sedatives pharmacology

7/28/2019 Sedatives Pharmacology

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SEDATIVES

These are drugs that are used to induce calmness

(anxiolytics or sedatives),or to produce sleep (

sedative-hypnotics).GOALS OF SEDATIVES

To enable the critically ill patient to tolerate

invasive and uncomfortable monitoring andtreatment procedures


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To reduce oxygen consumption by reducing

patient to arousal and activity.

To promote amnesia for events in the

intensive care unit

Sedatives may also used as treatment for

conditions such as epilepsy or tetanus.


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PURPOSE FOR USING SEDATIVES

Sedative agents are used in attempt to:

Allay anxiety over the patients own illness, the welfareof relatives or the risk of death.

Ensure adequate rest

Reduce the impact of unpleasant sensations, such asthirst

Reduce the distress of invasive treatment andmonitoring, such as endotracheal intubation

Blunt awareness, of the environment over which thepatient has very little control and in which he/ she maybe unable to communicate.


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TOOLS USED TO ASSESS LEVEL OF

SEDATION

The level of sedation required will vary depending on theindication e.g. heavy sedation may be necessary duringthe control of status epilepticus, while a much lowerlevel sedation will be required to tolerate endotracheal

intubation. The level of sedation can be assessed usinga number of measuring tools.

Scoring systems such as the Ramsay scale, which is a sixpoint that ranges from anxious and agitated (leve1) to

un responsive (level 6), judged in response to astandardized stimulus (loud auditory stimulus orglabellar trap).


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CONTI

Electroencephalography (EEG), which may beeither raw or processed and is able to provide a

measure of cerebral activity. It is suitable for

assessing depth of anesthesia.Visual analogue scales, they are more suited to

the assessment of pain or for use of a researchtool.

Evoked potentialsMonitoring physiological parameter for signs of

distress.


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SEDATIVE AGENTS USED IN ICU

BENZODIAZEPINES

These drugs provide hypnosis, amnesia andanxiolysis, they do not provide anagelsia.

BZA are good anticonvulsant drugs and alsoprovide for some muscle relaxation.

They act via the BZA receptors, which are closelyassociated with GABA receptors, resulting inintracellular influx of chloride when activated.

These drugs may be given by mouth, per rectumor IV, but they are mostly used through IVinfusion.


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Dosage of these drugs depends on the followingfactors;

Prior exposure to BZA ( increased tolerance)

Age and physiological reserve.

Volume status; hypovolemic patients are more

sensitive,


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Renal and hepatic dysfunction

Co-administered drugs i.e. whether BZA is

combined with opioids

History of alcohol consumption, there is

increased tolerance


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Cont

Examples of BZA that are mostly used in ICUinclude diazepam 5-10mg IV prn, it is a longeracting agent

Midazolam 0.002-0.2mg/kg/hr. it is a short actingagent

BZA are often combined with opioids in acompound sedative infusion. This allows lower

doses of a BZA to be used, while capitalizing onthe opioid effect of respiratory and coughsuppression, to facilitate mechanical ventilation.


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Pharmacokinetics

- sleep occurs within 15 to 45 mins

- Flurazepam has fastest on set of action. It isconverted to an active metabolite (N-desalkylflurazepam with a half-life of 50-100

hrs.

- the drugs and their metabolites are excreted

in the urine.


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CNS SIDE EFFECTS

Adverse reactions

1. Hangover and drowsiness occur in themorning after barbiturate use due to residual

depression of the CNS.

2. Effect on sleep: get satisfaction for the first

one or two weeks then get insomnia due tohabituation.

-


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SIDE EFFECTS CONT

- daytime drowsiness

- lightheadedness

- disorientation

- slurred speech

- memory impairment

- depression

- nervousness and irritability


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CNS: CONT.

