Pharm Final.pdf

Basic Principles of Pharm Pharmacology Pharmacotherapeutics ○ Branch of pharm that refers to use of drugs to prevent, treat, or Ddx disease ○ Pharmacokinetics How body absorbs, distributes, and eliminates drugs...

Basic Principles of Pharm Pharmacology Pharmacotherapeutics ○ Branch of pharm that refers to use of drugs to prevent, treat, or Ddx disease ○ Pharmacokinetics How body absorbs, distributes, and eliminates drugs ○ Pharmacodynamics Analysis of what drug does to body and exerts its effect Toxicology ○ Study of harmful effects of chemicals Drug Nomenclature Chemical Name Trade Name/Brand Name Generic name (Nonproprietary) ○ Shorter and derived from chemical name Brand vs. Generic Drugs Brand protected via patent Generic ○ Cheaper ○ Tested to assume bioequivalence Same type & amount of active ingredient Same administration route Same pharmacokinetic profile Same therapeutic effects Drug Approval Process Preclinical ○ Animals (1-2 yrs) Clinical (Human testing) ○ 3 phases w/ progressively larger subject sizes (5-6 yrs) Postmarketing Surveillance (Phase IV) ○ FDA monitors problems after drug intro to market (Indefinite timespan) Total time from conception to market 7-9 yrs ○ Orphan drugs (Dev for pop 5 min = medical emergency Keep them safe Parkinson’s Disease Introduction Slow, progressive degeneration of dopamine secreting cells within basal ganglia (substantia nigra) ○ TRAP - Resting Tremor, Bradykinesia, Rigidity, Postural Instability Dopamine & Acetylcholine are out of balance within the BG ○ Acetylcholine (excitatory) increasing inhibition → Leads to bradykinesia Causes No exact cause; likely multiple factors Genetic ○ Predisposition to developing lewy bodies ○ Free radical (O2) destruction of substantia nigra Environmental ○ Herbicides, Insecticides, Fungicides, industrial waste/heavy metals Drug Tx Overview Levodopa (Sinemet) ○ Converts to dopamine after crossing BBB ○ Best drug for resolving symptoms ○ Long term use limited by side effects are reduced efficacy Carbidopa (Sinemet) ○ Prevents premature conversion of levodopa to dopamine in periphery ○ Allows more levodopa to reach brain intact when given together Dopamine Agonists ○ Directly stimulate dopamine receptors in basal ganglia ○ May produce fewer side effects than Levodopa ○ Early use may delay progression of PD Anticholinergics ○ Inhibits excessive ACH influence caused by dopamine deficiency ○ Limited use due to side effects Amantadine ○ Inhibits effects of excitatory amino acid (Glutamate) in BG ○ May be used in early stages or added if Levodopa loses effectiveness  MAO-B Inhibitors ○ Inhibits enzyme that breaks down dopamine in BG ○ Dopamine may be able to be active longer ○ May improve symptoms in early stages ○ May be neuroprotective and delay progression COMT Inhibitors ○ Help prevent dopamine breakdown in peripheral tissues ○ Allows more levodopa to reach brain ○ Useful as adjunct Tx ○ May improve and prolong effects of levodopa Levodopa-Carbidopa (Sinemet) Background ○ Levodopa L-dopa that is converted to dopamine by Dopa Decarboxylase enzyme ○ Carbidopa Blocks the dopa decarboxylase enzyme from converting L dopa to dopamine until after it goes through the BBB ○ W/o chemical assistance only 1% of levodopa makes it through BBB & converts to dopamine ○ Initial Dosing: 25mg Carbidopa/100mg Levodopa 2-x/day Avg maintenance dosage of Levodopa 600-700mg/day Problems w/ sinemet ○ End of dose akinesia Drug wears off prior to next dose Leads to Sx towards end of dosage ○ On-Off Phenomenon Effectiveness spontaneously and suddenly reduces leading to significant increase in Sx May be due to altered absorption (levodopa absorbs erratically) May be due to extrinsic factors affecting absorption ○ Freezing Episodes Poorly understood, may not be meds related Recommended low protein meal if Sinemet is taken w/ meal ○ Protein breaks down into amino acids which compete for absorption w/ Sinemet Levodopa “Drug Holiday” ○ Systetic removal of Levodopa from pt drug regimen for 3 days - 3 weeks Allows body recover from toxicity and tolerance May cause med dosage to be reduced 30-50% after holiday w/ same therapeutic effect ○ No longer recommended  Pt of meds → Severe immobility (Due to increased risk of falls) Can lead to DVT, PE, Pneumonia ○ New meds & extended release formulas have improved long term use of PD meds Side Effects ○ GI problems ○ CV problems → OH ○ Dyskinesia ○ Behavioral Changes Too much dopa → hallucinations ○ Diminished response to meds ○ Fluctuations in response to meds New PD Research Focus on balance of NT w/ PD Depletion of dopamine causes an imbalance w/ ACH levels ○ Increased ACH originally associated w/ dyskinesia ○ Latest research shows balance between ACH and dopamine within the striatum as much more intricate ACH production in BG may decrease as well ○ May be cause for memory deficits/dementia w/ PD Newer PD tx looks to target both NT balances Neurosurgical Interventions Stem Cell Transplant ○ Stem cells placed in substantia nigra ○ Very controversial / Questionable efficacy Pallidotomy/Thalamotomy ○ Surgical lesion in specific neuronal pathways ○ Used in advanced stages Deep Brain Stimulation ○ Surgically implanting electrodes into thalamic area normalizes neuronal circuitry within BG