PHCP311 Clinical Pharmacy and Pharmacotherapeutics 1 Midterms PDF

PHCP311: CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 1 - MIDTERMS MR. KENNETH JAMES MAGKASI, RPh 3rd Year | 1st Semester | 2024 - 2025 specific TOPIC...

PHCP311: CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 1 - MIDTERMS MR. KENNETH JAMES MAGKASI, RPh 3rd Year | 1st Semester | 2024 - 2025 specific TOPIC ❖ Smaller diameter of stimulation MANAGEMENT OF NERVOUS SYSTEM DISORDERS: (unmyelinated fibers evoked) = aching only / PAIN MANAGEMENT poorly localized (cannot specify pain) PAIN 3) Transmission A subjective, unpleasant, sensory, and Afferent nociceptive fibers synapse in the emotional experience associated with actual or spinal cord’s dorsal horn, releasing potential tissue damage or abnormal functioning excitatory neurotransmitters (eg, glutamate of nerves and substance P). Transmission Pain It may be classified as: The spinothalamic tract and other pathways 1) Acute: saglit lang bring the signal to the brain’s higher cortical 2) Chronic: problem with nerves (disregulated; structures → translates what to feel / longer) perception 3) Cancer pain 4) Perception SIMPLE PATHOPHYSIOLOGY OF PAIN The experience of pain occurs when signals reach higher cortical structures. A. Adaptive (Physiologic) Pain ○ Relaxation, meditation, and distraction can lessen pain (counter activity used to Nociceptive (ex: from touching something too hot, too cold, or sharp) and inflammatory pain Perception lessen the pain) (ex: trauma or surgery) are both adaptive and ○ Anxiety and depression can worsen pain protective Examples of distraction: ❖ Pain: normal sensation; way of body telling 1) Pinch the earlobe → has quick stimuli you that something’s wrong → so we can 2) Counterirritant → use of heat address it Adaptive / ❖ Chronic pain: occurs with the nerves 5) Modulation Physiologic ❖ Extensive pain → due to damage nerves, Possible modulating factors: Pain CNS 1) Glutamate Normal steps in processing pain: 2) Substance P 1. Transduction 3) Endogenous opioids 2. Conduction 4) γ-aminobutyric acid (GABA) Modulation 3. Transmission 5) Norepinephrine & serotonin 4. Perception The interface between neurons and 5. Modulation immune cells in the central nervous system (CNS) may facilitate maintenance of 1) Transduction chronic pain. Stimulation of nociceptors → found in both somatic & visceral structures B. Maladaptive Pain ○ Nociceptors found in both somatic and visceral structures, are activated by Pathophysiologic pain (eg, postherpetic Transduction mechanical, thermal, and chemical stimuli. neuralgia, diabetic neuropathy, fibromyalgia, irritable bowel syndrome, and chronic Noxious stimuli (ex. excessive heat, wound, headaches) is often described as chronic etc) → release of cytokines & chemokines pain. that sensitive and / or activate nociceptors ❖ Chronic pain = pathophysiologic pain due For us to feel pain → activation of nociceptors Maladaptive to diseases and conditions 2) Conduction Pain ❖ Nociceptors react extremely 1) It results from damage or abnormal Receptor activation leads to action functioning of nerves in the CNS or potentials that continue along afferent fibers peripheral nervous system (PNS). to the spinal cord. 2) Pain circuits sometimes rewire themselves ○ Stimulation of large-diameter, sparsely anatomically and biochemically, resulting in myelinated fibers evokes sharp, chronic pain, hyperalgesia, or allodynia Conduction well-localized pain. ○ Stimulation of small diameter, An increased sensitivity to pain and a. Hyperalgesia unmyelinated fibers produces aching, extreme response to pain poorly localized pain. A type of neuropathic pain characterized ❖ Larger diameter of stimulation (more by extreme sensitivity to touch even to b. Allodynia stimuli that do not normally provoke pain. myelinated fibers evoked) = more localized & ❖ Pain even with featherlight touch  ❖ Extensive reaction to certain stimuli SIGNS AND SYMPTOMS 1. Acute pain can be sharp or dull, burning, shock-like, tingling, shooting (specific part of the body), radiating, fluctuating in intensity, varying in location, and occurring in a temporal relationship with an obvious Symptoms noxious stimulus 2. Chronic pain can present similarly and often occurs without a temporal relationship to a noxious stimulus. Over time, the chronic pain presentation may change (eg, sharp to dull) 1. Acute pain: can cause (1) hypertension, (2) tachycardia, (3) diaphoresis (sweating), (4) mydriasis, and (5) pallor. ❖ Hypertension: due to release of catecholamines ○ These signs are seldom present in chronic pain. ○ Outcomes are predictable In chronic non cancer pain: 1) Depression, sleep disturbances, anxiety, Signs and employment and family instability tend to dominate → amplifies the pain 2) Comorbid conditions are often present, and treatment outcomes are often unpredictable Treat the comorbid conditions first to treat ❖ When risks does not outweigh 1) Give Acetaminophen or benefits the pain NSAIDs (Ibuprofen, ❖ Pain comes with inflammation 3) An interdisciplinary approach (eg, pain Mild Pain mefenamic acid) (NSAIDs → inhibit prostaglandin clinic) is preferred synthesis = dec stimuli) People with chronic pain are those who 2) Always consider ATC regimens currently experience financial difficulty 1) Combination opioid and because they are more vulnerable to stress Acetaminophen / Moderate NSAIDs Pain TREATMENT 2) Always consider ATC regimens ❖ Alleviated by non-opioid medications: acute, chronic pain ❖ Opioids: usually given for moderate ❖ Alleviated by opioid medications: cancer pain to severe pain ❖ However, if a patient can tolerate non Pain: subjective due to differences in pain tolerance (based opioids, it’s better since opioids can on response of stimuli) lead to addiction, tolerance and dependence. Pain relief that allows for attainment of Severe Pain 1) Opioid analgesics ❖ Always monitor the patient & a) Acute Pain defined functional goals. dispensing; excessive sedation → Examples: analgesics can cause respiratory depression, dependence (hallucinations), b) Chronic or Improve level of functioning, decrease pain, tolerance Non Cancer reduce medication use if possible, and ❖ Tolerance: inc the dose = achieve the same effect Pain improve quality of life. Pain relief that enables patients to tolerate A. Non-opioid Agents (Acetaminophen & NSAIDs) diagnostic and therapeutic manipulations Non-opioid Preferred over opioids for mild to and preserves function as much as Agents moderate pain c) Cancer Pain possible while minimizing adverse effects. NSAIDS reduce prostaglandin Do not use ordinary NSAIDs → use of 1) Decreases the number of pain opioids (most of the time) impulses in the CNS Algorithm of Acute Pain Management 2) May be useful for cancer-related bone pain and chronic low back pain 1) Identify pain source and treat underlying disease 1) NSAIDS 2) Presence of pain: Chronic use: may cause GI, cardiac and No: monitor the patient renal toxicities (due to inhibited Yes: assess pain severity → mild, moderate, severe prostaglandins) Topical NSAIDs: for treatment of superficial joint arthritis  ❖NSAID-induced ulcer: due to inhibited analgesia in minor ear, neck, and nose prostaglandins release causing surgery ulcerations 2) Lozenge form: for sore throat ❖NSAID-induced asthma: (-) COX, ❖ Not common in Philippines arachidonic acid used to produce COX Simple derivative of phenylpropionic acid would now be used to LOX. In doses of about 2400 mg daily: ↑ LOX = ↑ leukotrienes and ibuprofen is equivalent to 4 g of aspirin in lipoxygenase (bronchoconstriction) anti-inflammatory effect. Has analgesic and antipyretic activity Oral ibuprofen: is often prescribed in lower but little anti inflammatory effect doses (4g The concomitant administration of per day ibuprofen and aspirin: antagonizes the irreversible platelet inhibition induced by A.1 NSAIDS (Selective COX Inhibitors) → coxib 3. Ibuprofen aspirin Selective COX-2 inhibitor—about 10–20 ❖ Aspirin (80-100 mg) → antiplatelet times more selective for COX-2 than for Not a pain reliever → more commonly COX-1. used as an antiplatelet for CHF, blood ❖ Has a black box warning as it can clotting, prone to ischemia (has ↑ ADR at cause cardiotoxicity > 80-100 mg) 1. Celecoxib ❖ Pain perception is regulated by COX2 MOA: irreversibly acetylates COX & Associated with fewer endoscopic ulcers COX2 than most other NSAIDs. ❖ Available to market: May cause rashes probably because it is a 200 mg: analgesia, antipyretic sulfonamide moiety 400 mg: anti-inflammatory ❖ Causes Steven-Johnsons Syndrome Potent nonselective COX inhibitor and Enolcarboxamide related to piroxicam may also: that preferentially inhibits COX-2 over 1) Inhibit phospholipase