Block 3

  1. Levodopa (L-DOPA)
    Rationale: restore levels of DA in basal ganglia

    • Mechanism: 
    • enters brain via amino acid transporters (crosses BBB)
    • decarboxylated to dopamine in DA cells and other neurons that express L-AAAD

    • Pharmacokinetics:
    • 2% gets to brain - remainder is metabolized to dopamine by L-AAAD in peripheral tissue and by COMT --> too much dopamine in periphery and too little in CNS -- coadminister with carbidopa

    T1/2=1-3 hrs

    Absorption dependent on gastric contents - competition for amino acid uptake sites

    Effectiveness: highly effective, treats all Parkinsons symstoms, beneficial effects outlast plasma half-life - wait to start treatment until patient shows debilitation

    • SE: come from conversion to DA
    • CNS: wearing off, dyskinesias, hallucinations and confusions (in elderly)
    • Peripheral:
    • GI problems
    • CV problems - hypotension, arrhythmias, hypertension

    Contraindications: glaucoma, psychosis, cardiac arrhythmias, malignant melanoma

    Drug interactions: pyridoxine, MAO inhibitors, halothane, typical antipsychotics 

    May make Parkinson's worse b/c of oxidative stress theory
  2. Carbidopa
    • Mechanism:
    • Inhibitor of L-AAAD
    • Does not cross BBB

    • Co--administer with L-DOPA for Parkinson's
    • Results in increased dose of L-DOPA to CNS - decreased peripheral side effects
  3. Pramipexole
    Rationale: mimic effects of dopamine without needing intact nerve terminals

    • Mechansim:
    • Selective D2 receptor agonist in the striatum

    Kinetics: titrated to therapeutic doses over a week or less

    • Use:
    • Parkinson's
    • initial treatment of disease over L-DOPA-->
    • fewer dyskinesia side effects 
    • longer T1/2
    • Less oxidative stress
    • Good for treatment of on/off phenomenon
    • Better in young patients
    • More useful in late disease b/c no conversion

    • SE:
    • nausea
    • fatigue
    • sudden attacks of sleep during daytime
    • CNS toxicity: worse confusion than L-DOPA, not as bad dyskinesia
  4. Ropinirole
    Rationale: mimic effects of dopamine without needing intact nerve terminals

    Mechansim: Selective D2 receptor agonist in the striatum

    Kinetics: titrated to therapeutic doses over a week or less

    • Use: 
    • Parkinson's
    • initial treatment of disease over L-DOPA-->
    • fewer dyskinesia side effects 
    • longer T1/2
    • Less oxidative stress
    • Good for treatment of on/off phenomenon
    • Better in young patients
    • More useful in late disease b/c no conversion

    • SE:
    • nausea
    • fatigue
    • sudden attacks of sleep during daytime
    • CNS toxicity: worse confusion than L-DOPA, not as bad dyskinesia
  5. Apomorphine
    Rationale: mimic effects of dopamine without needing intact nerve terminal

    Mechanism: Dreceptor agonist (moderate D2,3,4,5) in striatum

    Use: reserved for patients that are refractory to other treatments for Parkinson's, given subcutaneous injection as rescue therapy for treatment of "off" episodes

    • SE: 
    • nausea, used with trimethobenzamide
    • fatigue
    • sudden attacks of sleep
    • CNS toxicity
    • QT prolongation and injection-site reactions
  6. Selegiline
    Rationale: potentiate actions of endogenously produced dopamine with inhibitors of its catabolism by MAO, may reduce oxidative stress 

    Mechanism: selective, irreversible, inhibition of MAO-B (inhibit DA catabolism in striatum w/out effect on tyramine).  

    Inhibition of MAO in the periphery causes hypertension if patient consumes tyramine containing foods

    Use: Often given with L-DOPA to prolong therapeutic half-life and to decrease on-off effects.  Modest benefit in treatment and disease progression of Parkinson's disease

    • SE:
    • Well tolerated in early PD
    • Worsen L-DOPA induced CNS side effects in advaned disease
    • Metabolized to amphetamine and methamphetamine - causing anxiety, insomnia (redued via patch or fizzy to avoid first-pass)

    • Adverse Drug Interactions:
    • meperidine: combination can result in stupor, rigidity, agitation, hyperthermia
    • tricyclic antidepressants
    • serotonin-reuptake inhibitors
  7. Rasagiline
    Rationale: potentiate actions of endogenously produced dopamine with inhibitors of its catabolism by MAO, may reduce oxidative stress 

    Mechanism: selective, irreversible, inhibition of MAO-B (inhibit DA catabolism in striatum w/out effect on tyramine).  

    Inhibition of MAO in the periphery causes hypertension if patient consumes tyramine containing foods

    Use: Often given with L-DOPA to prolong therapeutic half-life and to decrease on-off effects.  Modest benefit in treatment and disease progression of Parkinson's disease

    • SE:
    • Well tolerated in early PD
    • Worsen L-DOPA induced CNS side effects in advaned disease

    • Adverse Drug Interactions:
    • meperidine: combination can result in stupor, rigidity, agitation, hyperthermia
    • tricyclic antidepressants
    • serotonin-reuptake inhibitors - Serotonin Syndrome
  8. Entacapone
    Rationale: COMT metabolizes dopamine and L-DOPA so its inhibition will increase L-DOPA access to the brain and prolong the action of dopamine

    Mechanism: COMT inhibitor, short T1/2, inhibits peripheral COMT primarily (does not get into CNS well so only useful when administered with L-DOPA)

    Use: Parkinson's

    SE: nausea, orthostatic hypotension, vivid dreams, confusion, hallucinations (d/t decreased dopamine)
  9. trihexyphenidyl
    Rationale: cholinergic interneurons in the striatum are normally inhibited by dopamine; loss of dopamine results in overactivity of these neurons

    Mechanism: antagonist of striatal muscarinic receptors

    Use: modest efficacy for Parkinson's, used in early disease in the elderly or as an adjunct to dopaminergic therapy, 3rd choice

    SE: sedation, mental confusion, atropine-like effects (mad as a hatter, etc.)
  10. benztropine
    Rationale: cholinergic interneurons in the striatum are normally inhibited by dopamine; loss of dopamine results in overactivity of these neurons

    Mechanism: antagonist of striatal muscarinic receptors

    Use: modest efficacy for Parkinson's, used in early disease, in the elderly, or as an adjunct to dopaminergic therapy

    SE: sedation, mental confusion, atropine like effects (mad as a hatter, etc.)
  11. amantadine
    Rationale: none, discovered by serendipity

    Mechanism: increases dopamine release; mildy anticholinergic; blocks NMDA receptors

    • blocks viral uncoating by interfering w/ influenza A M2 protein (an ion channel)
    • no significant hepatic metabolism; 90% excreted unchanged in urine - reduce dose in renal disease

    Use: short-lived benefits for Parkinson's, often in combo w/ L-DOPA or anticholinergics, not useful when L-DOPA is ineffective

    • Prophylaxis against influenza A but NOT B - reduces fever in 50% of patients and illness duration by 1-2 days if given w/in first 2 days of illness - for last few years, influenza A strains have been resistant to this drug
    • SE: CNS effects, dizziness, lethargy, anticholinergic effects, peripheral edema, sleep disturbances, slurred speech, anxiety, depression, headache, hallucinations

