Pharmacodynamics

Question 1

Explain Pharmacodynamics

Answer 1

• mechanisms of durg action
• drug receptors
• drug properties
• variation in drug response

Question 2

Explain Drug action

Answer 2

Drug molecules bind to cells

resulting in a drug receptor combination

Question 3

Explain Drug Effect

Answer 3

Biochemical and physiological changes as a consequence of drug action

Question 4

What are the three sites of drug action?

Answer 4

• Extracellular receptors
• Cell membrane receptors
• intracellular receptors

Question 5

Wat are some of the Drug receptors?

Answer 5

• Regulatory proteins
• enzymes
• transport proteins
• structual proteins
• mutisubunit ion channels
• G-protein coupled receptors
• Protein Kinases
• transcrption factors

Question 6

Intracellular receptors are important for..?

Answer 6

hormone binding

Question 7

which receptors are important or cytokine and peptide binding?

Answer 7

ligand-activated transmembrane enzymes

Question 8

the model that reflects the actions of receptors best is?

Answer 8

the lock and key model as receptors are highly specific

Question 9

explain E, Emax and E50

Answer 9

E: effect observed at concentraion

Emax: MAX response of drug, limited to availble receptors

EC50: conc. of drug that results in 50% of MAX effect

Question 10

explain,

C, Bmax, and KD

Answer 10

C: conc. of free unbound drug

Bmax: total conc. of receptor sites

KD: conc. of free durg at which half-max binding is observed (Drugs infinity for receptor)

Question 11

the dose response curve

Answer 11

answers Q’s about drug efficency, toxicity and potency

Question 12

response is proportional to the number to receptors occupied therefore

Answer 12

concentration to reach max reponse will decrease as he number of receptors increases.

Question 13

1. which is the most potent drug?
2. which drug has the lowest max efficency?

Answer 13

1. Drug X
2. Drug Y

Question 14

comparision of the curves with a known full agonist tells what about the antagonist?

Answer 14

about its potency

Question 15

Explain a full antagonist

Answer 15

ligand-receptor interaction results in no response at all

Question 16

What is A B and C

Answer 16

A: Full agonist (results in a full response)

B: Partial Antagonist (results in a partial response)

C: Antagonist

Question 17

What is a mixed agonist?

Answer 17

occurs when partial agonists compete with a full agonist to reduce Emax.

Question 18

Explain a competitive antagonist

Answer 18

• the antagonist will bind to the receptor but no response
• is reversible
• will shift the dose curve to the right
• higher concentrations the drug are required to achieve the max efficency (ie potency decreases)
  
  • can be overcome by adding more drug
• most antagonists are competitive

Question 19

explain the antagonist causing this response

Answer 19

a non competitve antagonist

• Emax will be less than for antagonist alone
• formation of non-reversable bonds
• curve becomes more narrow due to a decrease in receptors
• few antagonists are non-competitive

Question 20

what is

1. an agonist
2. an antagonist

Answer 20

1. agonist –> mimics/ stimulates
2. antagonist –> blocks (eg propanol beta-blocker, prevents adrenaline and decreases heart rate)

Question 21

explain Drug tolerance

Answer 21

response is proportional to the number of receptors occupied

Question 22

Explain Down-regulation and give an example

Answer 22

down regulation of number of receptors availble to down regulate response

e.g. in response to increased adrenaline

Question 23

explain up regulation and how it relates to the need for some animals to be weaned off drugs

Answer 23

• involves the upregulation of receptors to return to homeostasis
  
  • when HR is too low the receptors will be upregulated in response.
• also occurs when antagonists bind to receptors and more receptors are needed for normal function
• weaning off drugs –>
  
  • the receptors will be upreguated in response to increased antagonists and once off drug (ie loss of antagonist) too many recptors are present causeing in the example of propanol cardiac arrest. therefore drugs must be weaned off.

Question 24

Explain tachyphylaxis and give an example

Answer 24

• occurs when the body has a diminished response via an inhibitory feedback loop from:
  
  • repeated administration
  • Diminished responses to the same dose
• degree of tachyphylaxis is proportional to the degree of stimulus
• example:
  
  • nicotine
  • dobutamine
  • metoclopramide
  • nitroglycerine

Question 25

Explain the concept of tolerance and give an example

Answer 25

* shorter pharmacological response * OR: change in the drug receptor function * example: * morphine * heroin * more drug is needed to achieve Emax

Question 26

True or False Effect drug plasma concentrations are usually not preserved across the species

Answer 26

FALSE they are usually preserved e.g. phenobartitone at 15 microgram/ml will have anticonvulsant activity in a rat or ridgeback

Question 27

True or False ADME exhibits interspecies variation and due to this CL, Vd and T1/2 may vary

Answer 27

TRUE

Question 28

what are the phase II metabolism deficiencies in the feline, canine, porcine and humans.

Answer 28

* feline: SLOW glucuronidation * canine: acetylation absent * porcine: slow sulfation * humans: % of slow acetylators

Question 29

True of False: Drugs are less likely to exhibit pharmacokinetic variation if they are metabolised by the liver.

Answer 29

FALSE they are more likely

Question 30

True or False: Drugs that are elminated unchanged by the kidneys exhibit less interspecies variation.

Answer 30

TRUE

Question 31

Phenylbutazone has a low clearance in cattle and humans this means...

Answer 31

it stays in the system for too long and is therefore toxic to cattle and humans.

Question 32

True or False: Drug half lives are generally shorter in ruminants and horses compared with dogs and cats

Answer 32

TRUE

Question 33

True of False generally drug half lives are shorter in humans compared with domestic animals

Answer 33

FALSE drug half lives are considerably longer in humans compared with domestic animals

Question 34

Give an example of interspecies variability

Answer 34

* ruminants and xylazine (alpha 2 agonists) * 1/10th doses more sensitive to receptors * brahams and goats are even more sensitive * not the case for other drugs in this class * collies and some reptiles with ivermectin * not good at keeping them out of the brain * felines and NSAIDs * poor glucuronidators * clinical significance... minor --\> fatal