and reduces symptoms ○ Especially useful for tremor Anesthesia General Anesthetics Meds used to illicit unconsciousness for surgical procedures ○ Different anesthesia and depending on length of procedure/PMHx ○ Many are in gaseous form (Halothane, NO) ○ IV barbiturates, Benzodiazepines, & Opioid analgesics can be used as an adjunct, to provide pre-op relief, or as an alternative if PMHx contraindicates using gaseous forms  Propofol (diprivan) popular for shorter procedure for its ability to quickly allow the pt to “wake up” Three is not a single general anesthesia that can produce ○ Immobility ○ Unconsciousness ○ Amnesia ○ Analgesia ○ inhibition of autonomic reflexes ○ Is rapidly reversible ○ Very safe Need a combo of drugs = balanced anesthesia General Anesthetics MOA May bind to receptors (GABA, Potassium, Ach, NMDA, Opioids) depending on med and induce either inhibition or reduced excitation of neuron ○ Affects consciousness ○ At higher doses will illicit muscular paralysis (not good) Neuromuscular blockers ○ Used as an adjust to the anesthesia when pt required mechanical ventilation (Also used w/ vent dependent patients) Reduces muscular resistance to ventilation (Easier for machine and to ventilate) Pt will not “buck” the vent allowing for improved ventilation and comfort Prevents movement during surgery General Anesthesia Side Effects Too high dose = death Fatigue Confusion Shivers/Chills N/V Weakness ○ Seriously ill pt and geriatrics will metabolize meds more slowly ○ Effects of anesthesia take longer to wear off May take hours to days ○ Can lead to post-op delirium Malignant hyperthermia ○ Rare side effect ○ Causes rapid rise in body temp, sweating, mm rigidity & tachycardia ○ Medical emergence NSAIDS, RA, OA & PCA Nonsteroidal Anti-Inflammatory Drugs  Properties ○ Decrease inflammation (Anti-inflammatory) ○ Relieve minimal to mod pain (Analgesia) ○ Reduce elevated body temperature (Antipyretic) ○ Reduce blood clotting by inhibiting platelet aggregation (Anti-clotting) Mainstay of Tx inflammatory and mild/mod pain Many available OTC Aspirin Vs. Acetaminophen Aspirin original NSAID Acetaminophen not an NSAID Aspirin ○ Analgesic, Antinflammatory, Antipyretic, Blood clot inhibitor Acetaminophen ○ Analgesic & Antipyretic only ○ Does not Inhibit blood clotting or inflammation How do NSAIDs work: Prostaglandins Important hormones that promote cellular health ○ Inflammation ○ Pain response ○ Pyretogenic ○ Dysmenorrhea ○ Thrombus formation Implicated in various pathologies ○ HTN, neoplasms, MS, encephalomyelitis, DM NSAID MOA Inhibit prostaglandin & thromboxane production ○ Inhibit COX within the cell ○ COX1 Help regulate cellular hemostasis Platelet aggregation, stomach lining, kidneys ○ COX2 Produced by inj cell to mediate pain & inflammatory response Depending on NSAID, will be selective or non-selective COX1/COX2 enzyme ○ Determines specific efficacy profile Common NSAIDs Ibuprofen (Motrin) ○ Non selective ○ Fewer GI side effects NSAID Adverse Drug Reactions Heart attack & stroke  GI bleeding ○ (lower w/ selective COX2 inhibitors) Gastric ulcers Skin rash Renal insufficiency Management of RA Chronic, systemic autoimmune disease characterized by synovitis & destruction of articular tissue Affects small synovial joints in hands/feet & large joints like knee/hip Causes pain, stiff inflammation Periods of exacerbation/remission, but progressive in nature Affects 1% of population 3x more likely in women Pathophysiology of RA Autoimmune response in genetically predisposed people ○ Virus, infection ○ Environmental sources Causes formation of antibodies recognized by body as antigens Antibodies against these antigens cause immune response Immune response causes destruction of articular cartilage and bone ○ Essentially a defect in pt immune response People w/ RA have a higher incidence of A-fib RA Drug Tx 3 main classes ○ NSAIDs ○ Glucocorticoids Glucocorticoids = corticosteroids Powerful anti-inflammatories ○ Disease-Modifying Antirheumatic Drugs (DMARD) Typically alter immune system cell function modifying the immune response By altering immune response stop inflammation/joint destruction Glucocorticoids MOA Bind to receptors on macrophages/leukocytes ○ Move into cell nucleus and bind to genes that cause inflammatory response ○ Inhibit transcription factors to produce inflammatory cytokines ○ Inhibit inflammatory substances/promote anti-inflammatory protein production Blunt both cellular and chemical components of the inflammatory response Catabolic side effects on all supportive tissues ○ Increased bone loss, mm wasting/weak, HTN, aggravation, infection risk Corticosteroids (Glucocorticoids) Delivery can be oral, IV, topical, or injection Look for suffix: -SONE DMARDs MOA (Non Biological) Antimalarials ○ Affect immune function by stabilizing lysosomes, inhibiting T cell function, and impair RNA/DNA synthesis ○ Overall MOA unclear ○ Most are oral except Aurolate (IM) ○ Adverse effects Retinal toxicity at high doses HA GI Distress Gold Therapy ○ Inhibit enzymes that influence function of T cells and phagocytes May take long time for effect ○ Adverse effects GI distress Oral mucosa irritation Rashes/Dermatitis Proteinuria Conjunctivitis Thrombocytopenia, Leukopenia Other non-biologicals ○ Inhibit DNA/RNA synthesis altering immune function ○ Overall MOA not well known ○ Adverse effects GI distress Hepatotoxicity Hematologic disorders Hair loss Biologic DMARDs MOA (Tumor Necrosis Factor Inhibitors) Bind to tumor necrosis factor alpha ○ Key mediator promoting inflammatory and joint erosion ○ TNF unable to activate inflammatory response ○ Adverse effects URI Sepsis Malignancy HF  Overall adverse effects incidence fairly low Biologic vs. Non Biologic DMARDs What difference ○ Non biologic target the entire immune system ○ Biologic inhibit specific portion of the inflammatory process What does this mean ○ Biologic side effect profile is significantly less Hydroxychloroquine (Plaquenil) Medication normally used to prevent or Tx malaria Precise MOA is unknown, may interfere w/ cell wall or enzymes of parasite Indicated for RA & SLE (autoimmune disease) ○ Exhibits anti-inflammatory and immunomodulating effects ○ Can be very effective as a DMARD to reduce symptoms and exacerbations of RA and SLE Major side effects ○ Irreversible retinal damage ○ Prolong QT interval ○ Ventricular Arrhythmia ○ Heart block ○ Fatal cardiomyopathy ○ Myopathy ○ Neuropathy ○ Hypoglycemia Some evidence that Plaquenil has some antiviral benefits ○ Not approved for Tx of COVID OA Most common joint disease ○ 50% ppl over 65 Not an immune response ○ Intrinsic defect in cartilage and subchondral bone ○ Essentially the joint is overused and unable to repair self quickly enough Causes pain, weak, loss of ROM, localized edema Typically meds NSAIDs, Viscosupplementation, Glucosamine & Chondroitin ○ Acetaminophen first choice for mild/mod OA Viscosupplementation Hyaluronic acid injected into arthritic joint ○ Helps restore viscosity of synovial fluid ○ Typically 3-5 weekly injections ○ Some may be single injection ○ Can last 6 Mo - 1 yr  ○ Can delay knee for joint replacement No PT that day, do not want to move it around ○ Discuss w MD Glucosamine & Chondroitin Sulfate Key ingredients in production of components for articular cartilage and synovial fluid ○ Oral, dietary supplement (OTC) ○ Minimal side effects ○ Overall efficacy is questionable Patient Controlled Analgesia (PCA) Allows pt ability to self medicate (usually for pain) as needed rather than dependent on staff System can be modified to limit dosing ○ Can limit a specific amount for any time frame Allows for medication release directly to bloodstream (no first pass) Opioids usually used for pain relief Allows for consistent amount of drug in blood plasma improving pain relief PCA Types IV ○ Most common ○ Attaches to IV line w/ needle into peripheral vein Epidural ○ Catheter is placed in epidural space within spinal canal ○ Meds much more effective acting directly at spinal level Regional ○ Catheter placed directly into joint space/area above nerve ○ Usually used w/ local anesthetics Transdermal ○ Iontophoresis to deliver analgesic meds through skin Local Anesthetics Used to perform surgical procedures ○ Allows rapid recovery w/ lack of residual effects vs general anesthesia ○ No post op confusion or altered mental status ○ Also used for short term pain relief May be administered via phonophoresis or iontophoresis Most have suffix -caine ○ Derivative of cocaine ○ Lidocaine, Benzocaine, Etidocaine Anesthetics MOA Inhibits opening of Na channels on N. membranes ○ Block action potential propagation  Drug Deliver ○ Transdermal, Topical, Infiltration, Peripheral N. block, epidural or spinal n block (subarachnoid space) Global effect below site of administration (usually L3-L4) Delivery method determines overall effect Respiratory Drugs Respiratory System Responsible for mediating gas exchange between external environment and internal bloodstream The Upper Respiratory system warms and moistens the air ○ Protects lungs from environmental irritants Gas exchange occurs between alveoli and the pulmonary circulation Many pt have both acute and chronic pulmonary conditions ○ Understanding medication effects on PT is critical across all settings Respiratory drugs Responsible for maintaining proper airflow & gas exchange within the respiratory passages 2 main categories ○ Minor Nasal congestion, coughing, seasonal allergy ○ Chronic/Serious Asthma, bronchitis, emphysema COPD = Chronic bronchitis & Emphysema Respiratory meds may affect CV/aerobic function during PT Drugs for Cough/Cold/Allergies Antitussives Suppress cough Often combo w/ other meds for combo symptoms May not be justified for use w/ active and productive cough Generally not used kids under 6 ○ Not effective Questionable efficacy for OTC remedies ○ Dosage may be far less than needed for cough suppression Codeine antitussives inhibit cough reflex at brainstem level ○ Addictive effects Non-opioid antitussives inhibit histamine on respiratory mucosa or anesthetic on respiratory epithelium Decongestants  Help w/ congestion and mucous damage from respiratory system Most are Alpha-1-Adrenergic Agonists ○ Stimulate vasoconstriction in nasal mucosa Dries up mucosal vasculature ○ Can mimic effects of CNS stimulants at higher dose ○ Pseudoephedrine & Ephedrine used in manufacturing methamphetamines OTC sales now fellow the counter Only allowed specific amount May increase resting HR and overall HR w/ aerobic activity