Neuropharm- Comp 2 Flashcards
1
Q
Tricyclic Antidepressants
Mechanism of Action (general) and Names of drugs
A
NE, 5-HT reuptake inhibitor
Also muscarinic receptors block, a1 block, H1 block
Imipramine Amitriptyline Desipramine Nortriptyline Doxepin Clomiphene Amoxapine
2
Q
Tricyclic Antidepressants
Uses (including specific drugs)
A
General: Major depression chronic pain, obsessive- compulsive disorder
- Imipramine: bed-wetting
- Desipramine: least anticholinergic
- Clomipramine: OCD
- Amitriptyline: Neuropathic pain, migraine
- Amoxapine: some D2 blockade
3
Q
Tricyclic Antidepressants
Toxicities
A
Antimuscarinic: mydriasis, cycloplegia, urinary retention, sedation.
Alpha1 block: hypotension, orthostasis.
Histamine1 block: sedation, weight gain
Overdose: coma, convulsion, cardiotoxicity (Respiratory depression, fever, prolonged QT interval)
Treating TCA tox: Sodium bicarbonate attaches to sodium channel to decrease cardiovascular effects
CYP drug interactions; polymorphism a/w slow metabolism of TCAs
Serotonin Syndrome
4
Q
Bupropion
Mechanism of Action
A
- Reuptake inhibition of dopamine and norepinephrine.
- Noncompetitive antagonist at nicotinic receptor (smoking cessation potential)
- SEPARATE-> Varenicline: partial nicotinic receptor agonist (erratic behavior, suicide). Not related to bupropion mechanism
5
Q
Bupropion
Use
A
- Major depression
- Smoking cessation
6
Q
Bupropion
Toxicities
A
Lowers seizure threshold, caution in bulimic patients.
No sexual dysfunction
Little M, H1 effects
7
Q
Mirtazapine
Mechanism of Action
A
Alpha2 block to
increase NE and 5-HT release.
Opposite clonidine mechanism
8
Q
Mirtazapine
Use
A
Major depression
sedation
9
Q
Mirtazapine
Toxicity
A
Weight gain, sedation
10
Q
Serotonin-Norepinephrine
Reuptake Inhibitors
(SNRI)
MOA, examples of drugs
A
Inhibits reuptake of 5HT and NE
Duloxetine, Venlafaxine, Desvenlafaxine, Milnacipran
11
Q
Serotonin-Norepinephrine
Reuptake Inhibitors
(SNRI)
Use
A
Major Depression, chronic pain, fibromyalgia, neuropathic pain
12
Q
Serotonin-Norepinephrine
Reuptake Inhibitors
(SNRI)
Toxicities
A
Mechanism like tricyclics. No blockade of H1, alpha1, Muscarinic
Overdose: coma, convulsion, cardiotoxicity.
