Drug Classes, Types, and Routes of Administration PDF

# DRUG CLASSES, TYPES, AND ROUTES OF ADMINISTRATION ## PRESCRIBING MEDICATIONS FOR SPECIAL POPULATIONS Special populations include children, the elderly, pregnant women, immunocompromised individuals, etc. The vulnerability or risk for these groups comes from the fact that many drugs used in these p...

# DRUG CLASSES, TYPES, AND ROUTES OF ADMINISTRATION ## PRESCRIBING MEDICATIONS FOR SPECIAL POPULATIONS Special populations include children, the elderly, pregnant women, immunocompromised individuals, etc. The vulnerability or risk for these groups comes from the fact that many drugs used in these patients have not undergone adequate evaluation, making the efficacy and safety of these medications unreliable. A drug license implies proven efficacy, safety, and quality. The drug's label is the result of thorough, long-term testing. Prescribing outside of this label (off-label use) means that therapy is not based on evidence, but rather on judgment, experience, and extrapolation. There is the least amount of adequate research for neonates and pregnant women, as they are the most sensitive categories, and strict ethical laws have practically prevented any studies. ## Pregnancy One of the biggest challenges in treating a pregnant woman is choosing a medication that will be effective without having harmful effects on the fetus. Treatment protocols for diseases during pregnancy differ significantly from those used for the same diseases in other populations. The fear of possible teratogenic, embryotoxic, and carcinogenic harmful effects of medications arose after the tragic incident with thalidomide. Reproductive toxicity and its testing (see the first question) are now of utmost importance. Data obtained from animal studies cannot always be directly applied to humans. Medications that do not cross the hematoplacental barrier are the first choice for therapy during pregnancy. However, the majority of drugs with a molecular weight of less than 1000 Da can cross the placenta. Exceptions include conjugated steroids and peptide hormones (like insulin). When administering drugs to pregnant women, several questions must be considered: 1. Is the use of the drug absolutely necessary, considering the severity of the disease and the importance of the therapy for the health and life of the mother? 2. Could the drug have harmful effects on fetal development? 3. Do any pharmacodynamic effects of the drug influence the course of pregnancy and delivery? 4. How do physiological changes in the mother during pregnancy affect the pharmacokinetics and dosing of the chosen drug? ### Physiological Changes During Normal Pregnancy: - **Cardiovascular System (CVS)** - Increased cardiac output (up to 50%) and heart rate (up to 15%) - Increased blood volume (up to 30%) and plasma volume (up to 50%) - Increased venous pressure (especially in the legs) - Increased blood flow to vital organs - **Gastrointestinal Tract (GIT):** - Gums become spongy and prone to bleeding - Heartburn and nausea are common - Gastric secretion varies - Intestinal motility is reduced - The gallbladder becomes hypotonic - Vomiting is frequent - **Urinary Genital Tract (UGT):** - The renal pelvis and ureters are dilated - Relaxation of the bladder muscles increases its capacity - Renal blood flow and filtration increase - Levels of renin and aldosterone rise, leading to salt and water retention, which often causes edema, especially in the lower extremities - **Blood and Hematological Parameters** - Relative hemodilution: Red blood cells increase, but plasma volume increases even more - Several coagulation factors increase - Serum alkaline phosphatase levels rise - The albumin-to-globulin ratio is disturbed ### Factors Influencing Drug Kinetics in Pregnant Women - **Absorption:** progesterone levels increase, intestinal motility decreases, prolonging gastric and intestinal transit time; gastric acid levels decrease, and stomach pH increases - **Distribution:** The additional plasma volume may change the drug's volume of distribution, and total water retention in the mother's body increases by approximately 8 liters - **Plasma Protein Binding:** There are fewer available receptors, as most are occupied by steroid and placental hormones, resulting in relative hypoalbuminemia and reduced overall plasma protein binding - **Elimination:** changes in endogenous substances can either increase or decrease the hepatic elimination of drugs (microsomal enzymes); renal blood flow increases, raising renal drug elimination On the other hand, the effect of drugs on the fetus depends primarily on the stage of fetal development, the specific characteristics of the drugs, and the duration of exposure to the drug. The most critical period for teratogenesis is organogenesis (between the 3rd and 8th week). Today, about 30 drugs are