Decongestant nasal sprays should only be used short term (3 days) ○ Any longer can increase congestion Antihistamines Tx respiratory symptoms due to viral infection and allergic response to seasonal allergies Histamine is endogenous chemical used to modulate allergic reactions (among other functions) ○ H1 receptor implicated in allergic reactions and respiratory functions Located on respiratory and vascular tissues Medication blocks the H1 receptor Decrease nasal congestion Reduce mucosal irritation and discharge (H1 receptor can cause airway constriction/inflammation) Decrease coughing and sneezing in secondary effect Can cause sedation, fatigue, dizzy, blurred vision, GI distress, incoordination ○ New antihistamines do not cross BBB will not cause sedation Mucolytics and Expectorants Attempt to reduce the viscosity of respiratory secretions ○ Usually combined w/ decongestants & antihistamines ○ Some question beneficial effects ○ Mucolytics Acetylcysteine Breaks disulfide bonds in mucoproteins, forming less viscous secretions ○ Expectorant MOA is not fully understood Increases respiratory secretions which encourages ejection of mucous and phlegm Mucinex only FDA approves ○ Both drug classes have low side effect profiles Drugs to maintain airways in Obstructive Disease Asthma & COPD Characterized by bronchospasms, airway inflammation, mucous plugging  Meds goal is to prevent or reverse bronchoconstriction Meds of choice ○ Bronchodilators (Beta - adrenergic agonists, xanthine derivatives, anticholinergics ○ Anti inflammatories (steroids) Beta-Adrenergic Agonists Stimulate B2 receptors relaxes bronchiole smooth mm ○ Produce bronchodilation Administered orally, Sub Q, or inhalation ○ Oral and sub Q reaches distal branches or airways (w more side effects) Inhalation is primary method ○ MDI - Metered dose inhaler Spacers used to improve dose and compliance ○ Nebulizer ○ DPI - Dry powder inhaler “Rescue” Inhalers onset of action quicker, longer acting meds take longer for onset of action Adverse effects ○ W excessive use can increase bronchial responses to allergens and irritants ○ Airway irritation ○ Tolerance Used in combo w other meds ○ B-1 receptor agonists may cause cardiac irregularities ○ Nervous, Restlessness, Tremor ○ Alpha receptor agonists can increase HR Important to know w PT Anticholinergic Bronchodilator Block muscarinic cholinergic receptors in lungs and block ACH induced bronchospasm ○ Lungs innervated by vagus N receive efferent fibers that release ACH onto respiratory smooth mm cells ○ Emphysema/Chronic bronchitis bronchoconstriction appears due to increased vagal tone and ACH release ACH influence in lungs leads to airway inflammation, increased mucous production, and cell proliferation Cornerstone of COPD Tx (Ipratropium (atrovent), Tiotropium (Spiriva)) Side effects: dry mouth, constipation, urinary retention, tachycardia, blurred vision Overall low side effect profile Cholinergic Receptors ○ Nicotinic Mediates transmission to postganglionic neuron  ○ Muscarinic Mediates effects of ACH on brain, helps contract smooth mm, reduce HR, increase salivation, and sweat secretion Glucocorticoids Used to control inflammation mediated bronchospasm due to their powerful anti-inflammatory effects Glucocorticoid = Corticosteroid ○ Inhibit production of proinflammatory substances (prostaglandins, cytokines, leukotrienes) and increase production of anti-inflammatory proteins ○ Usually administered via IV in acute episodes ○ Given orally or inhaled for long term use Adverse effects greatly reduced w inhalation (rinse mouth out) Adverse effects ○ Catabolic effect, resistant to effect, HTN, hyperglycemia, aggravates DM, growth retardation in children Leukotriene Inhibitors Inhibit the production of leukotrienes ○ Leukotrienes help mediate airway inflammation ○ Similar structure and function to prostaglandins Medications will either inhibit an enzyme used to produce Leukotrienes or are receptor antagonists within pulmonary tissue Usually combined w/ other drugs to maintain asthma and COPD ○ Corticosteroids/Beta agonists ○ May help steroid work better and at a lower dose Common Brands - Singulair, Zyflo, Accolate Very minimal side effect profile due to specific action ○ Suicide rates increasing w/ singulair use in children Bronchial Asthma Bronchial smooth mm spasm, airway inflammation and mucous plugging due to stimulation ○ Allergens, exercise, cold, psychological stress, chemicals ○ Overall exact mechanism not known ○ Tx has changed recently Corticosteroid inhalers now first line Tx in addition to long acting Beta-2 agonists Tx combined (Advair, Dulera, Symbicort) ○ “Rescue” inhaler still standard Tx All pt w asthma need to bring rescue inhaler to PT ○ Drug regimen depend on pt COPD Bronchospasm Tx  Long standing inflammation & irritation causes frequent coughing Meds look to manage the bronchitis and emphysema Anticholinergic and long acting B2 agonists used to promote airway patency Theophylline may be used for anti-inflammatory properties Steroids may be used in conjunction w other Tx Medication mgmt will be tailored to individual pt Respiratory Issues w Cystic Fibrosis Disease results in thick, viscous secretions ○ Mucous plugs block pulmonary tree and ducts in glands & organs ○ Plugs