Serotonin Syndrome
13
Q
Selective Serotonin Reuptake Inhibitor (SSRI)
MOA and Examples
A
Inhibits 5HT reuptake
At least 4 weeks for full effect
Fluoxetine Fluvoxamine Citalopram Paroxetine Sertraline Escitalopram
14
Q
SSRIs
Use
A
- Major depression
- anxiety
- panic disorder
- OCD
- post- traumatic stress disorder
- premenstrual dysphoric disorder
- bulimia
- social phobias
15
Q
SSRIs
Toxicities
A
Insomnia, headache
Nausea, vomiting
Bleeding abnormalities (platelets)
Impotence (use phosphodiesterase 5 inhibitor)
Serotonin syndrome
Drug interactions (most w/ fluoxetine CYP450 2D6) –>least with sertraline, citalopram, and escitalopram
16
Q
Serotonin Syndrome
Symptoms
A
3 As: Increased activity (neuromuscular), Autonomic stimulation, Agitation
Specific symptoms:
- MYDRIASIS
- hyperthermia
- hypertension
- tachycardia
- myoclonus
- tremor
- delirium
- confusion
- within 24 hrs, unlike NMS
- GI symptoms
17
Q
- Trazodone
- Nefazodone
MOA
A
Serotonin reuptake inhibitor and blocker (SARI); Alpha1 and H1 block
18
Q
- Trazodone
- Nefazodone
Uses
A
- Major depression
- Sedation
- Sleep aid
19
Q
- Trazodone
- Nefazodone
Toxicities
A
- Alpha1 block (priapism, possible sedation)
- H1 block (sedation)
Increased levels of trazodone w/ CYP 3A4 inhibitors
- Nefazodone is hepatotoxic
20
Q
Phenelzine
Tranylcypromine
Isocarboxazid
Mechanisms of Action
A
Monoamine oxidase A inhibitors (prevents breakdown of (NE, Epi, 5-HT, DA, tyramine)
Exception:
Selegiline (MAOIb, prevents dopamine breakdown) –> Tx for Parkinson’s disease
21
Q
Phenelzine
Tranylcypromine
Isocarboxazid
(MAOIs toxicity)
A
- Hypertension with tyramine-containing foods or sympathomimetics (cold medicine)
- Must avoid tyramine foods: Aged cheese and meats, red wine, chocolate, avocado.
Serotonin syndrome (W/ SSRIs, TCAs, meperidine, dextromethorphan, triptans, linezolid, St. John’s Wort)
22
Q
Lithium
MOA
A
Blocks inosine 5’monophosphatase (Gq), PKC and decreases DAG, IP3 and therefore Ca2+
23
Q
Lithium
Use
A
Bipolar disorder
24
Q
Lithium
Toxicity
A
- Na+ loss promotes Li+ reabsorption (toxicity with diuretics)
- NSAIDs, ACEI facilitate Li+ reabsorption in PCT
Amiloride (enhances Li+ excretion) - Narrow therapeutic index (1.5 mEq vs. 2mEq)
- Tremors (use a beta blocker)
- Leukocytosis
- Polyuria, polydipsia (Loss of ADH response). Amiloride benefit here.
- Hypothyroidism
- Ebstein anomaly, a congenital heart condition (use lamotrigine in pregnancy)
25
Valproate
MOA
Broad-spectrum:
1. Blocks Na+ channels and T-type calcium channel
2. Decrease glutamate at NMDA receptors
3. Increases GABA receptor action
4. Increases GABA synthesis
5. Blocks degradation of GABA
26
Valproate
Use
Alternative to lithium in bipolar mania
Tonic-clonic, absence, and partial seizures, migraine prophylaxis
27
Valproate
Toxicity
"Valproate Syndrome” includes spina bifida, neural tube defects, autism.
- Weight gain
- Hepatitis
- Inhibitor of CYP2D6 and 3A4
28
Carbamazepine
MOA
Blocks sodium channels, blocks NE reuptake
29
Carbamazepine
Use
Bipolar disease
Tonic-clonic and partial seizures, trigeminal neuralgia
30
Carbamazepine
Toxicity
- Drowsiness
- Ataxia
- Diplopia
- SIADH (water “intox”)
- Aplastic anemia
- Teratogen (neural tube defects)
- Stevens-Johnson syndrome (HLA allele in ethnic population).
- Inducer of CYP 3A4
31
Lamotrigine
MOA
Potentiates GABA, blocks voltage-gated Na+ channels, glutamate blockade
32
Lamotrigine
Use
Manic phase of bipolar syndrome
Partial, tonic-clonic, and absence seizures, Lennox-Gastaut syndrome
33
Lamotrigine
Toxicity
Black Box Warning for Stevens-Johnson syndrome= rash
CNS effects
34
Atypical Antipsychotics
General Mechanism
5-HT2A >>>D2; D3 and D4 block
35
Atypical Antipsychotics
General MOA and ADEs
- Increase DA release to relieve negative symptoms of psychosis (and positive too)
- Few EPS effects
- Hyperprolactinemia
- All prolong QT interval, contraindicated with certain cardiovascular issues
36
Risperidone
MOA and Use
5-HT2A >>>D2; D3 and D4 block
- Atypical antipsychotic, approved for mania
37
Risperidone
Toxicity
- Hypotension from alpha1 blockade.
