Anxiolytics + Sedative/Hypnotics Flashcards
بسم الله الرحمن الرحيم وبه نستعين
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Anxioltics sedative hypnotics used in ?
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Define anxiety
Anxiety + insomina
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unpleaseant state of tension or apprhension in case of GAD (Generalized Anxiety disorder )
Phobia or Panic
Accompanied by?
Physical sytomps of Sympathatic overactivity as
Tachycardia , palpitations , sweating and trembling )
Classifications of anxio sed antihyp drugs according to Mechanism
mention
1-Drugs facilitating GABA action
2-5HT1A partial agonists Buspirone
3-Melationin Reamleton
Mention drug faciliating GABA CTION
Barbituarsas
benozdizepine
Zolepidem zoleplon
ALCOHOL
Mention Atypical anxiolytic and sedatives
=Antidepressants as TCA and nirtazapine
=Antipsychotocis as queitapine and clozapine
=Antihistamnics : Diphenhydramine and doxylamine
BBs as inderal propranolol
Compare between GABA A &GABA B receptros
GABA A :-
for sedatives and hypnotics
Benzo barb 2z alco
Working by its IoNotropc effect on Cl- channels casuing hyperplorization and Neuronal inhibiton in CNS
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GABA B: Metabotropic by G protein
casuing pre and post synaptic inhibiton in spinal cord
presunaptic by blocking Ca channels blocking NTs release
Postsynaptic opening K+ Channels casuing K outflux causing Hyperplorization
Baclofen type?
Working on GABA B receptors for Muscle relaxant and spasitisy and rigidity
GABA A receptor formed Of
2alpha 2 beta 1 gamma subunits with specific sites for
1-Benzodiazpinte to increase frequency of opening of the channel
2-Barbitureate increasing the duration of opening of the channel
Baributares is stonger than BZDS?
Yes is is more powerful CNS depressan since :
GABA mimetic effect
Glutamate AMPA receptor Antagonist inhibitory
but has Lower TI beacuse of Medullary inhibtion
Mention pharmacological actions of barbitaures ?
Sedation — hypnosis - anastheis - coma and death why ?
due to medullary depression and CVS And respiratory derpession as follow :
Making body insensitive to increased CO2
Inhibiting VMC
Mention members of barbituares and its uses
Thiopental ultrashort IV anasthetic
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Pentobarbital
Secobarbital
Short and Intermediate No longer used due to addiction
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Phenobarbital Long acting used as antiepleptic
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Mention side effects of barbiturates
N2D2EA
1- Narrow TI
2-No antidote
3-Tolerance dynamic and kinetic ?
4- Depedence
5-Enzyme induction as increasing CYP 1A2 2C9 2C19 3A4 increasing theri catabolism kinetic
6-Acute prophyria increasing ALA synthetase activity
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Tremors -vertigo - Nasues -dowisness
Prophyria =
NVDA
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Prophyria cutanea tarda
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Pschyosis
Neurological abnormalities
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muscle weakness
How to manage barbiturate toxicity ?
Correction of the life threatening conditions as Artifical respiration o2 and co2 and Giving fluid and vasopressores to correct BP
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Absorption prevention:
Emisis-gastric lavage - activated chracol -cathartics
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Removal Facilitation :
Urine Alkalinzation
Forced Diuersis
Peritoneal dialysis - hemodialysis - hemoperfusion
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Mention withdrawal effects of barbiturates and Mangemetn
Excitement - Insmonia - dilireum - hallucination and toxic psychosis
give:? antipsychotics : halopridol for higly agitated patients or Olanzopine
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Convulsions gives : ?
Antiepileptics: Valoprate and Carbamazebine for decreasing Impulsivty
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Corner stone :
PhenoBarbitone as Longer acting with smoother withdrawal over 3-4 weeks
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BZ receptors classified to BZ1 AND 2 ACCOEDING TO ?
Alpha subunit :
Alpha 1 = sedative hypnotics and Z hypnotic
Alpha 2= Anxiolytic + Muscle relaxant
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Benzodiaepine increases the Frequency of Cl - channel openings
GR/ Benzodiazpines has advantages over barbiutrates
1-Wide safety margin
2-Antidote (flumazenil)
3-Less tolerance and dependence
4-No enzyme induction
5-No prophyria
6-Less CVS and Resp dep
Classify BZs according to duration of action
Shote TM ;
Triazolam
Midazolam
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Intermdiatea ALO
AlprazolaM
Lorazepam
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Long DiC
Diazepam
Clonazepam
BZs is ……philic and absorbed …….. and distribute to …..and …..
