cumulative exam 1

What is the purpose of the preclinical investigation in the drug approval process?

determine drug toxicity prior to human exposure

What does the preclinical investigation step of the drug approval process include?

• chemical drug synthesis

• cell culture tests

• animal testing

• tissue testing

What is the purpose of clinical investigation phase I?

• determine optimal dosage range

• determine drug pharmacokinetics

• uses healthy subjects

What does clinical investigation phase I include?

• informed consent

• urinalysis in human subjects

What is the purpose of the clinical investigation phase II?

• determine drug effectiveness

• identify adverse effects

• refine therapeutic dosage ranges

What is the purpose of the clinical investigation phase III?

• uses large sample size

• establish:

  • drug’s clinical effectiveness

  • drug safety

  • dosage range

• double blinded investigational drug study

What is the purpose of the new drug application submission and review?

approval allows exclusive marketing of a new drug

What is the purpose of the clinical investigation phase IV?

obtain further proof of therapeutic and adverse effects of a new drug among general population (medwatch)

What are the classes of sedative-hypnotic drugs?

• barbiturates

• benzodiazepines

• miscellaneous

What is the mechanism of action of the barbiturates?

bind to GABA receptor mediated chloride channel prolonging channel opening, chloride influx and membrane hyperpolarization

What are the drug indications of barbiturates?

• sedation

• hypnosis

• anticonvulsant

• general anesthesia

What is an important adverse effect of the barbiturates?

automatism: elderly patients are sensitive to CNS side effects particularly with memory difficulties and mental confusion

What drugs are in the barbiturates class (SH)?

• phenobarbital

• pentobarbital

• amobarbital

• secobarbital

What is the mechanism of action of the benzodiazepines?

bind to receptor on chloride channel and combines with GABA activity to increase frequency of channel opening

What are the drug indications for the benzodiazepines?

• sedation

• hypnosis

• anxiety

• muscle relaxant

• anticonvulsant

• antiepileptic

• preoperative sedation

What drugs are in the benzodiazepines class (SH)?

• flurazepam

• temazepam

• triazolam

• ***flumazenil (benzo receptor antagonist)

What is the mechanism of action for the miscellaneous sedative hypnotics?

selectively bind to subunit of benzodiazepine receptor on chloride channel and increase inhibitory effects of GABA

What are the drugs in the miscellaneous category of sedative hypnotics?

• eszopiclone (Lunesta)

• zaleplon (Sonata)

• zolpidem (Ambien)

• ramelteon (melatonin agonist)

What are the drug classes of antipsychotic and antianxiety drugs?

• typical antipsychotics

  • phenothiazines

  • butyrophenones

  • thioxanthenes

• atypical antipsychotics

• anxiolytics (antianxiety)

  • benzodiazepines

  • miscellaneous

What is the mechanism of action of the typical antipsychotics?

block dopamine receptors

What are the drug indications of the typical antipsychotics?

• schizophrenia

• psychotic conditions

What are adverse effects of the typical antipsychotics?

• extrapyramidal syndrome (movement disorders)

• tardive dyskinesia

• neuroleptic malignant syndrome

What are the unique features of the phenothiazines?

• anticholinergic, antihistaminic, alpha adrenergic blocking, and antiemetic

• additionally used for nausea, vomiting, pruitus, and certain allergic reactions

What drugs are in the phenothiazines subclass?

• chlorpromazine

• fluphenazine

• thioridazine

• trifluoperazine

What are the unique features of the butyrophenones?

• used in highly agitated and manic patients

• ***highest incidence of EPS

What are the drugs in the butyrophenones subclass?

• haloperidol (Haldol)

What are the unique features of the thioxanthenes subclass?

• high potency

• less sedation, anticholinergic, and alpha blocking effects

What drugs are in the thioxanthenes subclass?

• thothixene

What is the mechanism of action for the atypical antipsychotics?

affect and reduce activity of serotonin receptors (more than dopamine)

What are the drug indications for the atypical antipsychotics?

• schizophrenia

• psychotic conditions

What drugs are in the atypical antipsychotics class?

• aripiprazole (Abilify)

• clozapine

• risperidone

• olanzapine

What are the drugs in the benzodiazepines drug subclass (anx)?

• lorazepam (Ativan)

• diazepam (Valium)

• alprazolam (Xanax)

• clonazepam (Klonopin)

What are the drugs in the miscellaneous subclass of the anxiolytics?

