ryad sedatives
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Mohammad Ryad Goulvaden
5th year, Faculty of Pharmacy
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y Asedative drug decreases activity, moderatesexcitement, and calms the recipient.
y B.Ahypnotic drug produces drowsiness andfacilitates the onset and maintenance of a state of
sleep that resembles natural sleep, and from whichthe patient can be easily aroused.
y C. An anxiolytic drug reduces anxiety.
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y Sedative-hypnotics are drugs which depress or slow
down the body's functions. Often these drugs arereferred to as tranquilizers and sleeping pills orsometimes just as sedatives.
y
They depress behavior, moderate excitement,induce calmness, and may produce drowsiness oreven loss of consciousness. The sedative-hypnoticsare used clinically as antianxiety agents, musclerelaxants, sleep inducers, antiepileptics, and as
preanesthetic medications.
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yBarbiturates and benzodiazepines arethe two major categories of sedative-hypnotics
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Mechanism of action
y Barbiturates and benzodiazepines act similarly toproduce depression of central nervous systemfunction and behavior.
y Both classes of drugs enhance the ability of theneurotransmitter, gamma aminobutyric acid(GABA), to activate a type of receptors known asGABA-Areceptors.
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y These drugs increase the effectiveness of GABAbyaltering the receptor so that GABAcan bind more
easily, an effect known as allosteric regulation.y Activation of the GABA-Areceptor opens an ion
channel, allowing negatively charged chloride ions toenter the cell, producing an inhibition of neuronal
activity.
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BENZODIAZEPINESANXIOLYTICS
y DIAZEPAMy ALPRAZOLAM
y LORAZEPAM
y CLONAZEPAM
HYPNOTICS
y
FLURAZEPAMy TEMAZEPAM
y QUAZEPAM
y MIDAZOLAM
y ESTAZOLAMy TRIAZOLAM
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OTHER ANXIOLYTICDRUGS
y BUSPIRONE
y HYDROXYZINE
y ZOLPIDEM
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BARBITURATES
y PHENOBARBITAL
y PENTOBARBITAL
y SECOBARBITAL
y THIOPENTAL
NONBARBITURATE
SEDATIVES
y ANTIHISTAMINES
y CHLORAL HYDRATE
y ETHANOL
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Anxiolytics and Sedative-HypnoticsSTAGES OF CNS DEPRESSION.
y
Withincreasingdosage:y Calming ordrowsiness {sedation}y Sleep {pharmacologicalhypnosis}y Unconsciousnessy
Surgicalanesthesiay Comay Fatalrespiratory/cardiovasculardepression
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BenzodiazepinesyDIAZEPAMy ALPRAZOLAMy
LORAZEPAMy CLONAZEPAM
y FLURAZEPAMy
TEMAZEPAMy QUAZEPAMy MIDAZOLAMy ESTAZOLAM
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Mechanism of actiony GABA RECEPTORS
y INCREASED ACTIVITY
y OPENS CHLORIDE CHANNELS
y CELL HYPERPOLARIZED.
y ACTION POTENTIALS DECREASED.
y BENZODIAZEPINE BINDS TO ITS RECEPTORSy POTENTIATES GABA ACTIVITY.
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ACTIONSCentral Nervous System
y ANXIOLYTIC
y HIGHERDOSES HYPNOTIC, STUPORy ANTI CONVULSANT
y RELAXATION OF SKELETAL MUSCLES
DOES NOT PRODUCE:
y ANALGESIA
y ANAESTHESIA
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y BZs decrease sleep latency, diminish the number of
awakenings, and increase the duration of sleep.y Triazolam may be a particularly good choice
y Muscle relaxation without interfering with normal
locomotor functiony Clonazepam especially is able to cause muscle
relaxation without significant sedation.
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y I.V. diazepam used for status epilepticus, but BZs notthat useful in chronic therapy of epilepsy.
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RespiratorySystem
y PHARMACOLOGICAL DOSES :---- NOT SIGNIFICANT.
y HIGH DOSES -- RESP. DEPRESSION
CVS :y USUALLY VERY LESS
IN PREANAESTHETICS :
y BP decreased
y HR may be increased
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CLINICALUSESy ANXIETY DISORDERS.
y NOT FOR EVERYDAYSTRESS
TREATMENT PLANy Diazepam long acting for anxiety
y Alprazolam panic disorders..
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CLINICALUSESy MUSCLE RELAXATION
CONDITIONS such as :y SPASTICITY.
y CEREBRAL PALSY
y MULTIPLE SCLEROSIS
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y ANTI CONVULSANT
DIAZEPAMy DOC STATUS EPILEPTICUS.
y CHRONIC Rx: CLONAZEPAM
y ALCOHOL WITHDRAWAL SYMPTOMS.
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SLEEPDISORDERSy FLURAZEPAM : LONG ACTING
y DURATION : INCREASED
y REBOUND INSOMNIA: LESSy HALF LIFE LONG (85 hours)
y SE: DAY TIME SEDATION
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SLEEPDISORDERSy TEMAZEPAM : INTERMEDIATE ACTING
y WAKENING FREQUENCY DECREASED.
y TRIAZOLAM: SHORTACTING
y SLEEP INDUCTION GOOD.
y REBOUND INSOMNIA HIGH.
