Term
|
Definition
| Desipramine, Amitriptyline, Imipramine, Nortriptyline |
|
|
Term
| By what mechanism do the TCAs work? |
|
Definition
MAJOR NEUROCHEMICAL ACTION is
blockade of reuptake for norepinephrine,
serotonin or both |
|
|
Term
| What are the adverse effects of the TCAs due to? |
|
Definition
| blockade of muscarinic cholinergic, alpha-adrenergic and histamine-1 receptors and cardiac ion channels |
|
|
Term
| What do the adverse effects of the TCA's include? |
|
Definition
**Tachycardia and tremor: enhanced
action of NE + other causes
�� Antimuscarinic effects: also contributes
to tachycardia
�� Antiadrenergic (alpha-1) effects:
orthostatic hypotension and contributes
to tachycardia
�� **Antihistamine: sedation, drowsiness
�� **Block cardiac sodium channels |
|
|
Term
MEDICAL CONTRAINDICATIONS TO
USE OF TCAs |
|
Definition
�� Cardiovascular disease
�� Seizure disorder
�� Bipolar disorder
�� High risk for suicide
�� Ineffective in children |
|
|
Term
|
Definition
| Don't use w inhibitors of Cyp 450, cimetidine, ranatidine, macrolide antibiotics, ciproflaxin, conozoles or SSRI's |
|
|
Term
|
Definition
• Depression (Other drugs are better)
• Neuropathic Pain
• Also enhance opioid analgesia in severe pain |
|
|
Term
| List the SSRIs that we need to know |
|
Definition
| fluoxetine* sertraline* paroxetine* escitalopram, fluvoxamine, Citalopram |
|
|
Term
|
Definition
|
|
Term
| List the atypical antidepressants |
|
Definition
| trazodone* bupropion* mirtazepine |
|
|
Term
|
Definition
| phenelzine, isocarboxazid, tranylcypromine, selegiline patch |
|
|
Term
| List the mood stabilizers |
|
Definition
| Lithium, Valproate, Carbamazepine, Lamotrigine |
|
|
Term
| Which SSRI has the longest duration of action? |
|
Definition
|
|
Term
Antidepressants in children and
adolescents |
|
Definition
TCAs are probably ineffective and potentially
dangerous.
�� SSRIs modestly effective in major depression
but very effective in anxiety disorders
�� Concerns on suicidal thought and attempts |
|
|
Term
| Are SSRI useful in neuropathic pain |
|
Definition
|
|
Term
|
Definition
| 1. GI: Diarrhea, loose stools and nausea. 2. Sexual: Decreased Libido. 3. Insomina (take in morning) |
|
|
Term
| Which SSRIs are P-450 inhibitors and what interactions are possible |
|
Definition
*Fluoxetine and paroxetine, avoid combos with TCAs, digoxin, antiarrhythmics, warfarin,
theophylline |
|
|
Term
| Differences between SSRI and SNRI |
|
Definition
| SNRI: may cause increased BP, more intense discontinuation syndrome, no P-450 inhibition, can also be used for Diabetic neuropathy/neuropathic pain, and fibromyalgia |
|
|
Term
| Are SSRIs and SNRIs useful in GAD |
|
Definition
|
|
Term
|
Definition
| Atypical antidepressant, Blocks Dopamine and maybe NE reuptake, partial nicotinic agonist(if they want to quit smoking,) No P-450 inhibition and no effect on sexual function. |
|
|
Term
| Adverse effects of Bupropion |
|
Definition
| Agitation, hostility, insomnia, increased risk of seizures, anorexia and weight loss |
|
|
Term
|
Definition
Atypical Antidepressant, Blocks Serotonin reuptake and acts as an agonist, v. strongly sedating (anti-H1 and
antiadrenergic effects); common use is to counteract insomnia (e.g.,from SSRI). |
|
|
Term
| Adverse effects of Trazodone |
|
Definition
| orthostatic hypotension and cardiac arrythmias, sexual dysfunctions |
|
|
Term
|
Definition
Blockade of presynaptic, inhibitory α2
adrenergic receptors, resulting in increased central release of norepinephrine. V. effective antidepressant, but strong
sedating action has limited its usefulness |
|
|
Term
| MAO inhibitors in general |
|
Definition
Effective Antidepressants and effective in social anxiety and panic
disorders but not first line agents |
|
|
Term
| MAO inhibitors adverse effects |
|
Definition
*Potentially lethal in overdose: hypertensive crisis, cardiac arrhythmias.
