RXRS 200 Drug Classifications and MOA's

Mood Disorders

Major Depressive Disorder (MDD) - where one loses joy in activities/loss of interest and depression continuing for more than 2 weeks

Bipolar Depression - mood swings between depressive episodes and manic/hypomanic episodes (highs)

Unipolar Depression - only lows

Selective Serotonin Reuptake Inhibitors (SSRIs)
Ex. fluoxetine (Prozac)

Reuptake inhibitor of serotonin transporter, increasing serotonin availability in the synapse; used to alleviate depression and anxiety

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

A class of antidepressants that inhibit the reuptake of both serotonin and norepinephrine in the brain, thereby increasing the levels of these neurotransmitters.

Tricyclic Antidepressants (TCAs)
Ex. amitriptyline

Reuptake inhibitor of serotonin and norepinephrine; also acts as antagonists at various receptors, contributing to side effects

Antipsychotics

Ex. risperidone (Risperdal) & olanzapine (Zyprexa)

dopamine receptor antagonists (D2 receptors) reducing dopamine hyperactivity implicated in psychosis and bipolar disorder

Mood Stabilizers

Regulate neuronal excitability via various mechanisms, including modulation of ion channels, second messenger systems. Used to prevent mood cycling in bipolar disorder

Benzodiazepines
Ex. diazepam (Valium) & lorazepam (Ativan)

Agonists at GABA-A receptor, increasing chloride ion influx causing neuronal inhibition, sedation, anxiolysis. Risks dependence, recommended for short-term use

Insulin Resistance and Diabetes

• Type 1: autoimmune destruction of beta cells leading to insulin deficiency; requires lifelong insulin supplementation

• Type 2: Insulin resistance and beta cell dysfunction with increased glucagon activity and systemic inflammation

• Metabolic Syndrome: predetermines T2D, with ≥3 risk factors: insulin resistance, obesity, hypertension, low HDL cholesterol, and elevated fasting glucose

Metformin (Glucophage)

Inhibitor of hepatic glycogenesis; improves insulin sensitivity primarily in muscle and adipose tissue by activating AMP-activated protein kinase (AMPK), decreasing blood glucose levels

Thiazolidinediones (TZDs)
Ex: pioglitazone (Actos)

PPAR-γ receptor agonists that enhance insulin sensitivity in adipose and muscle tissues vie gene transcription modulation

Secretagogues
Ex: sulfonylureas (glipizide, glyburide)

Stimulate pancreatic beta-cells by closing ATP-sensitive K+ channels, increasing insulin secretion

SGLT2 inhibitors

Ex: canagliflozin (Invokana)

Inhibit sodium-glucose contransporter-2 in renal proximal tubules, reducing glucose reabsorption and promoting glucosuria

Alpha-glucosidase inhibitors
Ex: acarbose

Inhibit intestinal alpha glucosidase enzymes, slowing carbohydrate digestion and absorption, blunting postprandial hyperglycemia

Recombinant Insulin

Agonist at insulin receptor, facilitating glucose uptake into cells; essential in T1D

Cardiac Diseases

• Dyslipidemia: Abnormal blood lipids, major risk factor for atherosclerosis. LDL (“bad”) cholesterol contributes to plaque buildup; HDL (“good”) cholesterol protects.

• Coronary Artery Disease (CAD): Plaque deposits in coronary arteries cause angina, myocardial infarction, and sudden death.

• Hypertension: Elevated blood pressure increases risk of heart disease, stroke, and kidney failure.

• Congestive Heart Failure (CHF): Reduced left ventricle pumping ability leads to fluid retention and systemic congestion.

Statins

Ex. atorvastatin (Lipitor)

HMG-CoA reductase inhibitors that reduce cholesterol synthesis in hepatocytes, lowering LDL cholesterol and stabilizing atherosclerosis plaques

Fibrates
Ex. fenofibrate

PPAR-alpha agonists that enhance lipoprotein lipase activity, lowering triglycerides and modestly increasing HDL cholesterol

Ezetimibe

Inhibits intestinal NPC1L1 transporter reducing cholesterol absorption from the diet

Diuretics

Ex. hydrochlorothiazide

Increase renal excretion of sodium and water, decreasing blood volume and pressure

Beta-blockers

Ex. metoprolol

Beta-adrenergic receptor antagonists reducing heart rate, contractility, cardiac output, and myocardial oxygen demand

ACE inhibitors

Ex. lisinopril

Inhibit angiotensin-converting enzyme, preventing formation of angiotensin II, leading to vasodilation and reduced aldosterone-mediated volume expansion