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ADVERSEEFFECTSy DROWSINESS, CONFUSION
y ATAXIA
y
AMNESIA
y DEPENDENCE : PSYCHOLOGICAL, PHYSICAL
WITHDRAWAL :
yANXIETY, TENSION,CONFUSION, INSOMNIA
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y They can cause both physical and psychological
dependence. Regular use over a long period of timemay result in tolerance, which means people have totake larger and larger doses to get the same effects.
y When regular users stop using large doses of thesedrugs suddenly, they may develop physicalwithdrawal symptoms ranging from restlessness,insomnia and anxiety, to convulsions and death.
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PRECAUTIONSy LIVER FAILURE.y Drugsthatcan begiveninliverdiseasesincludeOxazepam, Timazepam, Lorazepam. Thesedrugsarenotmetabolized inliver. ( rememberthe firstletters OTL Outside The Liver)
y # OTHER CNS DEPRESSANTS.y SUICIDE SUCCESS LESSy
UNLESS TAKEN WITH OTHER CENTRALDEPRESSANTS.FORBENZODIAZEPINE POISONING y DOC : FLUMAZENIL
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Benzodiazepine antagonistFLUMAZENIL
y GABAreceptor antagonist
y Reverses the effect of benzodiazepines..y I.V. route.
SE:
y Nausea, vomiting, agitation and dizziness.
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BARBITURATESMECH :
y INHIBITION OF RAS
y POLYSYNAPTIC TRANSMISSION IS INHIBITEDy SODIUMAND POTASSIUM CHANNELS
y PROLONG : GABAACTIVITY.
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y
Asaclass, the various barbituratesareremarkablysimilar;
y allarelipid soluble.
y Oncethe barbituratereachesthe
bloodstream, itisdistributed throughoutthe bodyand willaffectall bodytissues.
yWithinthe brain, barbiturateshavethegreatestimpactonawareness (the RAS -
reticularactivatingsystem)and respiration(medullaoblongata).
y Dependingon dose, barbituratesactaseitherasedativeorasahypnotic
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ACTIONSCNS :
y LOW DOSE : EXCITEMENT IS REDUCED
y HIGH HYPNOSIS- ANAESTHESIA- COMADEATH
y NOANALGESIC ACTION.
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CVS :
y LOW DOSES : MINIMUM
y POISONING : MYOCARDIAL DEPRESSION
y RESP. SYSTEM: DEPRESSION
y LIVER : INDUCES ENZYME P 450
y Barbiturates induce hepatic drug-metabolizingenzymes and can decrease the effectiveness of drugsmetabolized by the liver, including oral
contraceptives.
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DRUGSy PHENOBARBITAL LONG ACTING
y PENTOBARBITAL
y SECOBARBITALy THIOPENTAL ULTRASHORTACTING
( 20 MIN)
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USESy ANAESTHESIA
y ANTI CONVULSANTGRAND MAL
ECLAMPSIA
STATUS EPILEPTICUS.
y ANXIETY.
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ADVERSEEFFECTSy CNS : HANG OVER
y
METABOLISED IN LIVERy CI : ACUTE INTERMITTENT PORPHYRIA
y DEPENDENCE:
y
SEVERE: MAY CAUSE DEATH
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y Taking barbiturates with other CNS depressants, e.g.alcohol, tranquillizers, narcotics, or antihistamines,
can be dangerous, even lethal (A
RF).
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ADVANTAGESOFBENZODIAZEPINES
Over BARBITURATES
BENZODIAZEPINES show
y TOLERANCE - LESS
y DEPENDENCE - LESS
y DRUG TOXICITY LESS
y SUICIDAL RISK LESS
y BARBITURATES NOT FORANXIETY
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OTHERANXIOLYTICS - BUSPIRONEy Siteofaction: 5-HT1Areceptorsubtype.y Noanticonvulsantactivity.y No interactionwith benzodiazepine bindingsites
y No influenceoninteraction of GABA withtheGABAreceptor.
y Noteffectiveinmanagementofsevereanxiety/panicdisorder.
y No cross-tolerancewithothersedative-hypnoticdrugs
y Nomusclerelaxantproperties.y Minimaladverseeffectsy USED FOR GAD Generalized AnxietyDisorders
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ZOLPIDEMy ACTS ON BENZODIAZEPINE RECEPTORS.
y HYPNOTIC
yNO ANTI CONVULSANT
y NO MUSCLE RELAXTION
y ONSET OF ACTION FAST
y HALF LIFE SHORT ( 3 HOURS)y SE: NIGHTMARES, GI UPSET, DAYTIMEDROWSINESS
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OTHERSEDATIVESy ANTI HISTAMINES
CHLORAL HYDRATEy SEDATIVE AND HYPNOTIC
y SE: GI UPSET
y TASTE CHANGES
y PREFERRED ROUTE : PER RECTAL
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y LIVER:y CHR: CIRRHOSIS
y RESPIRATORYDEPRESSION
y CHRONIC :IMPOTENCE, TESTICULAR ATROPHY,GYNAECOMASTIA
y PREGNANCY: FETAL ALCOHOL SYN.
y LOWIQ, MICROCEPHALY, FACIALABNORMAILITIES.
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