Pharmacology 3 Flashcards
1
Q
Def of neuromodualtor
A
Any substance that has an effect on neurotransmission
2
Q
What are the types of transmission in the brain
A
Chemical and voltage
3
Q
What is essential for CNS drugs
A
Selectivity
4
Q
What influx signals NT’s
A
Calcium
5
Q
Two methods of NT action
A
Degradation via enzymes
Reputable into the presynaptic neuron
6
Q
What activates para and sympathathetic systems and is degraded by acetylcholinesterase
A
ACH
7
Q
What amino acids are degraded by transaminase?
A
GABA (sedative)
Glutamate/aspartame (stimulating)
Glycine/taurine (INHB /+ Excitatory)
8
Q
Amines degraded by Monoamine Oxidase
A
Dopamine
NE
Serotonin
Histamine
[Excitatory or Inhibitory based on class]
9
Q
Neuropeptides degraded by peptidses
A
Opioid
Techykins
10
Q
Define sensitization
A
Up regulation of receptors, caused by long term antagonism or reduction of NT release
** may be more sensitive to medications **
11
Q
Define desensitization
A
Down regulation of receptors, caused by sustained release or slower elimination of NT’s
Examples = Opioids
12
Q
What defines a major depressive episode
A
Period of 2 weeks with 5 or + depressive symptoms
*Depressed mood
*Anhedonia (inability to feel pleasure)
Insomnia
Hypersomnia
Change in appetite or weight
Psychomotor retardation or agitation
Low energy
Poor concentration
Thoughts of worthlessness or guilt
Recurrent thoughts about death or suicide
13
Q
Patients that had one major depressive episode and do not have a history of mania or hypomania.
A
Unipolar Major Depression or MDD
14
Q
Depression that lasts 2 or more years with symptom-free periods being less than 2 consecutive months. (May include periods of MDD)
A
PDD or dysthymia
15
Q
What causes mood disorders and how do we try to fix it?
A
Nearly all mood disorders are caused by an abnormal functional activity of neurotransmitters in the brain
By enhancing or blocking the presence (effect) of the neurotransmitters in the synaptic cleft, we are attempting to change or “normalize” the mood
16
Q
3 main types of depression
A
Reactive or Secondary (Most Common): response to grief, illness, drugs, alcohol, senility
Unipolar: genetically determined and unable to experience ordinary pleasure or cope with life events (Major Depressive Disorder)
Bi-Polar Affective: depression associated with mania (manic-depressive
17
Q
When are Psychotherapy and Exercise recommended
A
Recommended as monotherapy as initial treatment in patients with mild to moderate MDD
Cognitive Behavioral Therapy (CBT
18
Q
When would we use electroconvulsive therapy
A
Option for refractory depression, depression in pregnancy, psychotic depression, and other conditions for which medications may not be optimal or effective
Cycle is three treatments/week
19
Q
What preg category are most antidepressants
A
Cat C
20
Q
What happens in the absence of a serotonin reputable inhibitor
A
serotonin (5-hydroxytryptamine, or 5-HT) is released from raphe neurons that project to limbic structures.
Serotonin activates postsynaptic and presynaptic 5-HT receptors and undergoes reuptake into the presynaptic neuron
21
Q
What class of antidepressants blocks retake of 5-HT
A
TCA
SSRI
SNRI
22
Q
What happens with continued use of a TCA SSRI or SNRI
A
increased synaptic concentrations of 5-HT cause the down-regulation of presynaptic autoreceptors and an increase in the firing rate of raphe neurons.
23
Q
What is the efficacy of Benzo’s
A
Not classified as an anti-depressant
Used short-term in acute anxiety management while SSRIs are initiated
24
Q
What are the tertiary TCA’s and their role?
A
More potent at blocking reuptake of serotonin > norepinephrine
Include: amitriptyline, clomipramine, doxepin, imipramine
25
What are the secondary TCA’s and their role?
More potent in blocking reuptake of norepinephrine > serotonin
Include:
nortriptyline,
desipramine,
protriptyline
26
MOA of TCA’s
Block the reuptake of norepinephrine and serotonin (precursors to SNRI) into the presynaptic neuron which increases the concentrations of monoamines in the synaptic cleft (debated theory
Also block alpha adrenergic, histamine and muscarinic receptors (anticholinergic side effects
27
Clin use of TCA’s
Depression
(Not first line)
Anxiety Disorders
Numerous off labeled uses such as:
Treatment for pain syndromes: useful in chronic pain but the reason is not clear
Migraine prophylaxis
28
TCA Pharmacokinetics / Warnings
Dosage adjustments upward will be needed due to low and inconsistent bioavailability and adverse effects
Cautions/Warnings:
Most commonly used drug in an overdose
Can produce serious, life-threatening cardiac arrhythmias, delirium, coma, seizures, and psychosis
29
ADE’s of TCA’s
Anticholinergic Effects: dry mouth, urinary retention, constipation, blurred vision
Dry mouth is a suggested link to weight gain due to the tendency for patients to drink excessive caloric beverages
The anticholinergic effects will make BPH worse
α receptors antagonist: orthostatic hypotension
Antihistaminic effects: sedating
Cardiovascular:
Can worsen arrhythmias due to quinidine like effect
Use with caution in ischemic heart disease, arrhythmias or conduction disturbances
Withdrawal Syndrome (if discontinued quickly)
Symptoms:
GI complaints, dizziness, insomnia and restlessness
Flu like symptoms
COMMON DRUG INTERACTIONS
30
Which TCA’s have high sedation and anti-cholinergic affects? (3)
Amitriptyline
Doxepin
Clomipramine
31
Which TCA’s have low sedation and anti-cholinergic affects and alpha blockade? (2)
Desipramine
Nortiptyline
32
COMMON SSRI’S and others (2)
```
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Citalopram
Escitalopram
```
Vilazodone
Vortioxetine
33
MOA of SSRI’S
Inhibit serotonin reuptake, without affecting reuptake of norepinephrine or dopamine into the presynaptic neuron
SSRI’s do not significantly effect histamine, muscarinic or other receptors
** Onset of action takes 3-8 weeks (or even longer in some cases**
34
Clin use of SSRI’S
```
Depression
Obsessive Compulsive Disorder
Panic Disorder
Social Phobia
PTSD
Premenstrual Dysphoric Disorder (PMDD)
Generalized Anxiety Disorder
```
** Low cost and best tolerability**
35
Pharmacokinetics of SSRI’S
Elimination half-life of SSRI’s is about 1 day
Fluoxetine has the longest half-life at 1-3 days for parent drug and active metabolites are 4-16 days
Fluvoxamine is the shortest with half-life at 15 hours
36
Which SSRI’S do not interact with CYP 450?
citalopram and escitalopram
37
ADE’s of SSRI’S
Gastrointestinal: nausea, diarrhea, constipation
CNS: agitation, anxiety, tremor, or panic may be seen in during the early phase of therapy
Most activating: fluoxetine and sertraline
Avoid in patients having trouble sleeping and give in the morning
Most sedating: paroxetine and fluvoxamine
Dose in the evening
Weight Gain (paroxetine is the worst)
Sexual Dysfunction
38
What are the three most severe ADE of SSRI’S
Serotonin Syndrome
Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
EPS side effects:
Include akathisia, dystonias, and parkinsonian symptoms
Reported with all SSRI’s, but paroxetine has the most reported
Especially with elderly
39
Treatment for Serotonin Syndrome
```
Withdraw offending agent(s)
Supportive care
Anxiety/seizures
benzodiazepines
Hyperthermia
ice, cooling blankets
Cyproheptadine
1st generation antihistamine, and 5HT1A and 5HT2 antagonist
```
40
Which SSRI does not cause withdrawal symptoms
Fluoxetine
41
Common drug interactions of SSRI’S
```
Bleeding Risk
Aspirin products
NSAIDS
Variable CYP interactions
Monoamine oxidase inhibitors (MAOIs)
```
42
Indication for Fluoxetine
PTSD
MDD
Premenstrual dysphoric disorder
43
Indication for Sertraline
PTSD
| MDD
44
Indication for Paroxetine
PTSD
Panic Disorder
MDD
* Not rec for children *
CAN CAUSE CARDIAC SEPTAL DEFECTS IN 1ST TRI EXPOSURE
45
Indication for Fluvoxamine
Clinical Use: MOSTLY Obsessive-Compulsive Disorder
Considered sedating and more serotonin selective than most of the other SSRIs
Potent 2D6 Inhibitor
46
At what dose should Citalopram not be used and why
Citalopram should no longer be used at doses > 40mg/day due to the potential to cause QT prolongation and other cardiovascular electrical abnormalities.
