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54 Cards in this Set
- Front
- Back
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what are the mechanisms of pain?
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o Transduction – tissue injury with release of mediators that activate or sensitize nociceptors
o Transmission – propagation of the signal up the nerve fibers (Type A, C) o Modulation – descending inhibitory neural pathways meet pain signal o Perception – the conscious awareness of the pain |
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Neuropharmacology
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The study of drugs and their interaction with the nervous system
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What are the possible ways that a cholinergic drug could act?
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oMimic ACh at a N or M receptor = Parasympathomimetic (agonist)
oBlock ACh at the N or M receptor = Parasympatholytic (antagonist) oInhibit ACh-esterase = Non-specific anti-cholinesterase (enzyme substrate) |
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tolerance
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physiologic finding; due to neuro-adaptation with a continued drug use
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physical dependence
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physiologic finding with a marked drop in dose (or drug discontinuation) following chronic use
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addiction
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behavioral finding; entails pre-occupation with obtaining drug despite no apparant indication
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Aspirin
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Indication – pain associated with inflammation
Mechanism – inhibits cyclo-oxygenase (COX) Dose – 650 mg q6h Onset/duration – within 60 min / 4-6 h Elimination – hepatic, then renal Adverse effects – GI distress, tinnitus, altered hemostasis (blood clotting - once it binds to the platelet it can't stick to anything for it's life of 7 days), renal dysfunction (prostaglandins influence blood flow to kidneys, so dec. prostag. = dec. renal blood flow); avoid if allergic interactions with warfarin, corticosteroids, ethanol |
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IBuprofen
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- also called motrin, advil, rufin
Indication – pain associated with inflammation Mechanism – inhibits cyclo-oxygenase Dose – 400 mg q4h Onset/duration – within 60 min / 4-6 h Elimination – hepatic, the renal Adverse effects – GI distress, tinnitus, renal dysfunction; avoid if allergic |
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Acetaminophen
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Indication – mild to moderate pain, fever
Mechanism – inhibits prostaglandin synthesis Dose – 650 mg q6h Onset/duration – ~15 min / ~4 h Elimination – hepatic Adverse effects – nausea, vomiting; caution in patients with hepatic dysfunction, alcohol use or with protein-calorie malnutrition - glucuronidation and sulfation (leads to toxicity of liver) are phase 1 |
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Tramadol
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Indication – mild-moderate pain
Mechanism – inhibition of NE, 5HT (serotonin) reuptake - it's a mu-opiod peptide receptor agonist Dose – 50-100 mg q6h Onset/duration – ~1 h / 6-8 h Elimination – hepatic metabolism, renal excretion Adverse effects – sedation, dizziness, dry mouth, constipation, seizure risk; additive effect with CNS depressants, hypertension risk with MAO-I, serotonin syndrome risk with SSRIs and TCAs |
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Morphine
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Indication – severe pain (acute or chronic)
Mechanism – -receptor agonist Dose – 10-30 mg q4h (IR - immediate release), q8-12h (CR - controlled release), q24h (SR - sustained release) Duration – ~4 h (PO, IV), ~12-24 h (epidural) Elimination – hepatic (metabolites excreted renally) Adverse effects – sedation, miosis, vomiting, constipation, urinary retention, cough suppression, respiratory depression; additive effect with CNS depressant and anticholinergic agents |
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Fentanyl
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Indication – severe pain (acute or chronic)
Mechanism – -receptor agonist Dose – 25 g/h Duration – ≤ 1 h (IV) (because of it's short half life it gets infused by IV), ~48-72 h (transdermal) Elimination – hepatic Adverse effects – sedation, miosis, vomiting, constipation, urinary retention, cough suppression, respiratory depression; additive effect with CNS depressant |
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Naloxone
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Indication – opioid reversal
Mechanism – -receptor antagonist Dose – 0.4 mg IV in overdose; 0.2 mg IV post-op Duration – ~1 h (IV), longer (SC) Elimination – hepatic (t ½ ~2h) Adverse effects – hyperalgesia, withdrawal syndrome |
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Epilapsy
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disorder of recurrent seizures
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how do the different anti-epileptics work?
