Prelim Chapter 2 Drug Receptor and Pharmacodynamics

Question 1

the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects

Answer 1

Receptor

Question 2

describes the actions of a drug on the body and the influence of drug concentrations on the magnitude of the response

Answer 2

Pharmacodynamics

Question 3

Most receptors are made up of——

Answer 3

Protein

Question 4

Drugs bind to them and then after binding there will be a series of events physiological events, then there will be effect or response

Answer 4

Receptor

Question 5

Macromolecular Nature of Drug Receptors

Answer 5

Note: we have alot of receptors inside the body, most of them made up of protein, some are lipids, nucleic acid. But we really have different types of receptors in our body and their effects

Question 6

Original substance in the body that bind to that specific receptor

Answer 6

Ligands

Question 7

•Their ligands are presently unknown
•May prove useful targets for the development of new drugs.

Answer 7

ORPHAN RECEPTORS

Question 8

Receptor that is manufactured itself by our body

Answer 8

Endogenous receptor

Question 9

•mediate the actions of endogenous chemical signals such as neurotransmitters, autacoids and hormones.

Answer 9

REGULATORY PROTEINS

Question 10

Once the drug bind sa mga protein na ni, there will be endogenous resposes, physiological responses sa body

Answer 10

Regulatory protein

Question 11

These are all chemical messengers in the body, they carry certain message inside the body, they carry it going to the different organs , now they reach the certain organs in our body, they will elicit thier pharmacologic action

Answer 11

• neurotransmitter
  -autocoids
  -hormones

Question 12

These are produce by pur neurons/nerve cells

Answer 12

Neurotransmitter

Question 13

Neurotransmitter
Ex.
Norepinephrine
GABA
Acetycholine
Glutamate
Dopamine

Answer 13

…..

Question 14

Local mediator, produce by our cells after a release, they will produce a response, after release by the cell automatic naa na dayon ilang receptor then mag react na dayon sila

Answer 14

Autocoids
Ex. Histamine

Question 15

Note: Neurotransmitter and Hormones they will travel all over your body just to cause and effect

Answer 15

…..

Question 16

These are produce by our glands

Answer 16

Hormones
Ex.
Insulin- pancrease
Epinephrine - adrenal medulla

Oxytocin- love hormones
Serotonin-happy hormones

Question 17

•also identified as drug receptors
•may be inhibited or activated by binding a drug
•Ex: dihydrofolate reductase for methotrexate

Answer 17

ENZYMES

Question 18

— its function in the body is to speed up chemical processess/speed up chemical reaction/speed up metabolism

Answer 18

Enzymes

Question 19

Enzymes example
dihydrofolate reductase for methotrexate

Enzyme: Dihydrofolate reductase(enzyme needed for cell division)
Drug: methotrexate(anti cancer drug)

Moa: Inhibits rhe cell division and ,ultiple of our cancer cells

Answer 19

….

Question 20

-considered as drug receptor
-its function is to transport of chemical from one part of the body to another
•Ex: Na+/K+ ATPase - membrane receptor for digitalis glycosides

Answer 20

TRANSPORT PROTEINS

Question 21

Board exam Questions:
Is Na+/K+ ATPase a enzyme or not?

Answer 21

Noo.😝😂,Na+/K+ ATPase is not an enzyme, but a transport protein or a pump

Question 22

Note: For Heart Failure drug : Digoxin, Brand: Lanoxin

Answer 22

…

Question 23

• These are protein original function is for cell structure
  -they contribute to the formation of certain structure in the body
  -they can also be a receptor, target by our drug
  •Ex: Tubulin - receptor for colchicine

Answer 23

STRUCTURAL PROTEINS

Question 24

Drug for gout

Answer 24

Cholchicine

Question 25

DNA contains Nitrogenous base : in Purine theres a Guanine and adenine, then if they degrade what do you call to that?

Answer 25

Uric Acid

Question 26

•receptors which are spare for a given pharmacologic response that are able to possibly elicit a maximal biologic response at a concentration of agonist that does not result in occupancy of the full complement of available receptors

Answer 26

SPARE RECEPTORS

Question 27

Spare meanss…

Answer 27

Extra Concept of Spare Receptor: Spare means extra, our receptor in the body is limited, kung unsa lang ang available na receptor, didto lang pud mag bind atung gi inum na tambal, what if na occupy na tanan ang receptor? -spare receptor

Question 28

Note: Receptors 90% proteins 10% Lipids and Nucleic Acid

Answer 28

…..

