Pain Management: NSAIDs and Acetaminophen

Pain Management

• First-line medications for acute pain are NSAIDs or Tylenol
• Prescribe according to guidelines and Shadow Health assignment for mild musculoskeletal pain

NSAIDs

• Indications: analgesic, antipyretic, and anti-inflammatory effects
• Examples: ibuprofen, naproxen, aspirin, toradol, mobic
• Adverse effects include GI upset, heartburn, mild headache, and dizziness
• Contraindications include a history of ulcers, Crohn's disease, GI bleeding, liver or kidney disease, heart disease, bleeding or platelet disorders, unmanaged hypertension, and pregnancy
• Drug interactions: Antihypertensives, warfarin, and digoxin require monitoring
• Salicylate toxicity: hyperventilation occurs before nausea/vomiting, diaphoresis, tinnitus
• All non-aspirin NSAIDs: these can increase the risk of heart attack and stroke.

Acetaminophen

• Non-opioid, non-NSAID analgesic: used to treat mild pain and fever
• Lacks anti-inflammatory properties
• Contraindications include alcohol abuse, liver or kidney disease, and malnutrition
• Acetaminophen toxicity: liver damage or failure
• Liver damage/failure symptoms: abdominal pain, nausea/vomiting, dark urine, and jaundice

Opioids

• Provide analgesia (absence of pain) without loss of consciousness/sleep
• Reserved for serious significant pain, acute injury, or post-surgery

Agonists vs Partial Agonists and Antagonists

• Agonists: interact with a receptor to achieve a response. Full agonists include morphine, codeine, and methadone with affinity plus efficacy
• Partial agonists: activate opioid receptor to a lesser degree, such as buprenorphine and tramadol with affinity but low efficacy
• Antagonists: bind to opioid receptors without activating them, such as naloxone (Narcan) with affinity but no efficacy
• Morphine: This is the prototypical opioid agonist

Gout

• Goals of therapy: reduce pain and acute attacks, lower uric acid levels, and manage lifestyle
• Allopurinol: First-line agent for lowering urate levels. Xanthine oxidase inhibitor

Allopurinol Adverse Effects

• Hepatotoxicity
• Gout flare at initiation of therapy needs proactive treatment
• Other Effects: Skin rash and multiple drug interactions
• Monitor LFT, BUN, creatinine, uric acid level and CBC periodically when drug is initiated

Gout Flare Medications

• Reduce pain and severity, examples: Colchicine, NSAIDs, and glucocorticoids
• Colchicine side effects: GI, but low doses have milder effects
• Low-dose colchicine is preferred to high-dose in treating acute gout flares

Corticosteroids

• Hormones produced: They affect almost all body organs and maintain homeostasis
• Disease results: Disease results from inadequate or excess secretion
• Actions and Effects:
  • Chapter 26 Figure 26-1 in the textbook
  • Decreased peripheral uptake of glucose and glycogenesis in the liver
  • Decreased protein synthesis (muscle, lymphoid tissue, skin, and bone)
  • Lipolysis in adipose extremities and lipogenesis in the face and trunk
  • Lowered circulating eosinophils, lymphocytes, monocytes, and increased PMN
  • Lowered leukocytes at inflammation sites
  • Inhibits production of IL-1 and IL-2
  • Blocks generation of fever and promotes gastric acid secretion and enhances urinary excretion
  • Decreased proliferation of fibroblasts in connective tissue; delayed healing
  • Maintains normal contractility of skeletal and cardiac muscle
  • Increased osteoclastic activity, decreases osteoblastic activity
  • Essential for normal arousal and modulates emotional and perceptual function
  • Maintains normal blood pressure and increases response of arterioles to NE
• Principles of Therapy: Risk to benefit should always be considered
  • Use local over systemic steroid therapy when possible
  • Risk to benefit should always be considered
  • Short term use for self-limiting acute conditions
  • Long term use reserved for life threatening conditions or severe disabling symptoms
  • Do not abruptly withdraw corticosteroids. HPA axis suppression
• Know why taper dose: HPA axis suppression if abruptly stopped, which can be life-threatening
• Adverse effects: osteoporosis, poor wound healing, peptic ulcers/GI upset, hyperglycemia, increased risk of infection, cataracts, mood changes/depression, insomnia, and thinning of the skin

Diabetes Medications

• Only focus on categories discussed individually below
• Note: this excludes most drug class names from this list

Biguanides - Metformin (Glucophage)

• First line medication in the treatment of Type 2 DM
• Improves: improves insulin sensitivity and physiological factors related to metabolic syndrome like PCOS. Given orally, alone or with other anti-diabetic drugs Adverse effects: Mainly GI, give with food to decrease side effects. Start low and go slow
• Actions: Know all of Metformin's actions that are listed on the slide in the lecture (Canvas)
• Black Box Warning: lactic acidosis, rare but more likely in the setting of renal impairment, dehydration, and elderly

Thiazolidinediones

• Treats type 2 DM used alone or in conjunction with other drugs given orally
• Actions: decrease insulin resistance via activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma)
• Adverse effects: Weight gain and edema due to fluid retention and plasma volume expansion
• Precautions: May cause ovulation to occur in anovulatory in women of reproductive age, avoid use in pregnancy unless benefit outweighs risk and avoid use in lactating women.