    Contraindicated in patients with CHF d/t sympathomimetic effects

  12. donepezil
    Mechanism: increase amt of ACh in cerebral cortex by inhibiting catabolism with cholinesterase inhibitors

    Use: Alzheimer's Disease

    • SE: many, 1/3 have GI problems
  13. rivastigmine
    Mechanism: increase amt of ACh in cerebral cortex by inhibiting catabolism with cholinesterase inhibitors

    Use: Alzheimer's Disease

    SE: many, 1/3 have GI problems
  14. galantamine
    Mechanism: increase amt of ACh in cerebral cortex by inhibiting catabolism with cholinesterase inhibitors

    Use: Alzheimer's Disease

    SE: many, 1/3 have GI problems
  15. memantine
    Mechanism: non-competitive NMDA channel blocker

    Use: Alzheimer's disease, associated with reduced rate of clinical deterioration
  16. riluzole
    Mechanism: inhibitor of NMDA channels - inhibits glutamate release, increases glutamate uptake, inhibits glutamate receptors

    Use: Amyotrophic lateral sclerosis - increases life span 2-3 months
  17. MAC
    minimal alveolar concentration that prevents movement in response to pain in 50% of subjects

    • advantages of measurement:
    • 1) can be continuously monitered by measuring end-tidal anesthetic concentration
    • 2) provides direct correlate to anesthetic concentration at the site of action in CNS
    • 3) simple to measure end point (lack of movement)
  18. Sodium thiopental
    barbiturate - parenterally administered anesthetic

    Use/administration: induce anesthesia, typical inudction produces unconsciousness in 10 to 30 sec; duration of action of single dose is abt 10 min.

    T1/2= 12 hrs --> residual effects (hang over) after anesthesia wears off

    Dose should be reduced if patient has been premedicated with other CNS depressants, including opiates, benzodiazepines, and alpha2 agonists

    Intra-arterial injection can produce severe inflammation and necrotic

    Can be administered to pediatric patients rectally if needed

    • SE: 
    • 1) CNS depression: reduces cerebral oxygen utilization, bloow flow and intracranial pressure (protective agent for tx of cerebral ischemia/swelling in brain)
    • 2) CV: produces vasodilation on venous side, decreasing preload and BP, demand on heart is reduces with coronary artery disease
    • 3) Respiratory depression
  19. Propofol
    parenterally administered anesthetic

    GABAA activation

    Onset and duration of anesthesia same as barbiturates

    • Use:
    • maintain and induce anesthesia - short procedures
    • Antiemetic
    • Shorter half life than thiopental; used when rapid return to normal mental status is desired (out-patient surgery)

    • SE:
    • sexual dreams
    • elicits pain on injection
    • excitation during induction
    • CNS
    • CV (more severe decrease in BP than thiopental), 
    • Vasodilation and depression of myocardial contractility
    • Blunts baroreceptor reflexes - careful w/ patients intolerant to decreases in BP
    • More respiratory depression than thiopental
  20. Etomidate
    parenterally administered anesthetic

    Use: induce anesthesia in patients at risk for hypotension

    High incidence of pain on injection and myoclonus (pain dealt w/ using lidocaine and myoclonus reduced by medication with benzodiazepines or opiates)

    • SE: 
    • CNS: like thiopental
    • CV: less than thiopental and propofol - small increase in HR, little or no decreas in BP
    • Less respiratory depression than thiopental
    • Lots more nausea and vomiting
    • Increased post-surgical mortality d/t suppresion of adrenocortical stress response; primarily when anesthetic given for prolonged time - only used to induce anesthesia in patients prone to hemodynamic problems
  21. Ketamine
    parenterally administered anesthetic

    Use: reserved for patients with bronchospasm, children undergoing short painful procedures

    • produces hypnotic state: dissociative anesthesia
    • unresponsive to commants even though eyes open
    • spontaneous respiration - no respiratory depression - bronchodilator

    also used as a drug of abuse: drunken state, numbness of extremities, etc.

    • SE: 
    • nystagmus, salivation, lacrimation, spontaneous limb movements, and increased muscle tone
    • increased intracranial pressure (d/t increased cerebral blood flow)
    • emergence delirium: hallucinations, vivid dreams, illusions
    • increased BP d/t indirect sympathomimetic activity
  22. Midazolam
    Short acting benzodiazepine (half life = 1-5 hrs), parenterally administered anesthetic

    Use: conscious sedation, anxiolysis and amnesia during minoar surgical procedures

    • induction agent
    • adjunct during regional anesthesia (tooth extraction)
    • anti-anxiety effects make it useful preoperatively

    slower induction time and longer duration than thiopental

    • SE: 
    • respiratory depression/arrest (especially when used IV to produce conscious sedation)
    • CV: like thiopental

    Used w/ caution in patients w/ neuromuscular disease; Parkinson's; biopolar disorder
  23. Isoflurane
    inhalation anesthetic

    Use: commonly used in US, used to induce and mostly maintain anesthesia, co-administered w/ nitrous oxide to allow for reduced dose

    • Kinetics: 
    • moderate blood:gas partition coefficient
    • 99% excreted unchanged from lungs

    • SE:
    • respiratory: airway irritant, coughing, decreases tidal volume and increases RR, respiratory depressant, increases PaCO2

    CV: myocardial depression, decrease BP, arrythmias; sensitizes heart to catecholamines, dilates cerebral blood vessels increasing intracranial pressure
  24. Desflurane
    inhaled anesthetic

    Use: outpatient surgeries, can cause coughing and bronchospasm in awake patients so anesthesia is induced w/ IV agent, produces direct skeletal muscle relxation

    Kinetics: volatile at room temp., special equipment to administer, LOW blood:gast partition coefficient(rapid induction & recovery), predominantly excreted unchanged

    • SE:
    • CV: similiar to isoflurane
    • Respiratory: similar to isoflurane and is a respiratory irritant
  25. Sevoflurane
    inhaled anesthetic

    Use: inpatient and outpatient; induction and maintenance; children and adults, not a respiratory irritant

    • Kinetics:
    • LOW blood:gast partition coefficient
    • 5% of administered dose is metabolized to fluoride ion in the liver - renal damage
    • Ex vivo degradation by CO2 absorbants in the anesthesia circuit forms compound A (nephrotoxic in rats)
    • SE:
    • CV: similar to isoflurane
    • Respiratory: similar to isoflurane but less respiratory depression
  26. Nitrous Oxide
    true gas inhaled anesthetic

    • Use:
    • weak anesthetic, only gets to full efficacy under hyperbaric conditions - cannot be used at greater than 80% oxygen requirements
    • used to produce sedation and analgesia in outpatient dentistry
    • used as an adjunct with other inhalation anesthetics, allows for a reduction in their dose

    • Kinetics:
    • very insoluble in blood and other tissues -- rapid equilibration -- rapid induction and recovery

    rapid uptake from alveolae result in concentration of gases that are administered at the same time - co-administered with other inhalation anesthetics

    dilute oxygen when its use is discontinued, need to place patients on 100% O2 during emergence

