Pharmacology PRITE Review (JB PPT) Part 2 Flashcards
1
Q
Compare FGA and SGA.
A
FGA: more selective (dopamine blockade in all 4 dopamine pathways)
SGA: less selective (both dopamine and serotonergic activity)
FGA: acts mostly on positive symptoms via D2 antagonism
SGA: acts on both positive and negative symptoms via D2 and 5HT2A antagonism
FGA: side effects - motor symptoms (EPS/TD)
SGA: metabolic effects (DMII/HLD)
2
Q
MOA - aripiprazole
A
Partial agonist at D2 and 5HT-1A
Antagonist at 5HT-2A receptor
3
Q
MOA - cariprazine
A
Partial agonist at D2, 5HT1A
Antagonist at 5HT2A
4
Q
What is the only antipsychotic primarily processed by the kidneys?
A
Paliperidone (good choice if compromised liver function)
5
Q
List the fast-inactivated state sodium channel blockers.
A
Phenytoin
Carbamazepine, oxcarbazepine, eslicarbazepine
Lamotrigine
6
Q
List the slow-inactivated state sodium channel blockers.
A
Lacosamide
7
Q
List the low voltage activated calcium channel blockers.
A
Ethosuxmide
8
Q
List the high voltage activated calcium channel blockers.
A
Gabapentin
Pregabalin
9
Q
MOA - vigabatrin
A
Inhibits GABA-transaminase
10
Q
MOA - tiagabine
A
Blocks synaptic GABA reuptake
11
Q
MOA - levetiracetam
A
Synaptic vesicle protein 2A modulation
12
Q
MOA - acetazolamide
A
Carbonic anhydrase ihibtion
13
Q
Multiple MOA - valproate
A
GABA potentiation
Glutamate (NMDA) inhibition
Na+ channel blockade
T-type calcium channel blockade
14
Q
Multiple MOA - topiramate
A
GABA potentiation
Glutamate (AMPA) inhibition
Sodium and calcium channel blockade
15
Q
Suspected MOA of lithium (remains unclear)?
A
Inhibition of inositol phosphate metabolism
16
Q
Key medications that are exclusively renally excreted?
A
Lithium
Acamprosate
Gabapentin
17
Q
Discuss amoxapine and loxapine.
A
Loxapine is an antipsychotic with antidepressant properties (metabolized to amoxapine)
Amoxapine is an antideressant with antipsychotic properties (can cause EPS/TD, avoid in Parkinson’s)
18
Q
Which cholinesterase inhibitor is NOT metabolized by liver CYP?
A
Rivastigmine
19
Q
MOA - rivastigmine
A
Dual enzyme inhibition - AChE + BuChE
20
Q
MOA - galantamine
A
AChE + modulates nicotinic acetylcholine receptors
21
Q
Which cholinesterase inhibitor has a competitive MOA?
A
Galantamine
22
Q
Less than 3% of levodopa would make it to the brain if it wasn’t combined with ___. How does this work?
A
Carbidopa; slows/decreases the peripheral conversion of L-Dopa to dopamine
23
Q
MOA - carbidopa
A
Inhibits DOPA decarboxylase
24
Q
MOA - Catechol-O-methyltransferase (COMT) inhibitors
A
Prevents both peripheral and central degradation of L-dopa
25
MOA - clonidine and guanfacine
Pre-synaptic alpha-2-receptor agonist
26
MOA - buprenorphine
Partial agonist at mu
Antagonist at delta
Antagonist at kappa
27
MOA - amphetamine
Increases dopamine release
| Inhibits dopamine reuptake
28
MOA - triptans
Agonist at 5-HT1B and 5-HT1D - promotes vasoconstriction, blocks pain transmission
29
Notable CYP-4500 inducers (psych meds)
```
Carbamazepine
Rifampin
Phenytoin
Primidone
Phenobarbital
St. John's wort
```
30
Notable CYP-4500 inhibitors (psych meds)
```
Fluoxetine
Fluvoxamine
Sertraline
Other SSRIs
Isoniazid
Cimetidine
Grapefruit
Erythromycin
ETOH
```
31
Fluoxetine is an important ___ inhibitor.
2D6 (can increase toxicity)
32
African Americans have higher activity of CYP ___.
3A4
33
Higher risk of SJS in Asians is due to ___.
HLA B*1502 allele
34
Grapefruit is an important CYP ___ inhibitor.
3A4
35
Drug-drug interaction - depakote + lamotrigine
Depakote inhibits glucuronidation of lamotrigine -> risk of lamotrigine toxicity
36
Drug-drug interaction - carbamazepine + clozapine
Increased risk of marrow suppression
37
Drug-drug interaction - erythromycin + carbamazepine
Increased risk of side effects such as heart block
38
Which 5 antipsychotics are affected by smoking and why?