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o Mechanisms of Action – reduce neuronal discharge or propagation of seizure activity
– Decrease sodium influx – phenytoin, carbamazepine, valproic acid – Decrease calcium influx – valproic acid, ethosuximide – Block glutamate activity – topiramate – Increase GABA activity – benzodiazepines, barbiturates, gabapentin |
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Phenytoin
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Indication – partial seizure, tonic-clonic seizure
Mechanism – Na-channel inhibition Dose – ~150 mg bid; serum level of 10-20 mg/L Duration – drug t½ varies with dose Elimination – hepatic (saturable); highly protein-bound Adverse effects – sedation, nystagmus, ataxia, diplopia, cognitive impairment, gingival hyperplasia, hirsutism, rash, teratogenic; increases drug metabolism, additive to CNS depressants Na-phenytoin – capsule, injectable Phenytoin (free acid) – suspension, chewable tablet Fosphenytoin – injectable (in Na-phenytoin equivalents) |
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Carbamazepine
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Indication – partial seizure, tonic-clonic seizure
Mechanism – Na-channel inhibition Dose – 100-200 mg bid; serum level 5-12 mg/L Duration – drug t½ decreases with treatment Elimination – hepatic metabolism Adverse effects – neurologic side effects without cognitive impairment, bone marrow suppression, hyponatremia, rash NOTE: oxcarbazepine not associated with hematologic effects but possible cross-sensitivity for skin reactions Extended release tablet, capsule (Tegretol® XR, Carbatrol®) |
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Valproic Acid
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Indication – partial seizure, generalized seizure
Mechanism – inhibits Na & Ca-channels, GABA Dose – 2.5-7.5 mg/kg bid; serum levels 50-150 mg/L Elimination – hepatic metabolism, renal excretion Adverse effects – GI complaints, weight gain, rash, hair loss, tremor, hepatotoxicity, pancreatitis Valproic acid – capsule, syrup, gelcap (delayed-release) Na-divalproex – sprinkles (enteric coated), tablet (enteric-coated) and tablet (extended release) |
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Phenobarbital
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Indication – partial seizure, tonic-clonic seizure
Mechanism – GABA receptor binding Dose – 60-100 mg daily Duration – long t½ Elimination – hepatic metabolism, renal excretion Adverse effects – lethargy, cognitive impairment, depression, physical dependence; increases drug metabolism, additive to CNS depressants |
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Gabapentin
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Indication – adjunctive for partial seizure
Mechanism – increases GABA release Dose – titrate from 300 mg hs to 400-1200 mg tid Elimination – not metabolized, excreted renally Adverse effects – somnolence, dizziness, ataxia, fatigue, nystagmus |
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what is parkinson's disease?
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o Degenerative neurologic disorder affecting dopaminergic neurons in the substantia nigra from the striatum which regulates movement
o Manifestations include – tremor at rest, rigidity, instability, bradykinesia; depression, dementia, impaired memory |
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how do you treat parkinson's?
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o Therapeutic goal – control symptoms, slow degeneration, maintain QOL
o Pharmacologic approach – dec acetylcholine, inc dopamine |
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Levodopa
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Indication – Parkinson’s disease (most effective)
Mechanism – Dopamine precursor Dose – 500 mg bid; lower if combined with carbidopa Onset/Duration – months to response but then can provide control for 2-5 years Elimination –metabolized by decarboxylase & COMT Adverse effects – nausea, vomiting, dyskinesias, postural hypotension, tachycardia, psychosis, discolored secretions |
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Pramipexole
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Indication – Parkinson’s disease (in early disease)
Mechanism – selective D2 agonist Dose – 0.125 mg tid (1.5 mg tid max) Onset/Duration – therapeutic in few weeks Elimination – renally excreted (unchanged) Adverse effects – [alone] nausea, dizziness, somnolence, insomnia, constipation, weakness, hallucinations; [with levodopa] orthostatic hypotension, dyskinesias, hallucinations |
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Selegiline
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Indication – Parkinson’s disease (2nd line)
Mechanism – selective, irreversible MAO inhibitor Dose – 5 mg bid (morning and midday) Onset/Duration – benefit may not last > 1-2 years Elimination – hepatic metabolism and renal excretion Adverse effects – insomnia and possible interactions |
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Entacapone
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Indication – Parkinson’s disease (with levodopa)
Mechanism – selective, reversible COMT inhibitor Dose – 200 mg with each dose of levodopa Duration –t½ 1.5-3.5 h Elimination – hepatic metabolism, bile/urine excretion Adverse effects – increases risk of side effects from levodopa…; plus vomiting, diarrhea, constipation, and change in urine color |
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what is alzheimers?