known to have teratogenic effects at therapeutic doses, and one-third of these are anticonvulsants and antineoplastic drugs. For example, ACE inhibitors cause fetal renal dysfunction, tetracyclines prevent the normal development of bones and teeth, aminoglycosides are ototoxic, opioids cause fetal dependence, and warfarin leads to intracranial bleeding. The FDA (Food and Drug Administration) drug classification system helps guide drug selection during pregnancy: - **Class A:** Drugs safe for use during pregnancy, even in the first trimester, with controlled studies in pregnant women (e.g., folic acid) - **Class B:** Drugs safe in animals, with no controlled studies in pregnant women - **Class C:** Drugs teratogenic in animals, with no data for pregnant women - **Class D:** Drugs teratogenic in animals, with evidence of fetal risk - **Class X:** Drugs contraindicated during pregnancy **Note:** The above mentioned FDA drug classification is no longer in use. However, it is still recommended that you familiarize yourself with it since the medical community is still used to it. | Drug | Effect | |---|---| | ACE Inhibitors, ARBs (sartans) | Nephrotoxicity | | Tetracyclines | Teeth and bone growth damage | | Aminoglycosides | Ototoxicity | | Anticonvulsive drugs | Mental retardation | | Antithyroid drugs | Hypothyreosis, birth defects | | Corticosteroids | Slowed intrauterine growth, disorder in brain growth and development | | Beta blockers | Bradycardia, hypoglycemia | | Cytostatics | Mental retardation, death of fetus | | Warfarin | Fetal intracerebral hemorrhage | ## Safe Drugs to Prescribe in Pregnancy | Condition | Drugs | |---|---| | Hypertension | Methyldopa, Labetalol, Hydralazine, Nifedipine | | Diabetes Mellitus | Insulin, metformin | | Antibiotics | Penicillins, cephalosporins, erythromycin | | Thrombosis | Heparin, acetylsalicylic acid (low dose) | | Fever, analgesia | Acetaminophen | | Hyperacidity | Antacids, Lansoprazole | | Nausea and vomiting | Promethazine, Metochlorpramide, Ondansetron | | Epilepsy | Lamotrigine, levetiracetam | ## Pediatric Population A fundamental issue is the lack of pediatric-evaluated drugs. Depending on the therapeutic area, it is estimated that 50-90% of drugs have never been evaluated for use in children and newborns. The age of the child and the development of the body can influence the pharmacokinetics and pharmacodynamics of the drug. Factors affecting absorption include age, pathological conditions, method of administration, food, and other drugs. The distribution process is influenced by the ratio of body fluids, fat tissue, and muscle, as well as the underdeveloped liver and blood-brain barrier. Liver immaturity, especially enzymes, affects drug metabolism, while kidney and biliary system immaturity affects drug excretion. It is important to know that some diseases occur exclusively in children and that some diseases in children differ significantly in pathophysiology from the same diseases in adults (e.g., heart failure in children is often due to congenital heart defects). Some drugs used in adults are used in pediatrics for different indications (off-label drug use), such as indomethacin (a nonsteroidal anti-inflammatory drug) for closing a patent ductus arteriosus. The profile of adverse effects in children is similar to that in adults. Some drugs exhibit age-specific adverse effects, such as Reye's syndrome following the use of aspirin in children. Many antibiotics have serious adverse effects specific to the pediatric population: fluoroquinolones (arthropathy), tetracyclines (tooth discoloration, dental hypoplasia, bone deformities), and chloramphenicol (gray baby syndrome). ### Physiological Trends Related to Age | System | Neonates and young infants: | Pharmacokinetic Implication | Clinical Implication | |---|---|---|---| | **GIT** | reduced and irregular peristalsis followed by slow gastric emptying <br> Neonates: increased gastric pH (>4) in relation to infants <br> Infants: increased motility of the lower gastrointestinal tract | Slower absorption of the drug (e.g., elevated Tmax) <br> Faster absorption of acid labile drugs e.g., penicillin G, erythromycin <br> Reduced absorption of weak-acid drugs e.g., phenobarbital, phenytoin | Possible sustained action after oral administration of the drug <br> The possibility of altered bioavailability <br> The possibility of reduced bioavailability after rectal administration of the drug | | **Skin** | Neonates and young infants: a thinner stratum corneum (neonates), increased skin perfusion, increased water content and higher body surface area-to-weight ration | Decreased rate and extent of suppositories and increased absorption of the drug through the skin during the 1st year of life | Increased bioavailability and potential toxic of drugs applied topically <br> By the end of the second month of life it is