    99% excretion through the lungs unchanged

    • SE: 
    • can exchange with nitrogen in any air-containing cavity - contraindicated in pneumothroax

    negative inotrope but also sympatho-stimulant

    respiratory effects are minimal except for oxygen dilution issue 

    abuse liability
  27. Anxiety
    symptoms most commonly presented to family doctors & specialists

    affects 4-8% of general population

    Physiological correlates - general, persistent for 1 month duration

    Somatic correlates - tachycardia & palpitations

    Complications: abuse of alcohol, sedatives, and medications are common
  28. Benzodiazepine
    • Act on sites on GABA Cl ion channel complex
    • Enhances action of GABA
    • Increases frequency of GABA induced Cl channel openings

    Used for anxiety and used primarily to promote SLEEP, also for alcohol withdrawal

    Pharmacokinetics are related to relatively lipophilicity

    Most form active metabolites that can have very long half lives

    • Pharmacological effects:
    • decrease anxiety
    • sedation
    • hypnosis - decreased latency to sleep, increases stages 1 and 2, decreased time in stage 3/4REM
    • muscle relaxation 
    • anterograde amnesia - IV administration
    • anticonvulsant action
    • CV and respiratory actions - minimal at TD

    • Drug interactions:
    • Produce additive CNS depression w/ most other depressant drugs (ex: ethanol)
    • Drugs that affect hepatic metabolism

    • Tolerance
    • Dependence and withdrawl: anxiety, insomnia, irritability, headache, hyperacusis, hallucinations, seizures
    • Tx of abuse - gradual dose reduction, switch to longer acting drugs
  29. Barbiturate
    Act at site on GABA receptor-chloride ion channel complex

    • Use:
    • Among earliest sedative hypnotic pharmaceuticals used (rarely used today)
    • Anticonvulsant
    • Induction of anesthesia

    Weak acids and also salts of the compounds are formed

    • Metabolism/pharm:
    • absorbed and distributed to all tissues and body fluids.
    • highly lipid soluble, distribute rapidly to brain and redistribute to fat
    • induce their own metabolism and that of other drugs
    • renal excretion

    • Actions:
    • General CNS depression - sedation, hypnotic, anesthesia
    • Anticonvulsant
    • Respiratory depressioin
    • CV effects minimal but w/ high doses can produce decrease in MAP and pulse pressure
    • Exacerbation of acute intermittent porpyria - increased synthesis of d-aminolevulinic acid synthestase
    • Tolerance 0 both metabolic and pharmacodynamic
    • Physical dependence
    • Acute poisoning - stupor, compa, respiratory depression

    • Drug interactions: Additive with other CNS depressants
    • Drugs that affect microsomal drug metabolism
  30. Hypnotics
    Mostly benzodiazepines that induce sleep

    Includes flurazepam, triazolam, and lorazepam.
  31. GABA receptor-chloride channel complex
    Has sites to which benzodiazepines and barbiturates bind.

    GABAA receptor 

    High concentration in striatum, hippocampus, and spinal cord

    Binding of substrange increases chloride conductance

    Complex made of several subunits
  32. Sedation
    Induces nervous system to stay calm
  33. Buspirone
    Use: anxiety

    partial agonist for 5-HT1A - inhibits adenylate cyclase and opens K+ channels

    also binds dopamine receptors with less afinity

    not related chemically or pharmacologically to the benzodiazepines

    • T1/2 = 2-11 hrs
    • Less sedating than benzodiazepines
    • No cross-tolerance with benzodizepines

    Does not potentiate other sedative-hypnotics and depressants nor suppress symptoms of their withdrawl

    Used in tx of generalized anxiety syndrome

    Effects: 1-2 weeks to occur
  34. Alprazolam
    Use: treat anxiety, PANIC DISORDER!!!!!!!
  35. Clonazepam
    Use: treat anxiety, acute manic episodes - adjunct for quick control of manic symtoms - no extra pryamidal symptoms

    long lasting effects against absence seizure & some myoclonic seizures
  36. Chlordiazepoxide
    Use: anxiety, alcohol withdrawl (gradual reduction of dose "tapering off")
  37. Diazepam
    Benzodiazepine agonist

    Use: treat anxiety, muscle relaxant, IV sedation & anesthesia, used in patients with muscle spasm of almost any origin including local trauma, management of alcohol withdrawl (gradual reduction of dose "tapering off")

    IV: status epilepticus

    • fast onset of action - oral
    • high lipid solubility - rapid absorption/entry into brain (most rapidly absorbed benzodiazepine)
    • rapid redistribution after single dose
    • active metabolites change this in multiple dose situation

    Action in reducing spasticity is partly mediated in spinal cord

    Withdrawl: anxiety, insomnia, irritability, headache, hyperacusis, hallucinatinos, seizures 

    Tx of abuse: gradual dose reduction, switch to longer acting drugs
  38. Flumazenil
    Benzodiazepine antagnoist at receptor

    Used for benzodiazepine overdoses
  39. Lorazepam
    • Use: treat anxiety, hypnotic
    • IV: status epilepticus

    • less lipophilic than diazepam
    • absorption and onset of action are slower
    • longer duration of action after single dose
    • no active metabolites- glucuronidation occurs

  40. Baclofen
    Use: skeletal muscle relaxant

    • Gaba - mimetic agent that works at GABAB receptors
    • Results in hyperpolarization causing presynaptic inhibition
    • Decreases release of excitatory transmitters such as glu
    • As effective as diazepam in reducing spasticity and produces much less sedation

  41. Tizanidine
    Use: muscle spasm

    • alpha 2 agonist related to clonidine
    • enhances presynaptic and postsynaptic inhibition

    similar efficacy to diazepam 

    SE: drowsiness, hypotension, dry mouth, anesthesia

    Interacts w/ CYP1A2 inhibitors
  42. Chloral hydrate
    Use: sedative hypnotic

    Aledhyde hydrate with pungent taste and somewhat caustic taste

    • Metabolized to trichloroethanol - active form
    • Pharm similar to barbiturates
    • Less effects on stages of sleep
  43. Eszopiclone
    Newer hypnotic drug

    • Non-benzodiazepine, approved for long term use
    • Interaction w/ GABA-receptor complex at binding domains located close to/allosterically coupled to BZD receptors

    Similar mechanism to zolpidem and zaleplon
  44. Flurazepam
    benzodiazepine used as hypnotic

    rapid onset of action, long duration of action
  45. Pentobarbital


    rarely used today
  46. Ramelteon
    melatonin MT1 and MT2 receptor-agonist

    Specifically indicated for tx of insomnia characterized by difficulty in falling asleep - not a controlled substance
  47. Triazolam
    benzodiazepine used as hypnotic

    rapid onset of action and ultrashort duration of action
  48. Zaleplon
    Very similar to zolpidem

    • Non-benzodiazepine chemially
    • Bind to BDZ receptor on GABA receptor complex
    • Weak anxiolytic, muscle relaxant and anticonvulsant at hypnotic dose

    Stage 3 and 4 sleep preserved, minor effects on REM sleep
  49. Zolpidem
    Non-benzodiazepine chemically that binds BDZ receptor

    Weak anxiolytic, muscle relaxant, and anticonvulsant at hypnotic dose

    Sleep disruption of sleep architecture - Stage 3/4 sleep preserved, minor effects on REM sleep

    • Typial duration of action 5-6 hrs
    • Sustained release prep now available
    • Duration of action: 7-8 hrs
    • Antagnoized by flumazenil
  50. Alcohol dehydrogenase
    Enzyme in primary pathway for ethanol oxidation to acetaldehyde; rate limiting