- Increase prolactin, hyperlipidemia, hyperglycemia
Palperidone is active metabolite
38
Olanzapine
MOA and Use
Blockade of
5-HT2A > H1 > D4 > D2 > α1 > D1
Approved in combination with fluoxetine for mania
Atypical antipsychotic
39
Olanzapine
Toxicity
- Less ANS effects.
- Fewer extrapyramidal effects (EPS)
- Weight gain
- Sedation
Metabolic changes like risperidone - hyperglycemia, hyperlipidemia
40
Quetiapine
MOA and Use
Blockade of
H1 > α1 > M1,3 > D2 > 5-HT2A
D2 blockade, BUT binds for a short time.
- Atypical antipsychotic, approved for mania
41
Quetiapine
Toxicity
- Minimal muscarinic block
- H1 (sedation)
- alpha1 (orthostasis)
42
Aripiprazole
MOA and Use
- Partial D2 agonist
- 5-HT2A antagonist
Approved for mania, atypical antipsychotic
43
Aripiprazole
| Toxicity
- Weight gain
| - Akathisia
44
Ziprasidone
MOA and Use
Blocks 5-HT and NE reuptake
Atypical antipsychotic, approved for mania
45
Ziprasidone
| Toxicity
Skin reactions, eosinophilia
46
Chlorpromazine
| MOA and use
D2>> 5HT2 antagonist
- Typical antipsychotic; treats positive symptoms of psychosis
- low potency, inexpensive, used most often; phenothiazine
47
Chlorpromazine
| Toxicity
- H1 block (sedation), a1 block (orthostasis)
- M1 block
- Parkinsonian effects - EPS, dystonias, tardive dyskinesias
- Deposits in cornea and lens
- Neuroleptic malignant syndrome
- Increased prolactin
48
Fluphenazine
| MOA and use
D2>> 5HT2 antagonist, High clinical potency
Typical antipsychotic; A phenothiazine/piperazine
49
Fluphenazine
| Toxicity
High incidence of tardive dyskinesias, parkinsonian effects
less autonomic toxicities
50
Thiothixene
| MOA and use
D2>> 5HT2 antagonist, clinically most potent antipsychotic
Typical antipsychotic; a thioxanthene
51
Thiothixine
| Toxicity
- Mid level tox. of extrapyramidal symptoms
- Injectable form— less tardive dyskinesias, less upreg of D2 receptors
- Sedation and hypotension
52
Haloperidol
| MOA and use
D2>> 5HT2 antagonist; very potent antipsychotic
Typical antipsychotic; Also for Tourette’s
A butyrophenone
53
Haloperidol
| Toxicities
Most severe EPS: parkinsonism, akastheisa, akinesia, dystonias
54
Thioridazine
| MOA and use
```
More 5HT2 antagonist, less D2
low potency (M block)
```
Typical psychotic
55
Thioridazine
| Toxicity
-Low eps effects
- ocular toxicity- brown vision from deposits in retina
- cardiotoxic effects: t wave, AV block, arrhythmias
HIGHEST risk of prolonged QT interval
- Na+ channel block
56
Tardive dyskinesias
| Characteristics
- Drugs that decrease dopamine release will cause upreg of receptors
- occurs months to years later
- tongue protrusion, lip smacking, abnormal mvmts, “ rabbit nose”
- typically not reversible
- manage by starting with lowest dose, assess Pt periodically
57
Neuroleptic Malignant Syndrome
| Characteristics and Tx
Life threatening effect of typical antipsychotics, inhaled anesthetics, and succinylcholine
- occurs weeks to months later, unlike serotonin syndrome
S and S: muscle rigidity, hyperthermia, tachycardia, altered consciousness, rhabdomyolysis.