47
What drug is an analog but more potent than citalopram
Escitalopram (Lexapro)
48
Vortioxetine Indication
MDD
49
Vortioxetine Drug Interactions
Strong inhibitor of CYP2D6
(Reduce the dose)
Substrate of CYP2D6 and CYP3A4
(Increase the dose)
50
Main and Other SNRI’s
Main SNRI medications
Duloxetine (Cymbalta)
Venlafaxine (Effexor)
Desvenlafaxine (Pristiq)
Other SNRI medications
Levomilnacipran (Fetzima)
Milnacipran (Savella)
51
MOA of SNRI’s
inhibit the reuptake of 5HT and NE, increasing their levels; little activity for alpha adrenergic, cholinergic, or histamine receptor
52
Which SNRI’s are associated with elevated diastolic blood pressure at higher doses
Venlafaxine, desvenlafaxine, and duloxetine
53
Drug interactions of SNRI’s
Both substrates and mild to moderate inhibitors of CYP2D6
SNRIs should not be used with MAOIs or other serotonergic agents
54
What is the clin use of Venlafaxine
Severe or treatment-resistant depression
Generalized anxiety disorder (GAD)
PTSD (1st line agent along with SSRIs)
Benefits:
Safer than TCAs in overdoses
Not as activating as fluoxetine
Unique MOA so it can be used when SSRIs have failed
55
What is unique about the dosage of venlafaxine
Works as an SSRI at doses ~75mg/day; SNRI at >225mg/day.
56
Venlafaxine is contrained in what two cases?
MAOIs inhibitors and triptans
57
Clin use of Des venlafaxine
```
Clinical Use:
2nd line agent for MDD
No advantage over Venlafaxine
Adverse Effects: same as venlafaxine
Contraindication: same as venlafaxine
```
58
Clin use of Duloxetine
```
Severe or treatment-resistant depression
Generalized anxiety disorder
Diabetic peripheral neuropathy
Fibromyalgia
Chronic musculoskeletal pain caused by chronic lower back pain or osteoarthritis pain
```
59
What patients should not take duloxetine
Should NOT be used in patients with hepatic insufficiency, end-stage renal disease requiring dialysis, or severe renal impairment
60
What is unique about levomilnacipran / its clin use / and ADE’s
Mechanism of Action:
Stronger inhibitor of norepinephrine reuptake than duloxetine (Cymbalta) or venlafaxine (Effexor)
More active isomer of the SNRI milnacipran (Savella)
Milnacipran (Savella) approved for fibromyalgia, not depression
Clinical Use: only for depression
Adverse Effects:
May cause hyponatremia and increase bleeding risk
Blood pressure elevation and orthostatic hypotension can occur
61
What are the drug interactions of Levomilnacipran
CYP3A4 substrate
62
Drug class of BUPROPION and MOA
NDRI
dopamine and norepinephrine reuptake (at high doses) inhibitor with minimal activity on serotonin
63
Clin use and ADE of Bupropion
Clinical Use:
MDD
Brand Name Zyban indicated for smoking cessation
Unlabeled Use: adjunctive agent in ADHD in children and adolescents
Adverse Effects:
Headache, insomnia, irritability, nausea, vomiting, decreased appetite
Weight loss ~4kg
**Increased risk of seizures**
64
What is contrained with use of bupropion
Alcohol Benzos and MAOI’s
65
SRA’s and common effects
Medications:
Trazodone
Mirtazapine
Nefazodone
Common effects:
Antagonists of 5HT2 family of receptors
Antagonists of α1 receptors
Antagonists of Histamine1 (H1) receptors – causes drowsiness
66
What receptors are inhibited by Trazodone
5HT2A, H1, and α1 receptors
67
Clin use of Trazadone and main ADE
Clinical Use:
Can be used for depression, but usually in combination with SSRI/SNRI in patients with sleep disorders
At low doses used as an agent for sleep
Compared to TCAs, has fewer anticholinergic side effects and fewer effects on the cardiac system
**Drowsiness**
68
Receptors inhibited by Mertazapine
5HT2A, 5HT3, H1, α1 and α2
69
Clin use and clearances of Mirtazapine
MDD in combo w SSRI’S
Renally cleared
**Profound sedative efffect**
70
MOA of Nefazodone
: Inhibits 5HT2 family of receptors, α1 receptors, and reuptake of serotonin + norepinephrine
71
Clinical use of nefazodone
Anxious depression
or in SSRI use that is too activating/sexual dysfunction
Considered a 2nd or 3rd line agent
72
ADE’s (5) and Black box warning for Nefazodone
Common: GI complaints, dry mouth, constipation, confusion, and light-headedness
**Risk of liver failure**
73
Drug interactions of Nefazodone
INHB of 3A4
74
MOA of MAOI’s
blocks the enzyme responsible for the break down of norepinephrine, dopamine and serotonin
which increases the stores of these transmitters in the neurons
Two Forms: MAO-A and MA
75
Clin use and Interactions of MAOI’s
Clinical Use:
Atypical depression (hypersomnia, hyperphagia, and mood reactivity)
Patients refractory to other anti-depressant agents
Interactions: the infamous food-drug interactions caused by these medications occur because they inhibit MAO in the GI track that normally breakdown tyramine
Can cause hypertensive crisis
76
What are the MAOI’s
‘Phenelzine
| Selegilne
77
What are the regards for switching from an antidepressant to an MAOI
Wait 2 weeks after discontinuing antidepressant before initiating the MAOI
**Except Fluoxetine waiting period should be 5-6 weeks**
78
Clin use of Selegiline
MDD
MAO-B Inhibitor
79
What is the adequate trial of an antidepressant agent
full therapeutic doses for 2-8 weeks and in some cases for up to 12 weeks
80
Define response and remission
usually defined as a 50% reduction in symptoms
81
What antidepressant are likely to cause sexual dysfunction
SSRI’S
SNRI’s
82
What antidepressant are likely to cause Weight gain
Most all antidepressants
**except bupropion and fluoxetine
83
What antidepressant are likely to cause somnolence
TCA’s misrtazapine aroxetine trazadone
84
What antidepressant are likely to cause an increase in energy
Bupropion or an SNRI
Fluoxetine and Sertraline
85
What antidepressant are likely to cause anxiety
Bupropion
86
What antidepressant are likely to cause a reduction in pain
Duloxetine venlafaxine
| amitriptyline and imipramine
87
What patients would you consider Vortioxetine in?
Overweight
Sexual dysfunction
Psychomotor slowing
88
What two antidepressants/anxiety meds do not require tapering when discontinuing
Fluoxetine
| Bupropion
89
What are thyroid stimulants good for
Resistant depression
90
What atypical antipsychotics have approval as augmentations to antidepressant therapy
Aripiprazole and Quietiapine
91
What antidepressant can cause heart defects in pregnant patients newborn
Paroxetine
92
Mania vs/ Hypomania
Mania: the affective opposite of depression; characterized by at least 1 week of an abnormal and persistently elevated mood
Hypomania: similar to a manic episode, but it exists for 4 days or longer; not severe enough to warrant hospitalization, does not impair social or occupational functioning, and is not associated with psychosis
93
Cyclothymic disorder
Several periods of hypomania and mild depression that do not meet criteria for mania or MDD
94
BPI vs BPII
Bipolar I (BPI):
Chronic disorder marked by one or more manic or mixed episodes and major depressive episodes
Recurrent manic or mixed manic episodes more frequent and severe compared to depressive episodes; more hospitalizations
Bipolar II (BP II):
Chronic disorder marked by one or more major depressive episodes, accompanied by at least one hypomanic episode
Recurrent major depressive episodes alternating with hypomanic episodes; no mania, less hospitalizations, more common in females, more often rapid cycling
95
Define rapid cycling
four or more episodes of mania, hypomania, mixed mania, or depression in a one-year period; need to assess thyroid function
96
What overproduction is likely to cause a manic episode
NE and serotonin
97
Clin use of Lithium
Effective for manic and depressive components
Anti-manic effects can occur in 1-2 weeks
*discontinue after resolves
98
Discuss monitoring with lithium treatment
Narrow therap. Index
Half Life 20-24 hours
CBC, electrolyte, thyroid Preg Test
**anything that alerts GFR affects its clearance**
99
If pt has a tremor with lithium use, what do you do?
