Test 1 - modules 1 and 2 Flashcards

1
Q

what is another term for peak concentration

A

Cmax

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2
Q

What is another term for trough

A

Cmin

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3
Q

Maintenance dose formula

A

dose needed to maintain a steady state concentration

MD = Css x CL
MD = Css x Vd x Kel
vd = volume of distribution
Css = steady state concentration
kel = elimination rate constant
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4
Q

What would be the equation for the steady state concentration if I administered a particular dose at this dosing interval

A

Css = 1.5(t1/2) x dose
All divided by
Vd x dose interval

volume of distribution
Css = steady state concentration

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5
Q

loading dose equation

A

Ld= Co x Vd

Co = desired plasma concentration of drug 
Vd = volume of distribution
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6
Q

is the EC50 =/not= to the ED50?

A

same thing -

Effective concentration where 50% of max effect
Effective dose where 50% of the max effect

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7
Q

what is the difference between first-order kinetics and zero-order kinetics

A

in first order - constant fraction of drug is eliminated
This is where you have half-life calculated

in zero order kinetics. There is a constant amount of drug is eliminated. It does not matter how much you give (independent of concentration of drug)

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8
Q

in first order kinetics on a non-log scale, what kind of line?

A

curved

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9
Q

in first order kinetics on a log scale, what kind of line?

A

straight

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10
Q

Is ASA a first order kinetic drug or a zero order kinetic drug

A

zero order

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11
Q

Is Dilantin a first order kinetic drug or a zero order kinetic drug

A

zero order

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12
Q

on a non-log scale, what kind of line for zero order kinetic drug

A

straight

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13
Q

on a log scale, what kind of line for zero order kinetic drug

A

straight

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14
Q

in first order kinetic drugs the rate of drug elimination per hour is _______ on drug concentration.

A

dependent

The more drug in the body, the more eliminated per hour

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15
Q

in zero order kinetic drugs, the rate of drug elimination per hour is ______ of drug concentration.

A

independent

the same amount is eliminated per hour regardless of how much drug is in the body

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16
Q

in zero order kinetic drugs Cp decreases ______ with time

A

linearly

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17
Q

In first order kinetic drugs Cp decreases ______ with time

A

exponentially

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18
Q

gentamycin

zero order or first order

A

first order

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19
Q

Vancomycin

zero order or first order

A

first order

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20
Q

Ethanol

zero order or first order

A

zero order

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21
Q

phenytoin

zero order or first order

A

zero order

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22
Q

what is pharmacodynamics

A

once the drug has arrived to its site of action what is the effect on the body

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23
Q

formula for therapeutic index

A

IT = LD50/ED50

LD50 = lethal dose in 50 percent

ED - effective dose in 50%

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24
Q

the higher the Therapeutic index, the _____ the drug

A

safer

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25
Q

2 drugs have the same active ingredients and are identical in strength or concentration, dosage form, route of administration and F (fraction making it - how much of the drug actually makes it to the body)

they have ______

A

Bioequivalence

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26
Q

Fraction of the drug that makes it to the body

A

bioavailability (F)

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27
Q

Dosage formulation influences rate of _____

A

dissolution

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28
Q

where are drugs metbolized

A

liver
intestines
kidneys

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29
Q

What is the purpose of drug metabolism

A

to make active (or) inactive metabolites

and to make drug molecules more water soluble for easier elimination

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30
Q

what class of meds are known to significantly inhibit the metabolism of simvastatin because of inhibition of CYP3A4

A

Protease inhibitors

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31
Q

what meds will increase the levels of Warfarin via (S-warfarin due to CYP2C9)?

A

Amiodarone
Metronidazole
TMP/SMX
Fluconazole

increases risk of bleeding

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32
Q

Phenytoin brand names

A

Dilantin

Phenytek

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33
Q

Phenytoin are used for what type of seizures

A

primary generalized and partial seizures

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34
Q

what type of seizures does Phenytoin known to worsen

A

Absence

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35
Q

Dosage forms of Phenytoin

A

PO or IV (NO IM)

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36
Q

side effects for Phenytoin

A

Increase drugs associated with CYP3A4

Sedation and CNS depression

gingival hyperplasia (also Calcium channel blockers and Cyclosporine)

Hirsutism

coarsening of facial features

hyperglycemia

Hematologic effects

osteoporosis - due to reduction in Vit D

Rash (including DRESS) - drug reaction when eosinophils are high

Megaloblastic anemia - due to reduction in folate (macrocytosis)

