Class #7-Tolerance Flashcards

1
Q

Biological adaptation to Rx

A

tolerance, addiction, dependence, withdrawal

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2
Q

Tolerance definition?

A

No longer respond and or need higher dose to get same effect

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3
Q

Drug addiction =

A

Substance dependence: physiological and psychological

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4
Q

Can you get dependent to nasal spay?

A

yes

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5
Q

Studying dependence ways?

A
  1. Rat (Eg IV = more rapid dependence)

2. Before on human using heroin (1950s), 20Xtime fold over several months to get same effect.

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6
Q

Dose respond curve of tolerance in rats

A

Dose respond curve moves to right and max effect is less

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7
Q

Type of tolerance?

A

Acute : Greater effect as the blood {} is rising. Rapid adaptation of the CNS when a Rx is interfering with the CNS function.
Chronic: Repeated administration causes a decreased response to a test dose

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8
Q

Tolerance pharmacokinetics

A

Decrease [] at site of action, because increase Enz. activity = increase metabolism. When Rx metabolism is altered as a function of time

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9
Q

Tolerance Pharmacodynamics

A

decrease effect due to biological adaptation at the site of action. Adaptation of the tissues itselfs. The intrinsic responsivity of the receptor system diminishes over time.

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10
Q

Behavioral tolerance

A

decrease effect due to conditioned response

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11
Q

Innate tolerance (not used in this class)

A

Metabolizing enz. differ from one ind. to another.

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12
Q

High is connected to … in brain

A

Reward system

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13
Q

Resistance to chemotherapy?

A

Not tolerance in classical term, but cancer cell resist Rx, with different mechanism.

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14
Q

How to know if pharmacokinetics tolerance?

A

Rx blood {} get same response

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15
Q

How to know if pharmacodynamic tolerance “”?

A

Tissue is less responsive at same Rx blood {}. So need more of the Rx at site of action for same response.

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16
Q

Acute tolerance Eg?

A

Cocaine: Much lower response after the first dose

17
Q

Acute tolerance {} intoxication curve with EtHO

A

Brain fighting back to protect neural circuit the Rx affect.

18
Q

Rx dependence characteristics (3)?

A
  1. Pharmacodynamics tolerance: Physiological conterbalance
  2. Need Rx to avoid withdrawal
  3. Withdrawal effects are the opposite effects of the Rx
19
Q

Withdrawal?

A

The adaptation mechanism are now unopposed since the Rx intake is over.

20
Q

Factors controlling transmitters synthesis?

A
  1. Enz availability
  2. Substrate availability.
  3. Cofactor “
21
Q

1.Surmountable vs 2.insurmountable tolerance.

A
  1. Eg. Postsynaptic decrease in receptors.

2. Eg. Presynaptic decrease in neurotransmitters.

22
Q

Cross tolerance def?

A

All Rx in family are affected. (Eg. tolerance to morphine, dilaudid, fentanyl, etc.

23
Q

Differential tolerance def?

A

Don’t become equally tolerant to all effect of a Rx to the same extent. B/c receptors are all around in the body. (Eg. morphine, don’t become tolerant to lethal effect)

24
Q

Behavioral tolerance def?

A

Something that you learn (un/conscious) involves a conditioned response, an example of classical conditionning. (Eg. Rat lethality with morphine higher in novel environment.)

25
Q

Dependence with non-psychoactive Rx?

A

Eg antihypertensive. Need the Rx to keep BP stable.

26
Q

1.Dependence vs 2.Addition

A

Addiction is associated with dependence, but not always the other way around.

  1. Caracterized by Sx of tolerance and withdrawl.
  2. Compulsive intake, at first for pleasure, after to limit withdrawal.
27
Q

Acute ETHO withdrawl?

A
  1. Seizure
  2. Hallucinations
  3. Confusion
28
Q

Acute phase of heroine withdrawl (time)?

A
  1. start 6-12h
  2. Peak 1-3 days
  3. Subside ..
29
Q

Direct link between dose and intensity with withdrawl?

A

true

30
Q
  1. Severity of withdrawal related to?

2. Worst withdrawal?

A
  1. Half-life. Because if fall rapidly, adaption mechanisms don’t have time to adapt.
  2. Medium half-life
31
Q

Rebound with benzo?

A

(Eg. Benzo. withdrawl, get way more of this REM phase then before and during use of benzo.)

32
Q

Rebound effect how it works?

A

Eg. Rx tolerance increase creation of receptors but same effect since use more Rx. When stop using Rx, since more receptors = more effect.

33
Q

Rx addiction components (3)

A
  1. Setting
  2. Behavior
  3. Drug
34
Q

Drug dependence pharmacodynamics activate…. pathway

It releases… in … part of the brain

A

dopaminergic

dopamine - Nucleus Accumbens

35
Q

Signs of addiction?

A
Tolerance
Obsession
Increase intake
Loss of controle
Abuse despite harm
Withdrawal Sx
36
Q

Dopaminergic acts on what part of the brain?

A

Nucleus Accubens