L2 and 3 Pharmacodynamics II and III

Question 1

Are Kd and EC50 usually the same?

Answer 1

Yes, unless there are spare receptors

Question 2

What does the curve of an antagonist drug look like?

Answer 2

a FLAT LINE

Question 3

What does a competitive antagonist do to ED50 and Emax?

Answer 3

ED50 increases

Emax unchanged

Question 4

What does a non-competitive antagonist do to ED50 and Emax?

Answer 4

ED50 might change

Emax decreases

Question 5

Can you overcome the effects of competitive antagonists?

Answer 5

YES, by increasing the dose of the agonist

Question 6

As antagonist concentration increases the potency of the agonist _______

Answer 6

Decreases (increases EC50)

Question 7

What are the 2 mechanisms of non-competitive antagonists?

Answer 7

1. Bing to a secondary site and inhibit receptor binding (allosteric)
2. Covalently (irreversibly) bind to the same site as the agonist

Question 8

Can you overcome the effect of non competitive antagonism by increaseing the dose of the agonist?

Answer 8

NO

Question 9

What is an example of physical/functional antagonism/.

Answer 9

Reversing a fall in blood pressure due to histamine by giving epinephrine

Question 10

What is an example of chemical antagonism?

Answer 10

Neutralizing stomach acid with antacids

Also inactiviating heparin with protamine sulfate

Question 11

THe dose response curve for a partial agonist will have _______ Bmax and Emax compared to the full agonist

Answer 11

Lower

Question 12

In the presence of full agonists, partial agonists act like ________

Answer 12

Competitive antagonists

So you could overcome the effects of the partial agonist by giving increasing dose of the full agonist

Question 13

How do intracellular receptors and their ligands have an effect?

Answer 13

Modify gene transcription in the nucleus (slow effect but long lasting)

Question 14

What is an example of lipid soluble ligands and their intracellular receptors?

Answer 14

Binding of glucocorticoids to remove heat shock protein

Question 15

How do tyrosine kinase receptors effect biochemical processes

Answer 15

PHOSPHORYLATION of things

Often growth factors and insuliN

Question 16

What pathway is activated by cytokine receptors?

Answer 16

JAK/STAT

Question 17

What are examples of ligand gated ion channels?

Answer 17

Acetylcholine binging to Nicotnic receptors and opening Na+ channels

Question 18

What is an example of voltage gated ion channels?

Answer 18

Local anesthetics and anticonvulsants

Question 19

What kind of an effect does GABA have?

Answer 19

Sedative effect

Opens Cl- channels

Question 20

What effect do G protein coupled receptors have on signal magnitude?

Answer 20

The signal is amplified

One ligand results in multiple effector signals

Question 21

What does desensitization mean?

Answer 21

The response to a G-protein coupled receptor will decrease over time and the number of receptors will be lowered

Question 22

What pathway os activated by tyrosine kinases (TPK)?

Answer 22

Ras/RAF

Question 23

What pathway is activated by cytokines?

Answer 23

JAK/STAT

Question 24

What increases when Gq receptors are activated ?

Answer 24

Intracellular calcium

Phospholipase C, DAG, IP3 etc etc

Question 25

What is an example of Polyphospoinositide signaling? | IP3

Answer 25

M1 and M3 muscarinic receptors (ACh)

Question 26

What type of receptors are Gs

Answer 26

Beta

Question 27

What type of receptors are Gi

Answer 27

Alpha 2

Question 28

What type of receptors are Gq?

Answer 28

Alpha 1

Question 29

Which way does the dose response curve shift if a system has spare receptors?

Answer 29

Left

Question 30

Does an agonists have both efficacy and affinity?

Answer 30

Yes

Question 31

Does affinity have anything to do with drug efficacy?

Answer 31

NO

Question 32

Which kind of DR curve provides information regarding potency and Emax? Graded or quantal?

Answer 32

Graded

Question 33

Which tupe of DR curve indicates the variability among individuals: Graded or Quantal?

Answer 33

Quantal

Question 34

Which type of DR curve is used to determine the therapeutic index and margin of safety: Graded or Quantal?

Answer 34

quantal

Question 35

What number shows the amount either in percentage or as a multiplication factor, by which ED99 may have to be increased to produce death in 1% of the population?

Answer 35

Therapeutic index and margin of safety

Question 36

What is tolerance?

Answer 36

Response to a drug diminishes with repeated or chronic administration

Question 37

What is pharmacokinetic tolerance?

Answer 37

Response to a drug decreases because the enzymes that metabolize the drug are induced, and DRUG LEVELS CHANGE

Question 38

What is an example of pharmacokinetic tolerance?

Answer 38

Phenytoin increasing metabolism of leothyroxine

Question 39

Do drug levels change in pharmacokinetic tolerance?

Answer 39

YES

Question 40

What is pharmacodynamic tolerance

Answer 40

Response decreases due to changes in receptor number or function. DRUG LEVELS DO NOT CHANGE

Question 41

Do drug levels change in pharmacodynamic tolerance?