Teratogenicity

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37
Q

labs to monitor for Phenytoin

A
albumin
uremia (BUN)
TSH
Total Phenytoin level
Free Phenytoin level
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38
Q

How does Phenytoin work

A

blocks Na+ channels associated with depolarization, repolarization and membrane stability.

so if you have rapid firing this is to help stop the seizure

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39
Q

cardiac problems in TCA overdose or when you combine TCA with phenytoin

A

widen QRS
ventricular tachydysrhythmias
cause seizures

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40
Q

if someone has overdosed on TCA, now seizing….what should you avoid

(any tox case with seizures…NEVER give…)

A

Phenytoin -

blocks NA channels
worsen the seizures and cardiac conduction

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41
Q

what is the prodrug of phenytoin

A

Fosphenytoin (Cerebyx)

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42
Q

Prodrug of phenytoin is different from phenytoin and can be given by what route

A

This can be given IM

does not contain propylene glycol

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43
Q

Caution for phenytoin and kinetics

A

phenytoin will go from first order kinetics to a zero order kinetics at higher doses. overall phenytoin is considered to follow non-linear kinetics

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44
Q

what is the max rate for phenytoin on the IV load and why?

A

15-20mg/kg rate at no more than 50mg/min due to the presence of propylene glycol causes hypotension and cardiac arrhythmias

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45
Q

Phenytoin dose adjustments are based on ____

A

levels

Cp < 7mg/L - increase dose by 100mg/d

Cp 7-12 mg/L: increase by 50mg/d

Cp >12 mg/L increase by 30mg/d or less

0.74 mg/kg will increase level by 1 ug/ml assuming you haven’t reached the saturation point

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46
Q

Free fraction is what is pharmacologically ____

A

active

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47
Q

when you give fosphenytoin IM when can you check a phenytoin level?

IV?

A

4 hours

2 hours

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48
Q

Phenytoin toxic effects

levels and effect

A

Total >20mg/L = nystagmus

> 30mg/L = ataxia, increased seizures

> 40mg/L = Lethargy, altered consciousness and coma

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49
Q

drug of choice for trigeminal neuralgia

A

Carbamazepine

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50
Q

what type of seizures will Carbamazepine treat?

A

Partial and secondarily generalized tonic-clonic seizures

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51
Q

what type of seizures will Carbamazepine make worse

A

absence or myoclonic

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52
Q

what type of mental health disorder will Carbamazepine also treat

A

Mood stabilizer for bipolar disorder (esp mixed or rapid cycling)

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53
Q

other names for Carbamazepine

A

Tegretol, Tegretol XR

Carbatrol

Epitol

Equetro

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54
Q

Mechanism of Action Carbamazepine

A

Blocks Na channels

partial agonist at the adenosine A2A and A2B receptors

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55
Q

Therapeutic range for Carbamazepine

A

4-12 mg/L

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56
Q

Phenytoin (Dilantin) level reference range (total)

A

10-20mg/L

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57
Q

Can pregnant women take Carbamazepine

A

no

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58
Q

what genetic problem Carbamazepine

A

HLA-B 1502 allele - > severe rash (Stevens-Johnson Syndrome or Toxic epidermal necrolysis (TEN) - they need to be sent to the burn ICU - seen mainly in patients of Asian descent (Specifically Han Chinese)

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59
Q

Side effects of Carbamazepine

A

Leukopenia - caution in pt with Bone marrow suppression

Aplastic anemia and agranulocytosis (BBW)

Hyponatremia - stimulates release of ADH (SIADH)

Drowsiness

Fatigue

Nystagmus

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60
Q

Oxcarbazepine is also called

A

Oxtellar XR

Trileptal

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61
Q

what drug interaction is important to note for oxcarbazepine

A

contains ethanol

cannot take with flagyl or antibuse

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62
Q

what drugs mentioned cannot be taken with flagyl or antibuse

A

Oxcarbazepine (antiepileptic)

ritonavir (HIV)

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63
Q

what is the indication for Oxcarbazepine?

