Pharmacology ADME and Patient Considerations

Medication and Vaccination Considerations

• Various factors affect drug absorption, distribution, metabolism, and excretion (ADME)
• Food, gastric motility, and liver metabolism impact oral bioavailability
• IV administration bypasses first-pass liver metabolism, resulting in complete bioavailability and rapid distribution
• Controlled substances, like schedules III-V, have different prescription restrictions than schedule II in Oklahoma
• Patient factors, like allergies, dietary intake, and pregnancy/lactation, influence prescribing decisions
• Consider nationally recognized guidelines and patient-specific information when prescribing

Patient Factors

• Gut microbiome impacts drug metabolism, influencing drug efficacy and toxicity
• Age affects pharmacokinetics and pharmacodynamics, necessitating adjustments in elderly populations, using Beers Criteria
• Renal function affects drug excretion, notably in neonates and adults with declining function
• Excretion routes include unchanged or as metabolites in bile/feces, sweat, saliva, tears, and breast milk

Drug Interactions

• Co-administration with other drugs, supplements, food, and nutraceuticals can affect drug action
• Receptor desensitization occurs with continuous agonist stimulation, decreasing drug effect
• Drugs may compete for plasma protein binding sites, altering circulating levels and increasing adverse drug reactions
• Knowledge of CYP450 enzymes and their interactions (e.g. inhibition/enhancement) and effects on drug metabolism is crucial
• Drug-drug interactions affect absorption, protein binding, metabolism, and receptor binding. These affect the therapeutic effect or induce toxicity

Classifications and Considerations

• Agonists bind to receptors to elicit a response, while antagonists block agonist action
• Storage reservoirs (bone, fat) can influence drug distribution and duration of action
• Blood-brain barrier protects the central nervous system and only allows small molecules across; certain drugs mimic endogenous components to get across
• Factors affecting drug action (age, co-administration, and receptor desensitization)

Clinical Pharmacokinetics

• Bioavailability, volume of distribution, clearance, and elimination half-life determine drug disposition
• Therapeutic window defines the concentration range for desired effects with minimal adverse reactions
• Maintenance doses maintain steady-state concentration, while loading doses achieve steady state faster
• Dosing frequency depends on dose, half-life, and therapeutic range.

Vaccine Classifications

• Live attenuated vaccines use a weakened form of a virus, inducing strong immune responses but not suitable for immunocompromised patients or those with febrile illness and sometimes pregnancy
• Inactivated vaccines use killed pathogens, inducing a weaker immune response and requiring multiple doses or boosters
• Live attenuated vaccines are less stable and might require refrigeration
• Inactivated vaccines are more stable.
• Vaccine types include live attenuated, inactivated, subunit, polysaccharide, surface protein, toxoids, and mRNA.
• Vaccination considerations include age, comorbidities, risks for diseases, allergies to vaccine components and pregnancy
• Vaccination schedules for different vaccines have special considerations.
• Live vs attenuated vaccines: Live (weakened) and attenuated (killed) elicit strong, durable immune responses, but not for immunocompromised patients or during pregnancy; attenuated vaccines may be refrigerated. Inactivated vaccines elicit weaker responses, require multiple doses, and are stable, often suitable for certain healthcare settings or conditions.
• Pregnancy and lactation labeling rules are available (but not necessarily detailed in the notes).
• The Centers for Disease Control (CDC) Advisory Committee on Immunization Practice (ACIP) sets recommendations for vaccination schedules.

Drug Toxicity and Reactions

• Drug-induced toxicity results from ADME processes, leading to adverse drug reactions
• Allergic reactions are immune-mediated responses to drugs, ranging from mild rash to severe anaphylaxis
• Idiosyncratic reactions are unpredictable abnormal responses to drugs, often due to genetic predisposition
• Toxicology studies adverse effects of substances on living organisms

Drug Withdrawal and Abuse.

• Withdrawal symptoms, diagnosis, treatment, cross-tolerance to sedatives, and associations with mental/physical health conditions
• Pharmacotherapy of alcohol use disorder (AUD) after clinical evaluations and behavioral therapy (e.g. detoxification, anti-craving medication)
• FDA approved medications for AUD include Disulfiram, Naltrexone, Acamprosate
• Opioid use disorder (OUD) treatment involves detoxification, stabilization, and long-term management (especially with methadone, buprenorphine, or extended-release naltrexone).
• Treatment initially addresses physical dependence through detoxification and gradually reducing the dosage of opioids
• Long term treatment focuses on preventing relapse through relapse prevention, anti-craving medication, and cognitive-behavioral therapy
• Benzodiazepine use/abuse are commonly used as sedatives, hypnotics, and acutely for alcohol detoxification; Flumazenil (Romazicon) is an antidote.

Opioid Use Disorder.

• Opioid agonists activate mu opioid receptors (MOR) and are strong analgesics; tolerance, dependence, and withdrawal can develop

Cannabis

• Medicinal and psychoactive properties, A9-THC, legal implications, tolerance, dependence, and withdrawal, and adverse effects (also includes potential therapeutic uses)
• Synthetic forms of THC (e.g. dronabinol, Marinol) are used medically

Cannabidiol (CBD)

• Prominent cannabinoid in cannabis, not psychoactive, and available in hemp extracts (though less regulated)
• Potential therapeutic uses (pain, epilepsy, anxiety, mood disorders, neurodegenerative diseases, and opioid use disorder) and adverse effects.