Sulfonylureas

• Note: Out of all the classes of oral diabetic medications, these are most likely to cause hypoglycemia

Alpha-Glucosidase Inhibitors

• This treats type 2 DM and has to be used in combination with other medications, do not use as a monotherapy
• Generic Drug Name: Acarbose (precose)
• Actions: drugs act at the brush border of the small intestine to compete with complex carbohydrates for digestion
• Administration: Given Orally and lowers postprandial blood glucose
• Adverse effects: GI symptoms such as belching, bloating, flatulence- should be titrated slowly
• Patient education: must be taken with the first bite of a meal or it will not work, should not be used at same time as intestinal absorbents

Selective Sodium Glucose Co-Transport 2 Inhibitors (SGLT-2 inhibitors)

• Class: used in type 2 DM as monotherapy or in combination with other medications and is given orally
• Drug Names: Canagliflozin (Invokana), Empagliflozin (Jardiance), Dapagliflozin (Farxiga)
• Mechanism: inhibits the reabsorption of glucose in the kidney proximal tubule, which increased excretion of glucose
• Adverse effects: genital infections (fungal and bacterial), urinary tract infections and all happens because of the extra glucose (sugar) in the urine

Dipeptidyl Peptidase-4 Inhibitors

• Treats Type 2 DM as monotherapy or in combination with other medications and is given orally
• Drug name: Sitagliptin (Januvia)
• Mechanism: Slows the breakdown of Glucagon like peptide 1 (GLP-1) by DPP-4
• Adverse effects: hypoglycemia, skin rash, arthralgia, pancreatitis, renal impairment and heart failure-use cautiously in patients with these issues

Glucagon-Like Peptide 1 Receptor Agonists (GLP-1)

• Mechanism: incretin memetics, treats type 2 DM as monotherapy or in combination with other medications
• Drug names: exenatide (byetta), dulaglutide (Trulicity), semaglutide (Ozempic, Rybelsus)
• Actions/effects: reduction of triglycerides, systolic blood pressure, and weight due to reduced appetite/food intake
• Administration: Given through subcutaneous Injection
• Adverse effects: Nausea/vomiting, gallbladder disease, thyroid dysfunction, pancreatitis or pancreatic duct metaplasia, kidney failure/injury
• Contraindication: personal or family history of medullary thyroid carcinoma and endocrine neoplasia, moderate or greater renal disease, history of Gl disease.

Thyroid Disorder Therapy

• Hypothyroidism is treated with Levothyroxine, acts like the body's endogenous thyroid hormone
  • Regulates: It regulates metabolism, heart rate, respiratory rate
• Levothyroxine adverse affect
  • Diarrhea, weight loss, cardiac arrhythmias, menstrual irregularity, heat intolerance
  • The elderly are at a higher risk of cardiac arrhythmias
• Usage: Should be taken on an empty stomach at least 30 minutes before breakfast
• Monitoring: TSH, T3, and Free T4 levels

Hyperthyroidism

• Graves disease, toxic multi-nodular goiter
• Drugs: propylthiouracil (PTU), methimazole
• Action: Blocks synthesis of thyroid hormone by preventing iodination of tyrosine

Hyperthyroidism Drugs Adverse Effects

• Side effect: Agranulocytosis and aplastic anemia, hepatitis (black box warning PTU and liver failure), hair loss
• PTU: Use in the first trimester and methimazole in the second and third trimesters of pregnancy
• Assess risk factors: Must conduct a CBC and monitor for signs/symptoms

Drugs Affecting the Cardiovascular System

Antihypertensives

• RAAS-Active Drugs

ACE Inhibitors (Angiotensin Converting Enzyme Inhibitors)

• Indications: hypertension, diabetic proteinuric states, coronary artery disease with ischemia, post myocardial infarction and heart failure.
• Example drugs: lisinopril, enalapril
• Action: Blocks the conversion of angiotensin 1 to angiotensin 2, which prodcues less aldosterone. Vasodilation, decreased intravascular volume, increased bradykinin which causes cough and angioedema.
• If a cough occurs on patient taking ACE, stop medication and switch to ARB
• Side effects: Hypotension, tachyphylaxis, dry cough, angioedema
• Absolute Contraindications: pregnancy, lateral renal artery stenosis, and angioedema
• Evaluation: Labs to evaluate renal function-BUN, creatinine, potassium; can cause retention of potassium.

ARBs (Angiotensin II Receptor Blockers)

• Indications: hypertension, diabetic proteinuric states, coronary artery disease with ischemia, post myocardial infarction and heart failure
• Example drugs: losartan, valsartan
• Action: block binding at angiotensin 2 receptor
• Does not effect Bradykinin so theres a low risk of cough and angioedema.
• Side effects: Hypotension, tachyphylaxis
• Absolute Contraindications: Pregnancy, lateral renal artery stenosis, angioedema.
• Evaluation: Labs to evaluate renal function-BUN, creatinine, potassium; can cause retention of potassium.