A

Initial and/or adjunct therapy for partial seizures

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64
Q

MOA Oxcarbazepine

A

Structurally similar to carbamazepine

NOT a metabolite

Inhibit voltage sensitive Na+ channels and modulates activity of voltage activated calcium channels

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65
Q

pharmacokinetic difference between Oxcarbazepine and Carbamazepine

A

Oxcarbazepine is not metabolized by CYP450

but it does still induce CYP3A4

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66
Q

Oxcarbazepine and food

A

IR can be taken without regard to food

XR should be taken on an empty stomach (1 hr before or 2 hrs after food)

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67
Q

Pregnancy risk
Lactation risk
Oxcarbazepine

A

C

L3

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68
Q

Oxcarbazepine side effects

A
Headache
dizziness
nystagmus
blurred vision
n/v
rash
hyponatremia

overall lower risk

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69
Q

Eslicarbazepine indications

A

partial -onset seizures adjunct therapy

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70
Q

MOA Eslicarbazepine

A

thought to be sodium channel blocker but unknown

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71
Q

Eslicarbazepine pharmacokinetic

A

Induces CYP3A4

Inhibits CYP2C19 - problem if on plavix

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72
Q

Valproic Acid indications

A

Complex partial (mono or adjunct therapy)

Status epilepticus

Absence Seizures (alternative option for, not first line)

Bipolar Disorder

Migraine prophylaxis

Migraine abortive therapy

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73
Q

Valproic Acid Brand

A

Depakene and Stavzor - Caps/syrup

Depakote (enteric coated) - preferred due to the GI side effects

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74
Q

How does Valproic Acid work

A

Partially blocks Na currents

may increase GABA levels and its effects by inhibiting the degradation of GABA by inhibiting GABA-T enzyme on the brain

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75
Q

Reference range and Tox range for Valproic acid

A

Ref - 50-125 mg/L or mcg/mL

Toxicity starts between 150-200

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76
Q

Drug interactions with Valproic acid

A

Lamotrigine (lamictal) - inhibits metabolism - associated with a dose or concentration effect of skin reactions (Steven johnsons)

Phenytoin

phenobarbital

CBZ

Ethosuximide

AZT (zidovudine)

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77
Q

Valproic acid pregnancy and lactation

A

D - neural tube defects

L2

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78
Q

Side effects of Valproic Acid

A

GI is the most common - enteric coated will help

weight gain

hepatotoxicity

pancreatitis

tremors

thrombocytopenia

Teratogenicity - due to folate deficiency

Hyperammonemia (NH3) - consider L carnitine therapy (Carnitor) if this happens
- causes encephalopathy

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79
Q

how do you treat hyperammonemia from valproic acid

A

L carnitine therapy (Carnitor)

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80
Q

drug of choice for absence seizures

A

Ethosuximide (Zarontin)

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81
Q

mechanism of action for Ethosuximide (Zarontin)

A

blocks thalamic (T-type) Ca++ channels

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82
Q

reference range for Ethosuximide (Zarontin)

A

60-100mcg/ml (some go up to 125 mcg/ML

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83
Q

side effects for Ethosuximide (Zarontin)

A

Gastritis (primary)

fatigue

headache

neurologic (psychotic behavior)

Rash (SJS)

Leukopenia (check CBC periodically)

Lupus like syndrome

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84
Q

phenobarbital (luminal) indications

A

alternative for partial and generalized tonic clonic seizures

typically used as second line but may be preferred in pregnant women (cat B/D depending on manufacturer)

Avoid in absence seizures - can worsen like phenytoin

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85
Q

MOA phenobarbital (luminal)

A

enhances GABA via increase in cl channel opening and makes GABA work better

also decreases glutamate mediated excitation on AMPA

at higher concentrations may block Ca channels

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86
Q

herbal medicinals that work on GABA providing anti anxiety

A

GABA
Valerian root
Kava

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87
Q

phenobarbital (luminal) clinical issues

A

Inducer of CYP450 and UGT enzymes

main side effect is sedation

develop tolerance

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88
Q

Reference range phenobarbital (luminal)

desired
toxic

A

desired 15-40mg/L

toxic >50mg/L

89
Q

Primidone (Mysoline) metabolized to

A

PEMA (phenylethylmalonamide) by oxidation and phenobarbital

90
Q

what supplement do pt need if on phenobarbital (luminal)

A

folic acid

91
Q

what levels do you monitor for Primidone (Mysoline)

A
Primidone (8-12 ug/ml)
phenobarbital levels (15-30ug/ml)
92
Q

dose adjustments for Primidone (Mysoline)

A

renal dose adjustment after CrCl <50ml/min - metabolites can accumulate

93
Q

metabolism warning for Primidone (Mysoline)

A

CYP450 inducer

94
Q

Primidone (Mysoline) side effects

A
CNS depression
Sedation
Confusion
Suicidal ideations
megaloblastic anemia due to lowering of RBC and CSF folate levels

Avoid in pregnancy - crosses placenta and lowers folic acid

95
Q

Lamotrigine (Lamictal) approved for ….

