Comprehensive Pharmacology Study Guide: Modules 4-6

Gastrointestinal (GI) Medications

  • Proton Pump Inhibitors (PPIs)
    • Nomenclature: Suffix "-prazole."
    • Drug Examples:
    • Omeprazole (Prilosec): 1st line agent.
    • Lansoprazole (Prevacid).
    • Mechanism of Action: Inhibit the H+−K+−ATPaseH^+-K^+-ATPase (proton pump) located in the parietal cells of the stomach. This pump is responsible for the secretion of H+H^+ (a component of HClHCl). Under normal conditions, Chloride (Cl−Cl^-) and Potassium (K+K^+) are transported into the lumen; K+K^+ is then exchanged for H+H^+ from within the cell using energy from the pump. PPIs are also inhibited by prostaglandins.
    • Intended Effect: Used to treat Peptic Ulcers (perforations in the stomach or small intestine lining) and GERD (Gastroesophageal Reflux Disease caused by a weak lower esophageal sphincter).
    • Side Effects: Abdominal pain, dizziness, headache, diarrhea, increased risk of bone fractures, and low Vitamin B12B_{12} levels. Note: PPIs have mostly replaced H2 blockers because they act faster and with greater efficacy.
  • Histamine H2 Blockers
    • Nomenclature: Suffix "-tidine."
    • Drug Examples:
    • Cimetidine (Tagamet HB).
    • Famotidine (Pepcid).
    • Mechanism of Action: 2nd line agents. Competitive inhibitors of histamine at the H2H_2 receptors in gastric parietal cells. This suppresses gastrin-stimulated acid secretion.
    • Side Effects/Interactions: Confusion (especially with Cimetidine). Cimetidine inhibits liver drug-metabolizing enzymes, potentially leading to toxicity of other drugs such as Beta Blockers, Calcium (Ca2+Ca^{2+}) channel blockers, and Warfarin.

  • ### Laxatives

    • Bulking Agents: Psyllium Husk (Metamucil). Contains indigestible dietary fiber that absorbs and holds water.
    • Osmotic Agents: Milk of Magnesia. Attracts water from the bloodstream into the stool to soften it.
    • Irritants/Stimulants: Dulcolax. Directly stimulates peristalsis.
    • Stool Softeners: Colace. Acts as an emulsifier that allows fat into the stool to mix with water.

Insulin and Antidiabetic Agents

  • Insulin Classifications
    • Rapid Acting: Lispro (Humalog). Dissolves rapidly at the site of administration to lower blood sugar before meals. Increasing the dose increases the effect but not the duration.
    • Onset: 5 min5\,min.
    • Peak: 1 hr1\,hr.
    • Duration: 3−5 hr3-5\,hr.
    • Short Acting: Humulin R, Novolin R ("R" stands for Regular). Lower blood sugar roughly 1+ hour1+\,hour before a meal.
    • Onset: 30 min30\,min.
    • Peak: 2 hr2\,hr.
    • Duration: 6−8 hr6-8\,hr.
    • Intermediate Acting: Humulin N, Novolin N ("N" stands for NPH). Slower absorption than regular insulin.
    • Onset: 1−4 hr1-4\,hr.
    • Peak: 6−12 hr6-12\,hr.
    • Duration: 14−24 hr14-24\,hr.
    • Long Acting: Detemir, Glargine.
    • Onset: 1 hr1\,hr.
    • Peak: None.
    • General Adverse Effects of Insulin: Hypoglycemia (can lead to brain damage, tachycardia, HTN, palpitations, sweating, tremors, irritability, nausea, hunger, mental dullness, seizures, paralysis, paresthesia, and loss of consciousness).

  • ### Oral and Injectable Antidiabetic Agents

    • Biguanides: Metformin.
    • Mechanism: 1st line for DM2. Inhibits hepatic gluconeogenesis, increases glycolysis, and increases peripheral glucose uptake. Reduces insulin resistance (via GLUT4 transporters) and slows carb absorption.
    • Side Effects: Lactic acidosis, N/V, exhaustion, fatigue, muscle cramps, and respiratory compensation (fast, deep breathing). No weight gain or hypoglycemia.
    • GLP-1 Receptor Agonists: Liraglutide (Victoza). Suffix "-tide."
    • Mechanism: Enhances glucose-dependent insulin secretion, suppresses glucagon, and slows gastric emptying. Injected.
    • Side Effects: Nausea, vomiting, weight loss.
    • DPP-4 Inhibitors: Sitagliptin. Suffix "-gliptin."
    • Mechanism: Inhibit dipeptidyl peptidase-IV, which breaks down GLP-1. Allows GLP-1 to act longer.
    • Side Effects: GI distress, urinary/respiratory infections. No weight gain.
    • Amylinomimetic: Pramlintide (Symlin).
    • Mechanism: Synthetic analog of amylin (co-secreted with insulin). Prolongs gastric emptying and reduces glucagon secretion.
    • Side Effects: Reduced appetite; risk of hypoglycemia if used with insulin.
    • SGLT2 Inhibitors: Empagliflozin (Jardiance). Suffix "-egliflozin."
    • Mechanism: Inhibits the sodium-glucose co-transporter in the proximal nephron, increasing glucose excretion in urine.
    • Side Effects: Acute kidney injury, hypotension (fluid loss), UTIs, and yeast infections.
    • Thiazolidinediones (TZD): Rosiglitazone (Avandia).
    • Mechanism: Increases insulin sensitivity in muscle, liver, and adipose tissue.
    • Side Effects: Weight gain, fluid retention, fractures, Heart Failure (HF).
    • Alpha-Glucosidase Inhibitors: Miglitol (Glyset).
    • Mechanism: Inhibits the alpha-glucosidase enzyme in the intestine, preventing the breakdown of carbs into glucose.
    • Side Effects: GI symptoms due to fermentation of unabsorbed carbs.
    • Insulin Secretagogues:
    • Sulfonylureas: Glipizide (Glucotrol). Causes the pancreas to release insulin. Risk of hypoglycemia (especially in malnourished elderly) and weight gain.
    • Meglitinides: Repaglinide (Prandin). Stimulates insulin release from pancreatic beta cells. Lower risk of hypoglycemia/weight gain than sulfonylureas.

