Drug Administration and Dosage

Learning Objectives

• Become familiar with the principles of drug administration.
• List and give examples of different dosage forms.

Definition of a Medicinal Product

• A medicinal product is any product used for the prophylaxis or management of diseases.
• It affects body function or is used to make a medical diagnosis.
• Any product used to affect body tissues and cause specific physiologic action is a medicinal product.
• Angina, the pain of which is felt in the left arm or thigh, can be treated using nitroglycerin as a sublingual tablet due to increased absorption.
• If a sublingual tablet for Angina is given, and the pain is still felt, the patient may be experiencing myocardial infraction.

Sources of Drugs

• Animal sources include insulin and thyroid hormone.
• Plant sources include morphine, reserpine, and digoxin.
• Microorganisms provide antibiotics like penicillin and streptomycin.
• Minerals include Kaolin.
• Synthetic sources include aspirin and sulfonamides, and are the most common.
• Genetic engineering (DNA recombinant technology) allows for the production of human insulin and Human Growth Hormone.
• Human insulin and Human Growth Hormone are used when there is sensitivity to animal insulin.

Names of Drugs

• The chemical name states the chemical composition and molecular structure of a drug, otherwise known as an IUPAC name.
• The generic name is usually suggested by the manufacturer.
• The official name is as listed in the U.S. Pharmacopeia.
• The brand name is the trade or proprietary name.
• For example, the chemical name for Valium is 7-chloro-1, 3-dihydro-1, methyl-5-phenyl-2h-1.
• The generic name for Valium® is Diazepam.

Essential Drugs

• Essential drugs are of two types: core list and complimentary list.
• A core list includes minimum drug needs for a basic healthcare system, and lists the most cost-effective drugs for priority conditions.
• A complimentary list consists of drugs that are cost-effective or may need specialized healthcare facilities.
• The World Health Organization (WHO) defines essential drugs as those that satisfy the health care needs of the majority of the population.
• They should be available at all times in adequate amounts, in appropriate dosage forms, and at a price the individual and the community can afford.

Rights of Medicine Administration

• When administering medicines, ensure the right medicine is given at the right dose, in the right form.
• It should be administered to the right patient, at the right time, by the right route, using the right technique, and with the right documentation.

Drug Actions

• Drugs do not do anything new; they can only alter functions that are already occurring in the body.
• They can only replace, enhance, or interrupt a function.
• Drugs will always leave residual effects, even ones delivered to selective sites.
• Albuterol and muscle tremors are an example of a residual effect drugs can cause.
• Drugs usually have to bind to something, i.e. a receptor, before anything can occur.
• Antacids bind to receptors in the stomach.
• Morphine binds to euphoria, nausea, and vessel control receptors in the brain.

Routes of Drug Administration

• The possible routes of drug entry into the body can be divided into two classes: oral [enteral] and parenteral.
• New cancer treatment uses a catheter tube to inject the drug directly into the tumor to avoid killing healthy cells.

Drug Effects

• Drug effects can be subdivided into systemic and local effects.
• A systemic effect sees the drug distributed throughout the body to cause a general effect, such as with tablets.
• A local effect sees the drug limited to the area of the body where it is administered, such as with nose drops.

Factors Affecting Route of Administration Choice

• Factors include desired effect, i.e. for fast action, intravenous administration is preferred in emergency situations
• A local effect is desired to reduce side-effects.
• E.g. administration of bronchodilators and corticosteroids as inhalers in asthma.
• It depends on the absorption qualities of the drug.
• E.g. administration of gentamicin for a systemic effect has to be done parenterally.
• It depends on the ability of the drug to withstand the conditions of the gastrointestinal tract.
• E.g. insulin cannot be administered orally since it is degraded in the gastrointestinal tract.

Routes, Administration, and Dosage Form Examples

• Oral Route: solid oral dosage forms like tablets and capsules; liquid oral dosage forms like syrups and suspension.
• Topical route includes transdermal drug delivery (like nicotine patches), inhalation, and nasal or ophthalmic ear drops.
• Additionally, topical creams, ointments, lotions, and powders.
• Transdermal patches cause vasodilation, so avoid hot showers.
• Hot showers can also cause vasodilation, and increase absorption.

Other Routes of Administration

• Parenteral route: including intramuscular, subcutaneous, and intravenous via use of pumps and implants.
• Rectal route: enemas, suppositories.
• Vaginal route: pessaries, fluid solutions, creams.

Sublingual/Buccal Administration

• Some drugs are taken as smaller tablets which are held in the mouth or under the tongue, such as glyceryl trinitrate.

Advantages and Disadvantages of Sublingual/Buccal Administration

• Advantages: rapid absorption, drug stability, and avoid first-pass effect.
• Disadvantages: inconvenient, small doses, and unpleasant taste of some drugs.

Buccal Tablets

• Drug is placed between gum and mucous membranes.
• They are absorbed slowly and can be used for a local effect.