Reduce dose and add Beta blocker
100
If pt has CNS toxicity what should yo do with the lithium prescription
Reduce dose
101
If pt has GI issues on lithium what should you do
Reduce dose and try extended release product
102
If pt has hypothyroidism on lithium what should you do
Discontinue or give levothyroxine
103
Discuss lithium and sodium concentrations
If NA+ is not reabsorbed and hyper depleted remaining sodium and lithium are reabsorbed from proximal tubules and can increase concentration
104
Interaction of Lithium and NSAIDs
Decreased Li excretion causes increased Li serum levels; avoid use to reduce toxicity
105
What are the anticonvulsants
Valproic Acid derivatives
Carbamazepine (Tegretol, Equetro)
Lamotrigine (Lamictal)
Topiramate (Topamax)
106
When is valproic acid better than lithium
Rapid cycling
Comorbid substance abuse
Secondary bipolar disorder
Mixed mania
107
Preg Cat of Valproic acid and Divalproex
D
108
Clin use of Carbamazepine
Effective for acute mania and maintenance therapy
Used for long-term management
Can be added to lithium for patients who have not responded to monotherapy
Carbamazepine (Equetro) approved by the FDA for acute manic/mixed episodes
109
ADE’ s of carbamazepine
Hyponatremia, including SIADH can occur
Rash/Steven’s Johnson Syndrome
Agranulocytosis
110
Which anticonvulsant is effective for the depressed phase of bipolar disorder
Lamotrigine
111
If you give lamotrigine with carbamazepine what should you do
Primary concern of lamotrigine
Double the dose of lamotrigine
**RASH**
112
Use of BZD’s in bipolar disorder
Useful for insomnia, hyperactivity, and agitation
113
What are the acutely used BZD’s
Lorazepam, Diazepam
114
When is clonazepam used
Brief behavior symptoms
115
What two antipsychotics can control agitation and psychosis
Haloperidol
Olanzapine
116
What two antipsychotics are approved as mono therapy in bipolar disorder
Olanzipine and Aripiprazole
117
What is happening physiologically in Parkinson’s
Dopamine normally inhibits GABA in substantia nigra
Acetylcholine excites GABA in substantia nigra
In Parkinson’s there is a gradual loss of dopaminergic neurons
118
How does Parkinson’s affect mental status
Depression (50%)
Dementia (25%)
Psychosis
*May be precipitated or worsened by drugs
119
What are the secondary symptoms of Parkinson’s
Cognitive Dysfunction: amnesia, anxiety, dementia, confusion in the evening hours
Autonomic Dysfunction: dribbling of urine or leaking of urine
Speech Disturbances: impaired voice, soft speech, or voice box spasms
Micrographia “small handwriting”: handwriting appears cramped in patients with Parkinson’s
120
What are the drug induced dopamine antagonists
[Antipsychotics]
Prochloroperazine (Compazine)
Chlorpromazine (Thorazine)
Trifluoperazine (Stelazine)
Thioridazine (Mellaril)
Haloperidol (Haldol)
[Antiemetics]
Metoclopramide (Reglan)
121
What disease can induce Parkinson’s dz
Viral encephalitis
122
What drug can improve Parkinson’s motor disability
Drug that can Lessen motor complication?
Levodopa
Dopamine
123
What type of Parkinson’s pt receives monoamine oxidase inhibitor or dopamine agonist first
Younger
Bio fit
Mild symptomatics
124
What type of Parkinson’s pt receives L-DOPA therapy first
Bio unfit
Co-morbid
Cognitively impaired
125
If a Parkinson’s pt is experiencing the following symptoms what do you do
Dyskinesia
Motor Fluctuations
Tremors
Reduced L-DOPA
Subcutaneous aporphibe or duodopa
Deep brain stimulation
126
First line Txm in Parkinson’s dz
Dopamine agonist
127
Which drug has the greatest effect on bradykinesia and rigidity
Levodopa
128
Dopamine Agonists
Bromocriptine (Parlodel)
Pramipexole (Mirapex)
Apomorphine (Apokyn
Ropinirole (Requip)
129
Muscarinic antagonists
Benztropine (Cogentin)
| Trihexyphenidyl (Artane)
130
NMDA Inhibitor
Amantadine (Symmetrel)
131
COMT Inhibtors
MAO Inhibitors
Catechol-O-Methyl-Transferase (COMT) Inhibitors:
Tolcapone (Tasmar)
Entacapone (Comtan)
Carbidopa/levodopa/entacapone (Stalevo)
Monoamine Oxidase (MAO) Inhibitors:
Selegiline (Eldepryl, Zelapar, Deprenyl)
Rasagiline (Azilect) (Therapeutic effects are not robust)
132
MOA and main receptor for Dopamine agonists
Act directly on postsynaptic dopamine receptors
Do not require enzymatic conversion
D2 family receptors (D2, D3 and D4): stimulation of D2 family improves rigidity and bradykinesia
133
Treatment of this drug Delays levodopa for years and advantages
Dopamine agonists
Advantage: less dyskinesia and fluctuations than levodopa; long half-life results in less dyskinesias
Not oxidized into free radicals
134
What pt symptoms worsen with dopamine agonists
Psychotic and/or dementia pts
135
non selective dopamine agonists
Bromocriptine
| Rotigotine
Transdermal
136
Non selective dopamine agonist ADE’s
```
Pleuropulmonary and/or cardiac fibrosis is a concern
Chest x-ray with abnormal pulmonary exam
Postural hypotension, dizziness
Hallucinations, mental confusion
GI disturbances
Digital vasospasm and leg cramps
```
137
D2 and D3 selective agonists
Pramipexole (Mirapex)
Ropinirole (Requip)
138
ADE’s and contraindications of D2 and D3 selective agonists
Adverse Effects:
Postural hypotension (at the initiation of therapy)
GI problems
Mental confusion
Dizziness
Hallucinations
Somnolence (all dopamine agonist can cause daytime sleepiness)
Contraindications:
History of psychotic illness
Recent myocardial infarction (MI)
Active peptic ulceration
139
Clin use of pramipexole (4 things)
Clinical Use:
Effective as monotherapy for mild parkinsonism and in patients with advanced disease
Allows the dose of levodopa to be reduced and smoothing out response fluctuations in advance disease.
Possible neuro-protective effect
Ability to scavenge hydrogen peroxide and enhance neurotrophic activity
140
Clin use of ropinirole
Clinical Use:
Affective as monotherapy in patients with mild disease
Allows the dose of levodopa to be reduced and smoothing out response fluctuations in advance disease
141
D2 Selective agonist
Apomorphine (short acting)
142
Clin use of apomorphine
Clinical Use: acute, intermittent treatment of “off” episodes associated with advanced Parkinson disease; recurring hypomotility, “off” episodes
143
Most severe ADE and treatment of apomorphine
Severe Nausea/vomiting (98%)
Treatment: prophylaxis with trimethobenzamide (anti-emetic) 3 days prior to initiating apomorphine and continued for the first month of therapy, if not indefinitely
144
Contraindications of apomorphine
5-hydroxytryptamine-3 antagonists (5-HT3) antagonists
IV use (thrombus formation)
Sulfite sensitivity (preservative)
145
MOA of carbidopa
Aromatic Inhibtor that DOES NOT CROSS THE BBB
Prevents peripheral conversion of levodopa to dopamine
Increases avail of levodopa to cross into the CNS
146
Levodopa MOA
Mechanism of Action:
Precursor to dopamine that has the ability to cross the BBB and replenish depleted dopamine in the brain
Converted into dopamine in the periphery
147
Clin effects of levodopa
Clinical effects:
Improvement in disability and possibly mortality
Greatest effect on bradykinesia and rigidity; less effect on tremor and postural instability
148
How long is the honeymoon stage of levodopa
3-5 years
149
Main ADE of Carbidopa/Levodopa
Dyskinesias (excessive dopamine):
150
What dz is contrained or has precautions for the use of C/L
Contraindications:
psychotic illness, narrow-angle glaucoma, use of non-selective MAOI’s
Precautions:
Peptic Ulcer Disease (PUD)
Malignant Melanomas: levodopa is a precursor of skin melanin and conceivably may activate malignant melanoma
151
When should a pt take selegiline
Which is more potent selegiline or rasagiline
Early afternoon to prevent insomnia
[in conjunction with levodopa]
**RASAGILINE MORE POTENT**
152
MOA OF COMT INHB and Clin use
Mechanism of Action: prevents the breakdown of dopamine, more levodopa available to cross blood-brain barrier
Clinical Use:
Manage motor fluctuations (“wearing-off” effect)
Adjunct to levodopa/carbidopa in patients with response fluctuations or who have failed or can not use other therapies
153
Most commonly noticed ADE of Entacapone (COMT-INHB)
Orange Urine
154
COMT Inhibitors
Tolcapone [ EXTREME HEPTATOXICTY ]
Entacapone [ USE WITH C/L / DOES NOT CROSS BBB ]
Stalevo [ C/L/ENTACAPONE ]
155
Anticholinergic MOA and Clin use
Mechanism of Action: block the excitatory neurotransmitter acetylcholine to try and restore balance with dopamine
Clinical Use:
Most effective on tremors and rigidity
DOC for drug-induced (anti-psychotics) parkinsonism
Does not relieve symptoms of tardive dyskinesia
156
Anticholinergics
Benztropine [ controls EPS symptoms ]
Trihextphenidyl
157
N-methyl-D-aspartate (NMDA) Receptor Inhibitor / Clin Use
Amantadine
Clinical Use:
Posses symptomatic benefits and may reduce dyskinesias caused by levodopa or dopamine agonists
Not as effective on bradykinesia, rigidity, tremor and dyskinesia as anticholinergics
158
Most common ADE of Amantadine
Livedo Reticularis (rash)
159
Two categories of seizures
Generalized - originates at some point within and then engages neural networks
Focal - involves only a portion of the brain impaired consciousness or awareness
160
Tonic
Vs.