Thyroid and Bone Loss Medications

  • Hypothyroidism
    • Drug: Levothyroxine (Synthroid). Synthetic T4T_4.
    • Key Detail: Long half-life of approximately 6 days6\,days, making it beneficial if a dose is missed. Monitor via TSH levels.
    • Overdose Signs: Hyperthyroidism symptoms, osteoporosis, and increased fracture risk.
  • Hyperthyroidism
    • Drug Examples: Methimazole (Tapazole) and Propylthiouracil (PTU).
    • Contraindications: Methimazole is teratogenic; PTU is suitable for pregnant women.
    • Usage: often used before thyroid surgery or radioactive iodine treatment.

  • ### Bone Loss (Osteoporosis)

    • Bisphosphonates: Alendronate (Fosamax).
    • Mechanism: Inhibits bone resorption, increases mineralization, and stops bone breakdown. IV is preferred as oral absorption is poor.
    • Side Effects: GI disturbances, esophagitis (patient must remain upright after oral dose).
    • Calcitonin: Salmon calcitonin. Stops bone breakdown by inhibiting osteoclasts. Treatment for hypercalcemia and Paget's disease.
    • Parathyroid Hormone: Teriparatide (Forteo). Recombinant PTH. Stimulates osteoblasts via daily subcutaneous injections.
    • SERMs: Raloxifene, Tamoxifen. Raloxifene treats postmenopausal osteoporosis. Side effects include hot flushes and nausea.
    • Supplements: Vitamin DD and Calcium (Caltrate) are taken together to enhance absorption.

Antidepressants and Anxiety Medications

  • Key Neurotransmitters
    • Norepinephrine (NE) and Serotonin.
  • Antidepressant Classes
    • Tricyclic Antidepressants (TCAs): Amitriptyline (Elavil).
    • Mechanism: Inhibit reuptake of NE and serotonin; increase receptor sensitivity.
    • Side Effects: Narrow therapeutic index. Effects on AChACh, histamine, and adrenergic receptors (Sedation, Orthostatic Hypotension (OH), ECG changes).
    • Monoamine Oxidase Inhibitors (MAOIs): Phenelzine (Nardil).
    • Mechanism: Prevents breakdown of NE, dopamine, and serotonin.
    • Interactions: Tyramine-rich foods (cheese, wine) cause violent headaches, severe HTN, and potential CVA.
    • Selective Serotonin Reuptake Inhibitors (SSRIs): Escitalopram (Lexapro), Fluoxetine (Prozac), Citalopram (Celexa), Paroxetine (Paxil), Sertraline (Zoloft).
    • Mechanism: Blocks serotonin reuptake. Most widely prescribed. Suicide risk at 4 weeks.
    • Selective Norepinephrine Reuptake Inhibitors (SNRIs): Duloxetine (Cymbalta). Blocks reuptake of both serotonin and NE.
    • Bupropion (Wellbutrin): Increases activity of NE and dopamine. Used for both anxiety and depression.

  • ### Anxiety (Key NT: GABA)

    • Benzodiazepines: Alprazolam (Xanax), Diazepam (Valium), Lorazepam (Ativan). Suffix "-am."
    • Mechanism: Binds to GABA sites to provide sedation. Not for daily use (tolerance/dependence issues).
    • Beta Blockers: Propranolol (Inderal). Blocks adrenaline. Side effects include reduced circulation to limbs and lightheadedness.
    • Anxiolytic: Buspirone (Buspar). Reduces serotonin; does not work on GABA. Good for Generalized Anxiety Disorder (GAD) but not panic attacks.

Antipsychotics and Mood Stabilizers

  • Antipsychotics (Key NT: Dopamine)
    • 1st Gen (Typical): Chlorpromazine (Thorazine), Haloperidol (Haldol).
    • Mechanism: Block dopamine receptors.
    • Adverse Effects: Extrapyramidal Side Effects (EPSE) like Parkinson-like symptoms and tardive dyskinesia.
    • 2nd Gen (Atypical): Quetiapine (Seroquel), Aripiprazole (Abilify), Risperidone (Risperdal).
    • Mechanism: Modulate serotonin, NE, and histamine. Better for negative symptoms.
    • Side Effects: Weight gain, hyperglycemia, lipid abnormalities.