    Primarily in liver (but also in other tissues)

    Kinetics of ethanol elimination by this pathway are zero order at the concentrations of ethanol consumed
  51. Microsomal Ethanol Oxidizing System
    AKA Mixed Function Oxidase System (MFOS)

    High km - little contribution at concentrations below 100mg/dl

    Induced in alcoholics - CYP2E1 - influences metabolism of other drugs
  52. Aldehyde Dehydrogenase
    • Mitochondrial enzyme
    • Used for acetaldehyde metabolism
    • Oxidizes acetaldehyde to acetate
    • Genetic polymorphisms
    • Inhibition by disulfiram
  53. Naltrexone
    reduces "urge to drink"; increases control

    opioid receptor antagonist

    orally active w/ long half-life

    best together w/ psychosocial therapy
  54. Acamprosate
    agonist GABAA & NMDA competitive antagonist

    Decreases drinking frequency and reduces releapse

    Well tolerated - primary SE is diarrhea
  55. Disulfiram
    Aversion therapy

    Mechanism of action: inhibition of alehyde dehydrogenase

    Acetaldehyde syndrome - not very effective/ethical
  56. Caffeine
    • Blocks adenosine receptor
    • Inhibits phosphodieasterase
    • Increases Ca release from intracellular stores

    Less fatigue, etc.

    High doses stimulate medullary respiratory, vasomotor, and vagal center

    Stimulate myocardium

    Dilates general blood vessels but constricts cerebral blood vessels :) for headache

    Modest bronchodilator
  57. Adenosine
    Post synaptic receptors hyperpolarize membrane

    Presynaptic receptors inhibit glutamate release

    Caffeine blocks these types of receptors
  58. Cocaine
    Use: local anesthesia in upper respiratory track (nose surgery)

    • Weak base
    • Well absorbed through mucus membranes/lungs
    • IV = time to peak & duration shorter
    • Metabolized by serum & liver esterases
    • Metabolites seen in urine (drug test)

    • Mechanism: 
    • inhibitor of reuptake of NE, dopamine, serotonin, 
    • increases ligand in synapse b/c competes w/ dopamine transporter
    • increases tyrosine and tryptophan hydroxylase

    • Pharm effects:
    • vasoconstriction
    • tachycardia
    • increased alertness
    • euphoria
    • elation
    • well being
    • competency

    • Toxicity:
    • mild w/drawal symptoms
    • seizures/CV effects
    • fetal effects > alcohol (attachment disorder)
  59. Amphetamine
    Use: narcolepsy, ADHD

    • releases NE, dopamine, serotonin
    • Blocks transmitter uptake into presynaptic terminals
    • Direct partial agonist of alpha adrenergic receptors
    • MAO inhibition

    • Effects:
    • wakefulness, alertness, less fatigue
    • enhances athletic/intellectual performance
    • Mood elevation/self confidence
    • Speed
    • Respiratory stimulation
    • Decreases appetite

    • SE:
    • insomnia
    • abdominal pain
    • anorexia
    • growth suppression
    • fever

    Toxicity: restlessness, dizziness, tremor, psychosis, permament intellectual problems
  60. Methylphenidate
    structurally different from amphetamines 


    • Mechanism: 
    • release NE, dopamine, serotonin
    • blocks transmitter uptake into presynaptic terminals
    • direct partial agonist of alpha adrenergic receptors
    • MAO inhibition

    • Effects:
    • wakefulness, alertness, decrease fatigue
    • enhances athletic/intellectual performance
    • mood elevation/self confidence
    • speed
    • respiratory stimulation
    • decrease appetite

    • SE: 
    • insomnia, abdominal pain, anorexia, growth suppression, fever

    Toxcitiy: restlessness, dizziness, tremor, psychosis, permanent intellectual problems
  61. Methamphetamine
    better CNS bioavailability and effect than other amphetmines

    higher abuse liability

    • Mechanism:
    • release NE, dopamine, serotonin
    • blocks transmitter uptake into presynaptic terminals
    • direct partial agonist of alpha adrenergic receptors
    • MAO inhibition

    • Properties:
    • wakefullness, alertness, enhances athletic/intellectual performance, respiratory stimulation, decreased appetite

    SE: insomnia, abdominal pain, anorexia, growth suppression, fever

    Toxicity: restlessness, dizziness, tremor, psychosis, permanent intellectual problems
  62. Nicotine
    • agonist of nicotinic cholinergic receptors
    • NMJ not affected as much
    • Autonomic ganglia - release epinephrine & GI effects
    • CNS receptors - membrane depolarization

    Actions: alertness, activates domaine signalling, muscle relaxant

    • Tolerance/dependence: 
    • readily aborbed through mucus membranes (lungs -> brain in 7 secs)
    • Reinforcing (several puffs)
    • Tolerance throughout day
    • W/drawal: irritability, anxiety, depression, difficulty concentrating, increased appetite, weight gain
  63. Bupropion
    unknown mechanism - enhance noradrenergic & dopaminergic signalling (blocks NE and DA uptake)

    moderate effectiveness; reduce craving and withdrawal symptoms of nicotine addiction, atypical antidepressant, seasonal affect disorder

    SE: dry mouth & insomnia
  64. Varenicline
    partial agnoist of CNS nicotinic receptors - reduces cravings/withdrawal from nicotine

    significant improvement in abstinence

    SE: nausea, insomnia, headache, constipation, increased thoughts of suicide, depression
  65. Epilepsy
    A group of disorders characterized by excessive excitability of neurons w/in th CNS.

    Symptoms can range from brief periods of unconscioussness to convulsions.  Incidence is 5/1000.

    60% of those w/ the disorder can be rendered seizure free w/ drugs! :)
  66. Partial Seizure

    • Simple: no impairment of consciousness
    • Complex: dreamy dysaffective state
  67. Generalized Seizures
    impairs consciousness and distorts the electrical activity of the whole or a larger portion of the brain

    • Types:
    • Tonic-Clonic
    • Absence
    • Myoclonic 
    • Status epilepticus
  68. Tonic-Clonic Seizure
    grand mal

    loss of concsciousness, falling

    • rigid extension of trunk/limbs (tonic phase)
    • rhythmic contraction or arms/legs (clonic phase)
  69. Absence Seizure
    petit mal

    impaired consciousness with staring spells, with or without eye blinks
  70. Myoclonic Seizure
    • jerks/shocklike contractions
    • loss of muscle tone
    • falling
    • "drop attacks"
  71. Status Epilepticus
    seizures recurring so close together that baseline consciousness is not regained between seizures
  72. Phenytoin
    Use: tonic-clonic and partial seizures (NOT absence)

    • Alters ion conductases
    • Use dependent effect on Na channels
    • Inhibits generation of reptitive APs

    • Highly plasma bound
    • Dose dependent

    May interact w/ drugs metabolized by CYP & protein bound drugs

    • SE:
    • CNS: nausea, anorexia, apathy, sedation, ataxia, nystagmus, diplopia - dose dependent

    • Gingival hyperplasia 
    • Hirsutism 
    • Teratogenicity- fetal hydantoin syndrome - cardiac symptoms, cleft palate 
    • Hypersensitivity reactions - rash
  73. Carbamazepine
    All forms epilepsy EXCEPT absence seizures

