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Flashcards in Pharmacology Deck (80):
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Monoamine

NTs that contain one amino group that is connected to an aromatic ring
Ex) thyroid hormones, Histamine, catecholamines (EP, DA, NE), tryptamines (5-HT)

1

Catecholamine

precursor to EP
DA, NE

2

Where is ACh made?

Nucleus basalis of Meynert

3

Where is DA made?

substantia nigra and ventral tegmental area

4

Where is Histamine made?

Ventral Posterior hypothalamus (Tuberomammillary nucleus)

5

Where is NE made?

locus ceruleus in upper pons

6

Where is 5-HT made?

raphe nucleus in brain stem

7

NMJ-blocking Agents: What do they cause?

Used for skeletal muscle relaxation--> ONLY paralysis, NO analgesia or unconsciousness

8

Depolarizing Agents (mech, ex, use, side effects)

Mech: binds aggressively to AChR--> depolarizes--> resistant to AChE--> stays bound--> Na+ channels remain closed--> cannot depolarize. Cannot be reversed.
Ex) Succinylcholine
short-acting (onset 30sec, last 10min) due to Pseudocholinesterase
temporary muscle paralysis (surgery, intubation)

9

Non-depolarizing agents

Mech: competitive inhibition
Ex) MivaCURIUM, -curium
elimination depends on renal/hepatic activity
Side effects: resp. failure

10

How do you reverse Nondepolarizing Agents?

AChE inhibitors

11

Why can't you give AChE inhibitor to person w/ Depolarizing Muscle agent?

AChE inhibitors will also block Pseudocholinesterase, which is the main way to eliminate depolarizing agents--> prolong Phase I (aggressive binding)

12

Cholinesterase Inhibitors

Mech: inactivate AChE
used to reverse nondepolarizing NMJ agents
Ex) neostigmine, physostigmine
Side effects: bradycardia, broncospasm, pupil constriction, increased bladder tone, etc.

13

Anticholinergic Drugs

Mech: competitive inhibition
used in anesthesiology
Ex) Atropine
Side effects: decreased secretions, urinary retention, CNS stimulation, cutaneous blood vessel dilation

14

Atropine

first-line tx for organophosphate poisoning, w/ pralidoxime (2-PAM)
Effects: reverses bradycardia, bronchial smooth muscle relaxation, decrease resp. secretions, reverse psychotic effects

15

What are the 2 biggest concerns with benzodiazepines and barbiturates?

tolerance and withdrawal

16

Barbituates

Mech: increase DURATION of Cl- channel opening
Uses: anesthesia, anticonvulsants, anxiolytics, insomnia
*withdrawal is dangerous and pts must be hospitalized

17

What are 3 side effects of barbituates?

induce CYP-450
suppress REM sleep (even though given for insomnia)
Contraindicated in pts w/ Acute Intermittent Poryphyria b/c barbs activate ALA synthase--> heme synthesis

18

Benzodiazepines

Mech: Increase FREQUENCY of Cl- channel opening
Uses: anxiolytics, muscle relaxants, amnesic agents, anticonvulsants


19

Benzodiazepines and pregnancy

can cross placental barrier

20

How to reverse effects of benzodiazepines? How does withdrawal compared to that of barbiturates?

Flumazenil (competitive antagonist)
Withdrawal similar, but NOT as severe as barb withdrawal

21

How do benzodiazepines and barbituates affect sleep?

Benzo: decrease latency, increase Stage 2 of NREM sleep, decrease REM and slow-wave sleep
Barb: suppress REM sleep

22

Opiods

Mech: agonist at M-opioid receptors, with varying strengths
Uses: local analgesia, systemic pain relief, chronic pain management, antitussive
Side effects: tolerance, dependence, overdose

23

Buspirone

Mech: partial agonist of 5-HT-1A receptors
* NO EFFECT on GABA rec, does NOT interact w/ EtOH, NO sedating effects or euphoria (like with benzo, barb). Less potential for abuse!
Use: Generalized Anxiety Disorder (NO muscle relaxant or anticonvulsant properties)

24

What are endogenous endorphins made from?

POMC (proopiomelanocortin)

25

Which NTs do Antidepressants target? What can extended treatment lead to?

