Pharmacology - Block 3

Question 1

SSRIs

Answer 1

Fluoxetine and Sertraline
Used for major depression, OCD, panic, phobia, PTSD, anxiety, PMS
Take 3-4 weeks to work
Side effects: nausea, vomiting, insomnia, nervousness, sex dysfunction, acute toxicity
Serotonin reaction can occur w/ MAOIs -> hyperthermia, parkinsonian
Has black box warning for teens
SSRI discontinuation syndrome (not w/ fluoxetine) -> dizzyness, vertigo, anxiety, etc

Question 2

Fluoxetine

Answer 2

Prozac
SSRI
drug metabolism side effects
very long half life

Question 3

Sertraline

Answer 3

Zoloft
SSRI
shorter half life, no drug metabolism side effects

Question 4

Duloxetine

Answer 4

SNRI
like tricyclics, but side effects more like SSRIs
12-18hr half life
also used for fibromyalgia

Question 5

Bupropion

Answer 5

Atypical antidepressant
also used for nicotine withdrawal
blocks NE and DA reuptake
dry mouth, insomnia

Question 6

Mirtazapine

Answer 6

Atypical antidepressant
also used to increase appetite in AIDS wasting
Blocks presynaptic alpha2 receptors in brain (increases DA release)

Question 7

Tricyclic antidepressants

Answer 7

The first on market, now used second
long half lifes
takes 3 weeks to work
decreases REM, increases stage 4 sleep
anticholinergic effects
sedation
cardiac abnormalities
acute toxicity-> hyperpyrexia, cardia problems
has drug interactions with guanethidine, indirect sympathomimetic, other metabolism

Question 8

Amitriptyline

Answer 8

tricyclic antidepressant

used for chronic pain

Question 9

Clomipramine

Answer 9

Tricyclic antidepressant

used for OCD

Question 10

Phenelzine

Answer 10

Monoamine Oxidase inhibitor (irreversible)
takes 2 weeks to work
not for use in bipolar bc elevates mood to mania
acute toxicity-> hallucinations, hyperpyrexia
Tyramine from food can cause hypertensive crisis
Used for depression and narcolepsy

Question 11

Schizophrenia / antipsychotics

Answer 11

Dopamine hypothesis:
Mesolimbic: +symptoms, too much dopamine
Mesocortical: -symptoms, not enough dopamine
Nigrostriatal: EPS effects, parkinsonism
Tuber-infundibular: prolactin
D1-type-> Gs
D2-type-> Gi
Autoreceptors-> D2-like
most antipsychotics-> D2 blockers
usually lipophilic, large Vd, long half life

Question 12

Antipsychotic drug Effects

Answer 12

decrease psychotic behavior
sedation (worse w/ low potency)
Extrapyramidal actions (dystonia, parkinsonism, tardive dyskinesia)
neuroendocrine effects
orthostatic hypotension
weight gain/diabetes
Neuroleptic malignant syndrome- fever, EPS, death

Question 13

Chlorpromazine

Answer 13

Typical antipsychotic
Phenothiazine- aliphatic
low/med potency
sedative
pronounced anticholinergic

Question 14

Thioridazine

Answer 14

Typical antipsychotic
Phenothiazine- piperidine
low potency
sedative
less EPS action
anticholinergic

Question 15

Fluphenazine

Answer 15

Typical antipsychotic
Phenothiazine- piperazine
high potency
less sedative
less anticholinergic
more EPS reaction

Question 16

Haloperidol

Answer 16

Typical antipsychotic

similar to Fluphenazine (high potency)

Question 17

Clozapine

Answer 17

Atypical antipsychotic (DA4+5-HT2 blocker)
less EPS, may cause agranulocytosis, weight gain

Question 18

Olanzapine

Answer 18

Atypical antipsychotic (DA2+5-HT2 blocker)
more EPS, no agranulocytosis
weight gain

Question 19

Risperidone

Answer 19

Atypical antipsychotic (DA2+5-HT2 blocker)
low EPS
available as IM depot injection

Question 20

Quetiapine

Answer 20

Atypical antipsychotic (DA2+5-HT2 blocker)

Question 21

Aripiprazole

Answer 21

Atypical antipsychotic (DA2+5-HT2 blocker)
Abilify
D2 partial agonist
also approved as adjunct for depression

Question 22

Lithium

Answer 22

Anti-mania, mood-stabilizing
takes a month to work
Blocks recycling of Inositol->PIP3->DAG/IP3, depletes PIP2
increased Na excretion, decreased Li retention
narrow therapeutic window
interactions w/ ACE inhibitors and AngII blockers
Effects: fatigue, tremor, GI, goiter, not for pregnant, toxicity, no effect in ‘normals’
also used for cluster headaches

