Ryad Sedatives

8/8/2019 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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Ryad Sedatives

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