5-HT, NE, and sometimes DA
Extended treatment can lead to downregulation of postsynaptic NT receptors

26

Selective Serotonin Reuptake Inhibitors

*first-line tx for depressive and anxiety disorders*
Increases 5-HT levels
Ex) Citalopram, fluoxetine, paroxetine, sertraline, fluvoxamine
see effects after 3-6wks
Uses: depressive disorders, panic disorder, generalized anxiety disorder, OCD, etc.
Side effects: diarrhea, sexual dysfcn, Discontinuation Syndrome

27

For whom are SSRI's better to use? Who should NOT use them? For whom are they ineffective?

Good: Pregnant women, elderly
Bad: patients with Mania
Ineffective: mood is not elevated in non-depressed patients

28

What is the most common congenital defect with SSRI use?

ventral septum defect

29

SSRI Discontinuation Syndrome

dizziness, vertigo, nausea, fatigue, HAs, agitation, suicidal ideation, etc.

30

Monoamine Oxidase Inhibitors (contraindications)

IRREVERSIBLY inhibits MAO--> Increases NE levels
Ex) Phenelzine, tranylcypromine, isocarboxazid
Uses: depressive disorders, anxiety
Contraindications: tyramine-containing foods, SSRIs

31

What else is MAO responsible for?

breakdown of 5-HT and tyramine

32

What are some side effects if take MAOIs w/ tyramine-foods? What kinds of food have tyramine?

Side Effects: HTN crisis, diaphoresis, HA, vomiting
Foods: cheese, pepperoni, beer/wine, smoked/pickled meat, liver

33

What can happen if take MAOIs w/ SSRIs?

"Serotonin Syndrome": confusion, hyperthermia, myoclonus, hyperreflexia, diaphoresis

34

Tricyclic Antidepressants

Inhibit reuptake--> Increase levels of NE and 5-HT
ex) amytriptyline, imipramine, amoxaprine
Uses: chronic pain, major depression, anxiety
Side effects: Constipation, cardiac arrhythmia, coma

35

Noncyclic Heterocyclic Antidepressants (Bupropion)

inhibits reuptake of DA and NE--> Increase levels of DA and NE
Ex) Bupropion
Uses: 2nd and 3rd-line meds for major depression and smoking cessation. God for pts who do not tolerate TCAs.
Side effects: stimulant effects, tachycardia, insomnia

36

Noncyclic Heterocyclic Antidepressants (Venalfaxine, Duloxetine)

Inhibit reuptake of 5-HT > NE--> increase levels
Uses: major depression, melancholia, anxiety, chronic pain, diabetic peripheral neuropathic pain

37

Noncyclic Heterocyclic Antidepressants (Nefazodone, trazodone, mirtazapine)

5-HT modultors--> Block 5-HT2 receptors and inhibit 5-HT and NE reuptake
Uses: major depression, anxiety

38

Noncyclic Heterocyclic Antidepressants (Maprotiline)

inhibits reuptake of NE. ONLY one that does not affect 5-HT levels!
Uses: Major depression
Side effects: orthostatic hypotension, sedation

39

Neuroleptics

Anti-psychotics
Block Type 2 DA Receptors
Uses: positive symptoms of schizophrenia (hallucinations, delusions)

40

First-Generation Antipsychotics

Ex) Thioridazine (Low-potency) Haloperidol (High-potency)
Uses: acute psychosis, schizophrenia, bipolar disorder
Side effects: extrapyramidal signs, tardive dyskinesia, dystonia, hyperprolactinemia, prolongation of QT interval, neuroleptic malignant syndrome.

41

High-potency vs. Low-potency 1st generation antipsychotics

High-potency: greater affinity for D2 receptors
Low-potency: also have affinity for mAChRs, alpha-Adrenergic Rs, Histaminergic Rs

42

Side effects of Low-potency 1st generation antipsychotics due to blockade of Histamine and mAChRs?