3. Respiratory depression: occurs with about10 times hypnotic dose.

5. Drug automatism: it is a state of amnesia inwhich a patient takes repeated doses untilacute poisoning occurs.


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ANAESTHETIC AGENTS

Apart from Benzodiazepines there are also

some IV anaesthetic agents that are used as

sedatives, these include;

Ketamine which acts by blocking NMDA-

receptors. It produces a sedative state known

as dissociative anaesthesia with the following

characteristics; mild sedation, amnesia,analgesia and reduced motor activity.


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The lack of respiratory and cardiovasculardepression at lower doses makes this a verysafe drug to use in the ICU.

At KCH ketamine is used in patients withsevere head injury during the first 5 days ofadmission with an aim of completely sedatingthe patient.

It is also used when performing simpleprocedures


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cont

Propofol is also frequently used in ICU. It is fastacting, very effective and with a rapid offset ofaction, this is due to its rapid metabolism toinactive metabolites in the liver.

These features makes it very suitable for use inpatients requiring short term sedation or foranesthesia for procedures in ICU.

Caution is required in hypovolaemic patients or

those with impaired myocardial function assevere hypotension may result

.


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The diluent in which propofol is delivered is

lipid-rich and may have to be taken into

account as a source of nutrition and indeed

cause of hyperlipidaemia, depending ondosage and duration of therapy.

At KCH this drug is used after 5 days of

complete sedation with ketamine in patientswith severe head injury.


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Incases where the patient is presenting with

increased blood pressure, this drug is used

instead of ketamine until the increased blood

pressure subsides


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Cont

Thiopentone is reserved for specific indications,such as management of intractable intracranialhypertension (to reduce cerebral metabolism), orfor treatment of status epilepticus.

It is not commonly used as general sedativeagent. Its use is limited by its long duration ofaction and long half-life when used for prolongedinfusions

At KCH this drug is used in patients with headinjury during suction, in order to avoid irritatingthe client.


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THE IDEAL SEDATIVE

There is no ideal sedative agent. Sedatives in the futuremay target specific aspects of sedation such ashypnosis, Anxiolysis or amnesia without necessarilyproviding the whole spectrum of sedation for each

patient. Currently the ideal sedative would address the

following;

hypnosis or sleep

Anxiolysis

Amnesia

Anticonvulsant


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Be non-cumulative

Be independent of renal or hepatic metabolicpathways.

Not produce respiratory or cardiovasculardepression

Be of modest-cost

Have a rapid onset and short offset time

Have no prolonged effects on memory

Have no long term psychological effects.


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BRONCHODILATORS


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BRONCHODILATORS

These are drugs that help open the bronchial

tubes of the lungs allowing more air to flow

through them.

Bronchodilators are medicines used to open

up the small airways of the lungs (bronchi) to

make breathing easier.


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TYPES OF BRONCHODILATORS

Bronchodilators are often inhaled, but are also

available as tablets, syrup and an injection. There

are two types:

short-acting bronchodilators these provideshort-term relief from breathlessness

long-acting bronchodilators these have no

immediate effect, but can help control thesymptoms of conditions such as asthma if used

regularly, and have more long-lasting effects


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USES

They are often used to treat conditions that

can cause narrowing or inflammation

(swelling) of the airways. They are used for

bronchial asthma, bronchial spasm associatedwith bronchitis, emphysema, other obstructed

pulmonary diseases as well as prevention of

exercise induced asthma


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MECHANISM OF ACTION

Bronchodilator drugs relax the muscles in thelungs, which allows the airways to widen andmakes breathing easier. Some bronchodilatorsalso help to clear mucus and reduce

inflammation in the lungs. They are divided into; Anticholinergics, alpha-

beta adrenergic agonists, beta adrenergicagonists and phosphodiesterase inhibitors.

Anticholinergics act by inhibiting interaction ofacetylcholine at receptor sites on bronchialsmooth muscles.


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PHARMACOKINETICS

Onset, peak and duration vary widely among

products. Most products are metabolized in

the liver and excreted in urine.


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CONT

Alpha beta adrenergic agonists by relaxing

bronchial smooth muscles and increasing

diameter of nasal passages. Beta adrenergic

agonists by action on beta 2 receptors whichrelaxes bronchial smooth muscles.

