IV_Drug_Administration_handout_1_per_page.pdf

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Learning outcomes To explain the indications/contraindications for, the advantages/disadvantages of, and the risks associated with intravenous drug therapy. To identify the types of intravascular devices (including delivery devices and drivers) that may be used to deliver drugs and fluids. To interp...

Learning outcomes To explain the indications/contraindications for, the advantages/disadvantages of, and the risks associated with intravenous drug therapy. To identify the types of intravascular devices (including delivery devices and drivers) that may be used to deliver drugs and fluids. To interpret the effects of varying basic pharmacokinetic parameters (e.g. clearance) upon the plasma concentration of IV drugs following bolus, continuous or intermittent infusions. Intravenous drug administration. MD3001. 2 Lecture overview Indications for intravenous therapy Guidelines for the safe administration of intravenous drugs Hazards and complications of intravenous therapy Pharmacokinetics of intravenous drugs Indications for intravenous therapy Reasons for IV administration Medicine is not available in another form Cannot tolerate medication by another route Constant or high blood level of medicine is needed A rapid onset of effect is needed Some medications are more effective via IV Rarely, to ensure compliance Disadvantages of IV administration Increased cost and time to administer the medicine Requires trained staff to administer (plus location) Rapid onset of action Volume of fluid needed to dilute the medicine Can cause discomfort/pain to the patient Health risks (e.g. infection) When the oral route can be used, it should be used Safe administration of intravenous drugs Types of intravascular devices (IVDs) Peripheral venous catheters Central venous catheters (CVCs) – Peripherally inserted CVCs – Skin-tunneled CVCs (e.g. Hickman and Broviac lines) Arterial catheters Syringes, bags, pumps and drivers Methods of administering intravenous medications Continuous infusion – – – – Bolus injection Stable drugs Short half-life Time dependent effects Needs dedicated IV site Intermittent infusion – – – – Unstable drugs Long half-life Concentration dependent effects Less compatibility concerns – Rapid response required – Incompatibilities – Unstable drugs Hazards and complications of intravenous therapy Complications of IV drug administration Fear / Phobia / Pain Infection / Sepsis Thrombophlebitis Extravasation / Infiltration Emboli Anaphylaxis / Hypersensitivity Overdose Visual infusion phlebitis score (1-5) 13 Red man syndrome Hypersensitivity reaction due to histamine release – erythematous rash of face, neck, and upper torso – diffuse burning, itching, generalised discomfort – rare cases: hypotension, angioedema, chest pain, dyspnea Vancomycin – Treatment of MRSA Incidence reduced by – Slowing infusion rate – More dilute drug solution Nallasivan et al, BMJ Case Reports 2009 Vancomycin Complications of IV drug administration Insufficient mixing Stability of medicines in solution – Light (e.g. total parenteral nutrition [TPN]) – Temperature (e.g. insulin, TPN) – Concentration (e.g. amiodarone) – pH (e.g. midazolam) Interaction of medicines with the syringe/bag Pharmacokinetics of intravenous drugs Bioavailability Fraction of unchanged drug that reaches the systemic circulation. IV injection gives 100% bioavailability. Infusion vs repeated injections Plasma drug concentrations Time IF drug is infused at a constant rate AND no drug is removed from the body, then the graph of plasma concentration against time would be a straight line. Plasma concentration Plasma drug concentrations BUT drug is being eliminated from the body as soon as it is in the circulation (e.g. via the kidneys). For most drugs, the amount of drug eliminated per unit time is related to the concentration of drug in the plasma (first-order kinetics): – Higher concentrations, more drug is removed per unit of time. – Lower concentrations, less drug is removed per unit of time. THEREFORE the graph of plasma concentration against time for most infusions will bend towards a plateau when the rate in of drug equals the rate out. Plasma drug concentration during IV infusion Plasma concentration increases during infusion until rate of input equals rate of output • “Steady state” Clearance Clearance (CL) is defined as the volume of blood or plasma cleared of drug in a unit time – e.g. 10ml/min In first order kinetics, whilst amount of drug eliminated per unit time varies, CL is a constant: Time zero 1 min 2 min 3 min 100 ml 100 mg 100 ml 90 mg 100 ml 81 mg 100 ml 72.9 mg Clearance 10ml/min 10ml/min 10ml/min 10ml/min Drug eliminated 10mg 9mg 8.1mg Plasma steady state conc. (Css) The Css value reached depends on: the rate of drug administered (K0) volume of plasma cleared of drug per unit time (CL) The time taken to reach Css depends on: elimination half-life (t1/2) t1/2 directly depends on the volume of distribution (Vd) and inversely on the clearance (CL) of drug from the body: t1/2 = ln2 x Vd CL Half lives and IV administration Thomson, Paediatric and Perinatal Drug Therapy Volume 4, Issue 1, 2000 Clinical impact What contributes to CL? (MD3002!) What happens if your patient’s CL is lower or higher than expected? – To the steady state plasma concentration? – To the time taken to reach that steady state? What happens if you increase or decrease the dose of a drug? – To the steady state plasma concentration? – To the time taken to reach that steady state? Main points Potential for drug errors is high if careless and many other risks are involved in IV administration – Guidelines exist for a reason! The time taken to reach the Css of a drug depends on its half life (t1/2) The Css reached depends on the rate of drug in, and the rate of clearance of the drug from the plasma Learning outcomes To explain the indications/contraindications for, the advantages/disadvantages of, and the risks associated with intravenous drug therapy. To identify the types of intravascular devices (including delivery devices and drivers) that may be used to deliver drugs and fluids. To interpret the effects of varying basic pharmacokinetic parameters (e.g. clearance) upon the plasma concentration of IV drugs following bolus, continuous or intermittent infusions.

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