HMB200H1 Study Guide - Midterm Guide: Therapeutic Index, Drug Withdrawal, Leptin
Lecture 4: Addiction and Drugs
1. What is an agonist? What is an antagonist?
Agonist is when the ligand binds and activate the receptor
Antagonist is when the ligand binds but not receptor is activated
2. Explain how a competitive antagonist works.
Competitive antagonist is when the antagonist competes with the agonist
during binding.
3. Differentiate orthosteric and allosteric binding sites on receptor. Be prepared to
give examples (you can also give the ones covered in class)!
Orthosteric binding site is drug that binds to the ligand site
Allosteric binding site is drug that bind to the other sites that aren't use by
the ligands
4. Differentiate partial and full agonists.
Full agonist is when the agonist fully activate the receptor
Partial agonist partially activate the agonist.
5. Describe the mechanisms of any drugs emphasized in the lecture (e.g.
benzodiazepines, 9-tetrahydrocannabinol, morphine and haloperidol).
Benzodiazepines: affects GABA A receptor activity but on the allosteric site
that's not bound by GABA
9-tetrahydrocannabinol: agonist of CB1 receptor
Morphine: agonist of opioid receptor
Haloperidol: dopamine receptor antagonist, limits activation of dopamine
receptors
6. Describe tolerance and sensitization.
Tolerance: the reduce response to a certain drug
Sensitization: the increase response to a certain drug
7. What are some possible mechanisms of tolerance?
Metabolic tolerance: involves a change in metabolic pathways for the drug
Cellular tolerance: involves a change in how cells respond to the drug
Learn tolerance: involves a person being aware of and compensating for the
effects of the drug
8. Why is tolerance an issue? Why can’t we just keep increasing the dose of a drug?
Tolerance is an issue because people will continue increasing the drug dose,
ands eventually the concentration of the drug in the bloodstream will
become deadly for the person
9. What is cross-tolerance and when does it occur?
It occurs when the body develops tolerance for a drug and the response to
drugs of similar type are affected. (ex. Tolerance to alcohol leads to tolerance
of benzodiazepines)
10.Why do we get withdrawal from drugs?
Drug withdrawal occurs as the NS has adapted to the repeated drug use. So
we suddenly stop using the drug, the effects on the NS can alter mood and
create physical problems
11.Describe the concept of a ‘therapeutic window.’
Therapeutic window is the window wherein a drug dose will provide maximal
therapeutic effects and low to no harmful/ toxic effects. Most drugs have a
narrow therapeutic window, other drugs have a wider window.
12.Differentiate substance abuse, substance dependence and addiction.
Substance abuse: keep taking the drugs even though the negative health
effects are recognized.
Substance dependence: symptoms of withdrawal and tolerance
Addiction: substance abuse with withdrawal and tolerance.
13.Differentiate intrinsic and extrinsic rewards.
Intrinsic rewards: natural, feeding, drinking, sleep
Extrinsic reward; learned and not pleasurable without prior conditioning
(money)
14.Explain the ‘wanting versus liking’ theory. Why is the distinction of wanting and
liking important?
Wanting is the drive to attain some sort of reward, like is the actual act of
enjoying the reward. These two don't always go hand in hand. This distinction
is important for understanding addiction (addicts to not always like the drug
but certainly want it) and DA system
15.What specific projection pathway in the brain is associated with reward? What
part of this pathway is critical for goal-directed behavior? How is the activity of this
pathway affected by addictive substances? How is this pathway changed by
addiction?
Mesocortical pathway (VTA to NAc) plays an important role in reward and
goal directed behavior. Addictive substances essentially are the 'reward' and
create a surge in dopamine release in the MCL pathway. This creates a
problem as the body begins to recognize it 'wants' this harmful substance.
Unfortunately, the substance (in addiction) will shunt dopamine release after
repeated uses and decrease receptor density, creating an even larger desire
to abuse the drug in order to break out of the state in which basal dopamine
is so far reduced.
16.What role does the frontal cortex play in control of behavior? How might the
frontal cortex play a role in addiction?
Frontal lobe is involved in initiation, inhibition and organization of behavior
(in addiction, behavior control is shunted). These is an observed reduce
metabolism in the frontal lobe which may attribute to the loss of control.
17.Describe the possibility of other (non-drug) types of addictions.
Eating and gambling are forms of non-drug type addictions. In some obese
individuals, dopamine release is shunted. It's important to distinguish that
eating results in a much lower DA release and is a vital function unlike drug
use. As well, eating involved different chemical reinforcement mechanisms
(PPY, insulin, leptin and ghrelin)
18.How is the regulation of feeding behavior different than the regulation of drug-
taking behavior?
Different chemical reinforcement mechanism
19.What is heritability? Describe the heritability of addiction. What is one reason
addiction might be heritable?
Heritability is the estimate of variability in phenotype attributed to variability
in genetic factors. Genetic variations in the DA system are generally
associated with increased risk of addictive disorders
20.Why might there be greater risk for addiction in Parkinson’s disease?
In Parkinson's, there is damage to DA release in the substantia nigra. While
this is commonly involved in voluntary motion, other effects are certainly
seen. For example, those with Parkinson's are more susceptible to addictive
behavior such as gambling and binge eating. Because the link between low
dopamine activity and addiction (even though it's technically not occurring in
the addiction pathway, dopamine is still technically shunted in the body)
Study notes -L4
Tuesday, 30 January 2018
6:19 PM
Document Summary
Agonist is when the ligand binds and activate the receptor. Antagonist is when the ligand binds but not receptor is activated: explain how a competitive antagonist works. Competitive antagonist is when the antagonist competes with the agonist during binding: differentiate orthosteric and allosteric binding sites on receptor. Be prepared to give examples (you can also give the ones covered in class)! Orthosteric binding site is drug that binds to the ligand site. Allosteric binding site is drug that bind to the other sites that aren"t use by the ligands: differentiate partial and full agonists. Full agonist is when the agonist fully activate the receptor. Partial agonist partially activate the agonist: describe the mechanisms of any drugs emphasized in the lecture (e. g. benzodiazepines, 9-tetrahydrocannabinol, morphine and haloperidol). Benzodiazepines: affects gaba a receptor activity but on the allosteric site that"s not bound by gaba. Haloperidol: dopamine receptor antagonist, limits activation of dopamine receptors: describe tolerance and sensitization.