Answer 41

NO

Question 42

What explains decreased efficacy of opioids even though dosage is the same?

Answer 42

Pharmacodynamic tolerance

Question 43

What is physiologic tolerance?

Answer 43

Occurs when two agents with opposite effects are administered together Ex: histamine + norepinephrine

Question 44

What is competitive tolerance?

Answer 44

Occurs when a receptor antagonist is administered with an agonist Ex: yohimbine may block the hypotensive effect of clonidine

Question 45

What is Tachyphylaxis

Answer 45

VERY RAPID development of tolerance following repeated dose over short period of time Ex: Meth addict smoking every 15 minutes

Question 46

What usually causes tachyphylaxis?

Answer 46

Stimulants

Question 47

How does an ion channel respond to being desensitized?

Answer 47

Converts it to an altered state that remains closed | Ex: succinylcholine on nicotinic ACh receptor

Question 48

How does G-protein receptor respond to being desensitized?

Answer 48

The receptor coupling effector gets phosphorylation to an inactive form (GRK, B-arrestin) Ex: B-receptor

Question 49

What is “a process of ligand-induced endocarditis and degradation of receptors”

Answer 49

Down-regulation

Question 50

In general, agonists cause a ______-regulation of receptors if chronically administered

Answer 50

down

Question 51

What is the difference between summation and synergism?

Answer 51

Summation: 1+1=2 Synergism: 1+1=5

Question 52

Summation or synergism: two drugs acting by the same mechanism

Answer 52

Summation

Question 53

What is an example of synergism

Answer 53

Depression of CNS produced by diazepam plus ethanol. Act on GABA receptor but on different sites

Question 54

How does administration of an antagonist result in supersensitivity to a drug?

Answer 54

Up-regulation of receptors due to prolonged presence of antagonist

Question 55

What is denervation supersensitivuty?

Answer 55

Develops when presynaptic nerve has been destroyed, resulting in a decrease of endogenous ligand, but a HUGE increase in receptors. If you ever get that drug again, it’s a huge response.

Question 56

What happens if a drug is displaced from plasma binding sites?

Answer 56

The response to that drug is intensified Ex: 99% of warfarin is bound to albumin, and 1% is free and active. If only 98% is bound due to getting kicked off by phenytoin, you now have twice as much active warfarin.

Question 57

Do you increase or decrease a patients warfarin dose if they start taking phenytoin?

Answer 57

DECREASE

Question 58

What is another term for “overdose”

Answer 58

Overextension of the therapeutic effect

Question 59

What is the treatment for overextension-type toxicities (overdose)

Answer 59

Find approprotate dose that is effective but not toxic. If that cant be done (chemotherapy), give sub-therapeutic levels of two drugs that will act synergistically

Question 60

What usually causes an abnormal response to a drug that is NOT immunologically mediated/

Answer 60

PharmacoGENETIC disorders

Question 61

What happens when you give succinylcholine to patients with abnormal serum cholinesterase?

Answer 61

Apnea; prolonged paralyzation

Question 62

What could explain a patient not getting any pain relief from codeine?

Answer 62

Patient may have deficiency in CYP 2D6 codeine must be metabolized for full analgesic effect

Question 63

``` These are symptoms of what type of drug allergy: Gi allergy Hives Asthmma Anaphylactic shock ```

Answer 63

Type I-anaphylactic reaction

Question 64

What is the treatment for type I anaphylactic reactions?

Answer 64

Injection of epinephrine Corticosteroids

Question 65

Penicillin induced hemolytic anemia is what type of drug reaction?

Answer 65

Type II

Question 66

What mediates Type IV delayed hypersensitivity reactions?

Answer 66

CELL - MEDIATED | Sensitized T-cells

Question 67

Contact dermatitis is an example of which type of hypersensitive reaction/

Answer 67

Type IV- Delayed hypersensitivity reaction

Question 68

What type of hypersensitivity reaction causes serum sickness?

Answer 68

Type III Arthrus reactions

Question 69

What are the symptoms of serum sickness?

Answer 69

Urticaria Arthritis Lymphadenopathy Fever

Question 70

Erythema multoforme and SJS are forms of what?

Answer 70

Serum sickness- Type III Arthrus reaction

Question 71

What kind of drugs frequently cause Type III Arthrus reactions/serum sickness?

Answer 71

Anticonvulsants Sulfonamides Penicillins

Question 72

Smoking and charbroiled foods can increase the metabolism of many drugs including warfarin. What is this type of tolerance called?

Answer 72

Pharmacokinetic

Question 73

Why do you have to take a patient off propranolol if you give them epinephrine for bronchodilation?

Answer 73

Propranolol is a non-selective B-adrenoceptor antagonist that has anti bronchodilation effects. Verapamil is a better blood pressure drug since it is a calcium channel blocker with no effects on bronchodilation