Parenteral Products PDF Lecture 1

Parenteral Products Parenteral Products The term (Parenteral) derives from the Greek words “para enteron” meaning “to avoid the intestines.” - Para: outside. - Enteron: intestine. Parenteral preparations are defined accordi...

Parenteral Products Parenteral Products The term (Parenteral) derives from the Greek words “para enteron” meaning “to avoid the intestines.” - Para: outside. - Enteron: intestine. Parenteral preparations are defined according to the (USP) as “those preparations which intended for injection through the skin or other external boundary tissue, where the drug(s) are introduced directly into blood vessel, organ, tissue or lesion and are completely sterile and pyrogen free”. Parenteral products are classified according to their rout of administration and according to their volumes. A- Classification of parenteral products according to their rout of administration Parenteral routes of administration are categorized into common routes and specialized routes. I- Common routes include: 1- Intravenous Route (IV), 2- Intramuscular Route (IM), 3- Subcutaneous Route (SC), 4- Intradermal Route (ID). II- Specialized routes include: 1- Intra-arterial Route, 2- Intra-articular Route, 3- Intracisternal Route, 4- Intraventricular Route, 5- Intrathecal Route, 6- Epidural Route, 7- Intracardiac Route, 8- Intraocular Route. 9- Intraosseous 10- Intralymphatic  Parenteral Products I- Common Routes: 1- Intravenous Route (IV): Injection or infusion directly into a vein. Drug administered can be in the form of solutions, nanosuspensions, and oil/water emulsions. (N.B: the particle size of the dispersed phase (oil phase) is < 1µ). Nearly all drug classes can be injected via the IV route. Types of IV administration: a) IV Bolus or push: Rapid injection of a medications into the blood stream. The dose is administered by a syringe directly into the vein. Generally, bolus means a single dose of a drug given all at once. b) IV Infusion: “slow drip” of medications or fluids into the vein; given over a long time interval. The dose is administered via IV infusion setup  Parenteral Products c) Piggyback: If a patient is receiving continuous IV fluids or medication and in addition must receive a second kind of infusion, we use Piggyback. 2- Intramuscular Route: Injection directly into a relaxed muscle. Drug administered can be in the form of solutions, suspensions, oily preparations and emulsions. The IM route have a slower rate of absorption when compared with the IV route, while having a more rapid rate of absorption when compared with the SC route. Nearly all drug classes can be administered via IM route. The IM route should be avoided in patients with significant heart failure or shock, where uptake into the vascular compartment will be poor.  Parenteral Products 3- Subcutaneous Route: Injection into the subcutis, the layer of skin directly below the dermis and epidermis. Drug administered can be in the form of solutions, suspensions, oily preparations and emulsions. The absorption of drugs via SC route is slower than that of the IM route. Why? As the vascularity in the subcutaneous tissues is less than that of muscle tissues. This route is used when slow drug absorption is needed. Medications commonly administered subcutaneously include insulin, vaccines and epinephrine. As with the IM route, if heart failure or shock exists, this route should not be used. In IM and SC routs, there is a limit for the amount of fluids that can be injected Why? Because more than that will affect the tissues surrounding the injection site causing abscesses and granulomas. 4- Intradermal Route: Injection into the dermis, located just beneath the epidermis. Drug administered can be in the form of solutions, suspensions, oily preparations and emulsions. Absorption by the intradermal route is very slow compared with the SC or IM route. As a result, ID route is not frequently used to deliver systemic effects. This route is mostly used for diagnostic purposes (e.g., tuberculin) and sensitivity testing. It is very useful in sensitivity testing, as the body's reaction to the injected antigens will be easily visible.The volume of injected fluid usually does not exceed 0.1 mL.  Parenteral Products The rate of absorption decreases in the following order: IV > IM > SC > ID. II- Specialized routes: These routes are only handled by well-trained and highly experienced physicians. 1- Intra-arterial route: The intra-arterial route is infrequently used route. Injection of a drug into an artery or arteries to localize the drug effect to a particular organ or body region. It may be used as alternative for IV access. The intra-arterial route is generally used for diagnostic purposes, as injecting radiopaque substances to study the vascularity of organs or tissues “Angiography” (e.g., coronary, cerebral, pulmonary, renal, enteric, or peripheral arteries). The use of this route in treatment is very limited. It is used in chemotherapy or radiotherapy in order to limit the therapeutic effect to the diseased organ(s).  