• buspirone (BuSpar)

What are the subclasses of antidepressants?

• SSRIs

• SNRIs

• TCAs

• MAOIs

• miscellaneous

What is the mechanism of action of the SSRIs?

block reuptake of serotonin into serotonergic nerve endings, increases serotonin concentration in synaptic cleft and increases stimulation of receptors

What are the drug indications of the SSRIs?

• depression

• anxiety

• PTSD

• OCD

• PMDD

What are the drugs in the SSRIs subclass?

• fluoxetine (Prozac)

• citalopram (Celexa)

• escitalopram (Lexapro)

• paroxetine (Paxil)

• sertraline (Zoloft)

What is the mechanism of action for the SNRIs?

block reuptake of serotonin and norepinephrine in the brain, increases serotonin and norepinephrine concentration

What are the drug indications for the SNRIs?

• depression

• generalized anxiety

• chronic pain disorders

• fibromyalgia

What are the drugs in the SNRIs drug subclass?

• venlafaxine (Effexor)

• duloxetine (Cymbalta)

What is the mechanism of action of the TCAs?

possesses anticholinergic, alpha adrenergic blockage and antihistaminic effects, block reuptake of NE and 5HT into neuronal endings leading to accumulation, increased activity of NE and 5HT

What are the drug indications for the TCAs drug subclass?

• depression

What drugs are in the TCAs drug subclass?

amitriptyline (Elavil)

What is the mechanism of action of the MAOIs drug subclass?

• inhibit MAO (which normally breaks down NE and 5HT) to increase levels of NE and 5HT

What are the drug indications for the MAOIs?

• depression

  • primarily used when other antidepressants are ineffective

What are important adverse effects of MAOIs?

• liver damage

• CNS disturbances

• urinary retention

• constipation

What drugs are in the MAOIs drug subclass?

• phenelzine (Nardil)

What are the drugs in the miscellaneous category of antidepressants?

• trazadone

• bupropion

• mirtazapine

What is the mechanism of action of trazadone?

potent serotonin receptor antagonist, weak 5HT and NE reuptake inhibition

What is the mechanism of action of bupropion?

increase release and inhibit reuptake of NE and DA

What is the mechanism of action of mirtazapine?

increase release of NE and 5HT, antihistaminic (sedative effects)

What is unique about trazadone?

has alpha adrenergic blocking activity

What are the drug indications of bupropion (Wellbutrin)?

• bipolar disorder

• smoking cessation

• obesity

What are the drug indications of mirtazapine?

• sedation

What is the mechanism of action for the amphetamines drug subclass?

CNS stimulation and mood elevation by:

1) stimulate NE and DA receptors directly

2) stimulate release of NE and DA from nerve endings

3) inhibit reuptake of NE and DA into nerve endings

What are the drug indications of the amphetamines drug subclass?

• first few weeks of depression treatment

• narcolepsy

• hyperkinesis in children

What drugs are in the amphetamines drug subclass?

• amphetamine

• methylphenidate (Ritalin)

What is the mechanism of action for the lithium drug class?

not clearly understood, may decrease NE and other neurotransmitter levels

What are the drug indications for the lithium drug class?

• mania

• bipolar mood disorder

• ***do not use in pregnant patients or patients with existing thyroid conditions

• adverse effects include heart and kidney damage

• administered as a salt

What drugs are in the lithium drug class?

• lithium

What are the drug subclasses under the inhaled anesthetics?

• volatile liquids

• nitrous oxide

What is the mechanism of action of the volatile liquids?

bind GABA receptor and cause chlorine ions to move into the cell causing hyperpolarization of the cell and decreasing membrane excitability

What is the mechanism of action for the nitrous oxide drug subclass?

NMDA receptor antagonist, blocks cation movement and depolarization, blocking excitation

What are the drug indications for the inhaled anesthetics?

• general anesthesia

• bronchodilation

What are the adverse effects of inhaled anesthetics?

• drug induced hepatitis

• respiratory lining irritation

What are the drugs in the volatile liquids drug subclass?

• desflurane (Suprane)

• sevoflurane (Ultane)

What are the drugs in the nitrous oxide drug subclass?

• nitrous oxide

What are the drug subclasses under the intravenous anesthetics drug class?