dangerous to apply the drug topically! | | **Muscle Tissue** | Neonates: reduction in muscle perfusion, decreased muscle contractility <br> Infants: higher density of capillaries in skeletal muscles | Neonates: poor perfusion limits the absorption, unpredictable pharmacokinetics <br> Infants: increased absorption | The need for a reduced amount of the drug applied to the skin <br> Neonates: avoid intramuscular administration of drugs <br> Infants: effectiveness of drugs applied IM is higher e.g. epinephrine | | **Spatial Compartment** | Neonates and Infants: lower proportion of adipose tissue (10%), decreased muscle mass, an Increased amount of water related to the body weigh: (80%), an Increased proportion of the extracellular fluid (45%) as compared to the intracellular fluid | Neonates: Increased volume of distribution for water-soluble drugs (eg., gentamicin), and a reduced volume of distribution af drugs which are bind to the muscles and adipose tissue (eg., vancomycin, diazepam) | It is necessary to adjust the loading/ maintenance dosing (mg/kg) to achieve therapeutic concentrations of drug in plasma | ### Pharmacokinetic Implication | System | Neonates: | Pharmacokinetic Implication | Clinical Implication | |---|---|---|---| | **Plasma Binding Protein** | reduced concentrations of albumin and a-i acid glycoprotein, with a decreased drug protein-binding affinity relative to children and adults | Increased plasma concentration of unbound drug, with increased volume of distribution and the possibility el occurrence of toxic effects | For drugs with high binding affinity lor proteins (eg->70%), it is necessary to adjust the dose to maintain the drug levels in the plasma close to the lower limit of the recommended therapeutic range | | **Drug Metabolism** | Neonates and young infants: immature isoform of cytochrame P450 and phase II enzymes with harsh developmental expression <br> Children aged 1-6 years: Increased activity of certain enzymes over the normal values for adults (aflometrics) | Neonates and young infants reduced hepatic drug metabolism, with increase in half-life <br> Children aged 1-6 years: enhanced drug clearance (e-En decrease in half-life) for the specific pharmacological substrates | Neonates and young infants: Increase dosage interval of drug and/or reduce maintenance dose <br> Children aged 1-6 years: far certain drugs is necessary 20 increase the dose and/or reduce the dosage interval compared to recommended adult dose | | **Renal Drug Excretion** | Neonates and young infants decreased level of glomerular filtration rate (fest 6 months) and active tubular secretion (first 12 months). Adult values are achieved by the 24th month of life | Neonates and young infants: the accumulation of drugs that are secreted via the kidneys and/or the active metabolite, with a decrease in plasma clearance end Increase in half-life (the greatest during the first three months of life) | Neonates and young infants: increase dosage interval drug and/or reduce maintenance dose during the first three months of life | *Source: Samardzic J, et al. Developmental pharmacology: A moving target. Int J Pharmaceuticals. 2015; 492 (1-2):3 35-7.* ## Geriatric Population Pharmacotherapy in older adults requires special attention due to several age-related physiological changes and the presence of chronic diseases. Adults over 65 years old are categorized into three subgroups: young-old (65-75 years), middle-old (75-85 years), and old-old (>85 years). The percentage of older adults in developed countries is steadily increasing, and it is expected that they will become the largest consumers of medications in the latter half of the 21st century. Pharmacokinetic parameters are altered in this population. Changes include increased gastric pH, decreased absorptive surface, reduced blood flow, decreased gastrointestinal motility, reduced body surface area, reduced blood flow to tissues and muscles, and peripheral vascular diseases affecting drug absorption. Drug distribution varies due to loss of muscle mass, increased body fat relative to muscle and body fluids, changes in plasma protein concentration, and decreased efficiency of the blood-brain barrier. Metabolism is also altered, with a decrease in the number of metabolically active hepatocytes, unstable blood flow through the liver due to irregular cardiac output, decreased hepatic clearance, and impaired renal function, which slows drug elimination. Declining organ function may impact pharmacodynamics (e.g., fewer beta-adrenergic receptors, leading to reduced response to beta-agonists, but increased sensitivity to beta-antagonists). As people age, the incidence of adverse drug reactions and drug interactions increases. Older adults tend to use more medications (polypharmacy), sometimes up to 10 different drugs daily, which raises the risk of drug interactions. Reduced