Study of Orthopedic Drugs

Study of Orthopedic Drugs

Orthopedic Drugs are that used for the treatment in Orthopedic Diseases. The field uses a wide variety of medications for various conditions, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), muscle relaxants, and more. The specific drugs used depend on the patient’s condition, the severity of their pain, and other factors. 

Orthopedic Drugs for Pain Management

Orthopedic Pain Killer Drugs are NSAIDs, Acetaminophen, Opioids, and Corticosteroids:

• NSAIDs: These drugs help reduce pain and inflammation, including ibuprofen, naproxen, and celecoxib. 
• Acetaminophen: Often used in combination with NSAIDs for pain relief. 
• Opioids: May be used for severe pain, but with caution due to the risk of addiction. 
• Corticosteroids: Injected or taken orally to reduce swelling and pain. 

Other Common Orthopedic Drugs:

• Bisphosphonates: Used to treat osteoporosis and other bone diseases. 
• Hyaluronic Acid Injections: Used to treat osteoarthritis of the knee. 
• Muscle Relaxants: Used to relieve muscle spasms. 
• Disease-Modifying Antirheumatic Drugs (DMARDs): Used to treat rheumatoid arthritis and other autoimmune conditions. 
• Antibiotics: Used to prevent or treat infections, especially after surgery. 

NSAIDs are widely used Orthopedic Pain Killer Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed by orthopedic surgeons. They prescribe these drugs to manage orthopedic pain and inflammation like Osteoarthritis, rheumatoid arthritis, and post surgical pain. They work by inhibiting the cyclooxygenase (COX) enzyme, which reduces prostaglandin production, a key mediator of pain and inflammation. 

Mode of Action of NSAID Drugs (How NSAIDs work)

• Inhibition of COX:NSAIDs, like ibuprofen and naproxen, block the COX enzyme, which is involved in producing prostaglandins, substances that contribute to pain, inflammation, and fever.
• Peripheral and Central Effects:NSAIDs work at the site of pain (peripheral nociceptors) and also influence pain signals in the central nervous system.
• Pain and Inflammation Relief:By reducing prostaglandin production, NSAIDs help to alleviate pain and inflammation associated with various orthopedic conditions. 

Common uses of NSAIDs in Orthopedics

• Chronic Pain Management:NSAIDs are frequently used to manage pain and inflammation in chronic conditions like osteoarthritis and rheumatoid arthritis. 
• Post-Surgical Pain Relief:They are used to control pain and inflammation after orthopedic surgeries, often in combination with other pain management strategies. 
• Acute Injuries:NSAIDs can be effective in managing pain and inflammation following acute injuries like fractures, sprains, and strains. 
• Other Conditions:They are also used for conditions like bursitis, tendonitis, and gout. 

Examples of NSAIDs

• Ibuprofen (Advil, Motrin): A common over-the-counter NSAID used for pain relief and inflammation. 
• Naproxen (Aleve): Another widely used over-the-counter NSAID for pain and inflammation. 
• Celecoxib (Celebrex): A selective COX-2 inhibitor that is often used for osteoarthritis and rheumatoid arthritis. 
• Ketorolac: A potent NSAID used for post-surgical pain management. 
• Flurbiprofen: A commonly used NSAID in orthopedics, especially in major surgery. 

Important Considerations

• Side Effects:NSAIDs can have side effects, including gastrointestinal problems, cardiovascular issues, and kidney problems.
• Individual Variation:The response to NSAIDs can vary among individuals, and some people may be more susceptible to side effects.
• Prescription vs. Over-the-Counter:Some NSAIDs are available over-the-counter, while others require a prescription.
• Drug Interactions:NSAIDs can interact with other medications, so it’s important to inform your doctor about all medications you are taking. 

In conclusion, NSAIDs are valuable tools in orthopedic pain management, but their use should be carefully considered, taking into account potential side effects, individual variations, and drug interactions. 