  • ### Bipolar Disorder/Mania

    • Lithium: Reduces excitatory (dopamine, glutamate) and increases inhibitory (GABA) NTs. Narrow therapeutic window.
    • Anticonvulsants: Valproate (Depakene), Carbamazepine (Tegretol). Used to stabilize mood.

Neurological Disorders

  • Parkinson Disease (Key NT: Dopamine and Acetylcholine)
    • Levodopa (L-DOPA): Crosses Blood-Brain Barrier (BBB); converted to dopamine. Very large doses required.
    • Carbidopa: Dopa decarboxylase inhibitor. Prevents peripheral conversion of L-DOPA. Cannot cross BBB itself.
    • Sinemet: Combination of Levodopa and Carbidopa.
    • Dopamine Agonists: Ropinirole (Requip). Binds directly to post-synaptic receptors.
    • MAO-B Inhibitors: Selegiline (-line). Inhibits enzyme that breaks down dopamine in the brain.
    • COMT Inhibitors: Entacapone, Tolcapone (-capone). Prevents breakdown of dopamine to 3-OMD.
    • Amantadine: Increases action of dopamine; antiviral.
    • Anticholinergics: Benztropine (Cogentin). Inhibits AChACh to restore balance with dopamine.
  • Alzheimer’s Disease (Key NT: Acetylcholine)
    • Cholinesterase Inhibitors: Doneprezil (Aricept). Increases AChACh in the frontal cortex.
    • NMDA Receptor Antagonist: Namenda (Memantine). Blocks glutamate to restore balance.

  • ### Seizure Disorders (Key NT: GABA)

    • Phenytoin (Dilantin): 1st line. Blocks sodium current. Causes hair growth and rashes.
    • Carbamazepine (Tegretol): 2nd most common; for partial seizures only.
    • Phenobarbital (Luminal): Schedule 4 sedative. Increases threshold for firing.
    • Ethosuximide (Zarontin): Drug of choice for absence seizures. Blocks calcium channels in the thalamus.
    • Gabapentin/Pregabalin: GABA analogs that inhibit specific Ca2+Ca^{2+} channels to decrease glutamate release.

Antibiotics and Cancer Treatments

  • Antibiotics
    • Beta-lactams: Penicillins (Penicillin G, Amoxicillin) and Cephalosporins (Cephalexin). Inhibit cell wall synthesis by binding to penicillin-binding proteins. Bactericidal.
    • Glycopeptides: Vancomycin. Used for MRSA and C. Diff. Causes "Red Man Syndrome" and nephrotoxicity.
    • Aminoglycosides: Gentamicin. Binds to ribosomes causing mRNA misreadings. Ototoxic and nephrotoxic.
    • Macrolides: Azithromycin. Binds to ribosomes to prevent RNA transcription.
    • Fluoroquinolones: Ciprofloxacin. Blocks DNA gyrase. Risk of spontaneous tendon rupture.
    • Antimycobacterial: Rifampin. Inhibits RNA synthesis for TB. Causes orange secretions.

  • ### Cancer Treatments (Chemotherapy)

    • Antimetabolites: Mercaptopurine (Purine antagonist), Capecitabine (Pyrimidine antagonist), Methotrexate (Folic acid antagonist).
    • Vinca Alkaloids: Vinblastine, Vincristine. Prevents microtubule assembly.
    • Taxanes: Paclitaxel. Prevents microtubule disassembly.
    • Alkylating Drugs: Cyclophosphamide (Cytoxan). Prevents DNA division (mustard gas derivative).
    • Platinum Chemo: Cisplatin. Creates crosslinks in DNA strands.
    • Hormonal Chemo: Tamoxifen (SERM) and Anastrozole (Aromatase inhibitor). Used for estrogen-sensitive cancers.
    • Monoclonal Antibodies: Trastuzumab (Herceptin). Binds to specific antigens on cancer cell surfaces.

Alternative Medications and N/V Treatment

  • Antiemetics (Nausea/Vomiting)
    • Phenothiazines: Prochlorperazine. Blocks dopamine in the GI tract and chemoreceptor trigger zone.
    • Ondansetron (Zofran): Blocks serotonin release in the small intestine.

  • ### Alternative Meds

    • Ginkgo Biloba: Enhances vascular perfusion; risk of hemorrhage.
    • St. John’s Wort: Alters CNS NTs; many drug interactions (Warfarin, birth control).
    • Echinacea: Immune stimulant.
    • Ginger: Inhibits prostaglandin and leukotriene synthesis.
    • Ginseng: Antioxidant; reduces anticoagulant effectiveness.
    • Garlic: Contained Allicin; lowers BP and lipids.
    • Saw Palmetto: Treats Benign Prostatic Hypertrophy (BPH).
    • Valerian Root: Enhances GABA inhibition.
    • Melatonin: Endogenous hormone for sleep cycles.