drug elimination can lead to drug accumulation, and decreased attention along with complex dosing regimens may lead to accidental overdosing. Compliance is often inconsistent and incomplete, posing a significant challenge. ## Impaired Liver Function Liver diseases primarily affect drug metabolism, but they also impact absorption (due to portal hypertension and mucosal edema from hypoalbuminemia) and distribution (due to reduced plasma protein concentration). In the absence of precise tests, prescribing drugs to patients with liver diseases should be based on previous clinical experience. Each patient's risk-benefit ratio should be individually assessed, and drugs that are eliminated via the kidneys should be chosen. Effects and adverse reactions must be closely monitored. Hepatotoxic drugs, drugs that cause hypokalemia, drugs affecting hemostasis, as well as sedatives, analgesics, and MAO inhibitors should be avoided when possible. The most common method for assessing the liver's capacity for drug metabolism is by determining the Child-Pugh score (based on total bilirubin, albumin, prothrombin time, and the presence of ascites and encephalopathy). A score of 5 indicates normal liver function, and the maximum score is 15. If the score is 8-9, a 25% lower dose is recommended, and if the score is 10-15, a 50% lower dose should be administered. ## Impaired Renal Function The most common issues when prescribing drugs to patients with impaired renal function include inadequate drug elimination, increased sensitivity to adverse effects, and lack of therapeutic efficacy. Pharmacokinetic changes include increased gastric pH, which may impair absorption, changes in protein binding in patients with renal insufficiency, significant effects on drug distribution, altered distribution volume (e.g., in cases of edema or ascites), and changes in drug metabolism and excretion. Glomerular filtration rate (GFR) is the most sensitive and specific indicator of renal function. Normally, it is around 100 mL/min/1.73m². Based on the GFR, drug doses can be adjusted for medications that are predominantly eliminated by the kidneys. Nephrotoxic drugs should be avoided or used with caution. In conclusion, when there is a suspicion of renal or liver impairment, it is important to thoroughly assess the functional capacity of these organs with appropriate tests. If a deficit is confirmed, drugs that place the least burden on these organs should be used, while still being effective for treating the underlying condition. ## CLASSIFICATION OF DRUGS Drugs are categorized based on how they are prescribed into magistral, officinal, and ready-made drugs. According to the Law on Drugs and Medical Devices, a drug is defined as a product available in a specific strength, pharmaceutical form, and packaging that contains a substance or combination of substances proven to treat or prevent disease in humans or animals. This also includes substances used to restore, improve, or modify physiological functions through pharmacological, immunological, or metabolic effects, or to establish a medical diagnosis. A substance, according to this law, refers to any material of any origin, which can be: - Human origin (e.g., blood and blood products) - Animal origin (e.g., microorganisms, whole animals, organ parts, toxins, blood products) - Plant origin (e.g., microorganisms, whole plants, plant parts, extracts) - Chemical origin (e.g., substances, semi-synthetic and synthetic products, derivatives) ### Types of Drugs Defined by Law: 1. Biological drugs 2. Immunological drugs (e.g., vaccines, toxins, sera, allergens) 3. Advanced therapy drugs (e.g., gene therapy, tissue-engineered drugs) 4. Drugs derived from blood and plasma 5. Radiopharmaceuticals 6. Herbal drugs 7. Traditional drugs 8. Homeopathic drugs 9. Veterinary drugs 10. Magistral and galenic drugs (compounded medications made by pharmacists). ### Drug Classification Based on Usage: - For external use: Applied to the skin or visible mucous membranes, for localized effects - For internal use: Administered orally, parenterally (e.g., intravenous, intramuscular), or via inhalation In pharmacology, the term drugs refers to dried or raw parts of plants, animal tissues, or minerals, which are used to prepare medications. Pharmacognosy is the branch of pharmacology that studies drugs derived from natural sources. ### Anatomical Therapeutic Chemical (ATC) Classification According to the World Health Organization (WHO), drugs are classified based on the Anatomical Therapeutic Chemical (ATC) system. This system divides drugs into different levels: **Example:** Metoprolol (ATC Code: C07AB02) - C: Cardiovascular system (1st level, anatomical group) - C07: Beta-adrenergic receptor blockers (2nd level, therapeutic group) - C07A: Beta-blockers (3rd level, pharmacotherapeutic subgroup) - C07AB: Selective