Phosphodiesterase inhibitors by blocking

phosphodiesterase increasing cAMP whichmediate smooth muscle relaxation in the

respiratory system.


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Cardiovascular drugs in ICU


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ANTIHYPERTENSIVES

These are drugs that are used to treat high bloodpressure which is manifested by the readings of140/90mmHg.

Treatment of hypertensives has 2 objectives :

1. Reduction of the high blood pressure

2. Prevention of long term complications

The antihypertensive drugs work In reducing

blood pressure by decreasing heart rate,myocardial contractility, blood volume, venousreturn and the tone of arterial smooth muscles.


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ANTIHYPERTENSIVES USED IN ICU

VASODILATORS

These cause selective dilatation (widening) of

arterioles which results from a direct action

on the vascular smooth muscles. The precise

mechanism is not really known.

In response to arteriole dilatation, peripheral

resistance and arteriole blood pressure falls.


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Anti cont

Pharmacokinetics

The vasodilators are readily absorbed followingoral administration and its effectiveness is

apparent within 45 minutes and persist for 6hours or more.

When given parenterally, effects begin rapidly

within 10 minutes and last for 2 to 4 hours. Anexample of this type of drugs is hydralazinethat is given from 20mg to 40mg.


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Cont

Metabolism

It is inactivated by metabolic process calledacetylation which is

This acetylation is genetically determined and sothe people who are slow acetylators end uphaving increase concentration of the drug in

their blood which leads to excessivevasodilatation leading to hypotension thanfast acetylators.


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Calcium channel blockers

These are antihypertensives as well. Calciumchannels are pores in the cell membrane thatregulate the entry of calcium ions into cells.

Calcium plays a critical role in the function ofvascular smooth muscle for the heart. Theylower blood pressure by dilating arterioles ofthe heart. An example is Nifedipine that is

given 5-20mg repeated 4-6 hourly sablingual.


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VASOACTIVE DRUGS

These are drugs that have an inotropic and

chronotropic effect on the cardiovascular

system.

The examples of these drugs that are used in

ICU are Dopamine, Dobutamine, adrenaline

and nor adrenaline.


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Mode of Action

The dopamine and dobutamine are drugs thathave an inotropic and effect where they increasecontractility of the myocardium by directlystimulating the B-adrenergic receptors without

causing release of endorgenous nor epinephrine. In simple term they increase force of contraction

of the ventricles and thus also Improves the heartoutput showing a chronotropic effect.

Moderate doses decrease preload and haveminimal chronotropic and blood pressure effectsand very high doses can cause tachycardia.


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Cont

Both of these drugs are used to treat heart

failure.

Dobutamine should be given with controlled

infusion from 250mg in 500mls of normal

syline.

Dopamine is given in intravenous dilution of

400mg in 250mls of 5% dextrose.


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NURSING CONSIDERATIONS

Before administering any drugs, the nurse has to identifythe patient who is to receive the drug. This helps in that thenurse gives the right medication to the right patient.

After this, the nurse has to review the data of the patientwhich was corrected on admission and any additional datasuch as temperature, pulse rate, respiration rate and bloodpressure. She must also consider any statement made bythe patient him/herself.

She then has to analyse the condition of the patient anddecides whether to give or withhold the medication orcontact the patients physician if there is need for review.


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NURSING CONS. CONT

If the nurse is to give the drug ,he or she then plans themost convenient and individualized drug regimen (route,dosage and dosing schedule), taking into account the needsof the patient or family.

The nurse then explains the procedure to the patient.During this, the nurse has to inform the patient or familyabout the expected actions and adverse effects of aprescribed drug.

Then the nurse monitors the patient and identifies theearly onset of adverse effects and intervenes appropriately.She must also identify the safety needs of the patient andintervene appropriately to minimize the environmentalhazards and risk of injury.


