Lecture 10: Frozen Addicts and drug overdose

Question 1

Case of the frozen addicts: Initial presentation of patients

Answer 1

In 1982 – 7 young adults developed severe and irreversible movement disorder
including “freezing of gait” after self-administration of a new synthetic heroin.

Question 2

Freezing and gait

Answer 2

• Sudden episodes of inability to produce effective forward stepping
• (1) alternating trembling of legs with feet fixed in place
• (2) shuffling forward with very short steps
• (3) complete akinesia, no observable leg movement (observed in this case

Question 3

Symptoms of Parkinsons disease

Answer 3

-Tremor: an involuntary quivering of movement or shake
-bradykinesia: slowness of movement
-Akinesia: Lack of power in voluntary movements
-Rigidity: stiffness of limbs beyond normal aging or arthritis (tightness)

Question 4

Parkinsons and dopamine

Answer 4

-Lack of dopamine in patients with parkinsons

-Treatment consists of replacing dopamine but the body doesn’t replace the dopamine on its own at this point

Question 5

MPTP

Answer 5

The metabolism of MPTP in heroin is what makes the MPTP dangerous. (MPTP is converted to MPP+)

MPTP is not toxic itself in isolation, but is selectively neurotoxic in animals (human,
primate, mouse) to just the substantial nigral dopamine neurons (A8 and A9 cells),
but not dopamine neurons of the ventral tegmental area (A10 cells, mesolimbic
system).

Question 6

MPP+

Answer 6

MPP+ is a neurotoxic agent that kills dopamine neurons

Question 7

Subtypes of presentation (patient videos)

Answer 7

1) Milder subtype: prominent tremor (patients 4 and 5)

2) severe subtype: no or less tremor, pronounced bradykinesia, akinesia, and rigidity (patients 1,2,3)

Question 8

Levodopa therapy

Answer 8

• increases dopamine levels
• there is possibly a limited period of time when this is helpful

Question 9

Selegiline and Rasagaline

Answer 9

-treatment for Parkinson’s Disease
-MAO-B inhibitors
-Rasagaline did not have disease slowing effects but is still a treatment

Question 10

How are MPP+ and the pesticide paraquat similar?

Answer 10

-Have a very similar molecular structure
-Increased risk of parkinsons for people living in rural environments

Question 11

Heroin and opioids reduce what?

Answer 11

-Heroin and other opioids reduce
firing between neurons by
increasing the chloride ion levels
inside the neurons and blocking
calcium signaling

Question 12

Naloxone

Answer 12

-An opioid receptor antagonist; that competes for binding with drugs of abuse
-blocks the activation of the receptor
-very high affinity for the receptor at the same place the opioid wants to bind

Thus directly reverses the
effects of heroin or other
opioid.