Question 23

Valproic acid

Answer 23

Alternative to Lithium
Also anti-seizure (absence, myoclonic)
Blocks repetitive neuron firing
Reduces T-type Ca currents and increases GABA
inhibits metabolism (esp of ethosuximide)
GI upset, weight gain, teratogenicity

Question 24

Buspirone

Answer 24

Anti-anxiety
partial 5-HT1a agonist and D2 antagonist
delayed onset, little sedation/dependency

Question 25

Alprazolam

Answer 25

Benzodiazepine short duration, also anti-panic forebrain depression, dependence

Question 26

Diazepam

Answer 26

Benzodiazepine long duration, rapidly absorbed, also muscle relaxant CNS depression, dependence

Question 27

Lorazepam

Answer 27

Benzodiazepine long duration, delayed onset, does not form active metabolites also used as hypnotic

Question 28

Benzodiazepines

Answer 28

Enhance GABA (Cl channel) activity, frequency Used as anti-anxiety, hypnotic, relaxants Metabolism leads to long-half-life active metabolites effects: sedation, hypnosis, anterograde amnesia, anti-convulsant Tolerance and dependence is an issue, so is withdrawl

Question 29

Flumazenil

Answer 29

Direct GABA antagonist (via benzodiazepine site)

Question 30

Flurazepam

Answer 30

Benzodiazepine | used as hypnotic

Question 31

Zolpidem

Answer 31

Hypnotic/sedative Binds to benzodiazepine receptors mostly hypnotic, less side effects

Question 32

Pentobarbital

Answer 32

Hypnotic, rarely used Barbiturate has tolerance, dependence, poisoning effects

Question 33

Chloral Hydrate

Answer 33

Hypnotic/sedative pungent/caustic taste prodrug similar to barbiturates, less side effect

Question 34

Phenytoin

Answer 34

Used for partial seizures (and gen. tonic clonic) Use dependent effect on Na channels (prolongs inactivated state) dose-dependent May have drug interactions (protein bound) nausea, anorexia, sedation,, gingival hyperplasia, hirsutism, teratogenicity

Question 35

Carbamazepine

Answer 35

Used for anti-seizure except absence mechanism similar to phenytoin unpredictable absorbtion, induces hepatic enzymes toxicity-> diplopia, GI, drowsiness

Question 36

Oxcarbazepine

Answer 36

Newer Carbamazepine | less CNS side effects, less enzyme induction

Question 37

Phenobarbital

Answer 37

Oldest anti-seizure, not for absence Acts on GABA receptor, limits spread used in infants

Question 38

Ethosuximide

Answer 38

Used for absence seizures Reduces low-threshold (T-type) Ca currents in thalamic neurons not protein bound, lover metabolism, long half-life GI effects and lethargy

Question 39

Clonazepam

Answer 39

Benzodiazepine used for anti-seizure (absence) | long acting

Question 40

Felbamate

Answer 40

Anti- partial seizures (2nd line) NMDA antagonist, GABA potentiator aplastic anemia side effect, limits use

Question 41

Pregabalin

Answer 41

Anti partial seizures, and used for neuropathic pain | V-gated Ca channels, reduce neurotransmitter release

Question 42

Lamotrigine

Answer 42

Anti-partial and gen. tonic clonic seizures, also for bipolar Blocks Na channels (like phenytoin)

Question 43

Topiramate

Answer 43

Blocks spread of seizures, also for migraines | Blocks kainate-AMPA-type glutamate receptors, enhances GABA

Question 44

Tiagabine

Answer 44

Used for partial seizures inhibits GABA transporter GAT-1, blocks GABA reuptake dizzyness, tremor

Question 45

Zonisamide

Answer 45

Anti-seizure spread | inhibits T-type Ca and Na channels

Question 46

Vigabatrin

Answer 46

Anti- partial seizures blocks GABA metabolism restricted due to permanent vision effects

Question 47

Baclofen

Answer 47

muscle relaxant GABA-mimetic-> hyperpolarization less sedation than diazepam

Question 48

Tizanidine

Answer 48

muscle relaxant alpha2 adrenergic agonist, enhances inhibition drowsiness, hypotension, dry mouth

Question 49

Alcohol Dehydrogenase (ADH)

Answer 49

primary pathway for metabolizing ethanol-> acetylaldehyde mostly liver zero-order kinetics

Question 50

Microsomal Ethanol Oxidizing System (MFOS)