Clonic
Vs.
Myoclonic
Vs.
Atonic
Tonic: flexion and/or extension
Clonic: rhythmic, repetitive, jerking muscle movements
Myoclonic: brief, lightning-like jerking movements of the entire body or the upper and occasionally lower extremities
Atonic:
Characterized by a loss of muscle tone
161
What is an absent seizure
Typical seizures are brief and abrupt, last 10-30 seconds, and occur in clusters
Usually results in a short loss of consciousness, or the patient may stare, be motionless, or have a distant expression on his or her face
162
What is an epileptic seizure
2 or more seizures
Epileptic Seizure: clinical manifestation presumed to result from abnormal and excessive discharge of a set of neurons in the brain that results in abnormal movements or perceptions
163
Discuss cause and treatment of primary vs secondary epilepsy
```
Primary Epilepsy: no specific anatomic cause
Drug treatment (MAY) be for life
```
Secondary Epilepsy: reversible disturbances responsible for seizures
Tumors, trauma, hypoglycemia, alcohol withdrawal
Drug treatment is used until the primary cause of the seizure can be corrected
164
When do you perform Venus nerve stimulation
For difficult to manage partial seizures
| Implanted stimulator delivers stimuli on a regular basis and patients can use “on demand” stimulation
165
When can we attempt withdrawal from seizure therapy
Seizure free for 2-5 years
Single seizure type
Normal neurological exam and IQ
Normal electroencephalogram (EEG) with medication treatment
*withdraw slow and one at a time*
166
MOA of anticonvulsants (3 mechanisms)
blocking the initiation or preventing the spread of electrical discharge by several mechanisms
1) Enhancement of GABAnergic transmission
2) Diminution of excitatory transmission (i.e. Glutamate)
3) Modification of ionic conductance (i.e. Calcium, Sodium
167
What two drugs have a narrow spectrum in absent seizures
Ethosuximide
| Valproate (alternative)
168
MOA and Clin Use of Phenytoin
Mechanism of Action: fast sodium channel blocker
Clinical Use:
Generalized tonic-clonic (not 1st line)
Simple or complex partial seizures with or without generalization (not 1st line)
Status Epilepticus
**DO NOT USE in Absence seizures
169
Administration Considerations of Phenytoin = (Dilantin, Phenytex)
IV Formulation: very basic product
Prepare only in normal saline solution
Oral suspension: shake well; adheres to feeding tubes and is bound by enteral nutrition products
170
Non dose related ADE’s of phenytoin
Vs.
Dose related
Non Dose:
Sexual dysfunction
Hirsutism (excessive hair growth), gingival hyperplasia (40-90%)
Long term use causes coarsening of facial features
Dose:
Nystagmus (rapid eye movement), ataxia, drowsiness, cognitive impairment
171
Preg Cat of Phenytoin
Preg Cat D
172
Drug interaction of Phenytoin on
1) Anticoagulants
2) Contraceptives
Anticoagulants (oral): may increase phenytoin serum concentration; decreased/increased anticoagulant effects
Contraceptives: reduces efficacy of estrogen-containing contraceptives, oral progestin-only contraceptives, and the etonogestrel implant
173
Kinetics of Phenytoin
Zero-Order Kinetics: drug concentration changes with respect to time at a constant rate;
174
MOA for Fosphenytoin ; ADVANTAGES?
Mechanism of Action: PRODRUG for phenytoin; fast sodium channel blocker
Advantages over phenytoin:
Preferred when parenteral administration is needed (reduced extravasation, faster load)
1mg of phenytoin = 1.5 mg of fosphenytoin
175
MOA and Clin use of Carbamazepine
Mechanism of Action: fast sodium channel blocker
** CYP3A4 inducer and auto inducer (self induction)**
Clinical Use:
Only available orally
Primary generalized tonic-clonic, simple or complex partial
Newer anticonvulsants are beginning to displace it from this role
Other uses: trigeminal neuralgia and bipolar disease
176
Common ADE’s of carbamazepine
Diplopia
Rash
SIADH
177
Serious ADE’s of Carbamazepine
Hyponatremia
Bone marrow suppression (mild leukopenia)
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (especially patients of Asian heritage with HLA-B 1502 mutation)
Multi-organ hypersensitivity: potentially fatal reaction characterized by cutaneous eruption, fever, lymphadenopathy, hematologic abnormalities, and visceral manifestations
Hepatotoxicity (Very rare)
Osteomalacia
178
Drug interactions and pregnancy category of Carbamazepine
Pregnancy Category: D; teratogenic, neural tube defects
Drug Interactions: CYP 3A4 substrates
Lamotrigine may also increase carbamazepine epoxide levels
Reduces efficacy of estrogen-containing contraceptives
179
Genetic testing recommendations for carbamazepine
HLA-B*1502 is common in Asians ancestry (>15% of populations in Hong Kong, Malaysia, the Philippines, and Thailand)
HLA-A*3101 occurs more frequently in patients of African-American, Asian, European, Indian, Arabic, Latin American, and Native American ancestry
180
MOA : Fast sodium channel blockers
Oxcarbamazepine
Carbamazepine
Fosphenytoin
Phenytoin
181
Clin use of Oxcarbamazepine
General tonic clonic
Trigminal neuralgia
Bipolar
**Good for pts who do not tolerate carbamazepine***
182
What is more common in oxcarbamazepine than carbamazepine?
Hyponatremia
183
Carbamazepine or Phenytoin?
Carbamazepine FIRST!
- LESS SEDATING
- NO HIRSUTISM/ ACNE/ HYPERPLASIA
- NO LEARNING IMPAIRMENT
184
MOA of Phenobarbital and Primidone
Increases GABA mediated chloride influx
185
Clin use phenobarbital / preg category / ADE’s
Clinical Use:
Generalized tonic-clonic seizures, simple or partial seizures
Refractory status epilepticus; tried for virtually every seizure type, especially when attacks are difficult to control
Adverse Effects: sexual dysfunction, hyperactivity and cognitive impairment
Pregnancy category: D
186
Primidone special MOA characteristic
Metabolized to phenobarbital and phenylethylmalonamide
**may be used with carbamazepine and phenytoin**
187
Most common Benzo’s
Diazepam (Valium)*
Lorazepam (Ativan)*
Clonazepam (Klonopin)
188
What effect does high dose Benzo’s cause
Higher doses may cause ataxia (shaky movements and gait) and behavior changes
189
MOA of Gabapentin and Clin Use
MOA:
Inhibition of α2δ subunit of voltage-dependent calcium channels
An analog of GABA, but does not directly impact GABA receptor
Clinical Use:
Partial onset seizures
Neuropathic pain and post herpetic neuralgia pain
Spasmolytic
Diabetic neuropathy (off-label)
190
Pharmacokinetics of Gabapentin
| And ADE’s
Eliminated renally
Drowsiness, fatigue, dizziness, headache, weight gain, and tremor during initiation
191
Pregabalin MOA
Inhibition of α2δ subunit of voltage-dependent calcium channels.
GABA derivative similar to gabapentin that binds pre-synaptically to the alpha-2-delta subunit
192
Main Clin use of Pregabalin
Non-epileptic: neuropathic pain
193
Ethosuximide Clin Use
DOC in absence seizures
194
Serious ADE’s of Ethosuzimide
Neutropenia (rare, 7%)
Transient leukopenia (common)
Hematologic toxicity (extremely rare)
195
Derivatives of Valporic Acid (2)
Valproate (Depacon injection),
Divalproex (Depakote
196
What is the parenteral use of valporic acid
Parenteral Use: FDA indication only for replacement of oral dosing;
sometimes used for status epilepticus = [ seizure lasting longer than 5 minutes ]
197
ADE’s of Valporic acid
Common: alopecia, N/V, interferes with platelet aggregation, pancreatitis, sedation, weight gain (average of 2 kg after one year), rash
Serious:
Thrombocytopenia
Multi-organ hypersensitivity
Black box warning for hepatic failure fatalities
198
Preg category for Valporic Acid in migraine prophylaxis
X
**Substantial increase in the incidence of spina bifida**
199
Describe Valporic Acid Overdose
Can lead to CNS depression: somnolence and deep coma
** Naloxone may reverse CNS depressant effects, theoretically it can have a convulsant effect**
200
MOA of Lamotrigine
Decreases glutamate and aspartate release
Delays repetitive firing of neurons
Blocks fast sodium channels
201
How can yo avoid the Steven Johnson Syndrome Rash when administering Lamotrigine?