Question 29

Four Subtypes of Receptors

Answer 29

Class 1 Class 2 Class 3 Class 4

Question 30

Class 1 is also known as

Answer 30

Ionotropic receptors associated with ligand-gated ion channels

Question 31

•Ionotropic receptors associated with ligand-gated ion channels •Features: Location = cell membrane; Effect = millisecond Examples •Nicotinic Receptor - controls Na+ channels (Ligand-gated) -- inhibited by curare and derivatives, ganglionic blockers •GABAA-receptor complex - controls Cl- channels inward Cl- conductance = hyperpolarization of cell membranes stimulate GABAA - benzodiazepines, Barbiturates (GABAmimetic, GABA-ergic)

Answer 31

Class 1

Question 32

controls Cl- channels

Answer 32

GABAA-receptor complex

Question 33

- controls Na+ channels (Ligand-gated) -- inhibited by curare and derivatives, ganglionic blockers

Answer 33

Nicotinic Receptor

Question 34

hyperpolarization of cell membranes

Answer 34

inward Cl- conductance

Question 35

- benzodiazepines, Barbiturates (GABAmimetic, GABA-ergic)

Answer 35

Stimulate GABAA

Question 36

Note: Na+ activate the cell Result: -more Positibe inside the cell (called Depolarization) -become more active (CNS Stimulant)

Answer 36

….

Question 37

Note: Cl- activate the cell Result: -more negative inside the cell (called hyperpolarization) -become depress (slow down)

Question 38

Cl- ligand is called

Answer 38

GABAA-receptor complex

Question 39

Cl- drug that can help bind to the receptor

Answer 39

Benzodiazepines

Question 40

Diazepam,midazolam and alprazolam is an example of what therapeutic class?

Answer 40

Anti seizure drug

Question 41

Slow down the firing of neurons

Answer 41

Anti seizure drugs

Question 42

Note: class 1 or Ionotropic Receptors

Answer 42

…..

Question 43

aka: Metabotropic 7 transmembrane-spanning G-protein-linked

Answer 43

Class 2

Question 44

•aka: Metabotropic 7 transmembrane-spanning G-protein-linked •Features: Location = cell membrane; Effect= in seconds

Answer 44

Class II

Question 45

Other involved in chemical messenger in Class 2

Answer 45

G protein-coupled receptor Receptor Tyrosine kinase

Question 46

3 types of G-proteins

Answer 46

•Gs - activates adenylyl cyclase which produces the second messenger cyclic adenosine monophosphate (cAMP) •Gi - inhibits adenylyl cyclase •Gq - activates phospholipase C generating two secondary messengers: 1,4,5-triphosphate (IP3) & diacylglycerol (DAG)

Question 47

- activates adenylyl cyclase which produces the second messenger cyclic adenosine monophosphate (cAMP)

Answer 47

Gs

Question 48

- inhibits adenylyl cyclase

Answer 48

Gi

Question 49

- activates phospholipase C generating two secondary messengers: 1,4,5-triphosphate (IP3) & diacylglycerol (DAG)

Answer 49

Gq

Question 50

Notes Class 1 Ionotropic Receptor Class 2 Metabotropic Receptor

Answer 50

….

Question 51

Note: - Both are ligand-gated Transmembrane protein Metabotropic receptors do not have … channels Ionotropic Receptor change its shape to create a channel

Answer 51

….

Question 52

•Enzyme-linked receptors •Features: Effect = minutes to hours; posesses tyrosine kinase activity as part of their structure Examples: (endogenous Drug) •Epidermal growth factor •Atrial natriuretic peptide •Insulin

Answer 52

Class III

Question 53

•Intracellular receptors •Features: Effect = hours to days Examples •Tubulin is the target of antineoplastic agents such as paclitaxel

Answer 53

Class 4

Question 55

Notes Class 1 Ionotropic Receptor Class 2 Metabotropic Receptor Class 3 Enzyme-linked receptors Class 4 Intracellular receptors

Answer 55

….

Question 56

•the total number of cell-surface receptors is reduced, and the cell's responsiveness to ligand is correspondingly diminished because of the rapid degredation those receptors due to accelerated endocytosis

Answer 56

Down Regulation

Question 57

- pharmacologic potency and maximal efficacy – As the concentration of drug increases, its pharmacologic effect also gradually increases until all the receptors are occupied

Answer 57

•Graded Dose-Response Relations

Question 58

•Refers to the concentration or dose of a drug required to produce 50% of that drug's maximal effect. •Example: Candesartan (4-32 mg) is more potent than Irbesartan (75-300 mg) Example •If ED50 of two drugs for producing a specified quantal effect are 5 and 500mg, respectively, then the first drug can be said to be 100 times more potent than the second drug for that particular effect.