Calcium Channel Blockers

• Action: drugs-bind to voltage gated L-type channels in the heart and blood vessels preventing calcium from entering the cells=vasodilation/relaxation of smooth muscles, dilation of arterial beds and reduction of afterload

Calcium Channel Blockers indication

• Hypertension, chronic/unstable angina, CAD w/ ischemia, vasopastic angina, raynauds. migraine prophylaxis, supraventricular arrhythmias. Exercise use cautiously w/ hx of liver dysfunction, do not use while pregnant/lactating.

Dihydropyridines

• Drug examples: amlodipine, nifedipine, felodipine
• Preferred over non/dihydropyridines for HTN (why?)
• Long-acting forms for angina
• Adverse effects: Hypotension, dizziness, lower extremity edema, headache, reflex tachycardia

Nondihydropyridines

• Drug examples: verapamil, diltiazem
• Preferred during arrythmias
• Side effects: Fatigue, dizziness, Constipation.
• Action: Slows down contractility and heart rate
• Do not use when treating HFrEF

Antilipidemics

• HMG-CoA Reductase Inhibitors: Statins used for LDL and hypertriglyceridemia

Statins

• Drug examples: rosuvastatin (Crestor) and atorvastatin (Lipitor)
• Actions: - Blocks HMG-CoA reducatase, enzyme required in cholesterol synthesis in the liver
• Adverse effects: headache, GI, musclular complaints/myalgia (most common), myositis, rhabdomyolysis, flu-like symtpoms, liver dysfunction, increased risk of type two DM + memory loss
• Check Creatinine kinase for myalgias and levels
• Prevention of atherosclerotic disease and decrases pre-inflammatory cytokines + increases activity of endothelial nitric oxide + reduction of platelet activity
• Cannot use if patient has -Active liver disease should be used cautiously alcohol abuse or history of liver disease, pregnancy/lactation

Cholesterol Absorption Inhibitors

• LDL reduction
• Drug name: ezetimibe (zetia)
• Action: Inhibits the absorption of cholesterol (dietary and biliary sources), brush border of the small intestine.
• Adverse Effects: -Acute liver injury, myalgia, myopathy, and rhabdomyolysis Do not use with:Active liver disease

Fibric Acid Derivatives

• Uses: Reduced hypertriglyceridemia, indirect elevation of LDLs, lowering of triglyceride levels, helps to avoid pancreatitis in hypertriglyceridemia

Names/Drugs

• Gemfibrozil (lopid) and fenofibrate (tricor)
• Action: Act by causing an increase in lipolysis of triglycerides via protein lipase. Decreases VLDL synthesis via liver

Antithrombotic Drugs

Anticoagulants

• Interfere with coagulation cascade and fibrin formation
• Drug example: dabigatran (pradaxa)
• Action: Reversible competitive thrombin inhibitor and inhibits thrombin's conversion of fibrinogen to fibrin -Precautions: Avoid Activties w/ hi risk injuries/falls
• Precautions/Contraindications: Avoid hi risk injuries, activities, procedures, and disorders
• Praxibind is a reversal agent
  • Monocolonal antibody -Neutralizes w/ anticoagulant effect that could lead to life threatening bleeding

Antiplatelets

• Inhibits clot formation by preventing platelet activation + aggression
• Drug example: clopidigrel (plavix), reduction for MI if patients have ACS
• Contraindications: -active bleeding, Black Box Warning, Precautions.
• Effects: -pro platelet aggregation w/ drug ADP selectivity that produces platelets to inhibit complex platelet receptor.
• Precautions: Genetic testing to check for CYP2c 19

Drugs used in the Treatment of HFrEF

• First line includes four pillars of therapy:

RAAS System

• ARNI
  • Entresto: Reduces preload + afterload. Prevents breakedown of natriuertic peptides
  • Action-blocks aldosterone + decraeses H2O retention + decreases vascular fibroids + improves hi function.
• SGLT2 Inhibitors: Dapaglifizin. Action: Natruesis ( more glucose in urine). SGLT2s
  • Action-Decreases overload and BP and improves hi functions.
• Beta Blockers: Inhibits Synaptic functions. Decreases oxegen function and vascular tension.
• MRA: -Mineralcortiol. Action: Blocks aldosertone and decrases H2O function. -Effects: Prevents hi fibrosis causing cardiac function. -Effects: Prevents hi fibrosis causing cardiac function. -Monitiors: Hyperkalemia

Antiarrhythmics

• Drug: Amioadarone
• To treat ventricular arrhythmias and Artirial Fib

Artirial Fib Effects and Functions

• Effects: Fatigue, Lung Damage ,Thyroid Dysfunction
• Labs should assess Thyroid Functions b/c It can effect functions.