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o Degenerative neurologic disorder irreversibly affecting cholinergic neurons in the hippocampus and cerebral cortex
o Risk factors – family history, > 65 yo o Manifestations include short-term memory failures, language difficulty, loss of speech, incontinence, presence of neuritic plaques and neurofibrillary tangles |
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how do you treat alzheimers?
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o Therapeutic goal – improve symptoms, reverse decline (ideally); slow memory and cognitive losses, maintain independence
o Pharmacologic approach – acetylcholine o Cholinesterase inhibitors – donepezil (Aricept®), tacrine (Cognex®), rivastigmine (Exelon®), galantamine (Reminyl®, Razadyne®) o Antioxidants – selegiline (Eldepryl®), vitamin E, ginkgo o Others – memantine (Namenda®), antipsychotics, antidepressants |
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Donepezil
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Indication – Alzheimer’s disease (drug of choice)
Mechanism – reversible cholinesterase inhibitor Dose – 5-10 mg hs Onset/Duration – ≤ ⅓ patients respond / limited Elimination – hepatic metabolism, renal > bile Adverse effects – nausea, vomiting, diarrhea, dizziness, headache, bronchoconstriction; reduced effect with anticholinergic drugs |
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Memantine
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Indication – moderate-severe Alzheimer’s disease
Mechanism – NMDA receptor antagonist (↓ Ca entry) Dose – 5 mg daily – 10 mg bid (titrated every 1+ week) Peak – at 3-7h Elimination – renal (largely unchanged); t½ ~60-80h Adverse effects – dizziness, headache, confusion, constipation; caution with ketamine, Na-bicarbonate |
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What is schizophrenia?
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chronic psychotic illness with disordered thinking and limited ability to comprehend reality
o Characteristic symptoms Negative = social and emotional withdrawal, lack of motivation, poverty of speech, blunted affect, poor insight, poor judgment and poor self-care Positive = hallucinations, delusions, disordered thinking, disorganized speech, combativeness, agitation, paranoia o Etiology – unknown; appears to be associated with DA & Glut activation o Presentation Acute – delusions and hallucinations Residual – suspicious, poor insight, judgment, control over anxiety, and self-care Episodic – acute presentations between periods of residual symptoms or partial remission; progressive decline in mental status and social function |
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what are antipsychotic drugs/neuroleptic drugs?
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o Broad group of compounds for psychotic disorders
o Allow for patient management without “locking up” o Two classes of drug compounds: Conventional • Block CNS DA receptors; help manage (+) symptoms • Further classified by potency Atypical • Block 5HT > DA receptors; manage (+) & (–) symptoms • Better patient compliance generally |
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Chlorpromazine (Thorazine®)
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Indication – schizophrenia
Mechanism – blocks D2 in mesolimbic region of brain Dose – 25 mg tid (up to doses of 400 mg/d) Onset – 1-2 d for response (2-4+ wk max) Elimination – low bioavailability; renal excretion of metabolites Adverse effects – related to neurotransmitters involved Sedation, anticholinergic effects, orthostasis, gynecomastia, galactorrhea, seizures, sexual dysfunction; interaction with anticholinergics, CNS depressants, and levodopa |
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Haloperidol (Haldol®)
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Indication – schizophrenia
Mechanism – blocks D2 in mesolimbic region of brain Dose – 0.5-2 mg bid-tid (up to 100 mg/d) Onset – within 1-2 d for response (2-4+ wk max) Elimination – extensive hepatic metabolism; renal excr Adverse effects – related to neurotransmitters involved Neuroleptic malignant syndrome (NMS), sedation, gynecomastia, galactorrhea, seizures, QT prolongation Interaction with anticholinergics, CNS depressants, and levodopa |
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what are side effects of of antipsychotic/neuroleptic drugs - based on receptor blockade
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Extrapyramidal Symptoms (EPS) – movement disorders resulting from a low DA influence on the extrapyramidal motor system