beta-adrenergic blockers (4th level, pharmacological-chemical subgroup) - C07AB02: Metoprolol (5th level, individual drug) ### Drug Lists by the Republic Health Insurance Fund (RFZO) in Serbia - List A: Drugs prescribed and dispensed based on a doctor's prescription - List A1: Drugs that have a therapeutic alternative to those in List A, and patients contribute 5-75% of the cost - List B: Drugs dispensed on special request - List C: Drugs with a special dispensing regime - List D: Drugs not approved for marketing in the Republic of Serbia but are necessary for diagnosis and therapy, despite not being registered ## DRUGS FOR EXTERNAL USE ### Ointments Ointments are semi-solid medicinal preparations for external application, primarily intended for local action, though they can sometimes exert systemic effects. They contain medicinal substances that are dissolved or suspended in the base, such as: - Yellow wax (cera flava) – from beeswax - White wax (cera alba) – bleached yellow wax - Lanolin (cera lanae) wax from sheep wool - Liquid paraffin (paraffinum liquidum) a mixture of hydrocarbons obtained from petroleum distillation - Yellow petrolatum (vaselinum flavum) a petroleum derivative - White petrolatum (vaselinum album) – bleached yellow petrolatum - Polyethylene glycols Ointments are classified as hydrophobic, emulsifying, or hydrophilic depending on their water affinity. They are prescribed in total quantity as a single preparation and are dispensed in plastic containers or tubes. In prescriptions, the term “for external use” should always be included. Nowadays, ointments are rarely compounded (prepared in pharmacies) and are primarily dispensed as ready-made medications. Examples include Synoderm N and Acyclovir ointment. **Eye ointments (oculenta)** are a special type of medicinal ointment. They melt at body temperature, spread easily, and are sterile preparations for application in the conjunctival sac or along the eyelid margins. They remain longer at the site of application compared to eye drops, with therapy often starting with drops and followed by ointments. ### Creams (Cremor) Medicinal creams are multi-phase preparations for external use containing an active substance and a suitable fatty base emulsified with water. Due to the hydrating nature of the base, creams are more suitable for application on the face and on moist skin lesions. They have a softer consistency than ointments and can be easily removed from the skin with lukewarm water. Creams are produced only industrially and are prescribed as ready-made medications. Dermatosteroids, antifungals, psoriasis treatments, and local anti-rheumatic medications are often prepared in this form. Example: Canesten cream. ### Gels A gel is a preparation for local use that contains the active substance uniformly distributed in a base, most commonly composed of water, gelatin, or glycerol. Depending on the water affinity, gels can be hydrophobic or hydrophilic. They are used for medications that act locally on the skin and mucous membranes, such as local anesthetics, anti-inflammatory drugs, and antimicrobial agents. Gels are packaged in tubes of 5-30 grams and are prescribed as ready-made medications. ### Lotions Lotions are liquid or semi-liquid medicinal preparations containing active ingredients in an emulsion base. They are solely for local treatment, applied without rubbing, on uninjured skin, especially on the scalp and other hairy areas. They are primarily manufactured as treatments for scabies and lice and some dermatosteroids, and they are prescribed as ready-made medications. ### Pastes (Pastae) Pastes are semi-solid preparations for local use, containing finely powdered, inert substances suspended uniformly in a suitable fatty base. Pastes are considered obsolete, as other dosage forms have largely replaced them. For example, zinc paste was previously used for herpetic lesions, which is now replaced by Acyclovir ointment. ### Transdermal Patches (Emplastra transcutanea) Transdermal patches are pharmaceutical preparations of various sizes containing one or more active substances. They are applied to unbroken skin to release the active substance, which is then absorbed through the skin into the circulation for systemic effects. They are prescribed as ready-made medications. Benefits include ease of use, reduced dosing frequency, avoidance of first-pass liver metabolism, and higher bioavailability. ## Suppositories (Suppositoria) Suppositories are solid medicinal preparations, either conical, egg-shaped, or cylindrical, designed for insertion into body cavities. They are solid at room temperature and melt at body temperature. ### Types Include: - **Rectal suppositories for rectal use** - The base should not irritate the intestinal mucosa and is used when local action is desired, when the patient cannot take the medication orally, or when first-pass