lead to pneumonia, bronchiectasis, fibrosis & infections ○ Pulmonary issues usually lead to mortality Multiple drugs prescribed to improve breathing ○ Mucolytics to thin out mucus ○ Expectorants to help clear mucus plugs ○ Systemic glucocorticoids to reduce inflammation ○ NSAIDs to reduce inflammation ○ Bronchodilators to facilitate open airway passages ○ Respiratory hygiene Postural drainage, breathing exercises Mm Relaxants / Spasticity Tx Mm Relaxants Used to Tx hyperexcitable mm tissue: Spasticity & Spasms Largely prescribed Can complement PT therapeutic Tx Act at level of spinal cord, NMJ or mm cell Do not prevent mm contraction, they attempt to normalize mm excitability Spasm Increased mm tension due to injury or inflammation ○ Mm strains/N. Root impingement Not velocity dependent Continuous Tonic contraction May be caused by increased afferent nociceptive response at spinal cord, exciting AMN May be due to protective response to prevent mm tearing ○ Build up in lactate from tonic contraction causing pain Spasticity Occurs due to damage to spinal cord or brain ○ SCI ○ TBI ○ MS  Exaggerated stretch reflex ○ Velocity dependent Supraspinal inhibition or control is lost ○ Alters cortical control of stretch reflex and AMN excitability Graded via Modified Ashworth Scale Anti Spasm Drugs Diazepam (Valium) ○ Widely prescribed ○ Binds to receptors at synapse to increase GABA inhibition at synapse May help w mm relaxation by binding to GABA receptor on AMN in spinal cord Also has supraspinal effects leading to generalized sedation ○ Used to Tx mm spasms throughout the body, including the larynx ○ Can produce tolerance and dependency Sudden withdrawal can lead to seizures, anxiety, tachycardia, and death Taper dose Low therapeutic index Should only be used in the short term Centrally Acting Anti Spasm Drugs Not well defined MOA Referred to “polysynaptic inhibitors” ○ May reduce AMN excitability by inhibiting neurons along reflex arx ○ Some may affect GABA receptors similar to Diazepam ○ Some may affect serotonin levels Serotonin Syndrome (Cyclobenzaprine (Flexeril)) All likely cause global decrease in CNS excitability leading to mm relaxation as secondary effect Used for short term relief of spasm in conjunction w PT and other meds (NSAIDs/Analgesics) Agents ○ Norgesic = Orphenadrine + ASA + Caffeine Less Drowsy, All other Agents drowsy ○ Flexeril increases serotonin levels Anti Spasm Meds Side Effects Drowsy Dizzy Nausea Light headed Ataxia HA  Tolerance & physical dependence Should be used short term only Disorders Serotonin Syndrome “Hot & Wet” ○ Post Exposure to Serotonin Agonists ○ Develops within 24Hrs; resolves within 24Hrs w Tx ○ Sx Altered mental status Mm rigidity (esp in LE) Hyperreflexia Increased bowel sounds Diaphoresis Neuroleptic Malignant Syndrome ○ Postexposure to dopamine antagonist ○ Develops over a period of days to weeks; resolves approx 9 days w/ Tx ○ Sx Neuromuscular hyperactivity manifesting as rigidity and bradyreflexia Malignant Hyperthermia ○ Post Exposure to inhalation anesthetics or depolarizing mm relaxants (succinylcholine) ○ Develops within 24 hrs; Resolves within 24-48 hours with Tx ○ Sx Rising end tidal CO Mottled skin w areas of flushing and cyanosis Rigidity Hyporeflexia Anticholinergic Toxicity “Dry as a Bone” ○ Post Exposure to anticholinergic agents ○ Develops within 24 Hrs; resolves within hours to days w Tx ○ Sx Urinary retention Decreased bowel sounds Hot and dry erythematous skin w normal mm tone & reflexes Antispasticity Medications Used to reduce or inhibit spasticity at either a level of specific mm or cortex Multiple administration routes ○ Orally, IV, pump, injection Used for long term mgmt of spasticity ○ To reduce pain and improve function Diazepam (Valium)  ○ A Bind to receptors at synapse to increase GABA inhibition at synapse ○ U Spasticity related to SCI & CP ○ Pro Effective agent ○ Con Dosage required to reduce spasticity tends to cause significant sedation & psychomotor issues Addictive & pt can become tolerance Withdrawal symptoms can be significant Used for both Spasms & Spasticity Baclofen (Oral) ○ A Binds w/ GABA receptors becoming GABA agonist Inhibits transmission within SC Inhibits AMN by inhibiting excitatory neurons that synapse w the AMN (presynaptic inhibition) Acting on the AMN itself (Postsynaptic inhibition) ○ U Tx spasticity related to SCI & SC demyelination related to MS ○ Pro Causes less generalized mm weakness compared to other relaxants Fewer side effects ○ Con Drowsy Less effective w supraspinal lesions (CVA, Cerebral Palsy) as these pt more susceptible to adverse effects Baclofen (Intrathecal) ○ A Same as oral, catheter placed in to subarachnoid space giving localized action to SC & reducing dosage required Used for severe intractable spasticity ○ U Used for severe intractable spasticity w SCI, MS, CVA, TBI, and CP Does not have sedative effect that oral baclofen has w supraspinal inj Pain relief from severe spasticity ○ Pro Lower dosages and minimal side effects Ability to tailor dose  Ability to reduce spasticity and improve function that was masked due to spasticity ○ Con Pump malfunction Overdose Tolerance Dantroline Sodium (Dantrium) ○ A Binds to receptors in the calcium channel within mm sarcoplasmic reticulum