Answer 50

secondary pathway ethanol->acetylaldehyde high Km CYP2E1 induced in alcoholics

Question 51

Aldehyde dehydrogenase (ALDH)

Answer 51

metabolizes acetylaldehyde->acetate | genetic polymorphisms

Question 52

Alcohol

Answer 52

Not very potent, large quantities Vd=total body water leads to increased NADH, inhibits TCA cycle-> fatty liver also increased acetylaldehyde, decreased glutathione Activates GABA receptors (CNS depression) steatosis, HepC, cirrhosis, gastritis, pancreatitis, diarrhea, vitamin deficiency tolerance and dependence, withdrawl neurotoxicity, teratogenic

Question 53

Chlordiazepoxide

Answer 53

Benzodiazepine | used for tapering off alcohol withdrawl

Question 54

Naltrexone

Answer 54

Reduces urge to drink opioid receptor antagonist best used w/ psychosocial therapy

Question 55

Acamprosate

Answer 55

Decreases drinking frequency, reduces relapse GABA mimetic diarrhea

Question 56

Disulfiram

Answer 56

Aversion therapy for alcohol inhibits aldehyde dehydrogenase acetylaldehyde syndrome not super effective

Question 57

Caffeine

Answer 57

CNS stimulant blocks adenosine receptors, disinhibition postsynaptic adenosine-> IPSPs presynaptic adenosine-> inhibit glutamate high doses: inhibits PDE (increases cAMP), releases Ca increased alertness, nervousness, stimulates medullary respiratory, vasomotor, vagal centers stimulates myocardium, dilates usually but constricts in CNS (headaches), diuretic, GI secretion tolerance and dependence

Question 58

Cocaine

Answer 58

CNS stimulant weak base, free base form is lipid suluable (crack) very short half-life potent inhibitor of NE, DA, 5-HT reuptake DA-> reinforcing effects increases tyrosine and tryptophan hydroxylase local anesthetic and vasoconstrictor (used for upper resp tract) peripheral simpathomimetic (NE) euphoria (DA), reinforcing tolerance and dependence mostly phychological withdrawl seizures, fetal toxicity

Question 59

Amphetamine

Answer 59

``` CNS stimulant weak base orally absorbed longer half-life releases NE, DA, 5-HT (more NE) blocks reuptake direct a2 adrenergic partial agonist MAO inhibition (high dose) wakefulness, performance, mood elevation, speed, resp stimulation, decrease apetite, peripheral simpathomimetic used for ADHD, narcolepsy neurotoxicity, psychosis ```

Question 60

Methamphetamine

Answer 60

CNS stimulant | better CNS availability, more abuse potential

Question 61

Methylphenidate

Answer 61

CNS stimulant like methamphetamine used for ADHD

Question 62

Nicotine

Answer 62

CNS stimulant nAChR agonist autonomic ganglia (epinephrine, GI motility) and CNS (excitation) activates DA in nucleus accumbens (reinforcing) tolerance and dependence rapid action, reinforced withdrawl-> irratability, anxiety

Question 63

Varenicline

Answer 63

Partial agonist of CNS nAChRs used for nicotine withdrawl nausea, insomnia warning for suicide/depression

Question 64

Sodium Thiopental

Answer 64

``` General anesthetic Barbiturate (GABA) 10sec, then 10min action, 12hr half life (hang-over) reduces CNS O2 needs, blood flow vasodilation (venous) respiratory depression ```

Question 65

Propofol

Answer 65

``` Most common general anesthetic onset and duration similar to barbiturates used to maintain, induce is antiemetic shorter half-life (less hang-over) pain on injection decrease in BP, blunts baroreceptors, decrease contractility, vasodilates more respiratory depression abuse liability ```

Question 66

Etomidate

Answer 66

General anesthetic for use in hypotension risk pain on injection less CV effect less resp depression more nausea and vomiting post-surgical mortality due to suppression of stress response

Question 67

Ketamine

Answer 67

General anesthetic NMDA blocker dissociative anethesia (eyes open) analgesia, amnesia minimal resp or CV depression nystagmus, salivation, increased intracranial pressure, increased BP, muscle tone, hallucinations reserved for pts w/ bronchospasm or children

Question 68

Midazolam

Answer 68

General anesthetic short acting benzodiazepine conscious sedation induction agent anti-anxiety slower induction, longer duration, active metabolite resp depression , use w/ caution in neuromuscular disease/bipolar

Question 69

Isoflurane

Answer 69

``` Inhaled anesthetic moderate blood:gas partition coeff mot metabolized can induce and maintain often co-admin w/ NO airway irritant, increases resp rate, resp depressant CV depression, arrythmias (catecholemines) increased intracranial pressure ```