Haldol, chlorpromazine, clozapine, olanzapine, thioridazine; levels are decreased via CYP 1A2 induction
39
Typical impact of Depakote on other drugs? Exception?
Increases levels
Exception: increases epoxide metabolite of carbamazepine but overall there is a net decrease in carbamazepine
40
Typical impact of carbamazepine? Exception?
Decreases nearly everything; exception - it increases other inducers
41
List some non-SSRI/SNRIs that can increase the risk of serotonin syndrome when coadministered with MAOIs.
```
Ziprasidone
Dextromethorphan, chlorpheniramine
Fentanyl, meperidine, tramadol
Linezolid
MDMA, LSD
Methylene blue
```
42
List 4 cardiovascular agents that can cause depression.
1. Clonidine (reduces NE output via alpha-adrenergic receptor agonism)
2. Guanethidine (depletes neuronal NE)
3. Methyldopa (partial agonism of NE)
4. Reserpine (depletes neuronal NE, 5HT, dopamine)
43
Proposed mechanism of depression caused by isotretinoin?
Alters dopaminergic, serotonin, possible NE systems
44
List 3 anticonvulsants that can cause depression.
1. Phenobarbital (reduces unbound tryptophan -> influences plasma 5HT conentrations)
2. Topiramate (increases amount of GABA available)
3. Vigabatrin (ditto)
45
List 3 hormonal agents that can cause depression.
1. Corticosteroids (elevates cortisol)
2. GnRH agonists (reduces estrogen and androgen production)
3. Tamoxifen (reduces estrogen function via antagonizing estrogen receptors)
46
MOA of depression caused by interfron?
Increases IL-6 production
47
Typical side effects caused by MOA - 5HT3 agonism
Nausea
48
Typical side effects caused by MOA - 5HT reuptake inhibition
GI disturbances
| Activating effects
49
Typical side effects caused by MOA - 5HT2 agonism
Sexual dysfunction
| Activing effects
50
Typical side effects caused by MOA - DA reuptake inhibition
Psychomotor activation
| Psychosis
51
Typical side effects caused by MOA - H1 antagonism
Sedation/drowsiness
| Weight gain
52
Typical side effects caused by MOA - AcH antagonism
```
Blurred vision
Dry mouth
Constipation
Sinus tachycardia
Urinary retention
Memory dysfunction
```
53
Typical side effects caused by MOA - alpha1 antagonism
Priapism
54
Typical side effects caused by MOA - Alpha2 antagonism
Postural hypotension
Dizziness
Reflex tachycardia
55
Typical side effects caused by MOA - NE reuptake inhibition
```
Dry mouth
Urinary retention
Activating effects
Tremor
CV troubles
```
56
Which SSRI can have anticholinergic effects?
Paroxetine
57
Antidepressants - high risk for orthostatic hypotension?
TCAs, trazodone, MAOIs
58
Antidepressants - lower risk for orthostatic hypotension?
SSRIs, mirtazapine
59
Antidepressants - "no" risk for orthostatic hypotension?
Bupropion
60
Which antidepressant can increase LFTs and should be avoided in patients with liver disease and alcohol use disorder?
Duloxetine
61
___ ?may cause amenorrhea, galactorrhea, and hyperprolactinemia.
Fluoxetine
62
Notable side effects of lithium?
Weight gain (severe), lethargy (mild), ataxia (none or mild), nausea (moderate), tremor (severe); polyuria, nephrogenic DI, fatigue, reversible hypothyroidism, cognitive deficits, acne, headache, worsens psoriasis, benign leukocytosis, hyperparathyroidism (can lead to hypercalcemia)
63
Notable side effects of lamotrigine?
Weight gain (mild), lethargy (moderate), ataxia (moderate), nausea (moderate), tremor (none or mild); dizziness, headache, insomnia, severe skin reactions
64
Notable side effects of valproic acid?
Weight gain, lethargy, ataxia, nausea [all moderate], tremor (severe); headache ovarian cysts, rare hepatotoxicity, hyperammonemia, rare pancreatitis, alopecia, rare blood cell dyscrasias, teratogenicity
65
Side effects of carbamazepine?
Rare blood cell dyscrasis (aplastic anemia, agranulocytosis, thrombocytopenia), hepatoxocitiy, rash (including SJS), SIADH, heart block, ataxia, hyponatremia, teratogenicity risk, hepatitis
66
Monitoring needs - lithium
```
TSH
RFP
Electrolytes
Pregnancy test
[EKG for patients over 40]
```
67
Monitoring needs - valproic acid
LFTs
CBC (Plts)
Pregnancy test
68
Monitoring needs - carbamazepine
LFTs
CBC
Electrolytes
Pregnancy test
69
Monitoring needs - lamotrigine
Pregnancy test
70
Management of lithium-associated polyuria?
