Pharmacology and Bone Health Study Guide

HSV Drug Mechanisms: * Acyclovir: DNA chain terminator lacking a 3’ hydroxyl group; requires bioactivation by host kinases. Limited bioavailability due to polar hydroxyl group. * Valacyclovir: Prodrug of acyclovir with a lipophilic group for improved absorption. * Ganciclovir: High polarity due to two hydroxyl groups; administered $IV$ only. * Valganciclovir: Prodrug with higher bioavailability than ganciclovir. * Famciclovir: Highest bioavailability; metabolized to penciclovir.
Hepatitis C MOA: * NS5A Inhibitor (Velpatasvir): Synergizes with sofosbuvir. * NS5B Inhibitor (Sofosbuvir): RNA polymerase chain terminator; requires kinase bioactivation in hepatocytes.

Calcium Homeostasis Hormones: * PTH: Increases plasma calcium by stimulating bone release and kidney reabsorption. * Calcitriol: Increases intestinal calcium absorption; inhibits PTH production. * Calcitonin: Decreases plasma calcium by inhibiting bone release and kidney reabsorption.
Bone Mineral Density (BMD): Peaks in the 20s. Females experience a rapid decline after menopause.
Cellular Signaling: * RANKL: Binds to RANK to stimulate osteoclast development. * Osteoprotegerin (OPG): Inhibits RANKL binding, promoting osteoclast apoptosis. * Sclerostin: Produced by osteocytes; inhibits WNT signaling and osteoblast development. Inhibited by mechanical fluid flow (exercise) and PTH.

Anti-Resorptive Agents: * Bisphosphonates: Pyrophosphate analogs that inhibit Farnesyl diphosphate synthase (FPPS) in osteoclasts. Third-generation agents have higher binding affinity for hydroxyapatite and FPPS. * Denosumab: Monoclonal antibody against RANKL; discontinuation causes a rapid rebound in bone remodeling. * SERMs (Raloxifene): Tissue-selective estrogenic activity; inhibits osteoclast differentiation and apoptosis of osteoblasts.
Anabolic Agents: * Teriparatide / Abaloparatide: Synthetic PTH analogs. Intermittent administration increases BMD, while continuous infusion is resorptive. * Romosozumab: Anti-sclerostin monoclonal antibody that increases WNT signaling to stimulate bone formation.
Drugs Contributing to Bone Loss: Proton Pump Inhibitors (PPIs), Aromatase inhibitors, Thiazolidinediones (TZDs), and long-term Glucocorticoids (e.g., prednisone).

BMD Classification (T-score): * Normal: $-1.0$ or above. * Osteopenia (Low Bone Mass): between $-1.0$ and $-2.5$ . * Osteoporosis: $-2.5$ or below.
Screening Recommendations: * Women: Aged $\ge 65\text{ years}$ . * Men: Aged $\ge 70\text{ years}$ .
Calcium/Vitamin D Intake Guidelines: * Adults 19-50: $1000\,mg$ calcium, $400-600\,units$ Vitamin D. * Men 51-70: $1000\,mg$ calcium, $800-1000\,units$ Vitamin D. * Women $\ge 51$ and Men $\ge 71$ : $1200\,mg$ calcium, $800-1000\,units$ Vitamin D.

The 5 Ps of Sexual History: Partners, Practices, Protection, Past history, and Pregnancy Intentions.
Expedited Partner Treatment (EPT): A harm reduction strategy allowing the treatment of sexual partners without a physical exam.
Public Health Surveillance Goals: Identifying needs for prevention, characterizing at-risk populations, and measuring intervention impact.

Varicella (Varivax): Live attenuated virus; 2-dose series (12-15 months and 4-6 years).
Zoster (Shingrix): Recombinant Zoster Vaccine ( $RZV$ ); 2 doses administered 2-6 months apart for adults $\ge 50\text{ years}$ .
HPV (Gardasil 9): Recombinant 9-valent vaccine. 2 doses if initiated before the 15th birthday; 3 doses if initiated after. Approved for ages 9-45.
MPox (JYNNEOS): 2-dose series administered 4 weeks apart.

Hepatitis B Serology: * HBsAg: Indicates current infection (infectious). * HBsAb: Indicates immunity (via recovery or vaccination). * HBcAb: Indicates previous or ongoing infection (core antigen).
Hepatitis C Management: * FIB-4 Score: < 1.45 permits treatment in primary care; > 3.25 assumes cirrhosis. * Preferred Regimens: Mavyret (Glecaprevir/pibrentasvir) for 8 weeks or Epclusa (Sofosbuvir/velpatasvir) for 12 weeks.
HIV Pharmacotherapy: * Standard Regimen: 2 NRTIs (Backbone) + 1 Base (INSTI, PI, or NNRTI). * Tenofovir Formulations: TAF is safer than TDF regarding bone and renal toxicity.
HIV Prevention: * PrEP: Options include TDF/FTC, TAF/FTC, or long-acting Cabotegravir injections. * PEP: Must start within $72\text{ hours}$ of exposure; continued for 4 weeks using a 3-drug regimen.