liver metabolism needs to be avoided - They are commonly used in paediatric patients - **Vaginal suppositories for local treatment of infections** - These include broad-spectrum antimicrobials (e.g., povidone-iodine), antifungals, trichomoniasis treatments, and local contraceptives ### Enemas (Clysmata) Enemas are liquid preparations for rectal administration. They are introduced deep into the large intestine using an enema bag/syringe or into the rectum with a special applicator. - **Cleansing enemas (Clysmata evacuantia)** – used to empty the bowels before diagnostic or therapeutic procedures, often with 250-500 mL of lukewarm water or chamomile tea to stimulate peristalsis - **Microenemas containing laxatives in a small volume (5-20 mL) in a suitable vehicle** - **Nutritional enemas (Clysmata nutritientia)** contain absorbable substances such as NaCl, glucose, and amino acids, with a volume of 100-200 mL - They have largely been replaced by parenteral nutrition in modern medicine - **Medicinal enemas (Clysmata medicata)** contain drugs that act locally on the colon or rectum (e.g., prednisolone and sulfasalazine for ulcerative colitis) or that can be absorbed for systemic effects, with a volume usually between 50-100 mL - Before use, enemas should be warmed to body temperature, and the bowel should be emptied before administering medicinal enemas ## Medicinal Soaps and Shampoos (Sapones medicinales) Soaps are alkaline salts of higher fatty acids, typically of sodium and potassium, used to remove impurities, desquamated epithelium, and bacteria from the skin. **Medicinal soaps** contain therapeutic and auxiliary agents, such as dermatological antiseptic soaps for treating skin conditions. **Medicinal shampoos** are solutions primarily used in the treatment of scalp diseases. ## Bandaging Materials (Telamenta) This category includes cotton wool (Lana), gauze (tela), bandages (fasciae), fabric (linteum), and adhesive tape (collemplastrum). These materials may be made of cellulose, cotton, or mixed fibres. They are manufactured in various sizes and shapes, and prescriptions must specify width, length, and quantity. ## DRUGS FOR ORAL USE ### Powders (Pulveres) Powders are solid drug forms created by grinding and milling drugs and chemicals, then sieving them through pharmacopoeia-specified screens. They can be prepared with or without the addition of excipients. Based on composition, powders can be simple or compound. According to their application, they are divided into two categories: powders for internal (oral) and external (topical) use. Oral powders are primary forms from which other more user-friendly forms are made. Since the advent of tablets, few drugs are still available as powders. Non-divided powders are prescribed in pharmacies, primarily for antacids (e.g., sodium bicarbonate), laxatives (e.g., magnesium sulfate), and adsorbents (e.g., activated charcoal). Compound powders may also be prescribed, such as analgesic-antipyretic combinations (e.g., paracetamol 400 mg + caffeine 50 mg). ### Tablets (Tablettae) Tablets are one of the most commonly prescribed dosage forms in primary healthcare. These are dosed, solid drug forms in round or oval shapes, prepared by compressing powdered, crystalline, or granulated active ingredients, often mixed with excipients. Tablets are primarily used orally and allow for precise dosing, have a long shelf life, and are convenient to use. However, tablets are unsuitable for children, unconscious patients, or people with dementia. Official tablets are manufactured in compliance with pharmacopoeia regulations but are not initially individually packaged. In pharmacies, they are counted out of large packs (over 1000 tablets) into smaller containers. The prescription specifies the number of tablets to be dispensed. Finished tablets are prescribed by brand name, indicating the form and dosage of the active ingredient. If the tablet contains multiple ingredients, generic names and quantities are not listed. Tablets are usually packaged in bottles or boxes, with blister packs being the most practical in modern pharmacy. - **Chewable tablets** are single-layer tablets that are chewed before swallowing to accelerate their effect or reduce gastric irritation, often containing flavouring agents - **Extended-release tablets (retard, durules)** contain alternating layers of active and inert substances that dissolve slowly, allowing prolonged drug action and extended dosing intervals, which improves compliance - **Coated Tablets (Dragees)** Dragees are disk-shaped oral tablets coated with sugar or another protective layer. Coating masks any unpleasant taste or odour of the active ingredient. These are prepared as finished drugs. - **Buffered Tablets** Buffered tablets consist of an active ingredient combined with a buffering agent. Buffers enhance tolerance, particularly