- CK is elevated syndrome
DECREASED reflexes
Treatment: d/c drug, supportive care, and dantrolene or bromocriptine
- manage EPS and dystonias with anticholinergics or amantidine
- manage akasthesia (restlessness) with propranolol
58
Dantrolene
| MOA and use
- interferes with release of Ca2+ from sarcoplasmic reticulum via ryanodine receptor bind
- used IV for NMS, skeletal m. Relaxant, malignant hyperthermia
59
Dantrolene
| Toxicity
Hepatotoxicity
GI effects
CNS effects
60
Clozapine
| MOA and use
D4 = a1 > 5HT2a > D2 = D1
Atypical antipsychotic, not approved for mania
61
Clozapine
| Toxicity
- Nighttime drooling (paradox, ? M block)
- Weight gain
- Agranulocytosis- weekly blood counts for first 6 mo of Tx, every 3 wks after that
- Hypotension
62
Barbituates
General MOA and Use
- Short acting v. long acting?
- Bind to the Cl- channel and facilitate GABA action (prolong duration of channel opening)
- open channel in absence of GABA (independent)
Use: anxiety and insomnia (fallen out of use), seizures (phenobarbital), induction of anesthesia (thiopental)
Pentobarbital, Secobarbital- Short acting
Phenobarbital- long acting
Amobarbital, Thiopental - middle
63
Barbituates
| Toxicities
- Can induce FULL respiratory effect (b/c GABA independent)- "No ceiling effect"
- Highly sedative with a hangover effect
- Tolerance, physical dependence, and withdrawal. Taper slowly!
- Highly abused (pentobarbital esp., b/c short acting)
- CYP450 inducers
- Lipid-soluble (thiopental): redistributed from brain.
- Elderly/ liver disease may see an increase in t1/2.
64
Benzodiazepines
| MOA and General use
- Potentiates GABA by increasing frequency of
Cl- channel opening
- Needs GABA to open channel ("Ceiling effect", safer than barbs)
Use: anxiety, sedative-hypnotic, insomnia, anterograde amnesia, muscle relaxant, anticonvulsant.
65
Benzodiazepines
| Use of Specific drugs
- Chlordiazepoxide and Diazepam (long acting drugs): EtOH detoxification.
- Alprazolam: Panic disorder. Most abused b/c short acting.
- Lorazepam, Clonazepam, Diazepam: Seizure disorder.
- Midazolam: anesthesia
- Estazolam and Flurazepam: insomnia
- Oxazepam, temezepam, and lorazepam are the safest for the elderly --bypass phase I metabolism (Only undergo glucuronide conjugation, which is ).
- Flunitrazepam (Rohypnol)- "date rape" drug bc antergograde amnesia
66
Benzodiazepines
| Short acting v. Long acting
- Alprazolam (aka Xanax), Oxazepam- short acting
- Chlordiazepoxide, diazepam (aka valium), flurazepam: metabolites make drug long acting
- Lorazepam (aka Ativan), Temazepam- intermediate acting
67
Benzodiazepines
| Toxicities
- Respiratory depression ONLY when combined with other CNS depressants
- Drowsiness, hangover
- Mild euphoria (abuse potential)
- Anterograde amnesia
- Physical dependence, can built tolerance
- Withdrawal: rebound anxiety, insomnia, seizures (esp. with alprazolam)
- Fetal malformations (hypotonia)
68
Ethanol
| MOA and Toxicity
- Potentiates GABA. Euphoria (small doses)
- Reward center (release of dopamine)
- Increased norepinephrine release (cardiovascular effects)
- Zero-order elimination; CYP 2E1 induction- toxic with acetominophen
- Fetal Alcohol Syndrome (teratogen)
- Wernicke’s (thiamine deficiency)
- Loss of liver function; lose glutathione so unable to get rid of Reactive Oxidative Species
- ? Increased inflammation resulting in malignancy
- treat abuse with long-acting benzo, naltrexone (opioid blocker), or acamprostate (Glu blocker that increases GABA)
- Benzo for delirium tremens
69
Flumazenil
| MOA and Use
- Antagonist at BDZ binding site at the GABA receptor
- Blocks actions of benzos and “zz” drugs but not for other sedative-hypnotic drugs.