Oral Administration

• Advantages: simple and convenient, self-administration possible, can be self-administered, pain free and easy to take.
• Absorption takes place along the whole length of the GI tract.
• Cheap, compared to most other parenteral routes.
• Disadvantages: sometimes inefficient, only part of the drug may be absorbed and drugs absorbed orally are initially transported to the liver via the portal vein due to the first-pass effect.
• Also, irritation to gastric mucosa may bring on nausea and vomiting.
• Irregular absorption, ex. due to food, limitations when patient is unconscious, vomiting or in pre-/post-operative patients.
• Other disadvantages include destruction of drugs by gastric acid and digestive juices.
• It is not useful for emergencies, and is unable to use in unconscious patient, and unpleasant taste of some drugs

Modified-Release Oral Preparations

• Extended-release preparations are preparations that extend the release of a drug to achieve sustained plasma drug concentrations.
• This results in decreased requirement for frequent dosing and is typically used when more than one tablet is required to be taken, reducing the frequency of administration.
• Delayed-release preparations are those where release of drug is delayed so that absorption takes place at a later stage in the gastrointestinal tract, i.e. enteric-coated preparations.

First-Pass Effect

• First-pass effect is the term used for the hepatic metabolism of a pharmacological agent when it is absorbed from the gut and delivered to the liver via the portal circulation where drugs are metabolized by CYP-450 enzymes.
• The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is administered orally.

Formulations

• Tablets may be effervescent, enteric coated, or modified release.
• Capsules are easier to swallow but more costly to produce.

Capsules

• Soft capsules are a unit that is formed from one piece where the processes of filling and formation of the outer unit are carried out in a single operation.
• Hard capsules consists of two separate components, namely the cap and the body.
• Gelatin, which is a polymer, is used to prepare capsule shells, and is regulated by an EU Directive that specifies method for manufacture of gelatin so as to reduce the risk of bovine spongiform encephalopathy (BSE).
• Oral liquid formulations that are sugar-free are preferred to reduce the risk of dental caries and are administered to diabetic patients.

Parenteral Routes

• Intravascular (IV, IA) involves placing a drug directly into the bloodstream, which is the only route that provides 100% absorption.
• Intramuscular (IM): drug injected into skeletal muscle.
• Subcutaneous involves the absorption of drugs from the subcutaneous tissues.
• Inhalation involves the absorption through the lungs.
• Bioavailability is the amount of drug that reaches the blood.

Advantages and Disadvantages of Parenteral Administration

• Advantages: allows for systemic administration of drugs with erratic absorption or first-pass effects and to provide a fast onset of action or a prolonged action
• It is also useful for patients who are not cooperative.
• Disadvantages: formulation has to be sterile, also more expensive to manufacture, usually requires administration by a healthcare professional, and may not be well accepted by patients.
• This method only accepts clear solutions.

Other Information on Intravascular Administration

• Absorption phase is bypassed (100% bioavailability).
• Precise, accurate and almost immediate onset of action, making them viable in emergencies.
• Large quantities can be given, where volume varies from 1 mL to 3000 mL where the fluid is administered as an infusion and is fairly pain free.
• Greater risk of adverse effects due to high concentration being attained rapidly with a risk of embolism.
• Intravenous injections should be aqueous and should not contain particles.
• Antibacterials, corticosteroids and replacement fluids (e.g. saline) are examples of drugs that can be administered via means.

Intramuscular Administration

• Administered into a large muscle, usually in buttocks or anterior lateral thigh.
• Aqueous and oily solutions can be administered.
• A larger amount can be administered than subcutaneous injection (up to 5 mL).
• Absorption is more rapid than subcutaneous injection but can be modified by the addition of adrenaline or hyaluronidase.
• Used, for example, for immunization.

Subcutaneous Administration

• This route allows for slow and constant absorption, which is limited by blood flow; concurrent administration of vasoconstrictor will slow absorption.
• It is not useful for suspensions or oily fluids, where a small volume (2 mL) can be administered.
• Insulin is administered via this route.

Devices Required for Parenteral Administration

• Syringes and needles must be sterile to avoid infection such as septcemia.
• Syringes have a size variability of 0.5–50 mL with the position of the syringe hub either central for most uses, or eccentric for intravenous use.
• Insulin syringes are calibrated in units (U).

Needle Information

• Needle gauge (G) indicates the diameter of the lumen, with the size being, 16–30G; the larger the number, the smaller the diameter.
• Length of needle also may vary and the insulin syringe is used the same way.

Implant

• A device inserted surgically under the skin for delivery of medication, releasing drugs slowly and consistently.
• The disadvantage is that termination of therapy requires surgical removal, such as for levonorgestrel.
• Insulin is not an implant but a pump.

Pumps

• Medication is administered via pump to provide continuous flow into the system.
• The pump is electronically programmed to deliver a predetermined amount of drug over a predetermined amount of time.
• They can be used for opioid analgesia in postoperative or palliative care, and for insulin therapy.

