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 and treatment procedures

 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.

PURPOSE FOR USING SEDATIVES

Sedative agents are used in attempt to: Allay anxiety over the patients own illness, the welfare of relatives or the risk of death. Ensure adequate rest Reduce the impact of unpleasant sensations, such as thirst Reduce the distress of invasive treatment and monitoring, such as endotracheal intubation Blunt awareness, of the environment over which the patient has very little control and in which he/ she may be unable to communicate.

TOOLS USED TO ASSESS LEVEL OF SEDATION

The level of sedation required will vary depending on the indication e.g. heavy sedation may be necessary during the control of status epilepticus, while a much lower level sedation will be required to tolerate endotracheal intubation. The level of sedation can be assessed using a number of measuring tools. Scoring systems such as the Ramsay scale, which is a six point that ranges from anxious and agitated (leve1) to un responsive (level 6), judged in response to a standardized stimulus (loud auditory stimulus or glabellar trap).

CONTI
Electroencephalography (EEG), which may be either 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 research tool. Evoked potentials Monitoring physiological parameter for signs of distress.

SEDATIVE AGENTS USED IN ICU

BENZODIAZEPINES These drugs provide hypnosis, amnesia and anxiolysis, they do not provide anagelsia. BZA are good anticonvulsant drugs and also provide for some muscle relaxation. They act via the BZA receptors, which are closely associated with GABA receptors, resulting in intracellular influx of chloride when activated. These drugs may be given by mouth, per rectum or IV, but they are mostly used through IV infusion.

Dosage of these drugs depends on the following factors; Prior exposure to BZA ( increased tolerance) Age and physiological reserve. Volume status; hypovolemic patients are more sensitive,

 Renal and hepatic dysfunction Co-administered drugs i.e. whether BZA is combined with opioids History of alcohol consumption, there is increased tolerance

Cont
Examples of BZA that are mostly used in ICU include diazepam 5-10mg IV prn, it is a longer acting agent Midazolam 0.002-0.2mg/kg/hr. it is a short acting agent BZA are often combined with opioids in a compound sedative infusion. This allows lower doses of a BZA to be used, while capitalizing on the opioid effect of respiratory and cough suppression, to facilitate mechanical ventilation.

Pharmacokinetics
- sleep occurs within 15 to 45 mins
- Flurazepam has fastest on set of action. It is converted to an active metabolite (Ndesalkylflurazepam with a half-life of 50-100 hrs. - the drugs and their metabolites are excreted in the urine.

CNS SIDE EFFECTS

Adverse reactions 1. Hangover and drowsiness occur in the morning 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 to habituation. 11

SIDE EFFECTS CONT

- daytime drowsiness - lightheadedness - disorientation - slurred speech - memory impairment - depression - nervousness and irritability

CNS: CONT.
3. Respiratory depression: occurs with about 10 times hypnotic dose. 5. Drug automatism: it is a state of amnesia in which a patient takes repeated doses until acute 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 NMDAreceptors. It produces a sedative state known as dissociative anaesthesia with the following characteristics; mild sedation, amnesia, analgesia and reduced motor activity.

 The lack of respiratory and cardiovascular depression at lower doses makes this a very safe drug to use in the ICU. At KCH ketamine is used in patients with severe head injury during the first 5 days of admission with an aim of completely sedating the patient. It is also used when performing simple procedures

cont
Propofol is also frequently used in ICU. It is fast acting, very effective and with a rapid offset of action, this is due to its rapid metabolism to inactive metabolites in the liver. These features makes it very suitable for use in patients requiring short term sedation or for anesthesia for procedures in ICU. Caution is required in hypovolaemic patients or those with impaired myocardial function as severe hypotension may result .

 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 on dosage and duration of therapy. At KCH this drug is used after 5 days of complete sedation with ketamine in patients with severe head injury.

 Incases where the patient is presenting with increased blood pressure, this drug is used instead of ketamine until the increased blood pressure subsides

Cont
Thiopentone is reserved for specific indications, such as management of intractable intracranial hypertension (to reduce cerebral metabolism), or for treatment of status epilepticus. It is not commonly used as general sedative agent. Its use is limited by its long duration of action and long half-life when used for prolonged infusions At KCH this drug is used in patients with head injury during suction, in order to avoid irritating the client.

