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Pharmacology Flashcards

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0
Q

Catecholamine

A

precursor to EP

DA, NE

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1
Q

Monoamine

A

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

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2
Q

Where is ACh made?

A

Nucleus basalis of Meynert

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3
Q

Where is DA made?

A

substantia nigra and ventral tegmental area

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4
Q

Where is Histamine made?

A

Ventral Posterior hypothalamus (Tuberomammillary nucleus)

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5
Q

Where is NE made?

A

locus ceruleus in upper pons

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6
Q

Where is 5-HT made?

A

raphe nucleus in brain stem

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7
Q

NMJ-blocking Agents: What do they cause?

A

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

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8
Q

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

A

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)

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9
Q

Non-depolarizing agents

A

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

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10
Q

How do you reverse Nondepolarizing Agents?

A

AChE inhibitors

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11
Q

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

A

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

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12
Q

Cholinesterase Inhibitors

A

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

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13
Q

Anticholinergic Drugs

A

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

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14
Q

Atropine

A

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

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15
Q

What are the 2 biggest concerns with benzodiazepines and barbiturates?

A

tolerance and withdrawal

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16
Q

Barbituates

A

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

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17
Q

What are 3 side effects of barbituates?

A

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

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18
Q

Benzodiazepines

A

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

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19
Q

Benzodiazepines and pregnancy

A

can cross placental barrier

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20
Q

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

A

Flumazenil (competitive antagonist)

Withdrawal similar, but NOT as severe as barb withdrawal

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21
Q

How do benzodiazepines and barbituates affect sleep?

A

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

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22
Q

Opiods

A

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

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23
Q

Buspirone

A

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)

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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)

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