Question 70

Desflurane

Answer 70

Inhaled anesthetic very volitile very low blood:gas partition coeff, very rapid used for outpt surgery can cause coughing, so usually not used for induction

Question 71

Sevoflurane

Answer 71

Inhaled anesthetic very low blood:gas partition coeff some metabolized into F- ion-> renal damage? used frequently for everything for everyone not resp irritant less resp depression

Question 72

Nitrous Oxide

Answer 72

``` Inhaled anesthetic true gas, very insoluble, rapid equilibration often co-admin w/ other anesthetics 100% O2 when discontinued weak anesthetic alone contraindicated in pneumothorax minimal resp effects abuse potential ```

Question 73

Local anesthetics

Answer 73

Bind reversibly to site on interior of V-gated Na channels use dependent blockade, blocks action potentials and propagation sensory and motor (pain first, motor last) can be topical, local infiltration, nerve block, spinal, epidural Does not alter resting membrane potential, increases threshold potential weak bases (to get intracellular) pH can effect efficiency (low pH, less effective) (inflammation) often used in combo w/ vasoconstrictors (epinephrine) systemic toxicity -> mostly CNS first, convulsions then depression can be hypersensitivity (more w/ ester) esters-> metabolized by plamsa amides-> metabolized in liver

Question 74

Procaine

Answer 74

Ester local anesthetic short acting infiltration anesthesia low potency, slow onset

Question 75

Tetracaine

Answer 75

Ester local anesthetic long acting, more potent spinal and topical, opthalmic

Question 76

Benzocaine

Answer 76

Ester local anesthetic topical only wounds and ulcers

Question 77

Lidocaine

Answer 77

Amide local anesthetic intermediate duration faster, more intense anesthesia used w/ epinephrine

Question 78

Bupivacaine

Answer 78

Amide local anesthetic long acting more sensory than motor cardiotoxic

Question 79

Ropivacaine

Answer 79

Amide local anesthetic long acting more sensory than motor less cardiotoxic

Question 80

Endogenous opioids

Answer 80

Endorphins (co-release w/ ACTH, MSH)->mu Enkephalin->mu, delta Dynorphins (co-localize w/ ADH)->kappa

Question 81

Opioid receptors

Answer 81

``` Gi -> decrease cAMP, efflux K+ decrease neurotransmitter release Mu- most drugs, kappa- nalbuphine delta- no drugs ```

Question 82

Opioid effects

Answer 82

``` Analgesia, perception and appreciation cough suppression anti-diarrhea / constipation euphoria sedation respiratory distress nausea (at first) decreased LH, increased ADH (mu) miosis (no tolerance) tolerance/dependence ```

Question 83

Morphine

Answer 83

mu agonist high first pass effect 4-5hr duration

Question 84

Heroin

Answer 84

mu agonist more lipophilic metabolized to active

Question 85

Codeine

Answer 85

mu agonist metabolized to morphine mild pain or cough suppression

Question 86

Oxycodone

Answer 86

mu agonist | often used w/ NSAIDS or acetaminophen

Question 87

Methadone

Answer 87

mu agonist good oral availability longer duration used to treat opioid abuse, chronic pain

Question 88

Meperidine

Answer 88

mu agonist shorter duration toxic metabolite interacts w/ MAO inhibitors

Question 89

Fentanyl

Answer 89

mu agonist 100x potent short acting injectable and transderm patches and buccal

Question 90

Hydromorphone

Answer 90

mu agonist | 2-3x potent

Question 91

Hydrocodone

Answer 91

``` mu agonist like codeine (less powerful) ```

Question 92

Nalbuphine

Answer 92

``` mu antagonist and kappa agonist similar in efficacy to morphine less abuse potential precipitates withdrawal only injectable ```

Question 93

Buprenorphine

Answer 93

Partial mu agonist available as patch used with nalaxone to treat opioid abuse

Question 94

Naloxone

Answer 94

mu antagonist NOT orally available short duration used to treat opioid OD and to decrease IV abuse

Question 95

Naltrexone

Answer 95

``` mu antagonist orally active long half life treat opioid or alcohol addiction also can be for tamper-proofing ```

Question 96

Dextromethorphan

Answer 96

Opioid-like anti-cough (antitussive), but not analgesic NMDA antagonist (abuse potential)

Question 97

Tramadol

Answer 97

weak mu agonist also blocks NE and 5-HT reuptake mild to moderate pain, oral use

Question 98

Suboxone

Answer 98

Buprenorphine + Naloxone | used to treat opioid abuse