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ANTEDOTES

These are drugs that counteract effects of a

poison

Acetylcysteine

Acts by disrupting disulfide linkages of micro

proteins in purulent and non purulent

secretion

Lowers viscosity and facilitates the removal of

secretions


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Ant cont

It is an antidote for acetaminophen poisoning

DOSE: PO 140mg/kg followed by 70mg/kg 4hrly

for 17 doses

Charcoal activated (liquid antidote)

Available; 280mg/ml, 15g, 30g,50gliquid/suspetion


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Anti cont..

Acts by binding toxic substances thereby

inhibiting their GI absorption, enterohepatic

circulation, and thus bioavailability

USES: General purpose emergency antidote in

the treatment of poisoningss by most drugs

and chemicals

DOSE: Adult: PO 30-100g in 180-240mL ofwater


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Cont

Child 1-12yrs 15-30g in 180-240mL of water

AMYL NITRATE

Short acting vasodilator and smooth muscle

relaxant. Act in treatment of cyanide

poisoning.

Used in the treatment of cyanide poisoning


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Cont

Rapidly absorbed from the mucous

membranes

Onset 10-30s

Duration 3-5 minutes

DIGOXIN IMMUNE FAB (OVINE)

Available in 38mg, 40mg vialActs by selectively complexing with circulating

digoxin or digitoxin


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Cont

This action prevents the drug from binding at

receptor sites

The complex is then eliminated in urine

USES: Treatment of potentially life threatening

digoxin/digitoxin intoxication in carefully

selected patients


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ANTIBIOTICS

Antibiotics

Antibiotics are chemical substances

produced by microorganisms (fungi,

actinomycetes, bacteria ) that suppress the

growth of other microorganisms, and may

eventually destroy them.


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ANTIBIOTICS

Classification

1. According to the source

Antibiotics have been isolated from

three types of microorganisms.

(i) Antibiotics from fungi:

Penicllin from Penicillium notatum andpenicillin chrysogenum;

griseofulvinfromPenicillium greseofulvin andothers.


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ANTIBIOTICS

(ii)Antbiotics from actinomycetesStreptomycin from Streptomyces griseus;

chlortetracycline from Streptomyces aureofacines;

oxytetracycline from Streptomyces rimosus;

chloramphenicol from Streptomyces venezuelae;

erythromycin from Streptomyces erythreus


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ANTIBIOTICS

(iii)Antibiotics from bacteria

bacitracin from Bacillus subtilis;

polymixins from Bacillus polymyxa and

others.


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ANTIBIOTICS

2. According to the Mode of Action

(i)Inhibitors of bacterial wall synthesis

penicillins,

cephalosporins,

bacitracin, and others.


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ANTIBIOTICS

(ii) Inhibitors of protein synthesisaminoglycosides,

tetracyclines,

chloramphenicol,

macrolides and others.


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ANTIBIOTICS

(iii) Inhibitors of cell membrane function

polymixins,

nystatin,

amphotericin B.


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ANTIBIOTICS

3. According to the Antibacterial Spectrum

(i) Narrow spectrum antibiotics

penicillins, streptomycin. erythromycin,

lincomycin, polymixin B, vancomycin and others.

(ii) Broad spectrum antibiotics chloramphenicol,

tetracyclines, kanamycin, cephalosporins,ampicillin, amoxycillin and others.


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ANTIBIOTICS

INHIBITORS OF BACTERIAL CELL WALL SYNTHESIS

The most important of this group are the

penicillins and the cephalosporins, designatedas Beta-lactam antibiotics (see fig).


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ANTIBIOTICS

PENICILLINS

Comprise of substances some of which are natural

products while others are semisyntheticcompounds.

They have a common chemical nucleus, 6-

aminopenicillanic acid (6-APA), and a common mode

of antibacterial action, i e by the inhibition of cell

wall mucopeptide synthesis.


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Anti cont

Examples of antibiotics that are used in ICU

are Metronidazole ,Gentamycin , Ceftriaxone

and Benzyl penicillin.

sedatives pharmacology

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