Gout Medications: Colchicine and Allopurinol

Colchicine:

Decreases inflammation response to urate crystals.

Adverse effects include diarrhea, nausea, vomiting, abdominal cramps, and anemia.

A low dose is more effective without as many adverse drug effects.

Metabolized by the liver and excreted by the kidneys and bile.

Use cautiously in patients with peptic ulcer disease.

Monitor BUN, creatinine, and uric acid levels.

Used in heart disease for secondary prevention.

Allopurinol:

Xanthine oxidase inhibitor.

Inhibits the enzyme responsible for converting hypoxanthine and xanthine to uric acid.

First-line drug for gout maintenance.

Adverse effects include hepatotoxicity, gout flare at therapy initiation, and skin rash.

Multiple drug reactions possible.

Monitor LFT, BUN, creatinine, CBC, and uric acid levels initially and monthly until levels stabilize.

Takes time to be effective.

Febuxostat:

A urine-lowering agent that inhibits xanthine oxidase.

Highly protein-bound, taking a week to take effect.

Can cause liver function abnormalities.

Monitor uric acid levels.

Probenecid:

Inhibits renal tubular reabsorption of urate, increasing uric acid excretion.

Highly protein bound and lacks anti-inflammatory activity.

Most useful for patients with reduced urinary excretion of uric acid.

Metabolized in the liver and excreted in kidneys/bile.

Adverse effects include hypersensitivity, blood dyscrasias, and hepatotoxicity.

Use with caution in patients with sulfa allergies.

Pegloticase:

Converts uric acid into a water-soluble purine metabolite for renal excretion.

Administered parenterally.

Metabolized by the liver and excreted through kidneys and bile.

Associated with major cardiovascular events.

Pain Management:

For falls without fractures and mild pain, first-line treatments for non-cancer pain are NSAIDs, anticonvulsants, acetaminophen, and muscle relaxers.

Non-pharmacological treatments include exercise, physical therapy, acupuncture, TENS, chiropractic care, and RICE.

Avoid starting with opioids.

Topical NSAIDs are the initial recommendation.

Guidelines recommend topical NSAIDs first, followed by oral NSAIDs, and then opioids if necessary.

NSAIDs:

Include ibuprofen, naproxen, Toradol, Mobic, and aspirin (a salicylate).

Indications: analgesic, antipyretic, and anti-inflammatory.

High oral absorption and bioavailability lead to more drug interactions.

Highly protein bound.

Common adverse effects include nausea, heartburn, mild headache, and dizziness.

Take with food to reduce GI symptoms.

Contraindications: ulcers, Crohn's, GI bleed, liver/renal disease, heart disease, bleeding disorders, uncontrolled hypertension, and pregnancy.

Avoid in patients with low GFR.

Patients with uncontrolled hypertension should take acetaminophen instead.

Toradol is reserved for GI/renal issues, while Mobic is for long-term effects.

Salicylates (Aspirin):

Prototype salicylate with analgesic, anti-inflammatory, antipyretic, and antiplatelet effects.

Lowers body temperature and affects vasodilation.

Anti-inflammatory and analgesic effects are mediated through inhibition of prostaglandin synthesis.

Toxicity symptoms: nausea, vomiting, diaphoresis, tinnitus, and hyperventilation.

Diaphoresis is the first symptom.

Black Box Warning: Increased risk of cardiovascular events and GI bleeding.

Non-aspirin NSAIDs emphasize heart attack and stroke risk, contraindicated in heart disease.

Acetaminophen:

Non-opioid, non-NSAID analgesic and antipyretic.

Used for mild pain and fever, lacking anti-inflammatory properties.

Preferred in heart disease.

Contraindications: alcoholism, liver/renal disease, and malnutrition.

Toxicity signs: liver damage/dysfunction, abdominal pain, nausea, vomiting, dark urine, and jaundice.

Celecoxib:

A Cox-2 inhibitor.

Has anti-inflammatory properties and limited GI tract impact.

Black box warning exists for cardiovascular risks.

Opioids:

First-line for mild pain includes tramadol, codeine, and hydrocodone.

Second-line for mild-moderate pain is hydrocodone or oxycodone.

Third-line for severe pain is hydrocodone, oxycodone, or morphine.

MU receptor is the primary analgesic receptor in the CNS; MU-1 is outside the CNS, while MU-2 is inside.

Opiod analgesic causes absence of pain without loss of consciousness or sleep.

Full agonists examples are morphine and codeine, while partial agonists include buprenorphine and tramadol.

Antagonist example is Narcan (naloxone).

Corticosteroids:

Hormones produced by the adrenal cortex affecting almost all body organs and maintaining homeostasis.

Actions and effects on the body are decreased uptake of glucose, glycogenesis in the liver.

Also includes decreased protein synthesis in muscle, lymph tissue, skin, and bone, lipolysis in adipose tissue, decreased inflammatory response, and blocked fever generation.

Adverse effects include osteoporosis, poor wound healing, hyperglycemia, increased risk of infection, cataracts, and others.

Use should balance risks and benefits; avoid abrupt withdrawal if used chronically.

Insulins:

Most likely to cause hypoglycemia.

Type 1 diabetics always need insulin, and Type 2 diabetics may need it eventually.

Biguanides (Metformin):

First-line medication for Type 2 diabetes.

