Exam 4 lecture 4 Flashcards
What is GABA receptor coupled to? location? Inhibitory functions?
Gi/o coupled receptor
Location- brain, limbic system
Inhibitory- presynaptic- decreased Ca conductance
Postsynaptic- Increase K conductance
Postsynaptic- increase K conductance
Name GABA agonists and antagonists
Agonists- Baclofen (skeletal muscle relaxant that treats alcoholism(
-Gamma hydroxybutyric acid (GHB) (CNS depressant)
Antagonist- Phaclofen, saclofen and 2hydroxysaclofen
Difference between GABA a and GABA b
GABA a is an ion channel that takes a short time to act
GABAb is a GPCR hat takes a long time to act
What is Xyrem? what does it do?
C I illicit use and C III medical use that with concomitant stimulant use can decrease excessive daytime sleepiness and increase daytime wakefulness. It can also decrease cataplexy
GHB side effects and prodrugs
CNS depression (dose dependent)
-dizziness, drowsiness, coma
Prodrugs
GBL and 1,4 Butanediol
What are concerns about GHB
No antagonist to counter effects
What are the melatonin agonist drugs
Ramelteon and Tasimelteon
Ramelteon MOA, metabolism, abuse?
MOA- high affinity for MT1 and MT2 melatonin receptors. Melatonin is the master clock serving as circadian rhythms.
Metabolism- CYP1A2 substrate
No abuse, withdrawal or dependency
Tasimelteon MOA? Use?
MOA- high affinity for MT1 and MT2 melatonin receptors.
Treatment of non 24 hr sleep wake disorder
ORPHAN PRODUCT registration
Name orexin receptor antagonists? MOA? USE?
Suvorexant
MOA- high affinity antagonist for OX1 and OX2 orexin receptors located in HYPOTHALAMUS
It reduces rewarding stimuli (DA release) via receptors that modulate mesolimbic projections between the VTA AND THE NUCLEUS ACCUMBENS
Treats insomnia
What did the FDA require a label change of
Required a label change for all sleep disorder drug products
(including the newer nonbenzodiazepine drugs Eszopiclone, Ramelteon, Zaleplon, Zolpidem)
FDA required labeling needs to include information about sleep related behaviors (sleep driving, eating and cooking and phonecalls)
What are some more sedative hypnotics in history? Drugs/uses
Trazodone
-antidepressant
-hypnotic unlabeled/investigational use
Antihistamines (OTC drugs)
-diphenhydramine
-doxylamine-pyrilamine
Herbal and natural hypnotics
Melatonin
valerian (hepatotoxicity has been noted)
Sedative hypnotics overdose treatment
Flumenazil for BZDs and Z hypnotics
What are the types of anxiety
GAD
Panic disorder
Social anxiety disorder
OCD
PTSD
Anxiety associated with autism/depression
What are drugs and diseases that could cause drug induced anxiety
Cocaine, psychostimulants (Caffeine), social media withdrawal.
also antidepressant and anxiolytic drug withdrawal
What are some neurotransmitters in anxiety
NE
GABAergic system
serotonin
CRF
How does NE take part in anxiety
Over active locus coeruleus release NE
Dysregulated in GAD and other types of anxiety
Projects to amygdala (fear center)
GABAergic system role in anxiety
GABA system normally counteracts/balances stimulatory effects of excess NE
GABA/Glutamate is converted to GABA by glutamic acid decarboxylase, leading to generalized anxiety disorder in CNS
Agents that increase GABA are anxiolytic
Role of serotonin in anxiety
SSRIs are effective and partial agonists of %HT1A receptors are effective
Drug treatment choices of anxiety
BZDs (quick and effective)- there is an abuse potential
Antidepressants- SSRIs, SNRIs,- take weeks to act. Ketamine nasal spray is a game changer
BB
buspirone
How is Buspirone an anxiolytic
Partial agonist on brain 5HT1A receptor
Low abuse potential
Not good for panic disorders (BZD is much faster)
How is BB an anxiolytic
Propanolol- uses may need test dose initially
-social anxiety
-PTSD nightmare
decreased peripheral sx of anxiety
Name some miscellaneous anxiolytics
Hydroxyzine- H1 agonists
Clonidine- Alpha 2 agonist
What are some investigational anxiolytics
Glutamatergic agents
-NMDA receptor modulators
-mGluR5 antagonist
mGlu R2/3
What is ADHD? Pathophysiology? what type of drug do we use? WHen do symptoms start? What does interfere with?
ADHD shows changes in metabolic activity (Brain activity is lower)
genetic (2/3) vs non-genetic (1/3)
Use something to increase activity opposite to seizure
ADHD interferes with functioning and development
symptoms start at age 5-9 y/o
implicated systems in ADHD
Dopamine transporter, cholinergic, CNS
symptoms of ADHD
Inattention and hyperactivity
What part of the brain might not be fully functional in ADHD
prefrontal cortex (mPFC)
Explain methylxanthines and how the treat ADHD
Methylxanthines indirect acting sympathomimetics- stimulant compounds mimic the effect of endogenous agonists of the sympathetic nervous system.
Name a methylxanthine
Caffeine
methylxanthine effect on adenosine recetor
antagonizes it. Increases cAMP, leading to increased intracellular Ca
What are methylxanthines linked to with regard to A1 GPCR? What effect does this have on neurotransmitters? How does this affect the CNS and peripheral?
A1- Gi/o linked inhibitory modulation of many neurotransmitters
CNS activation- sedation, anxiolysis, anticonvulsant activity
Peripheral activation- Decreased heart rate
What effect do methylxanthines have on A2a receptors? A2b? A3?
A2a- Gs linked, causes vasodilation.
A2b- GS linked, mostly on glial cells
A3- Gq linked. hippocampus and thalamus activated
When are Gq linked hippocampus and thalamus activated
Only activated in states of excessive catabolism. Seizures, hypoglycemia, stroke, not antagonized by methylxanthines.
WHat are two things we need to do to treat ADHD
Increase alertness
Reduce fatigue
What are some monoamine transporters
Dopamine, norepinephrine, serotonin
What are some indirect acting sympathomimetics
Cocaine (3-phenyltropanes)
Amphetamines
Explain how cocain and amphetamine work
Cocaine directly blocks NET (blocks transporter)
Amphetamine- mimics and leads to reverse transportation.
What does cocaine inhibit? WHat us ut used as
Inhibits monoamine transporters (NE, 5-HT, DA)
used as anesthetic and blocks transporter
Amphetamines MOA
Non selective activation of monoamines.
Highly reqarding, abuse potential
Name some examples of amphetamines
Dextroamphetamine
Lisdexamphetamine
Amphetamine vs methamphetamine
Methylphenidate
Dexmethylphenidate
Aderall
Mydayis (mixture of amphetamine salts)
Uses of amphetamines
Narcolepsy, anorexiant/weightloss
non stimulants for ADHD
Atomoxetine- NET inhibitor
TCAs
Bupropion
Clonidine
Modafinil (approved for narcolepsy not ADHD)
Alternative therapies approaches for ADHD
EEG biofeedback
essential fatty acid supplementation
Yoga/massage
Green outdoor spaces
elimination of artificial food addiives, colors and or preservatives
Narcolepsy symptoms
Excessive daytime sleepiness
Wakening of muscle
Poor quality of sleep
sleep paralysis
Hypnogogic hallucination
Treatment of narcolepsy
Stimulants for sleepiness
-Solriamfetol- NET and DAT
treats obstructive sleep apnea and narcolepsy excessive sleepiness (TONES)
-modafinil
-antidepressants
-xyrem
-pitosilant- H3 receptor antagonist