CNS stimulation: anxiety, agitation, increased risk of seizures
�� orthostatic hypotension (alpha-1 blockade)
�� anticholinergic (antimuscarinic) effects
�� sexual dysfunctions (like SSRIs)
�� *Potentially lethal in overdose: hypertensive
crisis, cardiac arrhythmias
�� Severe discontinuation syndrome w/ nausea, vomiting and seizures |
|
|
Term
| Drug interactions with MAO inhibitors |
|
Definition
�� With TCAs, sympathomimetics: hypertensive
crisis, seizures
�� With SSRIs: Serotonin Syndrome
�� *With meperidine (Demerol ® ):
�� generation of neurotoxic metabolite; Serotonin
Syndrome
�� *With tyramine-containing foods:
hypertensive crisis |
|
|
Term
| What are the first line agents for depression |
|
Definition
|
|
Term
| Clinical use of mood stabilizers |
|
Definition
manic and depressive stages of
bipolar disorder, but are not effective in major depression |
|
|
Term
| Indications for use of lithium |
|
Definition
�� Acute manic episodes of bipolar disorder
�� Acute depressive episodes of bipolar disorder
�� Long term maintenance of recurrent bipolar disorder
�� Long term maintenance of recurrent mania
�� Augmentation of antidepressant action in treatment resistant major depression |
|
|
Term
| Predictors of poor response to lithium include: |
|
Definition
�� Rapid cycles -- Mixed symptomatology
�� Family Hx -- Hx of drug abuse |
|
|
Term
| Does Lithium have a high or low therapeutic index |
|
Definition
|
|
Term
| ADVERSE EFFECTS OF LITHIUM |
|
Definition
�� **Cardiac arrhythmias, conduction
deficits
�� Diarrhea and vomiting
�� Signs of CNS depression
�� Hypotension |
|
|
Term
| How is Lithium cleared from the body |
|
Definition
|
|
Term
| Lithium and drug interactions |
|
Definition
�� Plasma lithium levels (and potential for toxicity) are increased by:
�� Thiazide diuretics
�� ACE inhibitors
�� * NSAIDS
�� All of which decrease renal clearance of lithium |
|
|
Term
|
Definition
Depakote, alone is effective as lithium in Rx of acute
mania; is somewhat effective in maintenance; valproate + lithium effective in acute and in maintenance. |
|
|
Term
|
Definition
| Tegretol, effective against mania in some lithium non-responders; carbamazepine + lithium effective in maintenance |
|
|
Term
|
Definition
| effective alone in bipolar depression but not mania; is effective in maintenance |
|
|
Term
| Which mood stabilizers alone are NOT effective in bipolar depression. |
|
Definition
| valproate nor carbamazepine |
|
|
Term
| List the Typical Neuroleptics (antipsychotics) |
|
Definition
| Chlorpromazine, Haloperidol, Fluphenazine |
|
|
Term
| List the Atypical Neuroleptics (antipsychotics) |
|
Definition
| Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprasidone, Paliperidone |
|
|
Term
| List the Atypical, Atypical Neuroleptics (antipsychotics) |
|
Definition
|
|
Term
| Typical Neuroleptics block what type of schizophrenic symptoms? |
|
Definition
Positive/active symptoms including
thought disturbances, delusions, hallucinations |
|
|
Term
| How long does it take to get a response to the typical neuroleptics |
|
Definition
| Latency to beneficial effects; response by 4-6 weeks is common |
|
|
Term
| What % of patients respond to Neuroleptics and what is the relapse rate |
|
Definition
70-80% of patients respond, but 30-40% show only partial response. Relapse, recurrence of symptoms is
common ( approx. 50% within two
years). Noncompliance is also very common 33% in patient, 65% outpatient within 6 weeks |
|
|
Term
| What are the therapeutic effects of the Typical neuroleptics due to? |
|
Definition
| blockade of DA receptors. |
|
|
Term
| What are most of the adverse effects of the typical Neuroleptics due to? |
|
Definition
blockade of DA, alphaadrenergic,
muscarinic cholinergic and histamine H1 receptors. They also increase the risk of ventricular arrhythmias and sudden cardiac death due to prolonged qt interval |
|
|
Term
| What are the 5 EPS effects seen with the typical neuroleptics |
|
Definition
1. dystonia
2. neuroleptic malignant syndrome
3. **Parkinsonism
4. **tardive dyskinesia
5. **akathisia |
|
|
Term
| dystonia definition and incidence in typical neuroleptic treatment |
|
Definition
| (1-10% incidence):severe muscle contraction in face and neck; occurs early in treatment |
|
|
Term
| neuroleptic malignant syndrome definition and incidence in typical neuroleptic treatment |
|
Definition
(1% incidence; with 10%
mortality); occurs early in treatment:
severe muscular rigidity and akinesia
sympathetic hyperactivity
hyperthermia and severe dehydration
loss of consciousness, potential death |
|
|
Term
|
Definition
(incidence is high [60-80%] early; 25% by 6
months)
resting tremor
truncal and head rigidity
bradykinesia (slowness in initiating movement)
impairment of postural balance |
|
|
Term
|
Definition
(overall 50% incidence); occurs late in
treatment, may be viewed as the converse of Parkinsonism and may
result from a compensatory hyper-dopamine activity.