Intravenous and Intramuscular Comparison

• Intravenous Administration: most are aqueous with a large volume (<1 mL to >3000 mL).
• Commonly administered at the internal flexure of the elbow or the back of the hand.
• This may adopted in emergency situations when an immediate effect is required, when drug is not available in other routes or required to deliver large volumes of fluid (IV infusion).
• Intramuscular Administration: aqueous and oily suspensions in small doses up to 5 mL.
• Administered into a large muscle, usually into buttocks or anterior lateral thigh, needle is inserted at a 90° angle.
• Used for aqueous and oily suspensions in doses up to 5 mL, such as with immunizations.

Inhalation

• Useful for gaseous and volatile agents and aerosols, for rapid onset of action due to rapid access to circulation.
• Thin membranes separate alveoli from circulation, large surface area, and high blood flow increase absorption/bioavailability.
• Airway must have increased vascularity.
• Asthma treatments utilizes this administration route.
• Bronchoconstriction or bronchoinflammation produces a wheezing sound.

Metered-Dose Inhalers

• A specific dose is inhaled with each press.
• Inhalers present the drug as an aerosol, usually as liquid, sometimes as a powder formulation, and are intended for topical application in the respiratory tract for the management of respiratory disease, such as asthma.
• Proper technique is required and they can provide rapid onset of action and minimal side effects due to topical action.
• Examples: salbutamol, salmeterol and budesonide.
• Always inhale the drug, and hold your breathe for some time then release your breathe.

The Administration of Oxygen

• Oxygen therapy is by inhalation and is prescribed by specifying the flow rate, concentration, method of delivery and length of time of administration.
• Note that 100% oxygen may result in oxygen toxicity, presenting with symptoms such as alveolar collapse, intra-alveolar hemorrhage and disturbance of the central nervous system.
• Masks are required to administer oxygen to the patient.
• Patients may require domiciliary use of oxygen and therefore access to oxygen cylinders or oxygen concentrators and patient information on the safe handling of the equipment is required.
• Pressure gauge indicates amount available.
• Cylinder storage conditions include being upright, and kept in a dry well aired room, no smoking.

Topical Administration

• Topical medications are administered through the skin and mucosal membranes.
• Mucosal membranes include the eyes (eye drops), and areas requiring antiseptic, sunscreen, callous removal, and nasal administration.
• Skin administration includes applications of rubbing in of oil or ointment (local action).
• Also transdermal – absorption of drug through skin for stable blood levels and no first pass metabolism, drug must be potent or patch becomes to large (systemic action).

Advantages and Disadvantages of Topical Administration

• Advantages: may be adopted to have a localized effect and provides a systemic effect with first pass effect reduced
• Disadvantages: May cause local reactions and there is a need for patient advice to ensure safe and appropriate drug administration.
• When systemic absorption is required, lipid solubility of drugs is a required characteristic.

Transdermal Drug Delivery

• A system of drug delivery where drug molecules in a variety of sizes and shapes, provide absorption through the skin and into the bloodstream at various rates.
• Examples: nicotine patches.
• Advantages: ease of application, effectiveness for a long period of time allowing for retention of patch for a number of hours, and consistent blood drug level is achieved with stability
• Examples include nicotine patches and glyceryl trinitrate patches, with drugs released slowly and continuously.

Ophthalmic Administration

• Preparation must be sterile, and patient should be advised that once opened product should be discarded within 4 weeks.
• Good practice requires that the opening date is documented on the pack to ensure that products that have been opened more than 4 weeks previously are not used.
• Patients or their carers require knowledge of the proper technique for application of the product to avoid touching the container against the eye or anything else to avoid contamination of the containers.
• Ophthalmic preparations include eye drops, eye lotions, and eye ointments.

Otic Administration

• Patient must remain on his or her side for about 5 minutes to allow formulation to reach inner ear canal.
• If the eardrum is not patency, exercise caution when using ear drops.

Nasal Administration

• Nasal drops are preferred in infants due to better spread as opposed to spray.
• Nasal spray is preferred since they are less likely to be associated with postnasal drip of the drug leading to an aftertaste.

Rectal Route

• Advantages: bypasses the oral route and is useful when patient is nauseated or vomiting, postoperative and not able to take medicines orally.
• May be used for a local effect in the colon, such as to treat constipation w/ glycerine suppositories.
• Disadvantages include inconvenience and erratic absorption, which are not well accepted by patients.
• Suppositories are a solid dosage form, while enemas are oily or aqueous solutions.
• The patient should be advised to lubricate the suppository tip with a water-soluble lubricant or to moisten the tip with cool water, inserted pointed end first until past the muscular sphincter of the rectum.
• Where the patient needs to use half a suppository, the suppository should be split in half longitudinally.

Vaginal Route

• Advantages: may be used to treat local infections and allows for local application of hormone replacement therapy.
• Disadvantage: inconvenient and not well accepted by patients and it most dosage forms available is douches, creams and pessaries.

Take Home Message

• When administering medicines, the choice of product and route of drug administration depends on a number of factors including patient and drug characteristics.
• Pharmaceutical development of drugs is a time consuming process that requires a preformulation phase which takes into consideration drug characteristics required to establish the formulation for the different dosage forms.