Titration should be done slowly upward
202
Clin use of Topiramate / Preg Cat
Primary generalized tonic-clonic seizures, simple or complex partial with or without generalization
Absence seizure (adjunct)
Lenox-Gastaut
Non-epileptic: migraine prophylaxis
Preg Cat D
203
Common and Serious (Common and Serious) ADE of Topiramate
Common
:Memory Impairment
Serious
:Metabolic Acidosis
204
What can decrease Topiramate levels by 50%?
Carbamazepine and Phenytoin
**Reduced efficacy of Contraceptives**
205
Clin use of Levetiracetam
Myoclonic seizures 12 yrs and older
Lenox-Gastaut [severe childhood epilepsy]
General tonic clonic/epilepsy 6 yrs and older
206
What is another word for disorganized schizophrenia
Hebephrenia,
Extreme expression of disorganization syndrome, 1/3 factor of 3 factors of schizo. Others are :
- Delusions/hallucinations
- Psychomotor poverty (absence)
207
Paranoid vs. Residual vs. Undifferentiated Schizo
P = Delusions of deceit
R = Blunted inappropriate emotion
U = Prominent psychotic symptoms without top 3 factors
208
Primary NT’s of psychological abnormalities
Dopamine
5-hydroxtryptamine (5HT; serotonin)
Glutamate
209
Pneumonic for 1st gen Antipsychotics
-Zine, -Xene, -Xapine + Halodol
210
Pneumonic for 2nd gen Antipsychotics
-prazole, -pine, -done
211
Max treatment response rate in atypical antipsychotics
Response to medications is NOT immediate, maximal treatment response may take 6 months or longer to be observed
212
Which antipsychotic is common for and how does it exert anti emetic effect
(Most Typical Agents): due to blockage of D2 in the chemoreceptor trigger zone of the medulla
Prochlorperazine
213
Hiccups longer than 2 days can be treated with what antipsychotic
Chlorpromazine
214
Rapid acting Formulations of Antispychotics vs Long Acting Formulation use?
Rapid Acting Formulations: used to handle acutely agitated and disruptive behavior
Long Acting Formulations: used in patients that lack compliance
215
Brief Explanation of EPS symptoms
Dystonia: abnormal tonicity; severe muscle spasm of the head, neck and tongue
```
Tardive Dyskinesia (may not be reversible)
Syndrome of involuntary movements of the face, mouth, tongue, trunk and limbs
```
Akathesia (most common EPS)
Desire to be in constant motion (inability to sit still, pacing).
216
What drugs can cause Tardive Dyskinesia
High affinity D2 receptor drugs Ex: Haloperidol
217
How can you treat Akathesia
Low dose propranolol
Dose reduction
218
Black Box Warning of Antiphyschotics
increase mortality in elderly patients with dementia-related psychosis
219
Typical 1st Gen MOA
Competitive blockers of dopamine receptors D2 in the mesolimbic pathway
ALSO histamine, muscarinic, alpha receptors
**Less effective at negative symptoms**
220
Characteristics of Low Potency D2 Receptor Agents (3)
Low affinity for dopamine receptors, anticholinergic, a-adrengergic blocking
Less EPS
Highly sedative autonomic ADE’s
221
Characteristics of High Potency D2 Receptor Agents (2)
High affinity for the dopamine receptors; thus higher rates of extrapyramidal symptoms (EPS)
Less potency at the other receptors
222
High anticholinergic effects =
Fewer EPS symptoms
223
Pseudo Parkinsonism pharmaco TXM
Anti-cholinergic: Trihexyphenidyl or Benztropine
| Antihistamine: Diphenhydramine (Benadryl) IM/IV
224
Typical Antipsychotic ADE’s (6)
Worse Neg Symptoms
Prolonged QT interval
Postural hypotension
Weight Gain
Anticholinergic
Sedation
225
Define Neuroleptic Malignant Syndrome
High Potency induced agitation, fever, techs, hypertension
**MOST SEVERE REACTION TO 1st GEN’S**
226
Hyperprolactinemia
Blocked Dopamine = prolactin elevation
Women = galactorrhea and menstrual irregularities
Men = gynecomastia, sexual dysfunction and decreased fertility
227
Low Potency Antipsychotics
Vs
High Potency Antipsychotics
Chlorpromazine (Thorazine) IV/ PO
Thioridazine (Mallari) PO
Trifluoperazine (Stelazine) PO
Fluphenazine (Prolixin) IM
Haloperidol (Haldol) IV/IM/PO
228
Which med has the highest occurrence of sedation
Thioridazine
229
What is the most important ADDE of Chlorpromazine
May cause pigmentary deposits on the retina and corneal opacity
230
Which antipsyhcotic is affective in generalized non psychotic anxiety but can produce long term tardive dyskinesia
Trifluoperazine (Stelazine) PO
231
Which antipsychotic can mange prolonged paranteral neuroleptic therapy
Fluphenazine decanoate (Prolixin)
232
Clin use of Haloperidol
Clinical Use: management of schizophrenia, acute agitation, and for the control of tics and vocal utterances of Tourette’s Disorder
233
IV Halodol has been linked to toxicity including what dz?
torsade's de pointes
234
MOA of 2nd Gen Antipsychotics
Dopamine antagonists, but also block 5HT2A receptors (block 5HT to a greater extent than dopamine)
**Exception: Aripiprazole is a partial agonist at D2 and 5HT1A agonist and a 5HT2A antagonist**
235
What are the common ADE’s of 2nd gen atypicals
Weight Gain
Hyperglycemia
Diabetes Mellitus
Lipid abnormalities
236
What is the oldest atypical agent most effective in reserved patients resistant to 2 or 3 agents including typical and atypicals
Clozapine
237
Black box warning of Clozapine
Agranulocytosis
238
Abrupt discontinuation of clozapine can cause what
Fatal myocarditis
239
Serious ADE of Olanzipine
Excessive weight gain, sedation, and hypotension compared to the other atypical agents
240
Risperidone clin use
Schizophrenia acute psychosis and prevention
Bipolar mania and maintenance therapy
More effective at combating the positive symptoms
Children 10-17 yrs old
241
Which antipsychotic has the MOST prolactin elevation
Risperidone
242
Risperidone is similar to what analog?
Paliperidone
243
What antipsychotic is a good choice for psychosis occurances with Parkinson’s Disease
Quetiapine
**also schizophrenia, bipolar, depression
244
ADE’s of quetiapine (3)
```
Very sedating (antihistamine effects)
Significant orthostatic hypotension should monitor BP
Cataracts
```
245
Advantage and Disadvantage of Ziprasidone
Advantage: lower risk of metabolic syndrome and prolactin elevation
Disadvantage: Higher risk of QTc prolongation and cataracts
246
Aripiprazole Clin Use
Schizophrenia maintenance and acute agitation
Manic or mixed Bipolar disorder
Depression in combination with SSRI or other antidepressants
247
MOA, Clin Use, and Advantage of Asenapine
Mixed serotonin-dopamine antagonist
Clinical Use:
Schizophrenia maintenance and acute agitation
Manic or mixed Bipolar disorder
Adverse Effects:
Medium risk of sedation, tardive dyskinesia and EPS
248
MOA and Clin Use of iloperidone
Mechanism of Action: mixed D2/5-HT2 antagonist activity
| Clinical Use: schizophrenia only
249
Major ADE’s (3) of iloperidone
Higher risk of orthostatic hypotension and QTc prolongation
Esophageal dysmotility/aspiration
250
MOA no Clin Use of Lurasidone
Mechanism of Action: mixed serotonin-dopamine antagonist activity
Clinical Use: schizophrenia and bipolar disorder only
251
Sedative vs. Hypnotic
Sedative (anxiolytic): reduces anxiety and exerts a calming effect with little or no effect on motor or mental function
Hypnotic: produces drowsiness and encourages the onset and maintenance of a state of sleep resembling natural sleep
252
Two major classes of sedatives
Two major historical classes were benzodiazepines and barbiturates
253
What happens when GABA binds to the GABA receptor
relaxation and sedation
254
What type of binding do sedatives and hypnotics exert
Allosteric binding , enhanced inhibitory effect of GABA
-increases chloride influx
255
Disadvantages of barbiturates
ability to cause coma in toxic doses, physical dependence, and severe withdrawal symptoms
256
Which short acting barbiturate does not end in -barbital?
Methohexital
257
What can Phenobarbital treat?