Acetaminophene

Acetaminophen, also known as N-acetyl-para-aminophenol (APAP) or paracetamol in many countries, is a non-opioid analgesic and antipyretic agent utilized for treating pain and fever. Numerous diseases and conditions include pain as a significant component of their presentation.

Indication of Acetaminophene

Acetaminophen, also known as N-acetyl-para-aminophenol (APAP) or paracetamol in many countries, is a non-opioid analgesic and antipyretic agent utilized for treating pain and fever. Numerous diseases and conditions include pain as a significant component of their presentation.

Mode of Action of Acetaminophene (Paracetamol)

Acetaminophen is one of the most widely used over-the-counter analgesic and antipyretic medications. Although the exact mechanism of action of the drug remains unclear, it is historically categorized along with nonsteroidal anti-inflammatory drugs (NSAIDs) due to its inhibition of the cyclooxygenase (COX) pathways. Acetaminophen possesses analgesic and antipyretic properties similar to NSAIDs but lacks peripheral anti-inflammatory effects.

Acetaminophen may inhibit the COX pathway in the central nervous system (CNS) but not in peripheral tissues. In addition, acetaminophen does not appear to bind to the active site of either the COX-1 or COX-2 enzyme. Instead, it reduces the activity of COX through an alternative mechanism.

Regardless, the reduction of the COX pathway activity by acetaminophen is thought to inhibit the synthesis of prostaglandins in the CNS, leading to its analgesic and antipyretic effects. The analgesic properties may be due to a stimulating effect on the descending serotonergic pathways in the CNS.

Pharmacokinetics of Paracetamol

Absorption: Oral acetaminophen is rapidly and efficiently absorbed from the gastrointestinal tract, achieving peak plasma concentrations within 30 to 60 minutes. Intravenous (IV) administration of acetaminophen resulted in immediate and higher peak plasma concentrations. The rectal route is preferred for administration to bypass first-pass metabolism, especially in unconscious patients and children. This approach offers an alternative to parenteral administration, thereby mitigating gastric irritation and enabling efficient absorption due to the rich vascular supply in the rectum. Absorption in the upper rectum guides medications into the portal circulation through the superior hemorrhoidal vein, whereas lower rectal absorption results in direct entry into the systemic circulation.

Distribution: Acetaminophen exhibits low plasma protein binding of 10% to 25% and shows extensive distribution throughout the body, excluding fat tissue.

Metabolism: Acetaminophen undergoes primarily hepatic metabolism via first-order kinetics, utilizing 3 distinct pathways—conjugation with glucuronide, conjugation with sulfate, and oxidation facilitated by the cytochrome P450 enzyme system, predominantly CYP2E1. CYP3A4 plays a limited role in acetaminophen metabolism. This process forms a reactive intermediate metabolite known as N-acetyl-p-benzoquinone imine (NAPQI). At therapeutic doses, NAPQI swiftly combines with glutathione, subsequently undergoing further metabolism to generate cysteine and mercapturic acid conjugates.

Elimination: Most acetaminophen metabolites are excreted in the urine, with less than 5% appearing as unconjugated or free acetaminophen. Over 90% of the administered dose is eliminated within 24 hours.

Available Dosage Forms of Paracetamol

Acetaminophen can be administered through oral, rectal, or IV routes.[10]

• Oral: Acetaminophen is available in various formulations, including tablets, capsules, syrup, oral solution, or suspension. 
• Rectal: Acetaminophen is available as a rectal suppository for adult and pediatric patients.
• IV: Acetaminophen is also available as an IV infusion for administration.

Dosages of Paracetamol for Adults and Adolescents

Adults and adolescents (13 or older) with a body weight of ≥50 kg: The recommended dosage of acetaminophen is 1000 mg every 6 hours or 650 mg every 4 hours. The maximum single dose should not exceed 1000 mg, and the minimum dosing interval is 4 hours. Notably, the maximum daily dosage of acetaminophen should not exceed 4000 mg.