Histamine Rec: weight gain, sedation, orthostatic hypotension, tremor, sexual dysfunction
mAChRs: facial flushing, dry mouth, urine retention, constipation

43

Neuroleptic Malignant Syndrome

Muscle rigidity, fever, autonomic instability, and cognitive changes such as delirium
Associated with elevated plasma creatine phosphokinase

44

Second Generation (Atypical) Antipsychotics (advantages)

Ex) clozapine, Risperidone, olanzepine
Advantages: more effective against negative/chronic symptoms (flattened affect, alogia). Less risk for tardive dyskinesia, neuroleptic malignant syndrome, extrapyramidal signs
Side effects: cardiotoxicity, neuroleptic malignant syndrome, hyperprolactinemia, prolongation of QT interval

45

Anticonvulsants (mechanisms?)

suppress uncontrolled neuronal discharge
epileptic seizures
Mech: 1) increase GABA-ergic activity 2) block VG-Na+ channels 3) block VG-Ca2+ channels

46

Valporic Acidd

Mech: 1) binds to VG-Na channels--> keep in inactivated state. 2) block VG-Ca2+ channels (Type T channels in Thalamus)
Uses: partial and generalized tonic-clonic seizures, bipolar disorder
Side Effects: GI upset, sedation, increased appetite, weight gain

47

Ethosuximide

Mech: Block VG-Ca2+ channels (Type T channels in Thalamus)--> stop rhythmic discharge
Uses: First-line for ABSENT seizures
Side Effects: GI upset, lethargy, HA, Stevens-Johnson Syndrome

48

Phenobarbital

Mech: Barbiturate (increases DURATION of GABA receptor)
Uses: Status epilepticus
Side Effects: sedation, tolerance, dependence, Induce P450 (Barbiturate side effects)

49

Carbamazepine

Mech: reduces rate of recovery of Na+ channels--> block rapid firing
Use: First-line for partial seizures, tonic-clonic seizures, TRIGEMINAL NEURALGIA, bipolar disorder
Side Effects: hyponatremia, Induces P450

50

Phenytoin

Mech: reduces rate of recovery of VG-Na+ channels
Uses: First-line PROPHYLAXIS for Status Epilepticus, all types of partial/generalized seizures (EXCEPT Absent seizures)
Side Effects: nystagmus, diplopia, Fetal Hydantoin Syndrome, Induce P450

51

Lamotrigine

Mech: reduces rate of VG-Na+ channels AND reduces glutamate release
Uses: partial seizures, generalized seizures, focal epilepsy, Lennox-Gastaut syndrome, bipolar disorder
Side Effects: Dizziness, Nausea, HA, Stevens-Johnson Syndrome

52

Pregabalin

Mech: binds to alpha2-delta subunit of high-VG-Ca2+ channels, increases density of GABA transporter/increases rate of GABA transport, AND decreases glutamate, NE, and substance P release
Uses: Anitnociceptive AND antiseizure. Neuropathic pain (diabetic neuropathy and postherpetic neuralgia, fibromyalgia, partial seizures
Side Effects: dizziness, somnolence, weight gain

53

Gabapentin

Mech: GABA-analog, BUT does NOT work at GABA receptor. Binds to alpha2-delta high-VG-Ca2+ AND decreases glutamate release
Uses: partial seizures, pain, peripheral neuropathy, bipolar disorder, anxiety
Side Effects: sedation, weight gain

54

Lithium

Uses: Mood stabilizer. Bipolar disorder, augment antidepressants
Mech: UNKNOWN, may interfere w/ monoamine synthesis, release, reuptake.
*Low Therapeutic Index*
Side Effects: Can be toxic to thyroid and kidney--> MUST monitor. Hypothyroidism, nephrogenic diabetes insepidus

55

What happens to NT levels in Alzheimer's?

Decrease in ACh
Increase in glutamate--> influx of Ca2+ can lead to neuronal cell damage

56

Memantine

Mech: Non-competitivelyblocks NMDA receptors in CNS
Uses: moderate to severe Alzheimer AND vascular dementia
Side effects: agitation, urinary incontinence, insomnia, diarrhea

57

Tacrine, Donepezil, Rivastigmine, Galantamine

Mech: Selective AChE in the CNS! Crosses BBB (less peripheral side effects)
Use: Alzheimer
Side effects: nausea, vomiting, diarrhea, insomnia

58

What are the 3 ways to increase CNS levels of DA?

1) prevent degradation of DA
2) add exogenous precursor
3) give D2 receptor agonists

59

Bromocriptine (extra effects?), Pergolide, Ropinirole, Pramipexole

Mech: DA receptor agonists. Different effects on different types of receptors. Bromocriptine ALSO antagonizes D1 receptors in hypothalamus.
Uses: Parkinson. Bromocriptine can ALSO be used to reduce growth rate of pituitary adenoma (prolactinoma)
Side Effects: HA, nausea/vomiting, epigastric pain, Hypotension---> HTN

60

Levodopa (L-dopa) (Contraindications?)