Lipophilic
Orally
Body+ CNS
IMI of BZs describe
SLower erratic than oral absorption except ? Lorazepam
IMI of BZs SLower erratic than oral absorption except ?
Lorazepam
BZs and theri metabolites are excreted in ?
Urine
What are the casues of the long duration of BZs?
ASF
Active metabolites having t1/2 more than parents
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Slow Receptor Disscoication rates
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Resditribution to Fatty tissue
Give example of BZs has metabilites with longer T1/2
Flurazepam &Diazepam
Lorazepam
oxazepam
Temaepam
are conjgate directly
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less cumultice and resiudla effects
not affected by enzyme inducers and inhibitors as other BZs
Mention uses of benzodiazepines
Anxiolytics
sedative hypnotics
Anasthesia
Anticonvulsant
Skeletal muscle relaxant
Alcohol withdrawal
Describe use of benzodizepines as anxiolytics
Potentiate GABA in limbic system
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Anxiety disorders
Intermediate + Long acting
Alprazolam + Lorazepam + Clonzepam + Diazepam
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Panic disorders :
Alprazolam +Clonzaepam
Describe use of BZs in Sedation and hypnosis
Sedation in low but hypnosis in high dose
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Treating insomnia by :
Promotion of sleep
Inceasing Stage 2NREM
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Treating Night mares by decreasing REM but casuign loss of consolidation and anterograde amnesia
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Treating night terroes by dcreasing deep sleep as stage 3.4 but casuing impaired quality sleep
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Mention the effects of BZs in sleep patterns ?
Decreasing sleep latency + Increasing Stage 2 NREM CAUSING? less insomina
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decrasing stage 3,4 NREM of deep sleep treating Night terrors but causing imparired qulaity sleep
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Decreasing REM Sleep casuing ? trasting night mares but? Less consolidation so anterograde amenesia
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not used more than 4-6 weeks for no depedncece
Describe use of BZs as Anasthertic drug ?
Due to its amenisa and sedation effect
and Potentiation of Narcotics as Opioids
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Consoucs sedation : Midazolam + Fentanyl
Pra anasthetic
Balanced Anasthesia as midazolam
Descrtibve BZs as anticonvulsant ?
=Epilipsy not 1st line as clonazepam
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Status epiliptxus First line as LMD
lorazepam Midazolam and Diazepam
Describe BZs as sKELETEAL MUSCLE RELAXANT
work on spinal and supraspinal levels to be inhibited
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Diazepam !
Used in Muscle spasticity due to ? ctmi
1-Inflammation
2-Trauma
3-Cerebral palsy
4-MS
uSed for smoother withdrawal of Alcohol ?
Diazepam BZs long acting smoothing Withdrawal replacing alochol from receptor
Mention BZs adverse effects
1-Drowisness confusion and less cognition with Hangover in Intermediate and long acting
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2-Amenisa anterograde
3-ataxia
4-addiction
5-additive CNS depression
6-abnormal response as paradoxical excitements due to genetic receptor alteration
7-withdrawal of hypnotics casuing > Rebound insmonia + Increased REM night mares
Mention BZs adverse effects
1-Drowisness confusion and less cognition with Hangover in Intermediate and long acting
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2-Amenisa anterograde
3-ataxia
4-addiction
5-additive CNS depression
6-abnormal response as paradoxical excitements due to genetic receptor alteration
7-withdrawal of hypnotics casuing > Rebound insmonia + Increased REM night mares
WAD X5
وادي
Rebound insomina increases with withdrawal of?
Short and intermdeiate BZs
Why shold we decrease the dose of BZs in elderly ?