inhibiting channel opening and release of calcium during excitation thereby reducing contraction and enhancing relaxation ○ U Severe spasticity from SC lesions and cerebral lesions Tx malignant hyperthermia (side effect of certain anesthesia/meds) ○ Pro Only mm relaxant that works directly at skeletal mm level ○ Con Generalized mm weakness Non-specific hepatotoxicity Drowsiness Dizziness Gabapentin (Neurontin) ○ A Inhibits Calcium entry into presynaptic nerve terminals reducing excitatory NT release and decreasing CNS excitation ○ U SCI & MS Also Tx neuropathic pain ○ Pro Well tolerated Easy administration ○ Con Sedation Fatigue Dizzy Ataxia Tizanidine (Zanaflex) ○ A Alpha2 adrenergic agonist that inhibits interneuron firing to the AMN Reduced stimulation of AMN leads to mm relaxation  ○ U MS, SCI, CVA, TBI May slow neuronal recovery in acute phase ○ Pro Well tolerated Easy administration (oral) Less side effects ○ Con Sedation Dizzy Dry mouth Overall minimal side effects Botulinum Toxin (Botox) ○ A Inhibits release of ACH from presynaptic terminals at the skeletal NM junction Results in mm paralysis of mm fibers supplied at the terminal ○ U TBI, CVA, SCI, MS Used in plastic and reconstructive surgery on the face and neck to relax mm and reduce lines ○ Pro Injected directly at mm level Only need injection about every 3 Mo Allows physician to be selective w inhibition to maximize function ○ Con Limited amount can be used, wears off after 3 Mo Need appropriate injection site identified (NM junction) EMG can be helpful Can be fatal systemically Endocrine Pharmacology Endocrine Drugs Homeostasis by secreting endogenous chemicals used to mediate various processes Hormone supplementation mainstay of many medications Many endocrine glands ○ Hypothalamus ○ Pituitary ○ Thyroid ○ Parathyroid  ○ Pancreas ○ Adrenal ○ Gonads Hypothalamus connects the NS w the endocrine system to regulate bodily function. Regulates the release of hormones from the pituitary gland and makes hormones. It is the “captain of the ship” for endocrine control Adrenocorticotropic hormone (ACTH) is a hormone produced in the anterior or front, pituitary gland in the brain ○ The function of the ACTH is to regulate levels of the steroid hormone cortisol, which is released from the adrenal gland Adrenocorticosteroids Adrenal Cortex produces 2 adrenal steroids ○ Glucocorticoids Cortisol, Corticosterone Control metabolism and body's response to stress ○ Mineralocorticoids Aldosterone Maintain fluid and electrolyte balance Can be administered 2 ways ○ Physiologic dose Dose equivalent to endogenous production (hormone replacement) ○ Pharmacologic dose Higher dose than physiologic to capitalize on specific effect Anti-inflammatory effects of corticosteroids Glucocorticoids Glucocorticoids = Cortisol = Hydrocortisone Normal cortisol release peaks at 8 am (Circadian Rhythm) ○ Prepares body for increased activity Role is to increase blood glucose and liver glycogen ○ Facilitates breakdown of mm to be transported to liver and stores as glycogen ○ Inhibits glucose uptake into mm & fat allowing more glucose available in bloodstream Can indirectly influence type II DM formation if person is stressed Glucocorticoids & Endocrine Disorders Cushing Syndrome: Excessive Cortisol secretions from Adrenal glands ○ Results in “moon face”, excessive central fat, weakness, HTN, glucose intolerance ○ Tx is Adrenalectomy w supplement therapy Addison Disease: Lack of aldosterone & cortisol production ○ Extreme fatigue, low BP, salt craving, N/V mm & joint pain, depression  ○ Acute adrenal failure (Addisonian crisis) Severe low BP, LOC, hyperkalemia/hyponatremia, pain, death ○ Tx is HRT (Hormone Replacement Therapy) Male & Female Hormones Androgens: Testosterone ○ Produced in gonads in men Estrogen & Progestins ○ Produced in ovaries in females Control reproduction and expression of secondary sexual Cx Many uses medically ○ Contraception, disease modification Potential for abuse ○ Anabolic steroids Androgens Clinical Use ○ Replacement Therapy Used w testes removal, lack of production due to aging ○ Catabolic states Severe illness May be used to help build mm ○ Delayed puberty ○ Breast cancer ○ Anemia Stimulates erythropoietin synthesis from kidneys ○ Hereditary Angioedema Androgens act on liver to restore certain clotting factors Abuse ○ Anabolic steroids Used to increase mm power, strength & bulk Stacking, taking several to max effects ○ Adverse effects Liver damage CVD Abnormal bone mineralization Mood swings/aggression Altered sexual function Impact on rehab ○ At physiologic doses - no impact ○ Possible benefit to supplement w older men  Inconclusive evidence, however, some studies show modest improvement in function, strength, and cognition ○ Major impact Schedule III substance Illegal Detrimental health effects Banned by most sporting agencies Need to educate pt on risks Estrogen/Progesterone Vital for sexual maturation, development of female sexual characteristics Regulates uterine cycle/menses ○ Cyclic production - follow 28 day cycle ○ Estrogen steadily increases during first 1/2 of cycle Cumulative in ovulation mid-cycle Can vary greatly, especially in younger women ○ Progesterone increases during 2nd half of cycle Prepares body to implant