automatic involuntary movements (AIMS) chiefly in face,
mouth, eyes, (orofacial dyskinesia), sometimes, trunk and
limbs; in severe cases may interfere with eating |
|
|
Term
|
Definition
(50% incidence); onset is early in treatment, but is long lasting
motor restlessness, e.g., jitteriness, stereotyped trunk rocking, pacing, finger or toe tapping |
|
|
Term
| What drugs may cause an elevation of prolactin resulting in infertility |
|
Definition
|
|
Term
| Typical nueroleptic hypothesized mechanism for antipsychotic effect |
|
Definition
D2 receptor blockade in mesolimbic (system 2) and mesocortical (system 3)
system |
|
|
Term
| Typical nueroleptic hypothesized mechanism for EPS |
|
Definition
| D2 receptor blockade in nigrostriatal system (basal ganglia) |
|
|
Term
| Typical nueroleptic hypothesized mechanism for tardive dyskinesia |
|
Definition
| D2 receptor supersensitivity in nigrostriatal (basal ganglia) system |
|
|
Term
| Typical nueroleptic hypothesized mechanism for PRL elevation |
|
Definition
| D2 receptor blockade in anterior pituitary gland |
|
|
Term
| Management of dystonia and Parkinsonism due to typical neuroleptics |
|
Definition
anticholinergic antiparkinson drugs:
- benztropine (Cogentin®) (most widely used)
- trihexiphenidyl (Artane®)
- biperiden (Akineton®)
- procyclidine (Kemadrin®)
-diphenhydramine (Benadryl®) (both antiH1 and anticholinergic)
- routine use is controversial; anticholinergics may interfere with
antipsychotic effect |
|
|
Term
| Management of Neuroleptic malignant syndrome due to typical neuroleptics |
|
Definition
| muscle relaxants, DA agonists, supportive |
|
|
Term
| Management of Akathisia due to typical neuroleptics |
|
Definition
| benzodiazepines, propranolol |
|
|
Term
| Management of Tardive dyskinesia due to typical neuroleptics |
|
Definition
increase neuroleptic dose;
switch to clozapine |
|
|
Term
| Atypical Neuroleptics in general |
|
Definition
| All bock Dopamine and Serotonin receptors. Less EPS then typicals. Tend to be more effective against negative symptoms of Schiz. Most cause weight gain and increased risk of sudden cardiac death. |
|
|
Term
| Major adverse effect of clozapine and other adverse effects |
|
Definition
agranulocytosis (approx. 1%)
b. Blockade of alpha-1 adrenergic receptors
c. Blockade of muscarinic cholinergic receptors,
d. Blockade of H1 receptors
e. weight gain, hyperglycemia and increased risk of developing
type 2 diabetes |
|
|
Term
|
Definition
| Olanzapine is “clozapine without the agranulocytosis”. |
|
|
Term
|
Definition
Quetiapine is olanzapine without the anticholinergic effects.
Quetiapine is now most prescribed neuroleptic in U.S. |
|
|
Term
| What are the adverse effects of the "dones" i.e. Riperidone |
|
Definition
�� EPS incidence is dose-related
�� Alpha-1 receptor blockade
�� No anticholinergic; weak antihistamine effects
�� Weight gain, PRL elevation |
|
|
Term
| ARIPIPRAZOLE (ABILIFY ®): Mechanism of action |
|
Definition
partial D2 agonist at pre and postsynaptic receptors.
3. By providing a low level of D-2 stimulation, aripiprazole may reduce
dopamine transmission in areas thought to have excess dopamine activity (e.g., mesolimbic).
The D-2 receptor is also a prejunctional inhibitory autoreceptor, so by
stimulating this, aripiprazole may also decrease dopamine release.