for drugs intended for long-term, daily use or in larger doses. - **Buccal Tablets** Buccal tablets are designed for drug absorption from the oral cavity. They are placed between the gums and cheek mucosa and held in the mouth until they dissolve, bypassing gastrointestinal degradation and hepatic first-pass metabolism. - **Orodispersible Tablets (Oriblettes)** These tablets dissolve in the oral cavity and have a local effect. They are not swallowed or chewed but dissolve slowly in the mouth. They are typically used to treat oral cavity conditions. - **Sublingual Tablets (Lingualettes)** These are small, round or flat tablets placed under the tongue for rapid absorption and effect due to the rich vascularization under the tongue. Sublingual veins bypass hepatic first-pass metabolism, providing a systemic effect. Nitrates, adrenal cortex hormones, sex hormones, and adrenaline derivatives are commonly administered in this form for treating bronchial asthma. - **Effervescent Tablets** Effervescent tablets dissolve in water before ingestion, creating a beverage. Carbon dioxide is released by the reaction of sodium bicarbonate and citric acid in water. They are significantly larger than regular tablets. - **Medicinal Capsules (Capsulae medicinales)** Capsules are solid dosage forms of cylindrical shape, intended for oral use, containing accurately dosed active ingredients such as powders, oils, or solutions. Capsules are prepared to improve patient compliance (e.g., masking taste, smell, or color), avoid harmful effects on teeth, mouth, and stomach, or allow the drug to reach specific parts of the gastrointestinal tract unaltered. - **Soft capsules (Capsulae gelatinosae)** are round or oval, with varying sizes and firmness. They are usually filled with liquid drugs and less commonly with solid substances or pastes in quantities from 0.5-1g - Made of gelatin, these capsules dissolve in the stomach and completely in the small intestine - **Hard capsules with caps (Capsulae gelatinosae operculatae)** are cylindrical and firm, consisting of a body and cap that fit over each other - They are typically filled with powdered drugs, less commonly with dense liquids, and disintegrate entirely in the small intestine - **Gelatinized hard capsules (Capsulae geloduratae)** are made from gelatin treated with formaldehyde - These capsules are resistant to gastric acid and only disintegrate under the action of intestinal and pancreatic enzymes, containing substances intended to act in the alkaline environment of the intestine Capsules are usually prescribed as finished products in blister packs. Extended-release forms are rare, giving tablets an advantage for prolonged action. ### Medicinal Solutions (Solutiones medicinales) Medicinal solutions are clear liquid preparations containing one or more dissolved active substances in a suitable solvent. Solvents may include water, ethanol, glycerol, and oils. Purified water (aqua purificata) or injection-grade water (aqua pro injectione) is used for aqueous solutions. Olive oil is the most common oil solvent. Purified water is obtained by distilling or demineralizing drinking water, used for external solutions (except for eye drops) and oral solutions. Injection water is obtained by redistillation and sterilization and used for injections and eye drops. Solutions are dispensed in glass or plastic bottles and used externally or internally. Solutions for internal (oral) use are prescribed when tablet or capsule administration is impractical. Children commonly receive oral solutions as they are easier to swallow, with a lower aspiration risk than capsules or tablets. This form acts faster due to quicker absorption. Only soluble and stable substances can be formulated as solutions, and they must be freshly prepared as they spoil quickly. Dosing with spoons is imprecise, so only mild drugs are typically prescribed this way. Solutions of drugs for external use are intended for application on the skin and visible mucous membranes (such as for rinsing the mouth, eyes, bladder, and vagina), for the local treatment of wounds, for topical application, massage, and for preparing compresses. They are prescribed in amounts ranging from 50 to 300g, although sometimes more may be prescribed. The most common solvent used is purified water. In this form, antiseptics, protective agents, and similar substances are most commonly used. These solutions are dispensed in glass bottles, usually at a higher concentration than that needed for application. In the prescription signature for solutions intended for external use, the word "external" should always be included, followed by instructions for dilution. This method of dosing is not precise but is permitted since it involves medications intended for external use. ### Syrups Syrups are liquid preparations for internal use, with a sweet taste and thick