fertilized egg Regulates menstrual cycle Pharmacologic Use ○ Osteoporosis ○ Hypogonadism ○ Regulate irregular menstrual cycle ○ Menopausal symptoms Estrogen replacement therapy (fell out of favor) ○ Cancer Tx ○ Endometriosis ○ Oral Contraceptives Risks CVD, DVT (esp if smoker) Thyroid Hormones Main focus is controlling metabolism ○ Increase BMR ○ Increase body temp ○ Increase CO/respiration ○ Also promote natural growth & development Thyroid secretes 2 hormones ○ Thyroxine (T4) ○ Triiodothyronine (T3) 2 Autoimmune disease affect thyroid ○ Graves Disease causes your thyroid to overproduce hormones  ○ Hashimoto's Disease causes your thyroid to eventually reduce hormone production Normal TSH levels is.4-4.0 ○ If your already being treated for a thyroid disorder the normal range is.3-3.0 ○ A value above the normal indicates that the thyroid is underactive. Hypothyroidism Hyperthyroidism Sx ○ Nervousness ○ Weight loss ○ Tachycardia/Arrhythmia ○ Heat intolerance ○ Mm wasting ○ Dyspnea/Reduced vital capacity Meds ○ Antithyroid meds (methimazole) Inhibits Thyroid hormone synthesis ○ Iodide (high dose) ○ Radioactive Iodine Gland ablation Very safe Works w graves disease ○ Surgical removal Tricky surgery Extremely vascularized Hypothyroidism Sx ○ Lethargy ○ Weight gain ○ Bradycardia ○ Cold Intolerance ○ Weakness ○ Brittle hair & nails ○ Drooping eyelids/periorbital edema Meds ○ Hormone Replacement Therapy (HRT) Levothyroxine (Synthroid) drug of choice Need to have TSH level periodically checked-adjust dosage Very safe Tx Overdosing meds gives symptoms of hyperthyroidism  GI Pharm Normal Physiology When reflux occurs, body's defense mechanisms should take over ○ Mechanical clearance of refluxate by increased esophageal motility Secondary contractions ○ Chemical clearance achieved by increased salivation Both mechanisms work together to minimize damage to mucosa from acid exposure Pathophysiology of GERD 3 Mechanisms that result in pathologic GERD Transient Relaxation of the LEs (TLESRs) ○ Part of the physiologic mechanism of belching Hypotensive LES ○ Gastric distension ○ Foods/Hormones/Medications ○ PMH: Scleroderma Anatomic Disruption of the GEJ ○ Hiatal Hernia ○ Post-Op changes Non-Pharm Tx Lifestyle modifications ○ Weight loss ○ Elevate HOB ○ Smoking cessation ○ Stress mgmt Dietary Modifications ○ Avoidance of common triggers ○ Smaller meals, more frequent ○ Avoid lying down within 2-3 hours of meals Anti-Acid Medications Anti-acids H2 blockers Proton pump inhibitors Antacids Used PRN for symptoms occurring less than 1-2x per week “Neutralize” gastric pH within 5 min, lasting 30-60 min ○ Mechanism of neutralization of acid varies ○ Essentially a base that combines with excessive H+ ions to increase pH ○ Usually contain aluminum, magnesium ○ Taken as a tablet or liquid Histamine 2 Receptor Antagonist - “H2 Blockers”  Block the histamine receptor on the parietal cell of the stomach Cimetidine ○ First drug approved in this class - has most side effects and less effective ○ Can cause gynecomastia, loss of libido & impotence ○ Interferes w CYP450 metabolism so has more drug-drug interactions Famotidine ○ Generally, well tolerated, often used at first line in this class ○ Does not interfere w CYP450 metabolism pathways so few if any drug interactions Ranitidine ○ Currently on recall during NDMA contamination All take approximately 2.5 Hrs to reach peak concentration but last 4-10 Hrs Proton Pump Inhibitors Omeprazole, Lansoprazole, Pantoprazole, Esomeprazole, Dexlansoprazole, Rabeprazole MOA ○ Irreversibly binds to and inhibits the hydrogen potassium ATPase pump located on the surface of teh parietal cell PPIs are more effective than H2 blockers ○ Act on final pathway of acid rather than specific receptor ○ Relieve symptoms and heal esophagus in 85-90% of patients Side Effects ○ Long term PPI use ○ Few concerns are supported by consistent data demonstrating a causal relationship Infections Nutritional malabsorption Interactions w Plavix Kidney disease Dementia Antiemetics Prevent vomiting Commonly uses ○ W/after cancer Tx ○ Motion sickness ○ Post-op ○ As adjunct to other medical Tx Symptomatic relief only Drug Classes ○ Antihistamines ○ Anticholinergics ○ Cannabinoids  ○ Dopamine Blocker ○ Serotonin 5-HT blocker Anti-Diarrheals Intro ○ Generally avoid antidiarrheals if symptom is associated w abdominal pain, fever, distension or bloody stool Options ○ Antimotility agents - Loperamid ○ Other preparations - Bismuth Subsalicylate (Pepto-Bismol) Loperamide ○ MOA Inhibit peristalsis by directly interfering w mm contraction in the intestinal wall Also increase tone of the anal sphincter (may help w fecal incontinence) ○ Onset Within 30-60 min Bismuth Subsalicylate (Pepto Bismol) ○ Salicylate portion provides an anti-secretory effect ○ Bismuth exhibits an antimicrobial effect directly against bacterial and potentially viral pathogens ○ Undergoes chemical dissolution in the GI tract Metabolized to salicylate reaching plasma levels similar to a full dose of aspirin ○ Adverse Black stool/black tongue Bismuth can react to sulfa in saliva an dGI tract creating bismuth sulfide which gives the black appearance ○ Drug-Drug interactions Avoid in concomitant aspirin use ○ Avoid in pt w renal impairment Altered excretion