- These proteins activate caspases to trigger apoptosis of a cancer cell

38

What do SH2 and SH3 bind to, respectively

SH2: tyrosine kinases

SH3: proline rich 

39

What is SOS?

Actvates?

- Encodes guanine nucleotide exchange factor

- Activates Ras