Watts Set 4

Question 1

Identify and define the key means by which drug effect is quantified and compared.

Answer 1

• Onset: when it hits the desired response for the first time
• Intensity: rate of energy expenditure
• Duration: the time it takes for the action to take plac

Question 2

know the differences between quantal and graded drug responses

Answer 2

• Graded: maximal efficacy (progressive increase)
• Quantal: potential variability of response (all or none)

Question 3

how to compare and calculate therapeutic index between drugs

Answer 3

• Relative safety of a drug expressed as LD50/ED50 or TD50/ED50
• The larger the ratio presumably the greater the relative safety
  – Unfavorable (toxic and close together)
  – Favorable (spread out and safer drug)

Question 4

what are the factors that can modify the effects of drugs

Answer 4

• Drug tolerance
• Physiological
  – Age
  – Gender
  – Pregnancy
  – Food
  – Circadian clock
• Pathological
  – Liver disease
  – Renal disease
  – Malnutrition
• Genetic
  – Pseudocholinesterase deficiency
  – Malignant hyperthermia
  – Oxidation polymorphism
• Interaction with other drugs
  – Pharmacokinetic
  – Pharmacodynamic
  – placebo

Question 5

what is drug disposition tolerance

Answer 5

• Decrease in effective concentration of the agonist at the site of action
• Drug disposition/ metabolic tolerance
  — I.e. phenytoin increases rate of biotransformation of a number of drugs which are metabolized by liver enzymes
  — End result is decreased effect on drug

Question 6

what is pharmacologic tolerance

Answer 6

• Decrease in normal reactivity of receptor
• Cellular or pharmacologic tolerance
  — Downregulation of receptors
  — Change in receptor affinity
  — Most often seen with CNS drugs such as narcotics, depressants, and stimulants

Question 7

how can we apply cross tolerance to disease management

Answer 7

bases to opioid receptors and tachyphylaxis

Question 8

what are the opioid receptors doing

Answer 8

• Tolerance develops to one drug that is also seen with drugs belonging to the same class
  —– For example, an individual tolerant to morphine develops some level of tolerance to morphine develops some level of tolerance to opioids that act on same receptor (e.g. heroin, methadone, codeine)
  –> not always complete

Question 9

what is the tachyphylaxis doing

Answer 9

• Acute development of tolerance following rapid and/or repeated administration of a drug
  – The first administration of drug produces a much larger response than subsequent doses, when given after a brief interval
  – Can NOT overcome this type of tolerance with increasing dose
  —> Ex: amphetamine, ephedrine (norepinephrine release) and LSD

Question 10

what are the on and off target adverse effects for intended tissue

Answer 10

on-dose too high and chronic activation or inhibition effects
off- incorrect receptor is activated or inhibited

Question 11

what are the on and off target adverse effects for unintended tissue

Answer 11

on- correct receptor but incorrect tissue, dose too high, chronic activation or inhibition effects
off- incorrect receptor is activated or inhibited

Question 12

what are the physiological response in multicellular/multi receptor context.

Answer 12

altered gene expression, relaxation, contraction

Question 13

what causes gene expression changes

Answer 13

all pathways

Question 14

what causes relaxation changes

Answer 14

epinephrine and acetylcholine and BNP from cAMP and cGMP

Question 15

what causes contraction changes

Answer 15

angiotensin 2 from calcium, IP3, and adrenergic nerves