Pharmacodynamics - Sinal 1

Question 1

What is pharmacology?

Answer 1

What drugs are, how they work and what they do

Divided into pharmacodynamics and pharmacokinetics

Question 2

Drugs

Answer 2

Therapeutic agent

Any substance other than food, used in prevention, diagnosis, alleviation and treatment or cure of disease

Question 3

Pharmacy

Answer 3

Concerns with scientific, legal and managerial aspects of dispensing drugs

Question 4

Pharmacodynamics

Answer 4

Study of relationship of drug concentrations to drug effects

Biological effect is proportional to amount of drug-receptor complex

Question 5

Major classes of receptors targeted

Answer 5

1. Ligand-gated ion channels
2. Enzyme-linked receptors
3. G-protein coupled receptors
4. Ligand-activated transcription factors

Question 6

Agonist

Answer 6

A drug causing receptor to respond in same way as naturally occurring substance
Independent impact on receptor activity

Question 7

Antagonist

Answer 7

Drug that binds to receptor but does not produce a response
Inhibitory effect on naturally occurring substance
Impacts receptor activity only in presence of agonist (lacks efficacy)

Question 8

B

Answer 8

Fraction of total receptors bound

Question 9

Bmax

Answer 9

Maximal faction of total receptors bound

Question 10

Kd

Answer 10

Equilibrium dissociation constant
Drug concentration at which 1/2 of Bmax is achieved
A measure of the inherent affinity of the drug-receptor interaction
Constant and not altered by concentration of drug or receptor number

Question 11

Saturation point

Answer 11

Level out of B/[D] graph because all receptors are saturated

Question 12

High Kd

Answer 12

Low affinity

Question 13

Low Kd

Answer 13

High affinity

Question 14

Graded dose-response curves

Answer 14

Drug dose/Biological effect (%)

Question 15

Emax

Answer 15

Maximum response achieved by the drug

Question 16

ED50

Answer 16

Drug dose where 1/2 Emax is achieved

Also referred to as drug potency

Question 17

Concentration-Binding Curve

Answer 17

Drug concentration/fraction of receptors bound

Question 18

Quantal Dose-Response Curves

Answer 18

Used to describe population rather than single individual responses to drugs
Based on plotting cumulative frequency distribution of responders against the log drug dose, adding bars of histogram

Question 19

Graded phenomena

Answer 19

Infinite number of intermediate states

ie. vessel dilation, blood pressure change, heart rate change

Question 20

Quantal phenomena

Answer 20

All or none

ie. death, pregnancy, pain relief

Question 21

Potency

Answer 21

Amount of agonist needed to produce an effect of a given magnitude
Usually expressed as ED50: dose to achieve 50% of the maximum effect achievable with that agonist

Question 22

Efficacy

Answer 22

Maximum effect that can be achieved with a particular agonist
Usually expressed as Emax: maximum effect that can be achieved with that drug

Question 23

Full agonist

Answer 23

High/low potency, maximum efficacy

Question 24

Partial agonist

Answer 24

High/low potency, reduced efficacy

Question 25

Inverse agonists

Answer 25

Stabilize the inactive state or destabilizes the active state Reduces constitutive receptor activation Has an independent impact on receptor activity Opposite effect of agonist: classified as an agonist as it has a functional impact on the receptor

Question 26

Chemical antagonism

Answer 26

Direct interaction of two substances in solution such that the effects of one or both is lost ie. acid and base anticoagulant

Question 27

Physiological antagonism

Answer 27

Indirect interaction of two substances with opposing physiological actions ie. Histamine vs. EN

Question 28

Pharmacological antagonism

Answer 28

Blockage of interaction of one substance with receptor by another substance

Question 29

Pharmacological antagonists

Answer 29

Bind to receptors but do not activate signal transduction mechanisms Biological effects derived from blocking ability of agonist to bind/activate receptor

Question 30

Competitive antagonists

Answer 30

Bind reversibly to receptor Inhibition can be overcome by increasing agonist concentration Primarily affect agonist potency but can still achieve same magnitude of biological affect

Question 31

Non-competitive antagonists

Answer 31

Bind irreversibly to receptor or reversibly/irreversibly to allosteric site Inhibition cannot be overcome by increasing agonist concentration Primarily affect efficacy

Question 32

IC50

Answer 32

Inhibitory concentration

Question 33

Endogenous receptor ligands

Answer 33

``` Such as hormones and neurotransmitters Mostly are agonists Inverse agonists are rare Antagonists are rare Some drugs mimic effect of endogenous agonists and some block ```

Question 34

Epinephrine

Answer 34

Full agonist of cardiac beta2-adrenergic receptor to increase rate and force of heart contraction

Question 35

Agouti-related Peptide

Answer 35

AGRP Endogenous inverse agonist Reduces constitutive receptor activity of melanocortin receptor

Question 36

Kynurenic Acid

Answer 36

Endogenous pure antagonist NMDA receptor antagonist Physiological role unclear but may play a role in neurotransmission and neuropathologies

Question 37

Isoproterenol

Answer 37

Full agonist that mimics epinephrine at cardiac beta2 adrenergic receptor

Question 38

Buprenorphine

Answer 38

Partial agonist that mimics endogenous endorphins at n-opiod receptor Safer analgesic than morphine due to less rest of respiratory depression

Question 39

Superagonists

Answer 39

>100% Emax | Uncommon in clinical practice

Question 40

Propranolol

Answer 40

Pure antagonist of epinephrine at cardiac beta2-adrenergi receptor

Question 41

Drug desensitization

Answer 41

Effect of drug often diminishes when given continuously or repeatedly Receptor-mediated and non-receptor mediated mechanisms

Question 42

Receptor mediated drug desensitization

Answer 42

Loss of receptor function due to change in receptor conformation Reduction of receptor number

Question 43

Non-receptor mediated drug desensitization

Answer 43

Reduction of receptor-coupled signalling components Increased metabolic degradation Physiological adaptation

Question 44

Adverse drug effects

Answer 44

1. Side effect 2. Toxic reaction 3. Allergic reaction

Question 45

Side effect

Answer 45

Dose dependent Not directly related to desired effect of drug Action of drug at other sites to produce undesirable effects

Question 46

Toxic reaction

Answer 46

Dose-dependent Directly related to desired effect of drug Excessive action of drug at intended target site

Question 47

Allergic reaction

Answer 47

Not dose-dependent Not related to desired effect of drug Immunologic response to drug and largely unpredictable

Question 48

Cyclosporine

Answer 48

Promotes survival of transplanted organs | Increased susceptibility to infection, kidney damage, rash/hives/itching/breathing difficulties

Question 49

Paracelsus

Answer 49

It is not the nature of the drug that determines toxicity, but rather the amount Everything in excess is potentially toxic

Question 50

Therapeutic index

Answer 50

Measure of drug safety Considers dose required for a toxic or other adverse drug effect versus that required for the desired beneficial effect Toxic ED50/Beneficial ED50 A larger TI indicated a clinically safer drug

Question 51

Therapeutic window

Answer 51

Measure of drug safety that considers the range of blood concentration of a drug that are associated with toxic, therapeutic benefit or lack of effect within a population If drug falls between window, it fulfills clinical role