4. By providing a low level of post-junctional D-2 stimulation, aripiprazole may
increase dopamine transmission in areas thought to have deficient dopamine activity
(e.g., meso-cortical).
5. aripiprazole may be a “dopamine transmission stabilizer” |
|
|
Term
| Drugs used to treat short term stress |
|
Definition
| BZDs; antihistamines (H1) |
|
|
Term
|
Definition
| BZDs; buspirone, SSRI and SNRI antidepressants |
|
|
Term
| Drugs used to treat panic |
|
Definition
alprazolam; SSRI and SNRI
antidepressants |
|
|
Term
| Drugs used to treat social anxiety |
|
Definition
|
|
Term
| Drugs used to treat performance anxiety |
|
Definition
| ß-blockers (10 mg propranolol a hr before performance), antidepressants |
|
|
Term
| Drugs used to treat Post Traumatic Stress |
|
Definition
|
|
Term
|
Definition
| clomipramine, SSRI antidepressants |
|
|
Term
| Which BZDs are being used to treat anxiety and what are their relative durations of action |
|
Definition
| Diazepam-long duration, alprazolam and lorazepam-short duration. Long duration have active metabolites. Trend is toward using shorter duration drugs. |
|
|
Term
|
Definition
CLINICAL USES:
�� Conscious sedation
�� Skeletal muscle relaxation
�� Premedication for minor surgery,
diagnostic procedures
�� Adjunctive agent in anesthesia,
component of balanced anesthesia
�� CHARACTERISTICS:
�� Improved water solubility vs.
diazepam
�� Fast onset, short duration of action
�� very e y marked anxiolytic and amnesic effects
�� Effective routes:
�� IV; given slowly, to avoid cardiorespiratory
depression; or if bolus,
with respiration
�� Homemade oral prep w/ Kool-Aid
effective in children |
|
|
Term
|
Definition
�� ACTION: competitive antagonist at BZD receptors;
specific benzodiazepine antagonist
�� CLINICAL USES: reversal of benzodiazepine
sedation; Rx of overdose
�� ROUTE: only effective IV |
|
|
Term
|
Definition
�� Key concept: Buspirone is an anxiolytic but is not a sedative-hypnotic.
�� No effects on GABA system; serotonin and dopamine agonist
�� No abuse, addiction or physical dependence
liability; alternative for anxiety w/Hx of drug abuse |
|
|
Term
| Antihistimines used in anxiety |
|
Definition
| Rx for short term anxiety, diphenhydramine and hydroxyzine |
|
|
Term
| Microsomal ethanol oxidizing system |
|
Definition
(cytochrome P450 2E1)
a. metabolizes approx. 10% of ingested dose of ethanol to acetaldehyde
b. system is induced in alcoholics and plays a more prominent role with high levels of alcohol intake |
|
|
Term
| Why is the EtOH bioavailability so much higher in women and in some alcoholics |
|
Definition
| lower level of first pass metabolism by gastric ADH. 2-fold greater in women! |
|
|
Term
| NIAAA Healthy drinking limit |
|
Definition
| no more than 4 drinks on any day and no more than 14 drinks per week. Reduce for women and people over 65. One drink = 14 g EtOH = 1 can of beer |
|
|
Term
| Mechanisms of ethanol-induced toxicity |
|
Definition
A.Membrane disordering effects
B. Effects of acetaldehyde or acetaldehyde-protein adducts
C. Induction of CYP 2E1
D. Generation of fatty acid ethyl esters
E. Nutritional (esp. vitamin) deficiencies |
|
|
Term
| Legal limit of alcohol and lethal limit |
|
Definition
Legal limit- .08%
Lethal limit - about 0.40% |
|
|
Term
| Suggested neurochemical mechanisms of action of EtOH |
|
Definition
a. nonspecific membrane disordering (occurs only at very high concentrations)that interferes with action potential propagation
b. inhibitory effects on sodium and calcium ion channels to reduce response to excitatory neurotransmitters
c. enhancement of the action of the inhibitory transmitter, γ-amino-butyric acid (GABA-A) to open chloride channels |
|
|
Term
| Wernicke's encephalopathy |
|
Definition
1. results from thiamine deficiency;
2. acute confusional state (apathy, lethargy; inability to sustain mental or physical activity; impaired awareness and responsiveness; disorientation;
concentration and attention deficits; memory loss)
3. opthalmoplegia (nystagmus, ocular palsies)
4. ataxia, gait disturbances
5. responds to thiamine (100 mg daily) |
|
|
Term
|
Definition
1. result of direct neurotoxicity; observe in approx 75% with Wernicke's.