Parenteral Products Intra-arterial route is extremely hazardous, because products administered via this route are not sufficiently diluted or filtered by lungs, liver, or kidneys before contact with tissues or vital organs nourished by the artery. 2- Intra-articular route: Injection into the synovial sacs of joints. Antibiotics, analgesics, and anti- inflammatory drugs may be administered into joints for the treatment of infections, pain and inflammation. Also injection of hyaluronic acid to help in joint lubrication. Some drugs are administered in single injections and some by discontinuous infusion (e.g., antibiotics). N.B: Not used for LVP infusion. 3- Intracisternal route: Injection into the cisternal space surrounding the base of the brain. This route is usually used for diagnostic purposes. 4- Intraventricular route: Injection into the ventricles of the brain. This route is employed mainly in the treatment of infections and malignancies.  Parenteral Products 5- Intrathecal Route: Injection into the spinal canal (intrathecal; space surrounding the spinal cord that holds the cerebrospinal fluid). It is used in spinal anesthesia, chemotherapy and pain management. 6- Epidural Route: Injection into the epidural space. This route is particularly used for anesthesia “epidural anesthesia”. Epidural anesthesia is a regional anesthesia, which involves injection of anesthetic drugs through a catheter placed into the epidural space. The injection cause loss of sensation and analgesia by blocking signals transmission through nerves around the spinal cord. A specific type of needle known as a Tuohy needle is used for epidural injection. (A) Epidural route; (B) Intrathecal route. Tuohy needle for epidural injection (left), complete epidural set Tuohy needle and catheter (right).  Parenteral Products 7- Intracardiac Route: Injection into chambers of the heart or the cardiac muscle. The use of this route is not common for delivery of drugs. This route is used in certain emergencies, such as cardiac arrest, in which drugs must reach the myocardium immediately. 8- Intraocular Route: Injection into the various chambers of the eye. Detailed explanation of this route will be found under the ophthalmic products chapter. 9- Intraosseous Route: Injection into the bone marrow. It is an indirect route to intravenous access because the bone marrow drains directly into the venous system. This route is occasionally used in emergency cases when intravenous access fail (as in severe oedema, burns and obesity). This route may be used in certain cardiovascular conditions and in cardiopulmonary resuscitation. It is mainly used for fluid resuscitation but it can also be used to deliver some drugs like epinephrine. There are several types of needles depending on the exact site of insertion however, the most frequently used needles are known as EZ-IO®.  Parenteral Products 10- Intralymphatic Route: Direct injection into a lymph node or lymphatic vessel. This route is used for both diagnostic (injection of contrast reagent) and treatment purposes. It is mostly used in immunotherapy specially is case of IgE- mediated allergic diseases (immunoglobulin E). In addition, it is used in stem cell injection for the treatment of certain types of cancers. Indocyanine green fluorescence injected into a right external iliac sentinel lymph node. All specialized routes injections must be performed under strict aseptic techniques by highly experienced physicians and non- irritating substances should be injected.  Parenteral Products B- Classification of parenteral preparations according to their volume: Parenteral preparations are classified according to their volume into small volume parenterals and large volume parenterals. I- Small volume parenterals (SVPs): SVPs are injections and preparations having volumes below 100 mL. SVPs can be single dose or multiple dose. In case of multiple dose preparations, preservatives should be added and the total volume must be less than 30 ml. SVPs can be given by all parenteral routes (with respect to the volumes mentioned earlier). II- Large volume parenterals (LVPs): LVPs are injections and preparations having volumes above 100 mL and up to 5000 mL. LVPs are intended for single dose. N.B: LVPs must be preservative free and used as single-dose i.e., any unused portion should be discarded. LVPs are usually given by IV route (as IV infusion). However, in certain cases they can be given via intra-arterial route and intraosseous. IV infusions can be administered through peripheral veins, (mostly in the forearm), or through a central line that is surgically implanted in the subclavian vein. Infusion modes: there are four types of infusion:  Continuous (usually for common LVPs),  Discontinuous (related to patient’s needs as in analgesics),  Volume over time (blood components transfusion, TPN & PPN)  Dose over time (as in chemotherapeutics and certain antibiotics etc.).  