Angiotensin Receptor Blockers (ARBs)

Ex. losartan

Antagonists at angiotensin II type 1 receptors, preventing vasoconstriction and sodium retention

Calcium channel blockers

Ex. amlodipine

Inhibit L-type calcium channels in vascular smooth muscle, causing vasodilation and reduced cardiac contractility

Cancer Therapeutics

Breast Cancer

Cytotoxic Chemotherapy

Targets rapidly dividing cells by disrupting DNA replication or mitosis

• Alkylating agents: Alkylate DNA causing cross-linking and strand breaks

• Antimetabolites: Inhibit synthesis of nucleotides essential for DNA replication

• Topoisomerase inhibitors: Inhibit enzymes that modulate DNA topology during replication

Targeted Therapies

• HER2 inhibitors Ex. trastuzumab (Herceptin): Monoclonal antibody antagonist binding HER2 receptor, blocking oncogenic tyrosine kinase signaling

• Tyrosine Kinase Inhibitors (TKIs) Ex. imatinib (Gleevec): Inhibit kinase activity driving proliferation, such as BCR-ABL fusion protein in chronic myeloid leukemia

Monoclonal Antibodies

• Rituximab: Targets CD20 on B-cells, inducing immune-mediated cytotoxicity

• Bevacizumab: Binds VEGF inhibiting angiogenesis

Immunotherapy

Immune checkpoint inhibitors block inhibitory receptors such as PD-1/PD1-L1, restoring T-cell mediated immune recognition of cancer cells

Selective estrogen receptor modulator (SERM)

Ex. Tamoxifen

Antagonist at estrogen receptor in breast tissue, reducing tumor growth driven by estrogen

HIV Pharmacotherapy

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

Competitive analog inhibitors incorporated into viral DNA by reverse transcriptase and blocking its activity by reverse transcriptase causing chain termination

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Allosteric inhibitors binding reverse transcriptase and blocking its activity without incorporation into DNA

Protease Inhibitors (PIs)

Inhibit viral protease, preventing cleavage of HIV polyproteins and maturation of infectious virions

Integrase Strand Transfer Inhibitors (INSTIs)

Inhibit HIV integrase enzyme, blocking integration of viral DNA into host genome

Entry and Fusion Inhibitors

Block viral entry by antagonizing CCR5 co-receptor or preventing fusion of viral membrane with host cell membrane

Pre-Exposure Prophylaxis (PrEP)

Uses ARVs such as tenofovir/emtricitabine combination to inhibit early viral replication and prevent infection in high-risk individuals

Immune related Diseases

Asthma - allergens cause allergies

Allergic Rhinitis - hay fever, or seasonal allergies

Rheumatoid Arthritis - inappropriate immune response to internal self protein or cellular component

Urinary Tract infections (UTI) - caused by external pathogen (more in women) aka bacterial infection

antihistamines

Block H1 receptors to reduce symptoms like itching and swelling

Leukotriene Receptor antagonists
Ex. Montelukast

Selective antagonist of cysteine leukotriene receptor CysLT1 inhibiting leukotriene D4 from activating the receptor on airway smooth muscle - preventing bronchoconstriction and inflammation

Beta2 Adrenergic receptor Agonists

Ex. Albuterol

Stimulate beta2 receptors on bronchial smooth muscle to activate adenylate cyclase, increasing cAMP, activating PKA

Monoclonal Anti-IgE Antibody

Ex. Omalizumab

Prevents IgE from binding directly to high affinity receptors on mast cells thus inhibiting allergen-induced degranualtion and release of inflammatory mediators

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs; Ibuprofen)

COX enzyme inhibitors; Non-selective reversible competitive inhibitors of COX-1 and COX-2 enzymes, reducing prostaglandin synthesis

Disease-Modifying Antirheumatic Drugs (DMARDs)

Dihydrofolate reductase inhibitor; inhibits folate pathway essential for DNA synthesis in rapidly dividing immune cells

TNF-alpha inhibitors

Ex. Etanercept, Infliximab

Neutralizes TNF-alpha, a pro-inflammatory cytokine driving RA pathology

IL-6 receptor antagonists

Ex. Tocilizumab

Monoclonal antibody blocking IL-6 binding, reducing inflammatory signaling

B-cell depleting agents

Ex. Rituximab

Monoclonal antibody CD20 on B cells, inducing B-cell lysis via complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity

Antibiotics

• Beta-lactams inhibit bacterial cell wall synthesis

• Sulfonamides inhibit folate synthesis

Antivirals

Neuraminidase inhibitor, blocks neuraminidase enzyme needed for release of new viral particles from infected cells