M&R Session 8 (Lecture 8.1 + 8.2) Flashcards Preview

ESA 2 Brij > M&R Session 8 (Lecture 8.1 + 8.2) > Flashcards

Flashcards in M&R Session 8 (Lecture 8.1 + 8.2) Deck (32):
1

What is the formula for molarity (M) ?

Molarity (M) = g/L / MWt

2

How do most drugs bind to receptors?

Reversibly

3

What law does binding of drugs obey?

Law of mass action (related to concentrations of reactants & products)

4

What is drug action dictated by?

Affinity and intrinsic efficacy

5

What does an agonist have?

A ligand that causes a response
With both affinity and intrinsic efficacy

6

What is the difference between intrinsic efficacy and efficacy?

Intrinsic eff - ability for ligand to produce the AR*
Eff - Cell/tissue dependant factors that determine a response

7

What does an antagonist have and do?

Affinity ( NO INTRINSIC EFFICACY)
Block the effects of agonists i.e. prevent receptor activation by agonists

8

What is Bmax?

Maximum binding capacity - info about receptor no.

9

What is Kd and what type of graph can this be obtained from?

Kd = dissociation constant ( a measure of affinity) - concentration of ligand required to occupy 50% of the available receptors
From proportion of bound receptors vs [Drug] log10 nM

10

A lower Kd value indicates?

Higher affinity

11

What does -9log10 mean?

10-9 nM or 1nM

12

What responses are induced by a drug? (2 general points)

Change in a signalling pathway
Change in cell or tissue behaviour (e.g. contraction)

13

What can be obtained from a concentration - response curve?

EC50 and Emax

14

What is Emax and EC50?

Emax - Effect maximum
EC50 - Effective concentration giving 50% of the maximal response

15

What is the difference between concentration and dose?

Concentration - Known [drug] at site of action e.g. cells and tissues

Dose - [] at site of action unknown e.g. in patient

16

What is a measure of potency and what does it depend on?

EC50

Depends on agonist affinity and intrinsic efficacy and efficacy

Left shift = more potent

17

What factors affect the 'making' of a drug in clinical practice?

Affinity
Efficacy
Selectivity
PK
Physicochemical properties e.g. solubility, pH, stability

18

What is the problem with IV drip salbutamol?

Activates beta 1 and beta 2 receptors which can cure asthma by opening up airways (b2) but causes tachycardia and angina by activating b1 receptors on the heart

19

What property of cells allows <100% occupancy but generate 100% response?

Spare receptors
(Find that response curve is left shifted to binding curve) i.e. EC50 < Kd so that 50% binding causes 100% response

20

Why do spare receptors exist?

Amplification in the signal transduction pathway
Response limited by a post-receptor event

21

What do spare receptors increase?

Sensitivity - allow responses at low concentrations of agonist ([drug] below Kd)

22

How can changing the receptor number change the maximal response of a drug?

More receptors = lower [drug] for full response
Less receptors = if lower than Kd then 100% occupancy but insufficient receptors for full response

23

When do receptor numbers change?

Increase with low activity
Decrease with high activity

24

What are partial agonists and comment on their potency compared to full agonists?

Drugs that cannot produce a maximal effect, even with full receptor occupancy

PA can be more or less potent than full agonists.

PAs can act as an antagonist of a full agonist

25

Describe the clinical use of partial agonists?

Opioids : Pain relief, Recreational use (heroin) - euphoria
BUT respiratory depression

Acts via Mu opioid receptor GPCR

Give buprenorphine which has a higher affinity but lower efficacy than morphine >>> gives adequate pain control, less resp depression and stops other opioids from binding to receptors

26

How can a partial agonist be changed?

By changing the number of Rs on a cell - from PA to FA.

PA still has low intrinsic efficacy at each receptor but there are sufficient receptors to contribute a full response

27

Describe reversible competitive antagonists?

Relies on a dynamic equilibrium between ligands and receptors. Competitvely competes with agonist for binding site

Surmountable with increasing [agonist]

Cause parallel shift to the right in conc-resp curve

28

What is IC50?

[Antagonist] giving 50% inhibition

29

Give an example of a reversible comp antagonist and its clinical usage?

Naloxone - high affinity, comp ant at mu opioid receptors

Reversal of opioid-mediated resp depression- high affinity means it will compete effectively with other opioids for receptors.

30

Describe irreversible competitive antagonism.

Occurs when the antagonist dissociates slowly or not at all.

Non-surmountable

Cause parallel shift to the right on conc-resp cuve and at higher [] suppress the maximal response

31

Give an example of a irreversible comp antagonist and its clinical usage?

Phenoxybenzamine - non selec irr alpha 1 adrenoceptor blocker used in HT episodes in pheochromocytoma

Stops excessive vasoconstriction


Also clopidogrel (P2Y antagonist) so stops thrombosis

32

Describe non competitive antagonism.

Drug binds to allosteric site affecting receptor orthosteric ligand affinity and/or efficacy

e.g. NMDA R for ketamine causing analgesia at low []s
reduced central excitation