2. anterograde and retrograde amnesia
3. permanent brain damage, not as responsive to vitamins |
|
|
Term
| peripheral neuropathies, sensory and motor due to EtOH |
|
Definition
1. sensory neuropathies: loss of sensation, paresthesias, neuropathic pain
2. motor neuropathies: weakness, disturbances in gait
3. often respond to thiamine therapy |
|
|
Term
| Effects of EtOH on the GI tract |
|
Definition
1. Acute ingestion stimulates (at low-moderate dose) or inhibits (high dose)
gastric acid secretion
2. With long term high intake, increased gastric acid predominates
3. Acutely, ethanol decreases GI smooth muscle contractions
4. Chronically, ethanol increases propulsive waves in intestinal smooth muscle,
promotes diarrhea
5. With long term high intake, direct toxic effects at several levels of the GI tract
a. direct toxicity to cells in intestinal villi produces malabsorption of
nutrients, especially vitamins (recall contribution to neuropathies)
b. associated with increased incidence of gastritis, pancreatitis, gastric
ulcers and bleeding, and a variety of GI tract cancers, contributes to
diarrhea |
|
|
Term
|
Definition
inhibitor of aldehyde dehydrogenase; induces acetaldehyde syndrome when ethanol is consumed.
Appears to mainly reduce number of drinking days; does not appear to enhance abstinence (i.e., number of consecutive non-drinking days) or reduce feelings of craving |
|
|
Term
|
Definition
Opioid receptor antagonist
1. reduces number of drinking days and relapses
2. enhances abstinence and reduces feelings of craving
3. Animal studies suggest that ethanol enhances the release of endogenous opioid peptides (maybe through a pathway involving GABA), which in turn, increase the release of dopamine in the reward pathway. Thus, blocking the opioid receptor may reduce the rewarding actions of ethanol. |
|
|
Term
|
Definition
Campral-
1. Neurochemical mechanism not established, may be an antagonist at subtype
of glutamate receptor
2. reduces number of drinking days and relapses
3. may enhance abstinence by reducing physiological signs of withdrawal, esp.
anxiety, insomnia |
|
|
Term
| Fetal Alcohol syndrome facial dysmorphias |
|
Definition
�� Microcephaly
�� Small nose
�� Small palpebral fissures
�� Indistinct filtrum, small lips
�� Low set ears
�� Decreased growth in mid-face region |
|
|
Term
| The neurochemical actions of amphetamine include |
|
Definition
1. increase release of norepinephrine and dopamine, and serotonin
2. block the reuptake of these transmitters
3. inhibit degradation of these transmitters by MAO (weak)
KEY CONCEPT: Amphetamine and related drugs increase release by “reverse
transport”. |
|
|
Term
| Major acute pharmacological effects of amphetamine and cocaine |
|
Definition
1. psychomotor stimulation: increased attention, alertness, concentration, focus,
wakefulness, increased vigilance, decreased effect of fatigue
2. suppression of appetite
3. inhibition of REM sleep
4. elevation of mood, elation, euphoria |
|
|
Term
| Amphetamine-like drugs in clinical use |
|
Definition
- D-amphetamine (Dexedrine®), amphetamine mixed isomers (Adderall ®) (ADHD,
narcolepsy)
- methylphenidate (Ritalin®; Concerta) (ADHD, narcolepsy), dexmethylphenidate
(Focalin ® (ADHD)
- phentermine (Ionomin®, Phentrol ®) (obesity) |
|
|
Term
|
Definition
| D-amphetamine and methylphenidate |
|
|
Term
|
Definition
| D-amphetamine and methylphenidate, also used is Modafinal |
|
|
Term
|
Definition
1. blocks dopamine and norepinephrine reuptake
2. originally not classed as psychostimulant, but shows stimulantlike
effects, including abuse potential
3. reduces daytime sleepiness
4. now approved for sleepiness due to obstructive sleep apnea and
circadian rhythm disorder |
|
|
Term
| atomoxetine (Straterra ®), |
|
Definition
a new drug for ADHD; FDA approved for
children and adults
a. not classed as a psychostimulant; blocks reuptake of norepinephrine
only (dopamine rather than NE may be more important)
b. somewhat effective in children > 6 years, adolescents and adults (only
one approved for adult ADHD)
c. most common adverse effects are: decreased appetite, nausea and
vomiting, fatigue |
|
|