Anticonvulsant: sedation, management of seizures & eclampsia
258
Barbiturates ADE’s
CNS depression
Hangover
Withdrawal symptoms
Overdose TXM
Preg Cat D
259
Phenobarbital MOA and Clin Use
Mechanism of Action: increases GABA mediated chloride influx
Clinical Use:
Generalized tonic-clonic seizures, simple or partial seizures
Refractory status epilepticus
Can be tried for virtually every seizure type
260
Short, Long, Intermediate Benzos
Short Acting Agents
Midazolam (Versed)
Oxazepam
Triazolam (Halcion)
```
Long Acting Agents
Chlordiazepoxide (Librium)
Clonazepam (Klonipin)
Diazepam (Valium)
Flurazepam (Dalmane)
Quazepam (Doral)
```
```
Intermediate Acting Agents
Alprazolam (Xanax)
Estazolam (ProSom)
Lorazepam (Ativan)
Temazepam (Restoril)
```
261
Longer half life Benzo’s =
Short Half Life (Quick) Benzo’s =
More hangover symptoms
High tolerance for hypnotic effect/common withdrawal
262
Clin use of Benzo’s
Anxiolytic (Sedative)
Hypnotic: all benzodiazpines induce sleep if high enough doses are given
Muscle Relaxation
Anticonvulsant
Anesthesia/Amnesic actions
263
How do benzos exert relaxation
Central Action
264
What Benzo’s are best for alcohol withdrawal
Oxazepam, Lorazepam, Diazepam
265
What BZD’s are good for anxiety
Clonazepam and lorazepam and diazepam [ short term use ]
266
What BZD’s are good for panic attacks
Clonazepam, Alprazolam, Oxazepam
267
What is a good agent for PTSD
SSRI - 1st line
268
Short acting BZD’s for sleep induction
Triazolam
269
Intermediate acting sleep maintenance BZD (2)
Temezepam and Estazolam
270
Long acting BZD to reduce sleep, time, awakenings and increase duration
Flurazepam and Quazepam
271
Long acting coverage of alcohol withdrawal
Chlordiazepoxide
Diazepam
272
3 common complaints of BZD’s
Residual daytime sedation
Rebound insomnia
Anterograde amnesia
273
How long should you use BZD’s as Txm
3-4 months
274
Drugs that increase CNS depression
Alcohol
Antihistamines
Antipsychotics
Antidepressants
Opioids
275
CYP3A4 interactions are minimal with which drugs
lorazepam, oxazepam, and temazepam (weak substrate)
276
BZD’s are _____ recommended for peds geriatrics
NOT
LOT, if you must.
277
Shorter half life leads to ______ dependence liability and more withdrawal
Higher
278
BZD rescue agent
Flumazenil
279
Buspirone MOA most common Clin Use
Mechanism of Action: (Not fully understood)
Has high affinity for serotonin receptors
Has moderate activity at D2 receptors
Clin use
Often used as a second line agent or when BZD should avoided to manage anxiety
280
Zolpidem MOA and Clin Use
Mechanism of Action: acts on the benzodiazepine receptor by enhancing GABA activity (not chemically related to BZD)
Clinical Use: Only use is for insomnia
IR for difficulty going to sleep
CR for sleep maintenance issues
281
(3) Common ADE’s of Zolpidem
Depression and suicidal ideations
Associated with abnormal thinking and behavior changes:
Decreased inhibition, aggression, bizarre behavior, agitation, hallucinations, and depersonalization
Causes functional dependence but no physical cravings
282
Eszopiclone ADE common
Metallic taste
283
Zaleplon MOA and Clin Use
Mechanism of Action: acts on BZD receptor, but is chemically not related to BZD
Clinical Use:
Short-term treatment of insomnia
284
Which hypnotic is least likely to cause daytime somnolence?
Zaleplon
285
Suvorexant MOA and Clin Use
Mechanism of Action: orexin-receptor antagonist
| Clinical Use: treatment of insomnia
286
MOA of Ramelteon
Mechanism of Action: melatonin receptor agonist. [Melatonin maintains circadian rhythm (sleep-wake cycle)]
287
Tasimelteon MOA and Clin Use and ADE
Mechanism of Action: melatonin receptor agonist
Clinical Use:
Non-24-hour sleep-wake disorder that is generally present in blind patients due to lack of stimulus from the sun
Adverse Effects:
Headache and abnormal dreams
288
Antihistamines can do what for insomnia and act on what receptors?
Examples of 2?
(H1 antagonists)
Diphenhydramine or Doxylamine
Sedating and anticholinergic effects
289
Anxiety disorder acute management
benzodiazepines are the drug of choice for short term use
290
Buspirone and Pregabalin can be used for what
Second line Agents for augment of SSRI or SNRI if low response in GAD treatment
291
What Benzo’s is preferred for Panic Disorder Txm
Clonazepam
292
What subtype of Social Anxiety Disorder uses propranolol?
Performance anxiety
293
First line agent for OCD, what can be used to augment Txm
| ?
SSRI’S
Antipsychotics ; Halodol and 2nd Gen’s
294
What antipsychotics are approved for PTSD Txm and what is first line
quetiapine, olanzapine, and risperidone
First line = SSRI’S
295
What MDD med is significant for seizures?
Bupropion
296
What BAC level achieved in 2 hours is significant for binge drinking
0.08g/dL
297
What is the most severe form of alcohol withdrawal? When does it occur?
Delirium Tremens
1-10 days after last drink
298
What is a good Benzo’s for alcohol withdrawal?
Diazepam
299
What two benzos are associated with propylene glycol poisoning?
Lorazepam and Diazepam
300
What is Wernicke’s Encephalopathy?
Presence of neurological symptoms, a triad of confusion, ataxia and ophthalmoplegia associated with ethanol withdraw due to chronic alcoholism
Depleted B-Vit Reserves = CNS lesions
301
First line TXM of Alcohol dependence
Naltrexone and Acamprosate
302
```
What can Disulfiram (Antabuse)
Topiramate (Topamax)
Gabapentin (Neurontin)
Baclofen (Lioresal)
SSRI’s
Be used to treat?
```
2nd line for alcohol dependence
303
Naltrexone MOA and main Clin Use
Mechanism of Action: Derivative of naloxone. Competitive antagonist at opioid receptor sites, showing the highest affinity for mu receptors.
Clinical Use:
Reduces alcohol dependence, cravings and consumption
304
Naltrexone can have what effect on opioids?
Blocks effects of opioids
Will precipitate opioid withdrawal
If a patient is on Depo dose, opioids will not be adequate for pain control
305
Acampasate is similar to what? And must be taken how often?
GABA
3 times a day
**reduce or stop if renal insufficient**
306
MOA of Disulfiram
Inhibits aldehyde dehydrogenase (ALDH), blocking the metabolism of ethanol at the acetaldehyde step.
307
What accumulates in a disulfiram reaction?
Acetalaldehyde
308
What two drugs may also help in alcohol abuse?
Baclofen and Gabapentin
309
What supplements (2) can help with ADHD Txm?
Iron , if deficient
| And Zinc
310
How do drugs increase learning potential and productivity of adhd pts? (3)
Decreasing motor activity
Increasing coordination
Improving ability to attend to task
311
Stimulants for ADHD use (4)
Amphetamines
Dextroamphetamine
Methylphenidate/ Dexmethylphenidate
Lisdexamfetamine
312
Non Stimulants for ADHD
```
Atomoxetine (Strattera)
Clonidine XR (Kapvay)
Guanfacine XR (Intuniv)
```
313
Class of amphetamines and derivatives
Class 2
314
MOA and Clin use of Amphetamines and derivatives
Mechanism of Action:
Promote release of catecholamines (primarily dopamine and norepinephrine) from their storage sites in the presynaptic nerve terminals
May have some effect on decreasing reuptake also
Clinical Uses:
Attention-deficit Hyperactivity Disorder (ADHD)
Narcolepsy
Obesity
315
How do amphetamines effect the sympathetic nervous system?
Alpha and Beta
Increased BP
Increase in heart rate
Weak bronchodilation
316
Addererall is mix of what?
Dextroamphetamine + Amphetamine
317
Lisdexamfetamine is converted to what?
Dextroamphetamine in the blood stream
318
What is preferred stimulants or non-stimulants?
Stimulants are preferred to non-stimulants;
have a rapid onset of action and long record of safety and efficacy
319
First line non stimulant drug for ADHD and MOA
Atomoxetine
Blocks repute of NE
320
MOA of clonidine , treats what two main dz’s?
Central a2 agonist
Impulsive behavior and Tourette’s
321
Guanfacine MOA and is indicated for what children?
Central a2 agonist
| Children with tic disorders
322
What drug class is efficient for ADHD with depression
TCA’s
Impramine
Desipramine
323
Clinical Use: improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy or shift work disorder (SWD)
Modafinil
324
What is a mehtylzanthine antagonist of adenosine receptors that increases cAMP and equally response to CO2
Caffeine
325
BMI’s for obesity
Overweight = BMI 25 to 29.9 kg/m2
Obesity = BMI ≥ 30 kg/m2
Severe obesity = BMI ≥ 40 kg/m2
326
When should yo discontinue use of weight loss mediations?
advise discontinuing medication if at least 5% weight loss is not achieved after 12 weeks of use
327
Orlistat can do what?