Mech: precursor of DA. Enters brain through L-amino transporter (DA canNOT cross the BBB). In CNS, metabolized to HVA and DOPAC.
Uses: First-line for Parkinson's tx w/ Carbidopa.
Side effects: nausea/vomiting, tachycardia, dyskinesia, agitation, confusion, depression
Contraindications: psychosis and closed-angle glaucoma

61

Carbidopa

reduces peripheral conversion of L-Dopa to DA--> increases availability of L-Dopa for CNS

62

MAO Inhibitors (different Types)

MAO-A: metabolizes NE and 5-HT
MAO-B: metabolizes DA (striatum)

63

Selegiline and Rasagiline

Mech: IRREVERSIBLE selective inhibitors of MAO-B (striatum).
Uses: Parkinson. Selegiline given in LOW-dose--> no interaction w/ tyramine-containing foods
Side effects: Serotonin syndrome if taken w/ SSRIs, TCAs, merperidine

64

Tolcapone and Entacapone

Mech: COMT inhibitors--> prolong action of L-Dopa. Tolcapone (peripheral and central). Entacapone (peripheral ONLY)
Uses: Increase L-Dopa levels. Entacapone PREFERRED b/c less hepatotoxic.
Side effects: dyskinesia, nausea, confusion

65

General Anesthetics

Cause analgesia, amnesia, unconsciousness, muscle relaxation, suppression of reflexes

66

4 Stages of Anesthesia

1) Analgesia: "Conscious and Conversational"
2) Disinhibition: Autonomic variations (changes in BP, HR, RR)
3) Surgical anesthesia: Unconscious w/ relaxed muscles
4) Medullary depression: Respiratory and vasomotor center depression

67

Inhaled Anesthetics

Uses: MAINTENANCE of anesthesia b/c depth of anesthesia can be rapidly altered.
Mech: poorly understood.
Ex) Halothane, isoflurane, sevoflurane, desflurane
Side effects: resp. depression, nausea, emesis, hypotension

68

Toxicity of Inhaled Anesthetics

Hepatotoxicity, nephrotoxicity, convulsions, malignant hyperthermia (EXCEPT Nitrous Oxide)

69

What determines speed of anesthesia induction?

1) alveolar gas and venous blood partial pressures
2) solubility in blood
3) alveolar blood flow

70

MAC (Minimum Alveolar Concentration)

Similar to ED50--> Alveolar conc. of inhaled anesthetic that stops movt in 50% patients in response to incision

71

What is the difference between anesthetics with LOW and HIGH solubility in blood?

LOW solubility: Rapid induction and recovery. Not as potent.
HIGH solubility (in oil/lipid): Slower induction/recovery. Increased potency.
Higher lipid solubility--> higher solubility in blood.
Tradeoff between potency and speed of induction.

72

How do you treat Malignant Hyperthermia?

Dantrolene: interferes w/ Ca2+ release from SR in muscles by binding to ryanodine receptors

73

Intravenous Anesthetics (Types)

Rapidly INDUCE anesthesia
1) barbiturates
2) benzodiazepines
3) ketamine
4) opiates
5) propofol (can ALSO maintain anesthesia)
6) Etomidate

74

Benzodiazepines

Ex) Midazolam
Use: endoscopy
Side effects: severe postoperative respiratory depression and amnesia

75

Barbiturates

Ex) Thiopental
Highly lipid-soluble--> enters brain rapidly
NOT analgesic--> need supplementary
Side effects: severe Hypotension in hypovolemic/shock patients

76

Ketamine

Ex) Arylcyclohexylamine)
Dissciative anesthetic (Act via NMDA receptors)
Causes: sedation, amnesia, immobility, disorientation, hallucinations

77

Opioids

Ex) Morphine, fentanyl, sufentanil
*Used w/ other CNS depressants during anesthesia
Toxicity: hypotension, respiratory depression, muscle ridigity

78

Propofol

Rapid induction AND maintenance
*Excitatory phase: muscle twitching, hiccups
Uses: resection of spinal tumors. Can be used when assessing spinal cord function b/c less effect on CNS-evoked potentials

79

How can you reverse opioids?

Naloxone and naltrexone (Mu-opioid receptor antagonists)