Increase PO intake of salt-containing fluids
Lower dose
Once nightly dosing
Careful use of ameloride and potassium monitoring/supplementation
71
Management of lithium-associated tremor?
Avoid caffeine
Assess use of catecholamines and antipsychotics
Treat worsening anxiety
Consider use of propranolol or primidone
72
Management of lithium-associated diarrhea?
```
Avoid slow-release preparation
Lower dose
Monitor levels (diarrhea may result in toxicity)
Consider switching to lithium citrate
```
73
Management of lithium-associated thyroid abnormalities?
Monitor TSH, fT3, thyrotropin Q6 months
| Thyroid supplementation for subclinical hypothyroidism
74
Management of lithium-associated renal dysfunction?
Monitor serum Cr and BUN Q6 months
24-hour urine Cr Cl if there is a rise in serum Cr >1.5
Consider alternative treatment and nephrologist consultation
75
Which drugs can decrease renal clearance of lithium and increase the risk of toxicity?
NSAIDs and diuretics
76
Mechanism of lithium-induced nephrogenic DI?
Lithium competes with ADH -> increased urination -> volume depletion -> hyperNa
77
Treat lithium-induced nephrogenic DI?
Amiloride (best) or thiazides
78
Side effects of phenytoin?
Hirsutism
Fetal dysmorphism
Gingival hypertrophy
Cerebellar atrophy (long-term)
79
Signs of phenytoin toxicity?
Unsteady gait
Slurred speech
Nystagmus
80
True or false - VPA-induced hyperammonemia has been reported with acute and chronic use and can occur with therapeutic levels and in the absence of hepatotoxicity.
True
81
Acute dose-related adverse effects of valproic acid?
Tremor
82
Acute dose-related adverse effects of topiramate and zonidsamide?
Paresthesia
83
Acute dose-related adverse effects of carbamazepine and lamotrigine?
Diplopia, blurred vision, visual distortion
84
Acute dose-related adverse effects of topiramate?
Mental/motor slowing
85
Acute dose-related adverse effects of levetiracetam, ezogabine, perampanel?
Mood or behavioral changes
86
Acute dose-related adverse effects of carbamazepine, phenytoin, phenobarbital?
Changes in libido/sexual function
87
List long-term adverse effects of AEDs.
- Osteomalacia/osteoporosis: carbamazepine/oxcarbazepine, barbiturates, phenytoin, valproate
- Altered connective tissue metabolism or growth (facial coarsening, hirsutism, gingival hyperplasia/contractures): phenytoin, phenobarbital
- Neuropathy: phenytoin, carbamazepine
- Cerebellar degeneration: phenytoin
- Sexual dysfunction: phenytoin, carbamazepine, phenobarbital, primidone
88
List teratogenic AEDs from lowest to highest risk.
Lowest: lamotrigine, levetiracetam
- Carbamazepine, oxcarbazepine
- Phenytoin, phenobarbital, topiramate
Highest: valproic acid
89
List the 4 dopaminergic pathways.
1. Mesolimbic (excess dopamine -> positive symptoms)
2. Mesocortical (decreased dopamine -> negative symptoms)
3. Nigrostriatal (dopamine antagonism > EPS/TD)
4. Tuberoinfundibular (dopamine antagonism > hyperprolactinemia)
90
Effect of D2-receptor antagonism?
+ symptom alleviation, EPS, endocrine effects
91
Effect of 5-HT2A antagonism?
Negative symptom alleviation, less EPS
92
Effect of high 5-HT2A/D2 binding affinity ratio?
Better antipsychotic activity and lower EPS than D2 antagonism alone
93
Effect of 5-HT1A agonism?
Antidepressant and anxiolytic activity, improved cognition, reduced EPS, body weight changes
94
Effect of 5-HT1D antagonism?
Antidepressant activity
95
Effect of 5-HT2C antagonism?
+ symptom alleviation, weight gain (via satiety blockade)
96
Effect of alpha-1 adrenoceptor antagonism?
Sedation, hypotension, weight gain
97
Effect of H2-histamine antagonism?
Sedation, weight gain
98
Effect of M1-muscarinic antagonism
Memory impairment, GI symptoms, dry mouth, blurry vision, less EPS
99
Effect of mixed 5-HT/NE reuptake inhibition?