Reduce fat and absorption and digestion
328
Amphetamines can do what for obesity?
Suppress appetite
Increase thermogenesis
**Can lead to rebound binge eating**
329
SSRI’S can do what for obesity?
Suppress appetite
330
MOA of phentermine
promotes appetite suppression and decreased food intake secondary to its sympathomimetic activity
331
When should you take the combo of phentermine and Topiramate?
In the morning to avoid insomnia
332
Naltrexone and Bupropion can be used to do what?
Reduce cravings and appetite
333
How does orlistat inhibit lipase?
by inhibiting GI lipase activity in the small intestine
30% of fat excreted in feces
334
GLP -1 agonist for Type 2 Diabetic TXM
Liraglutide
335
How is gastric acid secretion regulated
Proton pup o activation at parietal cell
Acetylcholine
Histamine
Gastrin
336
What is a good start Txm after dietary and lifestyle mods;;;; and if that doesn’t work?
Start with H2 inhibitors in addition with antacids for breakthrough GERD symptoms
Make sure H2 is at max dose then after 4 weeks —> PPI
**more freq GERD starts with PPI**
337
Common causes of PUD (4)
H. Pylori
NSAID
Stress Ulcers or Stress- Related Mucosal Damage
Zollinger Ellison Syndrome
338
Gastric ulcer pain is worse when?
Duodenal ulcer pain is worse when?
G : When eating
D : At night, relieved by eating
339
Noninvasive Diagnostic tests for H. Pylori
Recall antigen assay
Urea breath testing
Serologic testing
340
Anti-secretory Txm for H. Pylori;;;;;; 1st and 2nd line therapies.
PPI
1st : Clarithromycin + Amoxicillin (or metronidazole)
2nd : tetracycline + metronidazole + bismuth subsalicylate
341
What happens after Txm for h.pylori?
Confirmation of Erradication:
Must be done on all patients treated
Urea-breath test (UBT) or stool antigen tests are preferred
Must be off PPI for 1-2 weeks prior to the test
Can wait to confirm until after completion of the PPI course
342
Two ways NSAIDs can induce mucosal injury
Direct irritation of gastric epithelium
Systemic inhibition of mucosal prostaglandin synthesis
343
Cyclooxygenase (COX):
rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins and is inhibited by NSAIDS
344
Role of COX-1
Produces PG that
Increase blood flow to gastric mucosa and kidneys
Increase platelet aggregation via thromboxane A2 pathway
345
Role of COX -2
Increase renal blood flow
| Makes PG that activate and sensitize nociceptors (increased pain)
346
What is a last line treatment for nsaid induced ulcers?
Celecoxib (Celebrex):
**Should be reserved as last line**
Associated with cardiovascular risk
Medical co-therapy with PPI (once daily) or misoprostol
347
Stress ulcer prophylaxis
Proton Pump Inhibitors (PPI)
| Histamine-2 Receptor Antagonists (H2RA)
348
MOA of Antacids and Clin indication
Mechanism of Action:
Weak bases that neutralize gastric acid
Reacts with hydrochloric acid to form a salt and water
Clinical Indication:
1st line therapy for intermittent symptoms (less than twice weekly)
Breakthrough therapy for those on PPI/H2RA therapy
349
ADE’s of antacids
Adverse Effects: constipation (aluminum & calcium), diarrhea (magnesium), accumulation of aluminum or magnesium in renal disease with repeated dosing
350
What drug class can cause Chelation (fluroquinolones, tetracyclines); avoid giving at the same time as other drugs due to interactions
Antacids
351
What effect do antacids have on pH and absorption? And what drugs are common for these?
Reduced ph:
ketoconazole, itraconazole, iron, atazanavir, delavirdine, indinavir, nelfinavir
Increased absorption:
raltegravir, saquinavir
352
Sodium bicarbonate does what with HCL?
Reacts with HCL to produce carbon dioxide and sodium chloride.
CO2 results in gastric distention and belching
Long term = METABOLIC ALKALOSIS
353
What caution do calcium carbonates have?
Caution:
excessive doses with other calcium-containing dairy products and renal insufficiency may cause
- Metabolic alkalosis
- Hypercalcemia
354
Magnesium hydroxide reacts with HCL and has what ADE’s?
osmotic diarrhea caused by unabsorbed magnesium saltsosmotic
355
Aluminum Hydroxide reacts with HCL and has what ADE’s (2)
Aluminum salts cause constipation
Aluminum is also absorbed and excreted in the kidneys (Renal insufficiency: should not take long-term)
356
What is commonly admin together to minimize impact on bowel fax
Aluminum and Magnesium
357
What is the action of Simethicone?
relieves flatulence with defoaming action (gas bubbles combine and are more easily freed)
358
What contains aligned acid and creates a foamy layer above the stomach contents (reduces reflux)?
Aluminum Hydroxide and Magnesium Trisilicate (Gaviscon tablets & liquid)
359
H2RA antagonist MOA
competitively block the binding of histamine to H2 receptors on the parietal cell, inhibiting gastric acid secretion induced by histamine
360
What are clinical uses of H2RA
Peptic ulcers, GERD, non-ulcer dyspepsia, Zollinger-Ellison syndrome, and prevention of bleeding from acute stress-related gastritis ulcers
**less effective than PPI’s at healing erosive esophagitis**
361
Prolonged cimetidine is associated with what?
Gynecomastia
362
Drug interactions common with H2RA
May affect the absorption of drugs dependent on lower gastric pH or increases in absorption leading to potential toxicity (raltegravir, saquinavir)
363
What drugs are dependent on lower gastric pH (6)
ketoconazole, itraconazole, iron, atazanavir, delavirdine, and nelfinavir
364
Which H2RA acts as an anti androgen and competes with creatinine for tubular secretion in the kidney?
Cimetidine
365
Low percentage of side effects nad good efficacy for duodenal ulcer GERD and gastric ulcers
Ranitidine
366
H2RA antagonists end in what?
-tidine
367
___ most effective for managing GERD and what are examples? (7)
PPI’s
-prazole
Rabeprazole (Aciphex)
Esomeprazole (Nexium)
Dexlansoprazole (Dexilant)
Pantoprazole (Protonix)
Omeprazole (Prilosec)
Omeprazole/Bicarbonate ion (Zegrid)
Lansoprazole (Prevacid)
368
MOA of PPI’s and administration guidelines
Irreversibly binds to the H+/K+ ATPase enzyme system (proton pump) of the cells suppressing secretion of hydrogen ions
30-60 mins before meals; longer duration than H2RA’s
369
4 common risks of PPI’s
Fx
Hypomagnesaemia
C diff
Community acquired pneumonia
370
PPI use is associated with a high risk of what?
CKD “chronic kidney disease”
371
What are FDA recommendations for Omeprazole and why
AVOID! CYP2C19 INHB
**use pantoprazole instead**
372
pH-dependent absorption PPI’s
Ketoconazole
Itraconazole
Protease inhibitors
373
Sucralfate is a mucousal protective agent that has what MOA
Covers the ulcer site and protects it against acid
Stimulates prostaglandin release
*NO ADVERSE AFFECTS*
**Multi dose daily** = limited use.
374
If you are concerned for nosocomial pneumonia what can you use for stress related bleeding
Sucralfate
375
Mechanism of Action:
Prostaglandin Analog
Synthetic, oral prostaglandin E1 analog that has both antisecretory and mucosal protective properties
Misoprostol
376
Clin use of Misoprostol most common ADE / preg cat
Prevent NSAID induced ulcers
LOTS of diarrhea
Preg Cat D
377
```
Bismuth Subsalicylate (Pepto-Bismol) and Bismuth Subcitrate Potassium (Pylera)*
Avail as combo product of what?
```
metronidazole and tetracycline for the treatment of H. pylori
378
Clinical Use:
Nonspecific treatment of dyspepsia and acute diarrhea
Prevention of traveler’s diarrhea
Used in quadruple drug regimens for H. pylori eradication
What med?
Bismuth Subsalicylate and BSPotassium
379
What are the ADE’s of Bismuth Subsalicylate (Pepto-Bismol) and Bismuth Subcitrate Potassium (Pylera) (2)
Harmless blackening of stool (may be confused with GI bleed)
Harmless darkening of tongue (liquid formulations)
*can lead to salicylate toxicity*
380
What metabolic disturbances occur at the chemoreceptor trigger zone, and medications are used?