    • Blocks Na channels
    • Unpredictable absorption
    • Hepatic enzyme induction

    • SE: 
    • diplopia, ataxia, GI upset, drowsiness, rare blood dyscrasias
  74. Oxcarbazepine
    newer carbamazepine analog

    • similar in action but less likely to cause CNS SE
    • Less enzyme induction
  75. Phenobarbital
    • oldest antiseizure
    • partial seizures and tonic clonic

    • Acts on GABA receptor Cl ion channel complex
    • Selectively suppress abnormal neurons by suppresing firing from the foci and inhibiting spread

    Well absorbed, long half life, induces hepatic enzymes

    SE: drowsiness, sedation, confusion, exacerbation of acute intermittent porphyria

    Drug interactions: CNS depressants, valproic acid
  76. Ethosuximide
    tx for ABSENCE seizures

    reduces low threshold(T-type) calcium currents in thalamic neurons

    • well absorbed
    • not protein bound
    • liver metabolism - inhibited by valproic acid
    • long half life

    • SE
    • among safest of antiseizure drugs
    • gastric disease, lethargy, fatigue
  77. Valproic acid
    • blocks reptitive neuronal firing
    • may reduce T-type Ca currents
    • Increase GABA concentration

    • well absorbed
    • bound to plasma protein - competes w/ phenytoin
    • inhibits metabolism of phenobarbital, phenytoin, and carbamazepine

    Use: absence seizures, tonic-clonic, partial, and myoclonic - may be used as a first-line drug in mania, mixed mania (sedating)

    • SE:
    • GI upset, weight gain, hair loss, hepatoxicity, teratogenicity (spinal bifida)
  78. Felbamate
    May act at glycine site of NMDA receptor, also potentiates GABA

    Used for partial seizures REFRACTORY to other drugs

    SE: aplastic anemia, hepatic failure
  79. Gabapentin
    • GABA analog 
    • Adjunct therapy for partial seizures

    • Not protein bound or metabolized by liver
    • Also used for neuropathic pain and ALS
  80. Pregabalin
    structurally similar to gabapentin but more potent

    may interact w/ calcium channels to reduce NT release

    • adjunct therapy for partial seizures
    • management of neuropathic pain associated w/ diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia

    limited abuse potential
  81. Lamotrigine
    Blocks repetitive APs and may block Na channels

    • Used for partial and tonic-clonic seizures
    • Approved for bipolar disorder

    SE: serious rash including Stevens-Johnson syndrome
  82. Topiramate
    • Structurally related to D-fructose
    • May block kainate-AMPA-type glutamate receptors and enhance GABA effects - may also block Na channels

    • Blocks spread of seizures
    • Used for partial seizures
    • Prevention of migraines
    • SE: weight loss
  83. Tiagabine
    inhibits GABA transporter GAT-1 and blocks GABA uptake

    Adjunct therapy for simple and complex partial seizures

    SE: dizziness, tremor, somnolence
  84. Levetiracetam
    adjunct tx of partial seizures & myoclonic seizures

    few drug interactions

    SE: somnolence, asthenia, dizziness
  85. Zonisamide
    • inhibits T-type Ca channels and Na channels
    • stops spread of seizures and suppresses their focus

    Adjunct tx of adults w/ partial seizures

    SE: ataxia, anorexia, nervousness, fatigue, speach impairment
  86. Vigabatrin
    irreversibly blocks GABA metabolism

    adjunct tx of refractory complex partial seizures and infantile spasms

    possible permanent effects on vision
  87. Procaine 

    Short acting; first synthetic local anesthetic

    Supplanted by newer agents but still used for infiltration of anesthesia

    Low potency, slow onset, short duration of action
  88. Tetracaine
    Long acting ester local anesthetic


    More potent & longer duration of action than procaine

    Used in spinal anesthesia & topical/ophthalmic preprations

    Not for peripheral nerve block
  89. Benzocaine 

    Anesthetic w/ low water solubility; too slowly absorbed when applied topically to be toxic

    Applied to wounds & ulcerated surfaces where it provides relief for long periods of time
  90. Lidocaine

    Intermediate duration of action

    Produces faster, more intense, longer lasting, more extensive anesthesia compared to procaine

    Often used w/ vasoconstrictors to decrease toxicity and decrease rate of absorption (epinephrine)

    Wide range of clinical uses

    metabolized by liver
  91. Bupivicaine

    Long lasting amide local anesthetic

    Capable of producing prolonged anesthesia

    Provides more sensory than motor block

    More cardiotoxic than equieffective doses of lidocaine (severe ventricular arrhythmias and myocardial depression) - dissociates from Na channels slowly resulting in increased potency for blocking cardiac conduction

    S-enantiomer is available that is less toxic
  92. Ropivacaine

    Long lasting amide local anesthetic consisting of S-enantiomer

    Anesthetic actions similiar to bupivicaine w/ less cardiotoxicity

    Suitable for epidural and regional anesthesia

    Even more motor sparing than bupivacain
  93. Major depressive disorder
    • depressed mood
    • diminished interest or pleasure
    • weight change
    • insomnia/hypersomnia
    • fatigue or loss of energy
    • feelings of worthlessness
    • inappropriate guilt
    • agitation/retardation
    • difficulty concentrating
    • preoccupation with death/suicidal ideation
  94. SSRI
    most commonly used antidepressant

    both long half life and short life available

    • SE: nausea, vomiting, insomnia, nervousness, sexual dysfxn
    • Acute toxicity less than TCAs and MAO inhibitors - less risk of overdose

    • Use:
    • major depressive disorder
    • OCD
    • panic disorder
    • social phobia
    • PTSD
    • generalized anxiety disorder
    • PMS
  95. Fluoxetine
    • SSRI
    • effects drug metabolism
    • active metabolite with long half-life
    • available as sustained release product

    in conjunction w/ olanzapine - tx of depressive episodes associated with bipolar disease
  96. Sertraline
    • SSRI
    • similar in action to fluoxetine w/ less effects on drug metabolism
    • shorter half-life
  97. Paroxetine
    • SSRI w/ highest specificity for serotonin
    • low anticholinergic activity
    • available in in sustained release form
  98. Citalopram

    also used for anxiety
  99. Escitalopram

    active s-enantiomer form of citalopram
  100. SNRI
    blocks both serotonin and norepinephrine uptake
  101. venlafaxine

    effective in severe depression and anxiety
  102. Duloxetine

    12-18 hr half life

    use w/ caution in patients w/ liver disease

    also approved for: fibromyalgia, diabetic neuropathy, back pain, and osteoarthritis pain
  103. milnacipran

  104. Mirtazapine
    atypical antidepressant

    blocks presynaptic alpha2 receptors in brain

    increases appetite
  105. tricyclic antidepressants
    • first highly effective drugs for depression
    • now secondary to SSRIs and other newer compounds

    • rapidly absorbed after parenteral or oral administration
    • relatively high concentrations in brain and heart

    long plasma half life (8-100 hrs)