THE IDEAL SEDATIVE

There is no ideal sedative agent. Sedatives in the future may target specific aspects of sedation such as hypnosis, Anxiolysis or amnesia without necessarily providing the whole spectrum of sedation for each patient. Currently the ideal sedative would address the following; hypnosis or sleep Anxiolysis Amnesia Anticonvulsant

 Be non-cumulative Be independent of renal or hepatic metabolic pathways. Not produce respiratory or cardiovascular depression Be of modest-cost Have a rapid onset and short offset time Have no prolonged effects on memory Have no long term psychological effects.

BRONCHODILATORS

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.

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 provide short-term relief from breathlessness long-acting bronchodilators these have no immediate effect, but can help control the symptoms of conditions such as asthma if used regularly, and have more long-lasting effects

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 associated with bronchitis, emphysema, other obstructed pulmonary diseases as well as prevention of exercise induced asthma

MECHANISM OF ACTION
Bronchodilator drugs relax the muscles in the lungs, which allows the airways to widen and makes breathing easier. Some bronchodilators also help to clear mucus and reduce inflammation in the lungs. They are divided into; Anticholinergics, alphabeta adrenergic agonists, beta adrenergic agonists and phosphodiesterase inhibitors. Anticholinergics act by inhibiting interaction of acetylcholine at receptor sites on bronchial smooth muscles.

PHARMACOKINETICS
Onset, peak and duration vary widely among products. Most products are metabolized in the liver and excreted in urine.

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 which relaxes bronchial smooth muscles. Phosphodiesterase inhibitors by blocking phosphodiesterase increasing cAMP which mediate smooth muscle relaxation in the respiratory system.

Cardiovascular drugs in ICU

ANTIHYPERTENSIVES
These are drugs that are used to treat high blood pressure which is manifested by the readings of 140/90mmHg. 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, venous return and the tone of arterial smooth muscles.

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.

Anti cont
Pharmacokinetics The vasodilators are readily absorbed following oral administration and its effectiveness is apparent within 45 minutes and persist for 6 hours or more. When given parenterally, effects begin rapidly within 10 minutes and last for 2 to 4 hours. An example of this type of drugs is hydralazine that is given from 20mg to 40mg.

Cont
Metabolism It is inactivated by metabolic process called acetylation which is This acetylation is genetically determined and so the people who are slow acetylators end up having increase concentration of the drug in their blood which leads to excessive vasodilatation leading to hypotension than fast acetylators.

Calcium channel blockers

These are antihypertensives as well. Calcium channels are pores in the cell membrane that regulate the entry of calcium ions into cells. Calcium plays a critical role in the function of vascular smooth muscle for the heart. They lower blood pressure by dilating arterioles of the heart. An example is Nifedipine that is given 5-20mg repeated 4-6 hourly sablingual.

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.

Mode of Action
The dopamine and dobutamine are drugs that have an inotropic and effect where they increase contractility of the myocardium by directly stimulating 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 heart output showing a chronotropic effect. Moderate doses decrease preload and have minimal chronotropic and blood pressure effects and very high doses can cause tachycardia.

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.

NURSING CONSIDERATIONS
Before administering any drugs, the nurse has to identify the patient who is to receive the drug. This helps in that the nurse gives the right medication to the right patient. After this, the nurse has to review the data of the patient which was corrected on admission and any additional data such as temperature, pulse rate, respiration rate and blood pressure. She must also consider any statement made by the patient him/herself. She then has to analyse the condition of the patient and decides whether to give or withhold the medication or contact the patient s physician if there is need for review.

NURSING CONS. CONT

If the nurse is to give the drug ,he or she then plans the most convenient and individualized drug regimen (route, dosage and dosing schedule), taking into account the needs of the patient or family. The nurse then explains the procedure to the patient. During this, the nurse has to inform the patient or family about the expected actions and adverse effects of a prescribed drug. Then the nurse monitors the patient and identifies the early onset of adverse effects and intervenes appropriately. She must also identify the safety needs of the patient and intervene appropriately to minimize the environmental hazards and risk of injury.

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

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,50g liquid/suspetion

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 of water

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

Cont
Rapidly absorbed from the mucous membranes Onset 10-30s Duration 3-5 minutes DIGOXIN IMMUNE FAB (OVINE) Available in 38mg, 40mg vial Acts by selectively complexing with circulating digoxin or digitoxin

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

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 and penicillin chrysogenum; griseofulvin from Penicillium greseofulvin others. and
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ANTIBIOTICS
(ii) Antbiotics from actinomycetes
Streptomycin 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 synthesis aminoglycosides, 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, designated as Beta-lactam antibiotics (see fig).

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ANTIBIOTICS
PENICILLINS Comprise of substances some of which are natural products while others are semisynthetic compounds.

They have a common chemical nucleus, 6aminopenicillanic 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.

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