Serotonin (5-HT3), dopamine (D2) receptors, histamine (H1) and muscarinic (M1) and substance P/neurokinin 1; and opioid receptors
Metabolic Disturbances: uremia, diabetic ketoacidosis, hypercalcemia, hypoxemia
Medications: opiate, dopamine agonists, digoxin, chemotherapeutic agents, macrolides, general anesthetics
381
Vomiting center is stimulated by what 4 different sources of affront input?
1) Solitary Tract Nucleus: (Visceral Stimuli: dopamine and serotonin (5-HT3) receptors located in afferent vagal and splanchnic fibers
2) Gastric irritants
3) Non-gastric stimuli (biliary or GI distention, mucosal or peritoneal irritation and infection)
4) Chemotherapeutic agents
382
Vomiting undigested food one to several hours after ingestion suggests
Gastroparesis
| Gastric outlet obstruction
383
Vomiting immediately after meals suggests
Bulimia
| Psychogenic causes
384
Morning vomit suggests
Pregnancy
Uremia
Alcohol Intake
Increased Intracranial Pressure
385
General nausea & vomiting
Phenothiazines and serotonin antagonists
386
Chemotherapy induced anti - emetics
Serotonin antagonists, phenothiazines, NK1 antagonist, dronabinol
387
Postoperative anti-emetics
Serotonin antagonist scopolamine
388
Motion sickness Anti-emetics
Antihistamine and scopolamine
389
Anti emetics for pregnancy
Phosphorylation carb, pyridoxine, antihistamines
390
Anti emetics for gastroparesis
Metoclopramide
391
5HT3 antagonist MOA
Mechanism of Action: block presynaptic serotonin receptors on sensory vagal fibers in gut wall as well as central blockade in the vomiting center and CTZ
392
ADE’s of 5HT3
Adverse Effects:
Well tolerated; most common is headache, dizziness, and constipation
QTc prolongation; small but statistically significant prolongation of QT interval (most pronounced with dolasetron)
393
5HT3 antagonists and ends in what?
-setron
Ondansetron (Zofran) IV/PO
Orally disintegrating tablet available.
Ondansetron has become a popular antiemetic associated with pediatric gastroenteritis as well as general adult nauseous and general post-op surgery nausea and vomiting
Granisetron (Kytril) IV/PO
Dolasetron (Anzemet) IV/PO
Palonosetron (Aloxi) IV/PO
394
1st gen Antihistamines
```
Meclizine (Antivert,Bonine)
Diphenhydramine (Benadryl)
Dimenhydrinate (Dramamine)
Doxylamine (Unisom)
Doxylamine/pyridoxine (Diclegis)
Pyridoxine = vitamin B6
Approved for women who do not respond to conservative management
```
Preg Cat A
395
MOA and Clin u se of Prochlorperzine (Typical Antipsychotic)
and Promethazine (1st Gen Antihistamine)
Phenothiazines
Mechanism of Action:
Block dopamine, muscarinic, and histamine receptors in Chemoreceptor Trigger Zone (CTZ)
Sedation is due to their anti-histamine activity
Clinical Use: effective oral, injectable, and rectal anti-emetics for inpatient and outpatient use
396
MOA and Clin use of Scopolamine
Mechanism of Action: cholinergic antagonist with greater central (more lipophilic; blocks muscarinic receptors in the vestibular system) than peripheral effects
Clinical Indication: motion sickness; surgical adjunct (blocks short-term memory and decreases saliva)
397
Droperidol MOA and Clin use
Mechanism of Action: blocks dopamine receptors in chemoreceptor trigger zone (CTZ) of the CNS
Clinical Use:
Butyrophenone antipsychotic, no longer used as antipsychotic
Indicated for Postoperative Nausea/Vomiting (PONV)
Most often used for sedation in endoscopy and surgery, in combination with opioids or benzodiazepines
398
Acid reducer : METOCLOPRAMIDE MOA
Dopamine and Serotonin antagonist ; enhances response to Acetylcholine
399
ADE’s of Acid Reducers
CNS are most common and it usually causes drowsiness but may also cause restlessness
Extrapyramidal effects (dystonias, akathisia, parkinsonian features)
400
Mechanism of Action:
Block emetic impulses in the chemoreceptor trigger zone (CTZ)
Does not cause extrapyramidal symptoms like metoclopramide
Clinical Use:
Used for apomorphine pre-treatment in Parkinson’s patients
Trimethobenzamide(Tiguan)
401
How can corticosteroid treat nausea and vomiting (DM)
Use in Chemotherapy Induced Nausea and Vomiting (CINV) with 5HT3 Antagonists
Corticosteroids improve the response rates of serotonin-receptor antagonists (5-HT3) by 15-30% when combined
Products:
Dexamethasone (IV/PO)
Methylprednisolone (IV)
402
Clinical Use: used before the initiation of chemotherapy to reduce anticipatory nausea and vomiting caused by anxiety
Products:
Lorazepam (Ativan)
Diazepam (Valium)
BZD’s
403
Mechanism of Action:
Synthetic cannabinoid
Targets central endogenous cannabinoid receptors
Clinical Use:
Nausea associated with chemotherapy (not responding to conventional therapy)
Anorexia associated with weight loss in AIDS patients
Drug Interactions:
May potentiate the clinical effects of other psychoactive agents
Dronabinol
404
NAbilone C-2 MOA and Clin use
Mechanism of Action:
Synthetic cannabinoid
Targets central endogenous cannabinoid receptors
Clinical Use:
Nausea associated with chemotherapy that is refractory to other anti-emetics
405
NK1 Agents (3)
-pitant
Aprepitant
Fosaprepitant
Netupitant/Palosetron
406
Secretory Diarrhea
Large watery volume with HIGH electrolytes
407
Altered Motility
Autonomic nerve dysfunction
408
Osmotic diarrhea
Hypersmolar gradients in intestinal lumen
409
Inflammatory diarrhea
Infiltration/invasion of intestinal mucosa
410
Mild Mod Severe Diarrhea and TXM
Mild Diarrhea: ≤ 3 unformed stools/day, minimal symptoms
Moderate Diarrhea: ≥ 4 unformed stools/day and/or systemic symptoms
Severe Diarrhea: ≥ 6 unformed stools/day and or temp > 101F, blood, or fecal leukocytes
Treatment:
Mild Diarrhea: rehydration fluids + lactose free diet, avoid caffeine
Moderate Diarrhea: anti-motility agents and rehydration fluids
411
ABX therapy for travelers diarrhea
Fluoroquinolones
Azithromycin
Rifaximin (Xifaxan) only works in the colon
Rifamixin treats IBS-diarrhea dominant
412
C diff Txm
C. difficile
| Treatment: metronidazole or oral vancomycin
413
Opioid antidiarrheal action
Activates presynaptic opioid receptors (mu receptors) in the enteric nervous system
Inhibit presynaptic cholinergic nerves in the submucosal and mesenteric plexuses
Lead to increase colonic transit time and fecal water absorption
Decreases mass colonic movement and the gastrocolic reflex
414
LOPeramide MOA, does it cross BBB?
Mu opioid agonist; activates opioid receptors in the enteric system, leading to inhibition of acetylcholine release and decreased peristalsis
Does not cross the BBB
**No analgesic properties**
415
Loperamide (Imodium) controls what?
Mild to mod symptoms of non invasive diarrhea
416
Osmotic laxative MOA
Rapid movement of water into the distal small bowel and colon, leads to high volume of liquid stool
Increase volumes leads to bowel distension and reflex urge to defecate
Followed by rapid relief of constipation
**intermittent constipation relief**
417
Osmotic Laxatives (4)
```
Magnesium Sulfate (EpSOM salt)
Magnesium Citrate
Non-absorbable salt
Magnesium Hydroxide (Milk of Magnesia; MOM)
Non-absorbable salt
Sodium Phosphate (Fleets)
```
418
Which osmotic laxative has a caution with existing electrolyte abnormalities
Sodium phosphate (Fleets)
419
Lactulose and Sorbitol are what?
Non-absorbable semisynthetic disaccharide sugars
That,
metabolize by colonic bacteria, producing increased osmotic pressure causing fluid accumulation, severe flatus, cramps, and defecation
420
What lax has severe flatulence an cramps
LActulose and 70% sorbitol
421
Pre op prep for endoscopic or radiologic procedures
Polyethylene Glycol (PEG) solutions (GoLyte, GoLYTELY)
**safe in renal and hepatic dz and pregnancy**
422
What lax is approved for IBS constipation dominant?
PEG 3350 powder (Miralax)
**safe hepatic/preg/renal**
423
Lubricating Agents
Glycerin Suppository - think peds
Mineral Oil
424
Bulk Forming Laxative that absorb and retain water in stool
Natural
- Psyllium(Metamucil)
- Wheat Dextrin(benefiber)
Synthetic
Calcium polycarbophil
Methyl cellulose
Bran powder
425
What do Bulk forming laxatives promote and require?
Peristalsis and requires adequate water intake