    • produces mood elevation in 2-3 weeks
    • decreases REM sleep and increases tage 4
    • prominent anticholinergic effects
    • sedation
    • orthostatic hypotension
    • demethylated to active metabolites

    cardiac abnormalities: d/t anticholinergic effects and increased NE concentrations - palpitations, tachycardia, and arrythmias - EKG changes (lengthened QRS intervals, flattened/inverted T waves)

    overdose/acute toxicity: hyperpyrexia, hyper/hypotension , seizures, coma

    • drug interactions:
    • guanethidine: blocks uptake
    • sympathomimetic drugs (indirect acting)
    • effects on absorption and metabolism of other drugs
  106. Imipramine
    tricyclic antidepressant

    enuresis in childhood
  107. amitriptyline
    tricyclic antidepressant

    chronic pain

    migraine prophylactic
  108. clomipramine
    tricyclic antidepressant

    obsessive compulsive disorder
  109. MAO inhibitors
    blocks oxidative deamination of naturally occuring biogenic amines (NE, DA, and 5-HT)

    MAO found in mitochondrial fraction of neurons (MAO A) and also liver, lung, and other organs

    MAO A inhibition for antidepressants
  110. phenelzine
    irreversible MAOI

    • Use: antidepressant action takes 2 weeks - not drug of first choice for major depression
    • narcolepsy

    mood elevation, may progress to hypomania in bipolar disease

    corrects sleep disorders - most potent REM sleep suppressant

    SE: orthostatic hypotension, agitation, hallucinations, hyperpyrexia, convulsions

    • Drug/food interactions:
    • sympathetic amines and their precursors
    • tricyclic antidepressants
    • tyramine from food - HTN crisis
  111. psychosis
    derangement of personality

    loss of contact w/ reality


  112. schizophrenia
    positive: delusions, hallucinations, hostility, disorganized speech

    negative: blunted affect, emotional withdrawal

    hyperactivity of DA neurons in limbic areas
  113. Mesocortical pathway
    cognitition, communication, social activity

    diminished DA activity: negative symptoms
  114. Mesolimic pathway
    arousal, memor, stimulus processing, locomotor activity

    dopamine hyperactivity: positive symptoms
  115. Tardive dyskinesia
    late reaction

    oral-facial dyskinesias, choreathetoid movements
  116. Atypical antipsychotic
    Uses: acute psychotic episodes, chronic schizophrenia, mani episodes, augmentation of antidepressant action, Tourettes, antiemesis

    • Less extrapyramidal syndrome (better compliance)
    • Lower tardive dyskinesia
    • Improves negatiive symptoms
    • Improves positiv esymptoms in resistant or refractory patients

    SE: aplastic anemia, weight gain
  117. Bipolar disorder
    back and forth between irritable, depressed mood and very good mood
  118. Chlorpromazine
    • Typical antipsychotic
    • Phenothiazine
    • Low/medium potency
    • Sedative
    • Pronounced anticholinergic actions
  119. Thioridazine
    • Typical antipsychotic
    • Low potency
    • sedative
    • Less extrapyramidal actions
    • anticholinergic
    • piperidine side chain
  120. Fluphenazine
    • Typical antipsychotic
    • High potency
    • Less sedative
    • Less anticholinergic
    • More extrapyramidal reactions
    • Piperazine side chain
  121. Thiothixene
    • Typical antipsychotic
    • similiar pharmacology to phenothazines (chlorpromazine) - low potency
    • non-nitrogen analog to phenothiazine
  122. Haloperidol
    • Typical antipsychotic
    • not chemically related to phenothiazines
    • pharmacologically similar to high potency piperazine derivates (fluphenzine)
  123. Pimozide
    • Typical antipsychotic
    • potent
    • many SE
    • used for Tourette's
    • commonly used when haloperidol doesn't work
  124. Clozapine
    • Atypical antipsychotic
    • Blocks D4 (little effect on D2)
    • muscarinic antagonist
    • Improves positive symptoms even in patients not helped by other drugs
    • Improves negative symptoms
    • Decreases seizure threshold more than other antipsychotics
    • Can cause fatal agranulocytosis - requires monitoring
  125. Olanzapine
    • Potent 5-HT2 antagonist
    • D1, D2, D4 antagonist
    • Few extrapyramidal symptoms (5-HT >D)
    • Less seizures
    • No agranulocytosis
    • Weight gain and diabetes risk

    In conjunction w/ fluoxetine - tx of depressive episodes associated with bipolar disease
  126. Risperidone
    • Combined D2 & 5-HT2 antagonist
    • Greater decrease in negative symptoms
    • Low incidene of extrapyramidal SE
    • Less seizure activity
    • Paliperidone is the active metabolite
  127. Quetiapine
    structurally related to cloazpine with effects on D2 and 5-HT2 receptors

    Approved for augmentation in depression

    Shorter T1/2
  128. Ziprasidone
    • May also have 5-HT1a agonist activity
    • No weight gain
  129. Aripiprazole
    • D2 partial agonist
    • Approved as adjunct in the tx of depression
  130. Lithium
    • low therapeutic index - plasma levels must be monitored
    • blocks manic behavior (takes some time to take effect)
    • reduces release of IP3 and DAG
    • readily absorbed - increased Na exceretion increases Lithium level in the cell - toxicity
    • Interactions w/ ACE inhibitors and Ang. II

    • Use:
    • manic episodes
    • bipolar depression
    • Aggressive, violent, anti-social behavior

    SE: fatigue, tremor, GI symptoms, goiter, don't use in pregnancy, slurred speech

    • Serious toxicit:
    • impaired consciousness
    • rigidity/hyperactive deep reflexes
    • Coma
  131. beta endorphin
    co-released w/ ACTH in response stress

    endogenous ligand of mu receptor
  132. dynorphins
    endogenous ligand for kappa receptor

    colocalizes with magnocellular cells of hypothalmus and posterior lobe of pituitary gland
  133. enkephalins
    endogenous ligand of delta receptor

    distributed widely throughout CNS
  134. Morphine
    • extensive first pass 
    • injectable, oral, suppository
    • 4-5 hrs
    • Mu receptor agonist
  135. Heroin
    More lipophilic than morephine

    Activated by metabolism

    High abuse potential
  136. Codeine
    • Mild to moderate pain
    • cough supression

    Morphine-like efficacy not achievable at any dose

    Some metabolized to morphine

    Often used in combination with aspirin or acetaminophen
  137. Oxycodone
    Moderate to severe pain

    often used in combination with aspirin or acetaminophen

    available as sustained release oral preparation-major abuse problem

    cough suppression
  138. Methadone
    • equipotent with morphine; good oral availability
    • longer duration of action
    • used in tx of opioid abuse
  139. Meperidine
    shorter duration of analgesia than morphine

    forms toxic metabolite that can accumulate with frequent use

    interactions with MAOI
  140. Fentanyl
    structurally related to meperidine

    100x as potent as morphine

    short acting 1-1.5 hrs

    available as injectable form and as transdermal patches - also available as buccal soluble film for breakthrough pain
  141. Hydromorphone
    2-3x as potent as morphine
  142. hydrocodone
    stronger than codeine, but not as strong as morphine
  143. nalbuphine
    mu and kappa agonist

    similar in efficacy and potency to morphine

    much lower abuse potential

    can ppt w/drawal in opioid dependent patients

    available only in injectable form
  144. buprenorphine
    • partial mu agonist
    • used to tx moderate to severe pain - now available as a patch

    orally combined with naloxone used to tx opioid dependence
  145. Naloxone
    opioid antagonist

    high affinity for mu receptors - significantly less for kappa/delta

    • much greater activity parenterally than orally
    • extensive first pass metabolism
    • short duration of action (1-2hrs)
    • used to tx opioid overdoses (used in combo w/ buprenorphine)

    can be combined w/ opioids to decrease abuse liability
  146. Dextromethorphan
    dextro-opioid isomer - antitussive, but not analgesic (cough suppression)
  147. tramadol
    • weak mu agonist
    • also blocks NE and 5-HT uptake
    • used for milkd to moderate pain
    • available for oral use including sustained release prep
  148. suboxone
    tx of opioid abuse
  149. tolerance
    decrease in response to a drug as a result of repeated tx w/ drug
  150. physical dependence
    physical symptoms produced by drug withdrawal
  151. psychological dependence
    compulsive feelings of the need to take a particular drug
  152. addiction
    maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by 3 or more of tehh following in 12 month period:

    • tolerance
    • withdrawal
    • substanec taken in large amts over long period than intended
    • persistent desire/unsuccessful efforts to cut down or control
  153. cannabis
    • unique marijuana plant
    • related to hop plant
    • main ingredient - 9-tetrahydrocannabinol
  154. 9-tetrahydrocannabinol
    • main active ingredient of marijuana
    • content determines potency
    • rapidly metabolized by liver to highly active compound
  155. marijuana
    use is age and sex related

    rapidly metabolized by liver to 11-oh-9-THC - highly active

    metabolites excreted in urine & feces - detectable for many days

    3-5x more potent when smoked

    • effects: euphoria, memory impairment, motor performance
    • CV: tachycardia, orthostatic hypotension, angina
    • pulmonary: bronchodilation, lung irritant, decreased ciliary fxn
    • reproduction: lower testoserone and sperm count, decreased fsh, lh, proloactin, abnormal menstrual cycle

    psychopathological: acute anxiety rxn, transient periods of paranoi

    tolerance/dependence: restlessness, irritability, sleep difficulties, decreased appetite, nausea, craving

    therapeutic use: control of nausea, MS pain and cancer pain
  156. Phencyclidine
    • PCP
    • weak base
    • soluble in water
    • lipid soluble
    • effects: tachycardia, HTN, potentiation of catecholamines
    • drunken state, numbness of extremities, convulsions

    NMDA antagonist

    tx of overdose: gastric suction, acidify urine, diazepam, anti-HTN, haloperidol
  157. Lysergic Acid Dyethylamide (LSD)

    • onset of action 15-20mins
    • duration: 2 hrs
    • <1% crosses BBB

    • tachycardia, increase BP
    • psychomotor stimulation
    • altered perception (visual)
    • lability of mood
    • impaired judgement
    • hallucinations, anxiety, panic, depersonalization
    • flashbacks
  158. Methylenedioxymethamphetamine (MDMA)

    substitude phenethylamine

    feelings of "well being," connection, altered time

    • onset of action: 20-40 mins
    • duration: 3-4 hrs

    • psychomotor stimulation
    • restlessness, anorexia, tremor, sweating

    hangover: anhedonia

    neurotoxicity: 5-HT damage
  159. Gamma-hydroxybutyrate (GHB)
    found naturally in brain as a precursor/metabolite of GABA

    • liquid ecstasy
    • tx of cataplexy associated w/ narcolepsy

    may have own receptor

    effects last 3 hrs

    depressant - state of relaxation and tranquility, tendency to verbalize, interacts w/ alcohol

    overdose: drowsiness, dizziness, nausea, vomiting, ataxxia, loss of bladder control, amnesia, conlus, seizures
  160. Toluene
    drug of abuse

  161. Salvia Divinorum
    K-opioid agonist

    • 20-45 mins action
    • dream like experience w/ open and close eyed visuals
    • dissociation at high doses w/ fear, panic, and perspiration
  162. Immunization
    most effective tx (prevention) 

    active: vaccination (polio, smallpox, measles, influenza, herpes zoster, hep a/b, rabies, etc.) - buildup long term immunity

    • passive: injection of immune globulin often blocks viral penetration, may modify course of disease if given during early incubation period, protective effect lts 2-3 wks, given IM or IV
    • viral replication rate is reduced by blocking viral entry into cells; may allow for active immunity to develop.
    • special hyperimmune globulins available for rabies, varicella-zoster, hep A, B, CMV, measles, RSV
  163. Oseltamivir
    • use:
    • tx of uncomplicated influenza A and B
    • given w/in 48 hrs of symptom onset
    • influenza prophylaxis

    • mechanism:
    • prodrug, competitive inhibitor of influenza neuraminidases; interferes with viral release and viral penetration

    SE: nausea/vomiting/diarrhea, bronchitis
  164. Trifluridine
    interferes with DNA synthesis; thymidine analog

    use: ophthalmic herpes simplex 1 & 2

    toxicity: burning, stinging, hypersensitivity
  165. Acyclovir
    • mechanism: inhibits DNA polymerase
    • phosphorylated form is produced 40-100x faster in infected cells by herpes thymidine kinase
    • initial herpes DNA polymerase 10-30x more than host cell DNA polymerase
    • acts as a competitive inhibitor of dGTP and as a DNA chain terminator

    • Use:
    • IV: - drug of choice for serious systemic herpes simplex & severe initial genital herpes and HSV encephalitis

    Oral: primary genital herpes, primary herpetic gingivostomatosis

    topical: some effect when applied early to primary genital herpes

    Miscellaneous: chickenpox (shortens disease by 1 day)

    • Toxicity: 
    • generally well-tolerated
    • rash, itching, nausea, vomiting, headache, fatigue
  166. Famciclovir
    Mechanism: similar to acyclovir: prodrug converted to penciclovir which is phosphorylated - inhibits viral DNA polymerase

    better absorbed than acyclovir because it's a prodrug - that's why it treats some things that acyclovir is not good at

    use: acute herpes zoster (shingles), < 3 days duration, tx and suppression of recurrent genital herpes & recurrent herpes cold sores

    toxicity: similar to acyclovir (rash, itching, nausea, vomiting, headache, fatigue)
  167. Penciclovir
    mechanism: very similar to acyclovir - very poor oral bioavailability

    acyclic structure, but technically not a chain terminator b/c it does have an unusual -OH group - little chain extension actually occurs

    use: recurrent herpes of the lips and face (for minor episodes where you don't want to use an oral drug)

    administration: topical
  168. Ganciclovir
    mechanism: similar to acyclovir, except the monophosphorylation is catalyzed by CMV protein kinase - inhibits DNA synthesis and terminates DNA elongation 

    Use: tx of CMV retinitis (in AIDS patients), CMV prophylaxis for transplant recipients

    Toxicity: bone marrow suppression, leukopenia, thrombocytopenia, anemia, may enhance bone marrow suppression when given with zidovudine (AZT), abnormal liver fxn
  169. Foscarnet
    • Mechanism: inhibits CMV DNA polymerase by binding to its pyrophosphate-binding site
    • does not require conversion to triphosphate form to be active

    use: CMV retinitis, acyclovir-resistant herpes simplex

    toxicity: renal damage, electrolyte imbalances, seizures
  170. Lamivudine
    Mechanism: nucleoside analog inhibitor of the reverse transcriptase domain of the hepB DNA polmerase