Parenteral Products In order to set these different modes there is a need for certain devices called infusion pumps as:  Patient-Controlled Analgesia Pumps,  Volumetric Pumps,  Syringe Pumps. As for continuous infusion no need for certain specific pumps. Uses of LVPs: 1) Supply electrolytes & nutrients, 2) Prevent tissue dehydration, 3) Restore blood volume, 4) Dilute toxic materials, and 5) IV admixture (premixed injectable drugs). According to purpose and type of LVPs preparation, they can be categorized into Common LVPs and Specialized LVPs. A- Common LVPs They include: 1) Lactated Ringer’s injection USP, 2) 0.9% Sodium Chloride (normal saline) injection USP, and 3) 5% Dextrose injection USP. B- Specialized LVPs and Sterile Solutions They include: 1) Hyperalimentation solutions, 2) Cardioplegic solutions, 3) Dialysis solutions (peritoneal dialysis solution and hemodialysis solution), and 4) Irrigating solutions. N.B: Dialysis solutions and irrigating solutions are not parenteral products; they are called sterile solutions.  Parenteral Products 1- Hyperalimentation solutions: They are used in TPN (total parenteral nutrition). It is an artificial way of supplying nutrients by administering a nutritionally adequate liquid through implantation of a central venous catheter into the subclavian vein. It is recommended to start hyperalimentation whenever a patient is to take nothing orally for more than five days. Indications for hyperalimentation administration: 1) Long-term coma, 2) Severe gastrointestinal syndromes, 3) Esophageal obstruction. Hyperalimentation solutions usually contain: dextrose, amino acids, lipids, electrolytes, minerals, trace elements and vitamins. They provide nearly 4000 kcal/day. 2- Cardioplegia/ Cardioplegic solutions: They are cold electrolyte solutions infused in the coronary circulation. Anterograde cardioplegia is administered into a small cannula placed in the ascending aorta or directly into the coronary ostia. Retrograde cardioplegia is delivered through a catheter placed through the right atrium into the coronary sinus. Cardioplegia is then delivered into the venous system of the heart. They are used to arrest the heart during open-heart surgery and cardiac transplantation. This procedure helps in:  Preventing ischemic injuries to the cardiac muscle (as the blood supply to the heart is stopped),  Maintaining a blood-free and motionless operating field. Cardioplegic solutions are typically electrolyte solutions of calcium chloride, magnesium chloride, potassium chloride, and sodium  Parenteral Products chloride , this electrolyte composition is intended to maintain diastolic arrest. These solutions are admixed by pharmacist in a hospital IV admixture program & are administered cold in order to cool the myocardium and minimize activity. Solution are slightly alkaline & hypertonic in order to compensate for metabolic acidosis and to minimize reperfusion injury resulting from tissue edema. Cardioplegic solution pumped into the heart  Parenteral Products 3- Dialysis solutions: a- Peritoneal dialysis solutions They are sterile solutions known as dialysate infused into the abdominal cavity to lavage (wash) the peritoneum, then continuously withdrawn. Toxins and metabolites (electrolytes, urea, glucose, albumin, and other small molecules) diffuse from the underlying blood vessels into the circulating dialysis fluid through the peritoneum (which act as semipermeable membrane), and are then withdrawn. Indication of peritoneal dialysis It is used to remove toxins from the body as in case of: 1) Acute renal insufficiency, 2) Intolerance to hemodialysis, 3) Hepatic failure. The Peritoneal dialysis solutions contain glucose, electrolyte, also an antibiotic is frequently added as a prophylactic measure. b- Hemodialysis solutions They are sterile solutions known as dialysate that are filled inside a dialyzer set, where hemodialysis procedure takes place. In hemodialysis, blood leaves the body from an artery through a catheter into the dialyzer, where exchange occurs between the blood and the hemodialysis solution through a semipermeable membrane, and then the blood enters the body through a vein. Hemodialysis is used in case of renal failure to:  Remove toxins and wastes from the blood,  Get rid of excess fluids, and  Restore electrolytes level in the blood. Hemodialysis solutions mainly contain: glucose and electrolytes.  Parenteral Products 4- Irrigating solutions: Irrigating solutions are intended to flush and clean body cavities and wounds. Certain IV solutions, such as normal saline, can be used as irrigating solutions, but solutions designed as irrigating solutions must not be used parenterally. Since irrigating solutions may diffuse into the bloodstream they must be sterile and pyrogen-free. Examples of irrigating solutions  0.9% Sodium Chloride (normal saline). It is used in wound irrigation as it aids in removing wound discharges and surface pathogens.  Urologic irrigating fluids. They are use during urinary tract surgeries particularly i.e. 1.5 % glycine irrigating solution and 3% sorbitol irrigating solution. They are used to aid in treatment of nephrolithiasis (kidney stones) by dissolving renal calculi. i.e. Citric acid, Magnesium Oxide and Sodium Carbonate Irrigation USP.