Adults and adolescents (13 or older) with a body weight <50 kg: The recommended dosage of acetaminophen is 12.5 mg/kg every 4 hours or 15 mg/kg every 6 hours. The maximum single dose should not exceed 15 mg/kg, and the minimum dosing interval is 4 hours. In addition, it is essential to adhere to a maximum daily dosage of acetaminophen not exceeding 75 mg/kg, up to a maximum of 3750 mg.

Contraindication and Considarations

Hepatic impairment: Acetaminophen is contraindicated in cases of active liver disease or severe hepatic impairment. Caution is advised for patients with mild hepatic impairment, necessitating a reduced total daily dosage of acetaminophen and regular monitoring of liver function.

Renal impairment: In severe renal impairment (creatinine clearance ≤30 mL/min), extending dosing intervals and reducing the total daily dosage of acetaminophen may be advisable.

Pregnancy considerations: Observational studies have associated prenatal acetaminophen exposure with potential reproductive and neurobehavioral effects, including the risks of cryptorchidism, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder with prenatal APAP exposure. However, The American College of Obstetricians and Gynecologists (ACOG) considers acetaminophen safe for pregnant individuals. ACOG emphasizes that current evidence does not conclusively link acetaminophen use to fetal developmental issues. As neurodevelopmental disorders have multifactorial origins and brain development extends beyond birth, allowing for various potential influences, obstetricians must maintain current practices until further research provides more clarity.

Breastfeeding considerations: Acetaminophen is suitable for pain relief and fever reduction in breastfeeding mothers. The levels detected in breast milk are significantly lower than typical infant doses, and there are infrequent reports of adverse effects in breastfed infants

Pediatric Dosage of Acetaminophen/ Paracetamol 

The recommended dosage for children aged 2 to 12 is 12.5 mg/kg every 4 hours or 15 mg/kg every 6 hours. The maximum single dose should not exceed 15 mg/kg, and the maximum daily dosage of acetaminophen is 75 mg/kg.

• Neonates: The recommended dosage for premature children born at ≥32 weeks gestational age or less than 28 days old is 12.5 mg/kg every 6 hours, with a maximum recommended daily dosage of acetaminophen set at 50 mg/kg.
• Infants: Infants aged 29 days to 2 years are typically administered a dosage of 15 mg/kg every 6 hours, with a maximum daily dosage of acetaminophen not exceeding 60 mg/kg.

Older patients: As per the American Geriatric Society, the recommended acetaminophen dosage is 325 to 500 mg every 4 hours or 500 to 1000 mg every 6 hours, with a typical maximum daily dosage of 4 g. In individuals with hepatic impairment or a history of alcohol misuse, it is advisable to reduce the maximum dose by 50% to 75%

Drug-Drug Interactions of Acetaminophen/Paracetamol

Warfarin: Prolonged oral administration of acetaminophen at 4000 mg/d has been associated with an elevated international normalized ratio (INR) in patients receiving warfarin. Due to the lack of studies evaluating short-term acetaminophen use with oral anticoagulants, increased frequency of INR monitoring may be advisable in these situations.

Alcohol: Chronic alcohol misuse increases the risk of acetaminophen toxicity by inducing CYP2E1, reducing hepatic glutathione (GSH) levels, and impairing NAPQI detoxification. Moreover, it may decrease glucuronidation, enhance oxidation, cause hepatocyte membrane disruptions, and reduce biliary excretion.

Define Opioid Drug

Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work in the brain to produce a variety of effects, including pain relief.

Opioid drugs include prescription pain medicine and illegal drugs. Some people use opioids because of the euphoria (“high”) they can produce. Opioid drugs can cause addiction and that is why these drugs are called Narcotic Drugs.

Common Opioid Drugs

• Oxycodone
• Oxymorphone
• Hydrocodone
• Hydromorphone
• Fentanyl
• Morphine
• Codeine
• Methadone
• Tramadol
• Buprenorphine
• Pathedine

Heroin, an illegal street drug, is also an opioid.