    Use: approved for hep B & HIV (synergistic w/ AZT)

    Toxicity: nausea & diarrhea
  171. Tenofovir
    • mechanism: adenosine monophosphate, inhibits reverse transcriptase domain of hep B DNA polymerase
    • nucleotide prodrug, results in chain terminiation

    use: Hep B & combination therapy HIV

    toxicity: GI upset
  172. Ribavirin
    • Mechanism: interferes with viral mRNA synthesis
    • inhibits inosine-5-p dehydrogenase and thus GTP synthesis
    • inhibits GTP- dependent capping of viral mRNA

    • use:
    • aerosol use:  infants and young children - documented severe lower respiratory syncytial virus (RSV) infections - no longer commonly used

    HepC (oral) in combination w/ interferon-alpha

    IV/oral use: anemia, bone marrow suppression

    • SE:
    • aerosol: drug may ppt in and clog resipratory equipment
    • pulmonary function deterioration, rash
    • IV/oral: anemia, bone marrow suppression
  173. Interferon
    • use for recombinant alpha-inteferons:
    • condyloma acuminata (venereal warts, papilloma virus)
    • hep B and C
    • PEG-alfa-2a and PEG-alfa-2b interferons in combination with ribafarin are specifically useful for hep C

    toxicity: flu-like syndrome, leukopenia, bone marrow suppression, neurotoxicity, myalgia
  174. Boceprevir
    mechanism: reversible inhibitor of hep C NS3 protease, blocking formation of infectious virus particles

    use: hep C genotype 1, combo w/ PEG-interferon + ribavirin

    Toxicity: anemia, neutropenia, contraindicated with drugs that are CYP3A substrates or inducers
  175. Zidovudine (AZT)
    mechanism: thymidine nucleoside analgog; phosphorylated by cellular kinases, inhibits reverse transcriptase, acts as DNA chain terminator

    Use: nucleoside RT inhibitor for tx of HIV in adults & kids

    • Toxicity:
    • bone marrow suppression, neutropenia, anemia
    • drugs which inhibit glucuronyl transferase increase hematologic toxicity and should be avoided
    • myopathy (w/ prolonged use)

    ALL NRTIs: lactic acidosis & hepatic steatosis 
  176. Emtricitabine
    mechanism: fluorinated analog of 3TC - inhibits RT by competing for dCTP incorporation into DNA, resulting in chain termination

    Use: combination therapy for HIV-infected patients
  177. Abacavir
    mechanism: nucleoside analog inhibitor of RT

    use: combination therapy for HIV-infected patients

    toxicity: hypersensitivity reactions (associated with HLA-B*5701 antigen)
  178. Efavirenz
    echanism: non-nucleoside inhibitor of reverse transcriptase; does not require phosphorylation for activity

    use: part of multi-drug therapy for HIV

    SE: rash, CNS/psychiatric symptoms, nightmares, vivid dreams
  179. Lopinavir
    use: combination with RT inhibitors, significantly decreases viral load

    mechanism: prevents viral protease from cleaving Gag-pol polypeptide into separate functional proteins, competitive inhibitor, results in non-infectious viral particles

    SE: diabetes, alterations in lipid metabolism, fat distribution, fat distribution, alters metabolism of many other drugs (potent CYP3A inhibitor), diarrhea
  180. Ritonavir
    use: combination with RT inhibitors, significantly decreases viral load - used to boost levels of other PIs (b/c it blocks their metabolism by CYP3A) - used as BOOSTER

    mechanism: prevents viral protease from cleaving Gag-pol polypeptide into separate functional proteins, competitive inhibitor, results in non-infectious viral particles

    SE: diabetes, alterations in lipid metabolism, fat distribution, fat distribution, alters metabolism of many other drugs (potent CYP3A inhibitor)
  181. Enfuvirtide
    use: HIV-1 only, detectable viral replication despite ongoing therapy

    mechanism: inhibits fusion of viral (HIV-1) and cellular (CD4+) membranes, binds to gp41 subunit of HIV glycoprotein, blocking membrane fusion

    SE: local injection site rxns, diarrhea, nausea, fatigue
  182. Maraviroc
    use: tx of CCR5-tropic HIV-1

    mechanism: chemokine co-receptor (CCR5) antagonist, blocks entry of HIV into cells - tends to predominate early in infection

    SE: hepatotoxicity, CV events
  183. Raltegravir
    use: tx of HIV-1, used on viruses resistant to other drugs

    mechanism: inhibits HIV-1 integrase, preventing integration of HIV-1 DNA into genome
  184. regular insulin
    • clear solution
    • IV use
    • human sequence
  185. NPH insulin
    cloudy suspension of insulin aggregated w/ protamine and zinc

    longer time course d/t breaking down aggregates

    human sequence
  186. Insulin Analogs
    synthetic insulins -

    1 or more amino acids of human insulins changed to yield short or long acting insulin

    lispro insulin & insulin aspart
  187. lispro insulin
    short acting

    pro-lys dipeptide at positions B28 and B29 are reverse
  188. insulin aspart
    short acting

    B28 proline replaced by aspartic acid
  189. insulin glargine
    long acting insulin analog 

    asparagine at A21 is replaced by glycine & 2 arginines added to C-temrinus of B-chain

    soluble at pH=4, poorly solubleat pH=7

    forms ppt when injected subQ
  190. insulin detemir
    intermediate/long term acting insulin

    threonine at B30 omitted and C14 fatty acid chain attached to AA B29

    long acting d/t self association at subQ injecting site and binding in albumin in blood stream
  191. sulfonylureas
    stimulate insulin secretion by pancreas

    interact w/ beta cells K+ transporter causing depolarization and secondary calcium influx

    SE: hyponatremia, disulfiram like reaction, rashes/GI upset/drug interactions, hypoglycemia

    • glipizide
    • glyburide
    • glimepiride
  192. glipizide
    type of sulfonylurea

    stimulates insulin secretion
  193. glyburide
    type of sulfonylurea

    stimulates insulin secretion
  194. glimepiride
    type of sulfonylurea

    stimulates insulin secretion
  195. metformin
    • makes liver more sensitive to insulin
    • biguanide

    SE: abdominal discomfort, diarrhea, lactic acidosis

    CI: renal insuffiency, elderly, CHF, binge drinking, liver disfunction
  196. Thiazolidinediones
    makes peripheral tissues such as fat and muscle more sensitive to insulin by activating PPAR

    SE: liver toxicity, weight gain, fluid retention

    CI: heart failure

    rosiglitazone, proglitazone
  197. rosiglitazone
    type of thiazolidinedione

    increases cardiac ischemic effects
  198. pioglitazone
    type of thiazolidinedione

    increases risk of bladder cancer
  199. acarbose
    glucosidase inhibitor

    inhibits enteric enzymes that break down complex carbs -- partial malabsorption of carbs

    decreases post-prandial hyperglycemia

    SE: bloating, abdominal discomfort, diarrhea, flatulence
  200. exenatide
    GLP-1 analog

    augments insulin secretion, increases beta-cell mass, inhibits glucagon secretion, promotes weight loss

    SE: nausea, emesis, diarrhea, headaches, pancreatitis
  201. sitagliptin
    DPP4 inhibitor - prolongs action of GLP-1

  202. sumatriptan
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