Antidepressant and anxiolytic activity, less weight gain
100
Hypothesis to explain why typical antipsychotics cause more EPS than atypical?
More rapid dissociation from D2 receptors
101
List the 3 most cholinergic and sedating antipsychotics.
Thioridazine
Chlorpromazine
Clozapine
102
Antipsychotic with the highest EPS risk? Lowest EPS risk?
Haldol; clozapine
103
Antipsychotics can cause poikilothermia - define this.
Inability to maintain constant body temperature
104
Which antipsychotic can cause cataracts?
Quetiapin
105
Which antipsychotics can cause retinal pigmentation?
Thioridazine; chlorpromazine
106
Adding ___ to clozapine may increase the risk of developing NMS, seizures, and delirium.
Lithium
107
When does clozapine-induced myocarditis typically occur?
Within the first month of use
108
MOA of clozapine-induced myocarditis?
Acute IgE mediated hypersensitivity reaction
109
True or false - agranulocytosis is not dose dependent with clozapine
True
110
WBC and ANC levels needed to start clozapine?
WBC>3500 (if 3000-3500, need 2x weekly monitoring)
ANC>1500 (or >1000 benign ethnic neutropenia)
111
Frequency of clozapine monitoring
First 6 months: weekly
6-12 months: Q2 week
12+ months: monthly
112
How long do you need to continue weekly labs after stopping clozapine due to side effects?
1 month after achieving normal labs
113
Why is clozapine thought to have lower than most risk of EPS/TD and hyperprolactinemia?
Weakest affinity for D2
114
Response to mild neutropenia (1000-1499)?
BEN: no additional monitoring needed
General: monitor ANC 3x weekly until 1500+; return to last monitoring interval
115
Response to moderate neutropenia (500-999)?
BEN: monitor ANC 3x weekly until 1000+ or patient's baseline; then monitor weekly for 4 weeks; then return to last monitoring interval
General: interrupt clozapine; monitor ANC daily until 1000+, restart clozapine; then monitor 3x weekly until 1500+; then monitor weekly for 4 weeks; then return to last interval
116
Response to severe neutropenia (<500)?
BEN: discontinue; daily ANC until 500+; 3x weekly until ANC is more than or equal to the patient's established baseline
General: as above; [until ANC 1500+]
117
Avoid concurrent use of clozapine and ___ due to agranulocytosis risk.
Carbamazepine
118
What is metabolic syndrome?
3+ of the following:
```
Blood glucose 100+ (or on hypoglycemic)
HDL <40 (M) or <50 (F)
Triglycerides: 150+ (or on statins)
Weight circumference >40" (M) or >35" (F)
BP 130/85+ (or on antihypertensive)
```
119
Frequency of A1C and lipid monitoring with atypical antipsychotics?
Baseline
3 months
Annually
120
Rx akathisia?
1st line - propranolol (20 mg PO TID)
| 2nd line - benzodiazepine
121
Rx dystonic reaction?
Anticholinergic (benztropine 1-2 mg PO BID or 2 mg IM, diphenhydramine 25-50 mg PO TID or 25 mg IM)
122
Rx drug-induced parkinsonism?
1st line - anticholinergic
| 2nd line - dopaminergic agent (eg, amantadine 100 mg PO BID)
123
Rx TD?
VMAT-2 inhibitor
124
Key differentiating features of serotonin syndrome vs. NMS?
```
SS:
Reflex - hyperreflexia, clonus
Pupils - mydriasis
Bowel sounds - hyperactive
[Increased tone, particularly in lower extremities]
```
```
NMS:
Reflex - hypreflexia
Pupils - normal
Bowel sounds - normal to decreased
[Lead pipe rigidity in all muscle groups]
```
125
Medication to treatment serotonin syndrome?
Cyproheptadine (serotonoin antagonist)
126
Medication to treat NMS?
Bromocriptine (dopamine agonist)
127
Which antidepressants can cause hyponatremia? MOA?
```
Sertraline
Fluoxetine
Paroxetine
Citalopram
Venlafaxine
```
Increased secretion of ADH in hypothalamus
Potentiates the effect of ADH in the kidneys
Lowers threshold for release of ADH
128
Which anticonvulsants can cause hyponatremia? MOA?
Carbamazepine, oxcarbazepine
Increased secretion of ADH by hypothalamus
129
MOA of antipsychotics causing SIADH?
Serotonin effects on 5-HT2 and 5-HT1C lead to increased ADH
Psychogenic polydipsia leads to excessive consumption of water resulting in hyponatremia
130
Symptoms of water intoxication?
```
Polyuria
Restlessness, tremor
Diarrhea, vomiting
Ataxia
Stupor
```