Due to reduced liver metabolism we need prevent accumulation of metabolites
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Ataxia + confusion
BZs toxicity and mangements DESCRIBE
CNS depression casuing prolonged sleep
CVS and resp depression esp IV rapidly Or with other CNS depressants
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Mangements:-
Support respiations and Circulation as barbituates
Antidote fLUMAZENIL
Describe flumazenil
Compettivive antagonist of Benzos & Z hypnotics ans zolpeidm
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Short t1/2 re adminstered after 1 hours
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indications :
BZs and Z hypnotic toxicity
Termination of action of Anasthetic BZs
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Adverse effects:
Agitation
Withdrawal syndrome of convulsions in BZs dependent
Benzodizepine withdrawal and magnements SHOW
Exictatio insmonia delerium hallucination psychosis
anti psychotics
Antidepressants
Convulsion
aniteplipetics
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Replacing short acting with Long acting
Diazepam for clonzepam and alprazolam
Z Hypnotics as ?
anatgonized by?
Selective,,,,,,,,, working on ……..
so not used in ,,,,,,,,,,
Zolpeidm + Zaleplon zopiclone Eszopiclone
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Flumazenil
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Sedative - alpha1 gaba A receptors
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Anxiety induced Insomnia
Mention advantages of Zhypnotics over BZs
Rapid onset short duration so less hangover
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Less SCTH
less supression of REM SLEEP so less ameisa
Less congitive inmpairment
less tolerance +depednence + wthdrawal + rebound insomnia but possibly occuring as nightcalm
less hangover
Zolpedim describe
short acting hypnotic
has SR Or Extending relaeas 5 hours
Z hypnotics cc by rapid elimnination ?>
Zaleplon
has fewer resiudal effects on cognitive and psychomoto functions
Eszopiclone
Night calm
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Anxiety
dry moth
Somonelence
Headache
Peripheral edema
Unpleasent taste
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Has risk of abuse and addiction
Selective hypnotic IS MT1 and MT2 receptors agonist in suprachiastmatic Nucleus
and casuign decreas in testosterone and Increase in Prolactin ?
Ramelton
A selectiv hypnotic decreasing lactency of sleep and with minimal abuse or withdrawal or rebound insomnia
? mentio side effects
Ramelton
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Dizzness
smonlence
Fatigue
Drug interactions of Ramelton mention
Never be taken with CYP inhibitor
CYP1A2 Ciproflxacin + fluvoxamine
CYP2C9 Fluconazole
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due to its effect on increasing Prolactin decreasing Testosterone
Selective Anxiolytic used in CHRONIC ANXIETY? METNION MEACHNISM OF ACTION
Buspirone
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5HT1A Agonist
Full presynpatic
partial postsynaptic
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working onD2 AND 5HT2A
USED IN GENRALIZED ANXIETY DIORDERS ONLY?
Buspirone
Buspirone differs fomr BZD in ?
Selective anxiolytic GAD
NO AAAAA
AMENISA
ATAXIA
ABUSE
ADDITIVE CNS Derpession
Mention disadvantages of Buspirone
Delayed onset 1-2 weeks
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Does not treat insomnia or panic attacks
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Nause headche dizzness
NVA
sEDATIV HYPNOTICS esp BZs used for?
4-6 WEEK FOR NO DEPNCENE
Termination of therapy should be?
Gradual to avoid withdrawal syndrome
Preferred for insomnia
Rapid Onset short duration drugs to avoid hang over
Midazolam
Insminic with ealy morning awakenings ?
needing anxiolytic
Longer acting BZD
Diazepam casuing hang over!!!!
Chronic insomnia due to anxiety and deprtsiion
gIVE Antidepressants as Mirtazapine
also hypnotic
increasing stage 34
GAD !
anti depressants
SSRI escitalopram +BZDs+ Inderal
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Benzo = rapid onset then gradual withdrawal ater month for month
SSRI = delayed onset for 6 months
Panic disorder
alprazolam with antepressant effect
buspirone not useful as it is anxioltiyc
Liver dysfunction which BZDs could be give?
Lorazepam
Temazepam
oxzaepam
Most BDZ are metabolized in liver so ?
Dose adjustment in liver cirrhosis is obligatory
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فلما جاءهم موسي بآيتنا بينات قالوا ماهذا إلا سحرٌ مفتري وماسمعنا بهذا في آبائنا الأولين وقال موسي ربي أعلم بمن جاء بالهدي من عنده ومن تكون له عاقبة الدار إنه لا يفلح الظالمون “
