INDIRECTLY Acting Sympathomimetics

Question 1

Whats the deal with the INDIRECT?

Answer 1

• increase the concentration of endogenous catecholamines in the synapse and circulation=activation of adrenergic receptors
• occurs via 1 or 2:
  1. release of cytoplasmic catecholamines
  2. blockade of re-uptake transporters

Question 2

Releasing agents: 
AMPHETAMINE
METHAMPHETAMINE
METHYLPHENIDATE
EPHEDRINE
PSEUDOEPHEDRINE
TYRAMINE

Answer 2

-most resistant to COMT/MAO degradation, so have relatively LONG t1/2 (**except for tyramine-MAO degraded, so has little effect unless pt is taking MAO inhibitor)

Question 3

How are drugs effects mediated?

Answer 3

• Amphetamine-like drugs are taken up by re-uptake proteins and subsequently cause reversal of the re-uptake mechanism resulting in release of NT in a CALCIUM-INDPENDENT manner
• drug effects mediated by resulting increase in synaptic NE

Question 4

Why is there high abuse potential?

Answer 4

Amphetamine-like drugs readily cross the BBB..reinforcing effects of central dopamine release

Question 5

CV

Answer 5

CV effects:
-due to NE release: peripheral vasoCONSTRICTION (INCREASED diastolic bp)
-BR–>positive inotropy and INCREASE conduction velocity (INCREASED systolic bp)
{-INCREASED bp can cause DECREASED HR due to baroreceptor activation, but this can be masked by direct chronotropic effect)

Question 6

CNS

Answer 6

CNS: stimulant, anorexic agent

Question 7

Toxicity

Answer 7

Toxicity: (anxiety), tachycardia

Question 8

Therapeutic Use

Answer 8

Therapeutic Use: ADD, narcolepsy, nasal congestion

Question 9

Ci

Answer 9

Ci: (hypErtension, severe artherosclerosis, history of drug abuse), Rx with MAO inhibitors within previous 2 weeks