04 CNS Review Alkana Flashcards
What is Parkinson disease pathology?
Striatal dopamine deficiency syndrome, less than 10% brain DA in basal ganglia (normally 80%)
What is Parkinson disease treatment designed to do?
Restore DA/ACh balance
What is the DOC for Parkinson Disease?
l-Dopa (plus peripheral decarboxlase inhibitor
What is the peripheral COMT inhibitor used?
Tolcapone
What is the DA potentiator used?
Amantadine
What is the DA receptor agonist used?
Bromociptine
What is the MOA-B inhibitor used?
Eldepryl
Parkinson Disease is believed to reflect destruction of what?
Dopaminergic cells in the substantia nigra
The therapeutic effects of l-dopa in PD results from increasing brain ______ and its action on ____ receptors?
Dopamine; D2
The mechanism of action of Pramipexole (Mirapex) in the treatment of PD is what?
Agonist action on D2 receptors
Classical antipsychotic medications are believed to produce their therapeutic effects by blocking what receptors?
D2
Classical antipsychotic medications are believed to produce many adverse effects by blocking what receptors?
D2
Atypical antipsychotic medications are believed to produce their therapeutic effects by blocking what receptors?
5HT2 (the thinking has shifted now to believe that its main mechanism is blocking D2)
Pseudoparkinsonism side effects from Haloperidol is most likely caused because of the blockade what receptors?
D2 receptors
What does traditional neurochemical theory propose that Schizophrenia is caused by?
Excess limbic dopaminergic (DA) function
What is the significant advantage of second generation antipsychotic agents?
Less EPS (<1% tardive dyskinesias)
What is the significant disadvantage of second generation antipsychotic agents?
Metabolic effects (weight gain; dyslipidemia, impaired glucose-insulin homeostasis)
For antipsychotic treatment, what two receptor binding may induce cascades that offset adverse effects and increase therapeutic effects?
Anticholinergic and 5HT2
The onset of therapeutic effects of atypical antidepressants corresponds best to?
Delayed autoreceptor desensitization and increase 5HT and/or NE
A primary therapeutic advantage of second generation vs. first generation antidepressants is?
Reduced affinity for mACh and adrenergic receptors (these are the receptors that cause the side effects, otherwise both generations are similar in their affinity for 5HT and NE transporters)
What happens with DA transporter blockade?
Associated with stimulant rather than antidepressant action
What are the three steps in therapeutic effect for antidepressants?
First (initial (acute): blocks reuptake of NE and/or 5HT via action on transporter protein). Second (compensatory change to offset blockade (downregulation of transmitter)). Third (delayed - autoreceptor desensitization, upregulation, increase synthesis and release of transmitter)
The anxiolytic lorazepam is thought to reduce anxiety by acting as an agonist on _____ receptors?
GABA** Slide 78
Benzodiazepines are believed to reduce the symptoms of anxiety by?
Potentiating GABAa receptors
The onset of therapeutic action or effect of SSRIs in treating anxiety disorders corresponds best to?
Delayed autoreceptor desensitization and increase 5HT and/or NE
Buspirone is believed to reduce the symptoms of anxiety by?
Agonist/partial agonist action on 5HT1A receptors
What are some fast onset (can be used PRN) drugs to treat anxiety?
Benzos. Beta adrenergic antagonists. Antihistamines
The onset of therapeutic action or effect of SSRIs in treating anxiety disorders corresponds best to?
Delayed autoreceptor desensitization and increase 5HT and/or NE
Alcohol is metabolized to _____, which is toxic and can cause flushing
Acetaldehyde
_____ is a signal of problem drinking?
Needing alcohol to cope with daily circumstances
Current theories suggest that alcohol cause its sedative, anxiolytic and amnesic effect by_____?
Potentiating GABAergic activity in the brain
Alcohol dependence is characterized by _____ when alcohol is abruptly discontinued?
CNS excitability
Women may be more sensitive to the acute and chronic effects of alcohol than men because women have ______ than men?
Less active gastric ADH
Individuals who lack _____ suffer flushing and other reactions when they drink alcohol because of the buildup of ______
AlDH; Acetaldehyde
Anti-Heartburn medications like Ranitidine (Zantac) and Famotidine (Pepsid) may block or reduce the flush reaction in individuals who lack ______ by blocking the formation of acetaldehyde from ethanol by _____
AlDH2 (form that works very quickly, found in mitochondria); ADH
Release of _____ in the brain is believed to be the final common pathway mediating the rewarding effects of alcohol and other drugs of abuse?
Dopamine
Current theories suggest that Naltrexone reduces ethanol stimulation and euphoria by ________?
Antagonizing the effects of ethanol mediated by endogenous opiate receptors
The highest risk for causing ethanol-induced brain damage in the fetus occurs with ethanol exposure during ______ of pregnancy?
The fist trimester
Ethanol can markedly increase the hepatotoxic effect of ______ by inducing ____ with a resultant increase in the production of a hepatotoxic metabolite
APAP; CYP 2E1
What are the two types of treatments for alcoholism?
Disulfiram (Antabuse), Anxiolytics (e.g. Benozs), Glutamate Receptor Modulation (Acamprosate (Campral))
How does Disulfiram (Antabuse) work?
Inactivates aldehyde dehydrogenase –> acetaldehyde build-up. Crutch to reduce intake. Dangerous adverse effects
How does Acamprosate (Campral) work?
Reduces craving. Caution in renal impaired
Triazolam (Halcion) is a/an ______?
Non-selective BZ receptor agonist
Zolpidem (Ambien) is a _______?
Selective BZ1 non-BZ receptor agonist
Rozerem (Ramelteon) is a ________?
MT1 and MT2 receptor agonist
How do BZ receptor antagonists (Flumazenil (Romazicon)) work for sleep disorders?
Blocks BZ non-selective and BZ1 selective agents
Marijuana may induce a neuroprotective effect by agonist action on _____ receptors which reduces ____ release
CB1; Glu
LSD may induce its psychoactive effects by acting as a _____ on ______ receptors
Agonist-partial agonist; 5HT2A