can result in accumulation Non Pharm Constipation mgmt Adequate fluid intake & dietary fiber Appropriate activity lvl Behavioral concerns ○ Potty training, Positioning for defecation Pharm Constipation Mgmt Bulk-Forming (Metamucil) ○ Hydrophilic - absorb water and swell (usually fiber based) ○ Increased fecal volume and soften stool  ○ Increase rate of transit Stimulant (Ex-lax) ○ Have a direct action on the intestinal mucosa resulting in increased GI Motility ○ More likely to result in water loss, abdominal cramping Hyperosmotic (Miralax) ○ Produce gradient to draw water into gut ○ Softens stool and stimulates peristalsis Stool Softener ○ Lowers the surface tension at the oil-water interference allowing water and lipids to enter the stool ○ Helps to hydrate and soften the fecal material, facilitating natural defecation Infectious and Neoplastic Diseases Antibacterial Drugs Types ○ Bactericidal - kill or destroy the bacteria ○ Bacteriostatic - limit growth and proliferation of bacteria ○ Broad spectrum - limit growth and proliferation of bacteria Inhibit bacterial wall synthesis and function ○ Penicillins First Abx Adverse - hypersensitivity, CNS problems, Steven-Johnson Syndrome ○ Cephalosporins Alternative the penicillins Adverse - hypersensitivity, GI problems ○ Carbapenems Wider spectrum than Penicilins & Cephalosporins Adverse - hypersensitive, GI problems, CNS disorder ○ Bacitracin Used as topical ○ Glycopeptides Adverse - hypersensitivity, GI upset, nephron/ototoxicity Drugs that inhibit bacterial protein synthesis ○ Aminoglycosides ○ Macrolides Used in pt allergic to penicillin ○ Tetracyclines May have anti inflammatory, neuroprotective and immunomodulation effects Adveres - photosensitivity Drugs that inhibit bacterial DNA/RNA synthesis and function  ○ Fluoroquinolones Wide spectrum Adverse - tendinopathy can lead to rupture ○ Sulfonamides Used in many topical drugs Silver sulfadiazine - used topically to control bacterial infection w burns Drug Resistance Overuse of antibiotics ○ VRS, MRSA, VRE, PRSP Antiviral Drugs (-VIR) Organisms made up of a nucleic acid core and protein shell Must rely on holt cell Difficult to treat w/o self harm Common side effects ○ Impair renal function ○ GI disturbance ○ Hematologic disorders ○ CNS toxicity ○ Skin reactions w topicals ○ Increased risk of CV disease ○ HA ○ Fatigue ○ Liver dysfunction ○ Peripheral neuropathy Interferons Proteins found to have pharmacological and physiological benefit Endogenous substances that can exert antiviral activity ○ Synthesized as part of immune system ○ Enable healthy cells to resist infection from virus Grouped into 3 classed ○ Type 1 - Alpha and beta interferons Chronic Hepatitis B, C; hairy cell leukemia, Kaposi Sarcoma, Condyloma Acuminatum, Malignant melanoma ○ Type II - gamma interferons MS ○ Type III - lambda interferons Chronic granulomatous disease, osteoporosis Exogenously administered interferons give same benefit as endogenous interferons Adverse ○ Flu like, very common w interferons used w MS  ○ Loss of appetite ○ Nausea ○ Fatigue ○ Depression - may inhibit serotonin activity in brain ○ Irritation around injection site HIV HIV ○ Retrovirus ○ Impairs function of specific immune cells T cells / T-Lymphocytes ○ Leads to severe immunocompromised state Pt w AIDs when immune system levels are reduced to certain level ○ 2 Form I: More prevalent II : less likely to progress to AIDs ○ No cure - die from opportunist infections preying on weak immune system Tx ○ Slow & control virus replication and treat and prevent opportunistic infection ○ Multiple drugs HAART (Highly active antiretroviral therapy) ○ Vaccination being developed ○ HAART Tx being studied as new drug class to combat various cancers (-utegravir) Concerns ○ Myopathy or peripheral myopathy due to HIV ○ Want to maintain strength, ROM & Function ○ Want to improve QoL ○ Maintain good infection control practices to prevent spread of HIV Pre-Exposure Prophylaxis (PrEP) ○ Prophylactic med to reduce risk HIV ○ Meds are essentially antiviral combos Truvida & Descovy ○ Side effects Kidney & liver dysfunction Lactic acidosis Immune system changes Antifungal (-Nazole) & Antiparasitic drugs Mycosis - disease caused by fungus Rehab concerns for fungal and parasitic infections Sportsmedicine  ○ Treated topically ○ Inspect skin areas prior to tapping/strapping Work in 3rd world countries Chemotherapy Cancer 2nd leading cause of death in US Basic strategy is to limit cell proliferation by killing or attenuating the growth of cancerous cells ○ Cancer divide at higher rate than surrounding tissue ○ Originally cancer Tx toxic to tissue that divides rapidly Hair, oral mucosa, GI tract, immune system, bone marrow, epithelial cells New cancer Tx targeting specific cancer cell than rapidly dividing cell Less side effects and greater efficacy Growth Fraction - % of proliferating cells relative to the total neoplastic cell population ○ Cells in growth fraction more susceptible to antineoplastic medications Must synthesize and replicate their genetic material Growth fraction decreases as tumor gets larger Blood flow and nutrients to tumor cannot sustain growth Cell Kill Hypothesis - each round of chemo kills a certain % cancerous cells ○ If cancerous cells depleted to