• Acute dystonia – muscle spasms • Parkinsonism – bradykinesia, rigidity, tremor • Akathisia – restlessness, agitation, anxiety • Tardive dyskinesia – choreoathetoid movements |
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Clozapine (Clozaril®)
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Indication – schizophrenia
Mechanism – blocks 5HT2 and D2 receptors Dose – 12.5-25 mg daily-bid (up to 300-450 mg/d) Onset – within a few days Elimination – 95% protein-bound, t½ ~12 h, extensively metabolized, with renal and biliary excretion Adverse effects – related to neurotransmitters involved Sedation, orthostasis, weight gain, hyperglycemia, QT prolongation, anticholinergic effects, seizures, myocarditis, agranulocytosis |
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Olanzapine (Zyprexa®)
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Indication – schizophrenia
Mechanism – blocks 5HT2 and D2 receptors Dose – 5-10 mg daily Onset – within a few days Elimination – t½ ~30 h, extensively metabolized Adverse effects – related to neurotransmitters involved Sedation, weight gain, hyperglycemia, anticholinergic effects |
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what is major depressive disorder?
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• Major Depressive Disorder
o Sx for 2+ weeks; not due to meds or medical illness o At least 5 of the following: Depressed mood most days * Anhedonia * Change in appetite or body weight Change in sleep Fatigue, loss of energy Poor concentration Feelings of worthlessness or inappropriate guilt Psychomotor agitation or retardation Thoughts of suicide |
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how do you treat major depressive disorder?
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o Non-drug therapy – psychotherapy, electroconvulsive therapy, phototherapy, and physical activity
o Pharmacologic therapy Selective serotonin reuptake inhibitors (SSRIs) Tricyclic antidepressants (TCAs) Other newer agents Monoamine oxidase inhibitors (MAO-Is) |
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what is the pathopysiology of major depressive disorder?
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o Pathophysiology
Focus on neurotransmitter (NT) systems symptoms – serotonin, norepinephrine, dopamine Monoamine hypothesis; permissive hypothesis; dysregulation hypothesis |
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Fluoxetine (Prozac®)
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Indication – major depressive disorder
Mechanism – selectively inhibits 5HT reuptake Dose – 10-20 mg daily Onset – several weeks for full effect Elimination – hepatic metabolism to an active metabolite (which has a week long half life!!) (norfluoxetine); t½ ~2d Adverse effects – nausea, headache, insomnia, anxiety, weight gain, sexual dysfunction, bruxism (teeth grinding), diarrhea, withdrawal syndrome; interaction with MAO-inhibitors |
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what is serotonin syndrome?
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• Cognitive-behavioral changes – agitation, anxiety, coma/unresponsive, confusion, hypomania, lethargy
• Autonomic instability – diaphoresis, diarrhea, dilated pupils, hyper/hypothermia, nausea, tachycardia, tachypnea, vomiting • Neuromuscular changes – ataxia, hyper-reflexia, muscle rigidity, myoclonus, restlessness, shivering, tremor, trismus |
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Imipramine (Tofranil®)
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Indication – major depressive disorder
Mechanism – inhibits NE and 5HT reuptake Dose – 50 mg daily (individualize, up to 150-300 mg/d) Onset – several weeks for clinical response Elimination – long half-life; serum level > 225 μg/L Adverse effects – sedation, orthostasis, anticholinergic effects, seizures, sweating, cardiotoxicity; interaction with MAO-inhibitors, sympathomimetics, anticholinergics, CNS depressants - it's a tricyclic antidepressant that prevents the reuptake of NE |
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Bupropion (Wellbutrin®)
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Indication – major depressive disorder
Mechanism – (?) reduces DA reuptake Dose – 75 mg daily-bid Onset – several weeks for clinical response Elimination –half-life < 24 h Adverse effects – seizures, insomnia, agitation, headache, blurred vision, xerostomia, GI upset, constipation, weight loss - an example of 2nd generation antidepressant |
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What is bipolar disorder?