A and C COX-1 2) Reduce neutrophil migration ○ Particularly at its lowest therapeutic dose 3) Decrease T-cell and B-cell proliferation of 7.5 mg/d. 4. Indomethacin 1) It has been used to accelerate closure of It is not as selective as celecoxib and may patent ductus arteriosus be considered “preferentially” selective ○ Patent Ductus Arteriosus: holes in the rather than “highly” selective. heart (arteriosus) fails to close; 2. Meloxicam It is associated with fewer clinical GI complications common in children symptoms and complications than 2) Can also be used for Rheumatoid arthritis piroxicam, diclofenac, and naproxen. Propionic acid derivative that inhibits both MOA: Blockade of thromboxane A2 does COX (nonselectively) and lipoxygenase not reach levels that result in decreased in 5. Ketoprofen 1) Concurrent administration of vivo platelet function (ex. aspirin) Probenecid elevates ketoprofen levels ❖ Meloxicam → even at high dose would and prolongs its plasma half-life. not inhibit the thromboxane A2 as much The only non-acid NSAID in current use; it as the aspirin is given as a ketone prodrug A.2 NSAIDS (Non-selective COX Inhibitors) Resembles naproxen in structure 1) Half-life of more than 24 hours Phenylacetic acid derivative, relatively 2) Permits once-daily dosing nonselective as a COX inhibitor 6. Nabumetone 3) Drug does not appear to undergo High dose: 150 mg/d, appears to impair enterohepatic circulation renal blood flow and glomerular filtration 4) Renal impairment: results in a 1. Diclofenac rate doubling of its half-life and a 30% Elevation of serum aminotransferases increase in the area under the curve. occurs more commonly with this drug than with other NSAIDs Naphthylpropionic acid derivative. The only NSAID presently marketed as a Propionic acid derivative with a possibly single enantiomer more complex mechanism of action than 7. Naproxen Naproxen’s free fraction: is significantly other NSAIDs higher in women than in men, but half-life is Its (S-) enantiomer: inhibits COX non similar in both sexes 2. Flurbiprofen selectively. Rarely associated with cogwheel rigidity, Propionic acid derivative NSAID. ataxia, tremor, and myoclonus 8. Oxaprozin 1) Has a very long half-life (50–60 1) IV: effective for perioperative hours), although oxaprozin does not  undergo enterohepatic circulation successfully to replace morphine in (similar with nabumetone) some situations involving mild to 2) Mildly uricosuric: ability to increase moderate postsurgical pain urination of uric acid An oxicam & nonselective COX inhibitor When used with an opioid: it may that at high concentrations also: decrease the opioid requirement by 1) Inhibits polymorphonuclear leukocyte 25–50% migration, Renal toxicity is more common with 2) Decreases oxygen radical production chronic use 3) Inhibits lymphocyte function A centrally acting synthetic analgesic, structurally related to opioids 9. Piroxicam One of the NSAIDs used for animals → dogs Naloxone: an opioid receptor blocker, C/I: PUD, hyperacidity, px prone to inhibits only 30% of the analgesic effect bleeding of tramadol 1) Long half-life permits once-daily dosing The drug may exert part of its analgesic 2) Dosages > 20 mg/d, an increased effect by (1) enhancing 3. Tramadol incidence of peptic ulcer and bleeding 5-hydroxytryptamine (5-HT) release A sulfoxide prodrug and (2) inhibiting the reuptake of Reversibly metabolized to the active sulfide norepinephrine and 5-HT metabolite and has enterohepatic cycling; ○ The mechanism of action of this drug this prolongs the duration of action to must involve both nonopioid and 12–16 hours opioid receptors 10. Sulindac ○ Tramadol does not have significant 1) Its rheumatic disease indications, 2) It suppresses familial intestinal anti-inflammatory effects polyposis S/E: Drowsiness 3) It may inhibit the development of colon, breast, and prostate cancer in humans A nonselective COX inhibitor with a short half-life (1–2 hours) and is not often used 11. Tolmetin Ineffective (for unknown reasons) in the treatment of gout A.3 Other Analgesics The active metabolite of phenacetin (toxic: produces NAP-Q) and is responsible for its analgesic effect It is a weak COX-1 and COX-2 inhibitor in peripheral tissues and possesses no significant anti-inflammatory effects ○ DOC for osteoarthritis (common in elderly = less prone to bleeding) 