• barbiturates

• benzodiazepines

• nonbarbiturates

What are the drugs in the barbiturates drug subclass (IA)?

• methohexital (Brevital)

What are the drugs in the benzodiazepines drug subclass (IA)?

• midazolam (Versed)

What are the drugs in the nonbarbiturates drug subclass?

• propofol

• etomidate

• ketamine

• dexmedetomidine

• fentanyl and droperidol mixture

What is the mechanism of action of propofol?

bind GABA receptor causing hyperpolarization and decreasing excitability, and NMDA antagonist

What is the mechanism of action of etomidate?

bind GABA receptor causing hyperpolarization and decreasing excitability

What is the mechanism of action of ketamine?

NMDA antagonist

What is the mechanism of action of dexmedetomidine?

alpha 2 adrenergic agonist

What is the mechanism of action of fentanyl and droperidol mixture?

rapid acting opioid and tranquilizer

What is the drug indication of propofol?

induce and maintain MAC sedation

***narrow safety margin

What is the drug indication of etomidate?

induction of anesthesia

What is the drug indication of ketamine?

induction of anesthesia, MAC

***dissociative anesthetic

What is the drug indication of dexmedetomidine?

short term procedural sedation, sedation of initially intubated and mechanically ventilated patients

***do not exceed 24 hours of continuous infusion

What is the drug indication of fentanyl and droperidol mixture?

neuroleptanalgesia

What are the drug subclasses of the typical antipsychotics?

• phenothiazines

• butyrophenones

• thioxanthenes

What are the drug subclasses of the anxiolytics?

• benzodiazepines

• miscellaneous

What is the mechanism of action of the opioid receptor agonists?

bind opioid receptors and mimic the effect of the endogenous peptides, inhibit neurotransmitter release and prevent nociceptor signals from reaching the brain

What are the drug indications for the opioid receptor agonists?

• analgesia

• preoperative sedation

• antitussive

• antidiarrheal

What are the drugs in the opioid receptor agonists drug class?

• codeine

• hydrocodone (Zohydro)

• morphine

• oxycodone

• methadone (Dolophine)

• hydromorphone (Dilaudid)

• fentanyl

What are the drug subclasses under the opioid receptor antagonists?

• pure antagonists

• partial antagonists

What is the mechanism of action of the pure antagonists?

competitive antagonism, bind opioid receptors and block agonist binding

What is the mechanism of action of the partial antagonists?

binds opioid receptors and produces little to no stimulation of receptors

What drugs are in the pure antagonists drug subclass?

• naloxone (Narcan)

• naltrexone

Which drugs are in the partial antagonists drug subclass?

• buprenorphine

• methylnaltrexone bromide

What is the mechanism of action of the opioid antitussives?

direct inhibition in the cough center of the medulla to decrease intensity and frequency of coughing

What drugs are in the opioid antitussives drug class?

• codeine

• hydrocodone

• dextromethorphan

What are the subclasses under the NSAIDs drug class?

• salicylates

• synthetic NSAIDs

What is the mechanism of action of the salicylates?

• anaglesia: inhibit prostaglandin synthesis and prevent bradykinin from stimulating pain receptors centrally and peripherally

• antipyresis: blockade of prostaglanding stimulation in hypothalamus; vasodilation

• anticoagulant: inhibition of thromboxane pathway

What are the drug indications for the salicylates?

• mild to moderate pain

• antipyretic

• anti-inflammatory

• osteoarthritis

• spondylitis

• gout

• management of ulcerative colitis

What drugs are in the salicylates drug subclass?

• aspirin

• methyl salicylate (Salonpas, BenGay)

What is the mechanism of action of the synthetic NSAIDs drug subclass?

inhibit prostaglandin synthesis and prevent bradykinin from stimulating pain receptors centrally and peripherally, block prostaglandin stimulation in hypothalamus and vasodilation (analgesia and pyresis)

What are the drug indications of the synthetic NSAIDs?

• mild to moderate pain

• antipyretic

• anti inflammatory

• dysmenorrhea

• juvenile arthritis

• rheumatoid arthritis

• degenerative joint

• osteoarthritis

• spondylitis

• gout

What are the drugs in the synthetic NSAIDs drug subclass?

• ibuprofen (Advil, Motrin)

• naproxen (Aleve)

• ketorolac (Toradol)

• celecoxib (Celebrex)