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o Sx for 1+ weeks; abnormally and persistently elevated, expansive, or irritable mood; not due to meds or medical illness
o At least 3 of the following during the mood disturbance (4 if only irritable): Inflated self-esteem Decreased need for sleep More talkative, or pressure to keep talking Flight of ideas, or racing thoughts Easily distracted by irrelevant external stimuli Increase in goal-directed activity, or psychomotor agitation Excessive involvement in pleasurable but high risk activities |
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What are the characteristic types of bipolar disorder?
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Mania – expansive or irritable mood
Hypomania – mild mania Depression – reduced mood, loss of pleasure Mixed – highly agitated with depression |
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how do you treat bipolar disorder?
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o Antipsychotic drugs – atypical class
o Antidepressant drugs – newer agents o Mood stabilizers – lithium, valproic acid (which is also an antidepressant) - never treat a bipolar w/just an antidepressant b/c they'll just become super maniac |
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Lithium (Eskalith®, Lithobid®)
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Indication – bipolar disorder (“euphoric mania”)
Mechanism – not known; effect on 2nd messengers Dose – 300 tid (individualize); levels 0.8-1.2 mmol/L Onset – ~1 wk (max by 2-3 wks) Elimination –renal excretion; short half-life Adverse effects – ANVD, bloating, transient fatigue and muscle weakness, tremor, headache, confusion, memory impairment, polyuria/thirst; interactions with diuretics (this and thirst are b/c it acts similarly to Na inside the body), NSAIDs (can hold onto Na in the body), anticholinergics |
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Valproic Acid
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Indication – bipolar (“psychotic mania,” mixed)
Mechanism – inhibits Na & Ca-channels, GABA Dose – 250 tid (~2 g/d); serum levels >100 mg/L - note: you're using higher levels for bipolar disorder than you would for epilepsy) Elimination – hepatic metabolism, renal excretion Adverse effects – GI complaints, weight gain, rash, hair loss, tremor, hepatotoxicity, pancreatitis |
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What are insomnia and anxiety disorders?
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o Drugs used for insomnia (sedative-hypnotics) and anxiety disorders (anxiolytics) overlap
o Insomnia – trouble falling asleep, staying asleep, or with early awakening o Anxiety – GAD (general anxiety disorder), panic, OCD(obsessive compulsive disorder), PTSD (post traumatic stress disorder), phobia; (psychologic, physiologic) |
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what are the treatments for insomnia and anxiety disorders?
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o Non-drug therapy – address etiology, behavior modification, sleep hygiene, and physical activity
o Pharmacologic therapy Classic drugs – barbiturates, others Newer drugs – benzodiazepines, BZD agonists, MT agonists, SSRIs |
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Lorazepam (Ativan®)
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Indication – insomnia, anxiety, ETOH withdrawl
Mechanism – potentiation of GABA at chloride channel, it opens the channels longer to inhibit axons Dose – 0.5 mg tid Onset/duration – within 30 min Elimination – hepatic phase II metabolism without active metabolites (yay) Adverse effects – drowsiness, difficulty concentrating, anterograde amnesia, paradoxical reaction(super agitated, irritable, etc); additive effects with CNS depressants note: it's a benzodiaqepine |
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Zolpidem (Ambien®)
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Indication – insomnia (short-term) - helps you fall asleep, not stay asleep
Mechanism – benzodiazepine receptor agonist Dose – 5-10 mg hs Onset/duration – within 15-30 min Elimination – half-life ~2.4 h, metabolized to inactives Adverse effects – drowsiness, difficulty concentrating, anterograde amnesia, paradoxical reaction; additive effects with CNS depressants - it's a benzodiazepine receptor agonist |
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Ramelteon (Rozerem)
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Indication – sleep induction
Mechanism – activates melatonin receptors (MT1, MT2) Dose – 8 mg hs Onset/duration – within 30 min / for ~2-4 h Elimination – hepatic metabolism (CYP1A2), active metabolite Adverse effects – dizziness, hyperprolactinemia, decreased testosterone; interaction additive effects with fluvoxamine - a melatonin agonist |