Improves insulin sensitivity and factors related to metabolic syndrome/PCOS.

Black box warning exists for lactic acidosis.

Improves insulin sensitivity, decreases hepatic gluconeogenesis and glucose absorption, decreases weight and viscosity, decreases triglycerides, increases HDL, and decreases LDL.

Thiazolidinediones (Pioglitazone and Rosiglitazone):

Given orally for Type 2 diabetes, alone or combined with other medications.

Decrease insulin resistance by activating PPAR gamma.

Adverse effects include weight gain and edema.

Alpha-Glucosidase Inhibitors (Acarbose):

Used in Type 2 diabetes in combination with other medications.

Acts at the brush border of the small intestine and delays complex carbohydrate digestion.

Lowers postprandial blood glucose and decreases A1C over time.

Can cause GI symptoms and can worsen Crohn's/ulcerative colitis.

Selective Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitors (Canagliflozin, Empagliflozin, Dapagliflozin):

Used for Type 2 diabetes, inhibits glucose reabsorption in the kidney, and increases glucose excretion in the urine.

Can cause genital infections, UTIs, decreased blood pressure, and increased LDL.

Black box warning for canagliflozin is risk of leg and foot amputations.

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors (Sitagliptin):

Used for Type 2 diabetes as monotherapy or in combination.

Slows GLP-1 breakdown, increases insulin secretion/synthesis, and suppresses glucagon.

Adverse effects: hypoglycemia, Steven Johnson syndrome, pancreatitis, and renal impairment.

Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist (Exenatide, Dulaglutide, Semaglutide):

Used for Type 2 diabetes, acts like endogenous GLP-1, and reduces triglycerides/weight.

Adverse effects can include nausea, vomiting, and pancreatitis.

Levothyroxine:

Used for hypothyroidism; start low and titrate slow.

Mimics endogenous thyroid hormone and regulates metabolism.

Adverse effects: diarrhea, weight loss, arrhythmias, and heat intolerance.

Thioamides (Propylthiouracil and Methimazole):

Treats hyperthyroidism, Graves' disease, and toxic multinodular goiter.

Blocks thyroid hormone synthesis by preventing tyrosine iodination.

Adverse effects include agranulocytosis and liver failure.

Black box warning for PTU is hepatitis.

Angiotensin-Converting Enzyme Inhibitors (ACEI):

Treats hypertension, diabetic proteinuria, CAD with ischemia, heart failure, and post-MI.

Blocks conversion of Angiotensin 1 to Angiotensin 2, decreasing aldosterone and increasing vasodilation.

Adverse effects include dry cough, angioedema, and hyperkalemia.

Angiotensin II Receptor Blockers (ARBs):

Treats hypertension, diabetic proteinuria, CAD with ischemia, heart failure, and post-MI.

Blocks angiotensin 2 binding, similar to ACEIs without affecting bradykinin levels.

Adverse effects include hypotension, tachyphylaxis and hyperkalemia.

Calcium Channel Blockers (CCB):

Bind to voltage-gated L-type channels in the heart/vessels, preventing calcium entry.

Treats hypertension, angina, and arrhythmias.

Dihydropyridines (amlodipine, nifedipine, felodipine) have more vasodilation effects and less effect on heart function.

Non-dihydropyridines (verapamil, diltiazem) have less vasodilation and more effect on heart function; used for supraventricular tachycardias.

HMG-CoA Reductase Inhibitors (Statins):

Used for LDL and hypertriglycerides.

Blocks HMG-CoA reductase, lowering cholesterol, LDL, and apo B lipoprotein levels.

Adverse effects: nausea, constipation, muscular complaints, and liver dysfunction.

Cholesterol Absorption Inhibitor (Ezetimibe):

Reduces LDL, can be used alone or with statins.

Inhibits cholesterol absorption at the small intestine brush border.

Adverse effects: GI upset, myalgia, myopathy.

Fibric Acid Derivatives (Gemfibrozil and Fenofibrate):

Decreases triglycerides and helps avoid pancreatitis.

Increases lipolysis of triglycerides and decreases LDL synthesis.

Antithrombotic Drugs:

Anticoagulants inhibit coagulation and fibrin formation, while antiplatelets prevent platelet activation and aggregation.

Anticoagulant (Dabigatran):

Decreases risk of CVA and PE.

Reversible thrombin inhibitor.

Adverse effects are heartburn, nausea, belching, and bleeding.

Administer Idarucizumab (praxbind) in the event of life threatening bleeding.

Antiplatelet (Clopidogrel):

Decreases risk of MI.

Inhibits ADP binding to platelet receptors, inhibiting platelet aggregation.

Adverse effects: bleeding, headache, and taste disorders.

Drugs for Heart Failure with Reduced Ejection Fraction (HFrEF):

First-line therapy are 4 pillars:

• Inhibition of the RAAS system-ARNI which is preferred, ACE or ARB.
• Inhibition of the SNS-beta blockers and alpha beta blockers.
• Mineralocorticoid receptor antagonist.
• SDLT-2 inhibitors.

Antiarrhythmics (Amiodarone):

Class 3 antiarrhythmic, used for atrial and ventricular arrhythmias.

Prolongs cardiac myocyte repolarization through potassium channel blockade.

Adverse effects include nausea/vomiting, fatigue, lung damage, and thyroid dysfunction.