Exam 4 lecture 4 Flashcards by Matti Daniel

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

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Name GABA agonists and antagonists

Agonists- Baclofen (skeletal muscle relaxant that treats alcoholism(
-Gamma hydroxybutyric acid (GHB) (CNS depressant)

Antagonist- Phaclofen, saclofen and 2hydroxysaclofen

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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

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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

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GHB side effects and prodrugs

CNS depression (dose dependent)
-dizziness, drowsiness, coma

Prodrugs
GBL and 1,4 Butanediol

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What are concerns about GHB

No antagonist to counter effects

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What are the melatonin agonist drugs

Ramelteon and Tasimelteon

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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

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Tasimelteon MOA? Use?

MOA- high affinity for MT1 and MT2 melatonin receptors.

Treatment of non 24 hr sleep wake disorder

ORPHAN PRODUCT registration

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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

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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)

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What are some more sedative hypnotics in history? Drugs/uses

Trazodone
-antidepressant
-hypnotic unlabeled/investigational use

Antihistamines (OTC drugs)
-diphenhydramine
-doxylamine-pyrilamine

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Herbal and natural hypnotics

Melatonin
valerian (hepatotoxicity has been noted)

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Sedative hypnotics overdose treatment

Flumenazil for BZDs and Z hypnotics

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What are the types of anxiety

GAD
Panic disorder
Social anxiety disorder
OCD
PTSD
Anxiety associated with autism/depression

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What are drugs and diseases that could cause drug induced anxiety

Cocaine, psychostimulants (Caffeine), social media withdrawal.

also antidepressant and anxiolytic drug withdrawal

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What are some neurotransmitters in anxiety

NE
GABAergic system
serotonin
CRF

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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)

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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

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