1) Although said to be equivalent to aspirin as an analgesic and antipyretic agent, 1. Acetaminophen acetaminophen lacks antiinflammatory Very limited data support the safety and efficacy of opioids for properties. chronic noncancer pain 2) It does not affect uric acid levels and Prone for misuse and abuse: before initiating opioid therapy, lacks platelet-inhibiting effects and employ treatment agreements outlining responsibilities 3) Dose greater than 4 g/d are not usually The onset of action of oral opioids is about 45 minutes, and recommended peak effect usually is seen in about 1 to 2 hours ○ Overdose = hepatic problems Onset of action: 45 mins Peak effect: 1-2 hrs Acute pain and fever may be effectively treated with 325–500 mg 4x a day q6h ATC An NSAID promoted for systemic use mainly as a short-term analgesic (not 2. Ketorolac longer than 1 week), not as an anti-inflammatory drug Effective analgesic and has been used B. Phenanthrenes E. Opioid Antagonists The first-line agent for moderate to A pure opioid antagonist that binds severe pain competitively to opioid receptors It is often considered the opioid of choice Does not produce analgesia or opioid side for pain associated with myocardial 1. Naloxone effects infarction → decreases myocardial oxygen It reverses the toxic effects of agonist and demand agonist–antagonist opioids ○ Oxygen demand: amount of oxygen Opioid antagonist → brings back the pain required for the heart to pump Also used for euthanasia F. Mixed Opioid Agonist-Antagonists Partial mu-agonist; kappa antagonist. 1) Itching/ pruritus: can cause allergic Like strong agonists but can antagonize reactions like itching or pruritus (before their effects 1. Morphine giving morphine, antihistamine first) 1. Buprenorphine Reduces craving for alcohol 2) Morphine-induced respiratory Uses: moderate pain & some depression: in patients with head trauma maintenance rehabilitation programs who are not ventilated, morphine-induced Kappa agonist; mu antagonist. respiratory depression can increase 2. Nalbuphine Similar to buprenorphine intracranial pressure and cloud the For moderate pain neurologic examination results. 3) Patients with underlying pulmonary Evaluation of Therapeutic Outcomes dysfunction are at increased risk for respiratory depression, which can be Pain intensity, pain relief, and medication side effects must be reversed by naloxone assessed regularly. Overdose: CPR (Coma, Pinpoint pupils, ○ The frequency of assessment depends on the type of pain, Respiratory depression) analgesic used, route of administration, and concomitant medications. Alone or combined with other analgesics ○ Postoperative pain and acute exacerbations of cancer (eg, acetaminophen) is commonly used for pain may require hourly assessment. 2. Codeine mild to moderate pain ○ Chronic nonmalignant pain may need only daily (or less Usually used as antitussive frequent) monitoring. Quality of life must be assessed Useful for moderate to severe pain, regularly. especially when combined with ○ NSAIDs can cause bleeding hence, not recommended for 3. Oxycodone nonopioids. laboring px ❖ Prone to dependence and abuse ○ Half life of NSAID should be complete before administering another medicine C. Phenylpiperidines The four A’s (analgesia, activity, aberrant drug behavior, and adverse effects) are key assessment measures for Less potent and has a shorter duration patients with chronic pain of action than morphine 1. Analgesia Do not combine meperidine with 2. Activity 1. Meperidine monoamine oxidase inhibitors because 3. Aberrant drug behavior severe respiratory depression or excitation, 4. Adverse effects delirium, hyperpyrexia, and convulsions Patients taking opioids should be counseled on proper intake may occur of fluids and fiber, and a stimulant laxative should be added Often used as an adjunct to general with chronic opioid use anesthesia, is more potent and faster 2. Fentanyl acting than meperidine. It is used for breakthrough cancer pain → sudden feeling of extensive pain D. Diphenylheptanes Has extended duration of action. ○ Studies show a growing number of methadone-related deaths. ○ Methadone + Chloral Hydrate intoxication = death 1. Methadone High doses cause cardiac arrhythmias. Do not titrate more frequently than every 5 to 7 days. Although effective for acute pain, it is used for chronic cancer pain