consistency due to high sugar concentrations. Syrups are formulated for children and adults with drugs that have an unpleasant taste or odour. Produced in volumes of 50 to 200 mL, syrups should be used quickly, usually within seven days. Each dose should be about 5 mL. Antibiotics, antipyretics, antitussives, expectorants, vitamins, and other drugs are commonly used in syrup form. ### Drops Drops are solutions of drugs prescribed in small quantities and dosed by drops. They are made by dissolving active substances in a suitable solvent (water, ethanol, oil) or by mixing active substances with a liquid. Drops are dispensed in bottles with droppers or pipettes. They can be used both externally and internally. For oral use, drops are often diluted in fruit juice or water before ingestion. For external use, drops can be formulated as eye, nasal, or ear drops. Eye drops are sterile, isotonic with tears, and instilled into the eye. ## PARENTERAL PREPARATIONS Parenteral preparations are sterile formulations administered via injection, infusion, or implantation. Alongside the primary drug, these preparations include excipients to achieve isotonicity, adjust pH, enhance solubility, increase the stability of the active substance, and preserve the formulation. ### Types of parenteral preparations: - Injections - Intravenous infusions - Concentrated solutions for injection and intravenous infusion preparation - Powders for injection and intravenous infusion preparation - Implants In a broader sense, parenteral drug administration includes any method that bypasses the digestive tract, such as inhalational administration. ### Injections (Injectiones) Injections are sterile solutions, emulsions, or suspensions with a maximum volume of 100 mL. Injectable solutions must be clear and free of particles. Injectable emulsions should not separate into phases, while injectable suspensions may form a sediment that can be easily resuspended by shaking. Injections can be packaged as single-dose or multi-dose preparations. Injections must be sterile, apyrogenic, free from hypotensive substances, and have a pH of 5-8. The volume of drug injected is usually up to 2 mL, rarely up to 10 mL. Injections are commonly prescribed as ready-to-use medications. The amount of active substance in each ampoule or vial is expressed in grams, international units, or percentages. Since injections are administered by healthcare professionals, the prescription signature often includes “Ad manum medici" (for the physician's hand). Drugs that are unstable in solution are stored as sterile powder in ampoules or vials (lyo-ampoules or lyo-vials). The unstable substance undergoes lyophilization by first freezing and then removing water under vacuum, resulting in a powder packed in hermetically sealed ampoules. This powder is dissolved just before use, typically in water for injection, although neutral olive oil may also be used. Injections are factory-produced and packaged in ampoules, vials, syringes, and cartridges. ### Types of Injection Packaging: - **Ampoules:** Hermetically sealed glass containers containing a single dose - The neck is cut with a saw before use, and the content is drawn into a syringe - Ampoules may contain powder medications - **Vials:** Containers sealed with a rubber stopper and an aluminum cap - They contain injectable solutions for single or multiple uses or powdered medications to be reconstituted in the vial before use - **Syringes:** Plastic bottles with an injection needle at one end, allowing patients to self-administer the drug into tissue - Often found in first-aid kits and used to package various antidotes - **Cartridges:** Cylindrical ampoules for multiple uses, containing injectable solutions (2-3 mL) - They have a plunger at one end and a rubber cap at the other, through which the injection needle is introduced - The cartridge is placed in an injector that depresses the plunger, allowing easy administration of multiple doses at home ### Injection Routes Injections can be administered in various ways: subcutaneously, intradermally, intramuscularly, intravenously, intra-articularly, intrathecally, intraperitoneally, intrapericardially, intracardially, intrapleurally, etc. ### Intramuscular Injections: These are sterile aqueous or oil-based solutions that must be isotonic, apyrogenic, and have a neutral pH. The drug is injected into the gluteus maximus, deltoid, or, rarely, the quadriceps muscle. Aspiration is necessary to ensure that a vein has not been punctured. Absorption is rapid and complete due to good vascularization, with effects occurring within 15-20 minutes. Depot preparations are used if delayed absorption and a prolonged release of the drug are desired. ### Subcutaneous Injections: Injected into loose connective tissue, commonly in the forearm, thigh, abdomen, upper arm, or gluteal region. These are sterile,