- IV increases recovery following BDZ administration in anesthetic procedures.
70
Flumazenil
| Toxicities
Agitation, confusion, and withdrawal symptoms (in chronic BDZ users)
71
Zolpidem, Eszopiclone, Zaleplon
| MOA and Use
- "Zzz" drugs; Ambien aka Zolpidem
- Benzo-like action on Cl- channels (Binds specific GABAa subunit)
- Sleep aid; Minor effect on REM sleep
- Shorter duration of action
- Less hangover effect and daytime sedation
- Potentiated by EtOH
72
Zolpidem, Eszopiclone, Zaleplon
| Toxicities
- Anterograde amnesia
- Hallucinations
- Delusions
- Impaired judgement
- Sleepwalking
73
Ramelteon
| MOA and Use
- MT-1, MT-2 melatonin receptor agonist
- Sleep aid; Not addictive (not a controlled substance); No GABA transmission
- No significant toxicity; Substrate for CYP 1A2
74
Suvorexant
| MOA and Use
- Orexin antagonist (blocks orexin normal action, which indicates arousal/wakefullness)
- Sleep aid/sedative
- No significant toxicity
75
Amphetamine and Dextroamphetamine
| MOA and Use
- CNS stimulation, inhibits reuptake of NE and DA
- increases release of these catecholamines from nerve terminals
Use: Narcolepsy
76
Amphetamine and Dextroamphetamine
| Toxicity
Sympathomimetic effects (cardiostimulation/CV, insomnia, weight loss)
77
Methylphenidate, Modafanil
| MOA and Use
- Inhibit DA reuptake
| - Use: Narcolepsy
78
Methylphenidate, Modafanil
| Toxicity
- Less anxiety and anorexia than amphetamines
| - Cardiovascular effects
79
Propranolol
| MOA and Use
- Beta-1, Beta-2 antagonist
- Blocks SANS contribution to anxiety
- “situational anxiety”
80
Propranolol
| Toxicity
- CNS depression
- Fatigue
- Bradycardia
- Asthma
- Hypoglycemia because of B2 blockade
81
Buspirone (Buspar®)
| MOA and Use
- 5-HT1 Agonist
| - Generalized anxiety; No sedation or addiction
82
Buspirone (Buspar®)
| Toxicity
- Headache, dizzy, nervous
| - Several weeks (3-4) for full effect
83
Sominex®, Unisom® Tylenol-PM®
| MOA and Use
- All have Diphenydramine as an active ingredient
| - OTC Sleep aid/sedative
84
Sominex®, Unisom® Tylenol-PM®
| Toxicity
- H1 block: orthostasis
- Lipophilic, cross the blood brain barrier
- Muscarinic dryness: Dryness, constipation, mydriasis, urinary retention, increase AV and SA node conduction
- Muscarinic blockade is not indicated in BPH and glaucoma.
85
Disulfiram
| Use
- Inhibits aldehyde dehydrogenase
- Anti-EtOH abuse
- CANNOT use with alcohol
86
Clonidine
| MOA and Use
- Alpha 2 agonist
| - Reduce sympathetic NS effects following EtOH, opioid, and nicotine withdrawal
87
Treatment of stimulant overdose
- Acidify urine
| - Supportive therapy (lorazepam and haloperidol)
88
Typical Antipsychotic Toxicities
- M, H1, alpha1 blockade
- EPS (dystonia, pseudoparkinsonism)
- Akathisia
- Menstrual irregularities (prolactin
release)
- Tardive dyskinesia
- Neuroleptic malignant syndrome
89
Hypertensive crisis symptoms
```
Occipital headache
Stiff neck
Nausea/vomiting
Photophobia
Palpitations
```
Due to drug interaction with tyramine and MAOI-A
