Abuse- Austin

Tolerance definition:

decreased effect with continued use—> larger doses required to produce same effect

Dependence definition:

biological adaptation caused by chronic use—> withdrawal generally reverse of normal effect

Are tolerance and dependence predictors of addiction?

NO

Addiction definition:

• chronic neurobiological disease

  • genetic, psychosocial, and environmental factors affect development and manifestation

  • drug seeking behavior

Pseudoaddiction definition:

• also shows drug seeking behavior

• preoccupation with getting the medication due to inadequate disease state management

• or

• fear/anxiety associated with condition/past experiences

What key PROJECTIONS of the brain are associated with addiction?

mesocorticolimbic

What is the mesocorticlolimbic project responsible for?

• DA transmission from ventral tegmental area (VTA) to prefrontal cortex and nucleus accumbens

• connects executive functioning to experiences of reward/aversion, pleasure, incentive, and reinforcement

What key AREAS of the brain are associated with addiction? what is the name of the loop?

reward pathway—> cortico-basal ganglia-thalamo-cortical loop

Expression of what genes can be changed in addiction?

FOSB, CREB, NF-kB—> decreased threshold for compulsive/reward seeking behavior, dependence, etc.

What are the PK requirements for a drug in order to cause addiction?

1. must have extensive BBB penetration or trigger a response that is directly interpreted by the CNS

2. rapid absorption (imp for elevation of C_max and reinforcement of acitvity)

What are the treatment strategies for addiction?

• pharm

  • traditional: acute detox/manage withdrawal

  • target craving/preventing relapse

• psychosocial/non-pharm

  • CBT, aerobic exercise, mutual support self-help

• combo of both is most effective

Disulfiram is used for addiction of …

alcohol

MOA of disulfiram?

• inhibits acetaldehyde dehydrogenase

  • enzyme responsible for converting acetaldehyde to acetic acid

What happens when you consume alcohol while taking disulfiram?

rapidly produces hangover-like symptoms

Do not administer disulfiram until the pt. does what?

abstinent from alcohol for ≥12 hrs

What is the antidote to APAP?

N-acetylcysteine

What is the antidote to Neuroleptic malignant syndrome (NMS)?

bromocriptine

What is the antidote to cardiac glycosides like digoxin?

digoxin immune Fab

What are the antidotes to methanol and ethylene glycol?

Ethanol and Fomepizole

What is the antidote to benzos?

Flumazenil

What is the antidote to methotrexate?

leucovorin calcium

What is the antidote to opioids?

naloxone HCl