Common Opioid Effects

What happens when a person takes opioids? Some of the effects can include:

• Sleepiness
• Relaxation
• Euphoria
• Nausea
• Vomiting
• Constipation
• Slowed breathing, which can result in hypoxia: a potentially dangerous reduction of oxygen circulating in the body.

Medical Uses of Opioids

Prescription opioids, when legally prescribed by a doctor and used as directed, can relax the body and relieve symptoms of an illness, an injury or a surgical procedure, such as:

• Post-surgical pain
• Severe pain due to trauma or disease
• Coughing
• Diarrhea

Opioids may be given orally, via a skin patch, under the tongue or by injection.

Dosage forms of Opioid Drugs

Oral Dosage Forms: Tablet, Capsule, Oral Sulution

Parenteral Dosage: IM Injection, IV Injection, SC Injection,

Rectal Dosage Form: Suppository

Sub Lingual Dosage Form: Tablet and Sprey

Nasal Dosage Form: Nasal Drop and Nasal Sprey

Study of Pathedine

Pethidine is an opioid pain-relief medicine that was once widely used for pain caused by a range of different conditions. Pethidine is now less often used because newer, safer opioids are available. Pethidine is sometimes used to reduce labour pain in childbirth.

Dosage Form of Morphine

Morphine comes in different dosages, and different forms including:

• tablets
• capsules
• oral liquid
• injection

Some formulations work immediately, while others work more slowly. All formulations of morphine are only available on prescription from doctor.

Indication of Morphine

Morphine is used to relieve severe pain, such as pain caused by:

• a major trauma (for example, an accident)
• surgery
• labour pain in childbirth
• cancer pain

Morphine should only be used when other forms of pain relief have not been successful in managing pain or if you are not able to take them (for example, because of side effects or because your doctor says you cannot take it together with another medicine that you are taking).

Uses of Bisphosphonates

• Osteoporosis: Bisphosphonates are widely used in osteoporosis treatment and prevention
• Paget’s Disease of Bone:Bisphosphonates are also used to treat this condition, which causes abnormal bone remodeling. 
• Hypercalcemia of Malignancy:They can help lower calcium levels in the blood for individuals with certain types of cancer. 
• Bone Metastases:Bisphosphonates can help manage bone pain and reduce the risk of fractures in individuals with cancer that has spread to the bone. 

Use of Bisphosphonates in Osteoporosis

Bisphosphonates are a class of drugs widely used in osteoporosis treatment and prevention because they inhibit bone resorption, slowing down bone breakdown and reducing the risk of fractures. They are effective in increasing bone density and are available in oral and intravenous forms. Bisphosphonates work by binding to bone surfaces and reducing the activity of osteoclasts, the cells responsible for bone breakdown, allowing osteoblasts to work more effectively. 

How Bisphosphonates Work?

• Inhibit Bone Resorption:Bisphosphonates reduce the activity of osteoclasts, the cells that break down bone, slowing down the natural bone resorption process. 
• Increase Bone Density:By slowing bone breakdown, bisphosphonates help maintain or increase bone mineral density, making bones stronger and less likely to fracture. 
• Reduce Fracture Risk:Studies have shown that bisphosphonates can significantly reduce the risk of hip, spine, and other fractures in individuals with osteoporosis. 

Commonly Used Bisphosphonates

• Alendronate (Fosamax): Often the first-line treatment, available as a weekly tablet. 
• Risedronate (Actonel, Atelvia): Another commonly prescribed bisphosphonate, available as weekly or monthly tablets. 
• Ibandronate (Boniva): Available as a monthly tablet or a quarterly injection. 
• Zoledronic Acid (Reclast): Given intravenously once per year. 

Long-term Use and Side Effects of Bisphosphonates

• Long-term Use:Bisphosphonates are often taken for several years to maintain their benefits. 
• Side Effects:While generally well-tolerated, bisphosphonates can cause side effects like gastrointestinal issues, bone pain, or rare but serious complications.