Answer 58

POTENCY

Question 59

•is the magnitude of response a drug causes when it interacts with a receptor •dependent on the number of drug-receptor complexes formed and the intrinsic activity of the drug

Answer 59

EFFICACY

Question 60

•crucial for making clinical decisions when a large response is needed •may be determined by the drug's mode of interaction with receptors Ex: Diuretics that act on one portion of the nephron may produce much greater excretion of fluid and electrolytes than diuretics that act elsewhere •Efficacy may be limited due to possible toxicity

Answer 60

Maximal Efficacy

Question 61

- determining the dose of the drug required to produce a specified magnitude of effect in a large number of individual patients or experimental animals

Answer 61

Quantal Dose-Effect Curves

Question 62

•ED50 •the dose at which 50% of individuals exhibit the specified quantal effect

Answer 62

Median Effective Dose

Question 63

•TD50 •the dose required to produce a particular toxic effect in 50% of the population

Answer 63

Median Toxic Dose

Question 64

•LD50 •If the toxic effect is death of the animal

Answer 64

Median Lethal Dose

Question 65

•the ratio of TD50 to the ED50 for some therapeutically relevant effect

Answer 65

Therapeutic Index

Question 66

•determines the drug's ability to fully or partially activate the receptors

Answer 66

INTRINSIC ACTIVITY

Question 67

•a drug that binds to a receptor and produces a maximal biologic response that mimics the response of the endogenous ligand

Answer 67

Full Agonists

Question 68

•have intrinsic activities greater than zero but less than one •cannot produce the same maximal efficacy as a full agonist even if all the receptors are occupied •becomes an antagonist if taken concomitantly with a full agonist

Answer 68

Partial Agonists

Question 69

•have an intrinsic activity less than zero, reverse the activity of receptors, and exert the opposite pharmacological effect of agonist

Answer 69

Inverse Agonists

Question 70

•bind to a receptor with high affinity but possess zero intrinsic activity •Antagonism - may occur by either blocking the drug's ability to bind to the receptor or by blocking its ability to activate the receptor

Answer 70

Antagonists

Question 71

- may occur by either blocking the drug's ability to bind to the receptor or by blocking its ability to activate the receptor

Answer 71

•Antagonism

Question 72

•prevents an agonist from binding to its receptor and maintains the receptor in its inactive state •Ex: Terazosin (Norepinephrine)

Answer 72

Competitive Antagonists

Question 73

•bind covalently to the active site of the receptor, thereby reducing the number of receptors available to the agonist

Answer 73

Irreversible Antagonists

Question 74

•also causes a downward shift of the Emax, with no change in the EC50 value of an agonist •binds to a site (allosteric site) and prevents the receptor from being activated by the agonist •Ex: Picrotoxin in GABA receptors

Answer 74

Allosteric Antagonists

Question 75

•an antagonist that may act at a completely separate receptor, initiating effects that are functionally opposite with the agonists

Answer 75

Functional Antagonism

Question 76

•usually caused by genetic differences in metabolism of the drug or by immunologic mechanisms, including allergic reactions

Answer 76

IDIOSYNCRASY

Question 77

•usually refers to allergic or other immunologic responses to drugs

Answer 77

Hypersensitivity

Question 78

•a state of decreased responsiveness to the drug's effect as a consequence of continued drug administration

Answer 78

Tolerance

Question 79

•a response in which responsiveness diminishes rapidly after administration of a drug

Answer 79

Tachyphylaxis

Question 80

Classification of Drugs •Functional Modifiers - alter normal physiological functions Tachycardia associated with anxiety - Beta blockers Fever (response to endogenous pyrogen IL-1) - antipyretics Naproxen - fever due to cancer

Answer 80

..

Question 81

•supplement or replace endogenous substance that are lacking or insufficient Ex: T1DM - absolute insulin deficiency - INSULIN

Answer 81

Replenishers

Question 82

•diagnosis of certain conditions Ex: Myasthenia Gravis = Tensilon test (Edrophonium)

Answer 82

Diagnostic Agents

Question 83

•drugs used to kill/ inhibit growth/ multiplication of cells or nucleic acids considered as foreign to the body a. Anti-infectives b. Antineoplastics

Answer 83

Chemotherapeutic Agents