A

adjunctive therapy in adults and children > 2 years with

Partial epilepsy refractory to other agents

Lamictal XR approved for once a day add on for primary generalized tonic clonic seizures

Lennox Gastaut (in children) seizures

Bipolar disorder

96
Q

MOA Lamotrigine (Lamictal)

A

block voltage sensitive Na+ channels -> inhibition of glutamate and aspartate

97
Q

what antiepileptic is available in ODT

A

Lamotrigine (Lamictal)

98
Q

drug drug interactions Lamotrigine (Lamictal)

A

Valproate - inhibits Lamotrigine (Lamictal) metabolism. start dose at 25mg qod when added

Carbamazepine: induces Lamotrigine (Lamictal) metabolism

99
Q

Side effects Lamotrigine (Lamictal)

A

nausea

diplopia

ataxia

Skin rash - typically occurs in first 8 weeks and can lead to SJS, peds seem to be risk - other risk are doses higher than recommended, rapid dose escalation, giving with valproic acid

100
Q

Gabapentin (Neurontin) indications

A

Partial seizures
postherpetic neuralgia

off label diabetic neuropathy
post op pain
restless leg syndrome
hot flashes

101
Q

MOA GAbapentin

A

water soluble anticonvulsant that is still able to penetrate BBB. Binds to amino acid carrier protein and elevates GABA levels (does this but not as much)

Binds to subunits of voltage-gated Ca++ channels (primary)

102
Q

metabolism consideration for gabapentin

A

renal dosing (CrCl <60)

103
Q

Pregabalin (Lyrica) indications

A

partial onset seizures (adjunct)

Pain associated with diabetic neruopathy, post SCI, post herpetic neuralgia, fibromyalgia

104
Q

MOA Pregabalin (Lyrica)

A

same as gabapentin but 3 xs more potent (I give less to have same pharm effect)

105
Q

max dose of Gabapentin vs Pregabalin

A

3600mg/day
vs
600mg/day

106
Q

metabolism consideration for Pregabalin (Lyrica)

A

renal dosing (CrCl <60)

107
Q

side effects Pregabalin (Lyrica)

A
edema
sedation
dizziness
blurred vision
weight gain
108
Q

Felbamate (Felbatol) used for

A

not first line agent

used in Lennox-Gastaut

109
Q

side effects Felbamate (Felbatol)

A
Aplastic anemia (within first 6 mos)
n/v
110
Q

Tiagabine (Gabitril) indication

A

Partial seizures (adjunct)

111
Q

Mechanism Tiagabine (Gabitril)

A

enhance activity of GABA by inhibition of neuronal uptake

112
Q

metabolism considerations Tiagabine (Gabitril)

A

no renal or hepatic dosing

major substrate of CYP3A4
- clearance increased if used with carbamazepine and phenytoin

113
Q

side effects Tiagabine (Gabitril)

A

Dizziness

drowsiness

difficulty concentrating

weakness

114
Q

Topiramate (Topamax) indications

A

epilepsy (adjunct and monotherapy)

migraine prophylaxis

essential tremor and cluster headache prophylaxis

115
Q

MOA Topiramate (Topamax)

A

inhibit Na channels, enhance GABA and antagonize glutamate receptors

116
Q

dose difference in Topiramate (Topamax)

A

renal dose reductions occur for CrCl <70 ml/min instead of 60

117
Q

drug interactions Topiramate (Topamax)

A

weak inhibitor of CYP2C19

118
Q

side effect of Topiramate (Topamax)

A

weight loss

ataxia

impaired concentration

Acute angle closure glaucoma

Metabolic acidosis due to reduction in bicarbonate

Nephrolithiasis

Hyperammonemia

Pregnancy Cat D

119
Q

Lacosamide (Vimpat) indications

A

adjunct partial onset seizures with epilepsy age>17 years (available IV and PO)

120
Q

dosing considerations Lacosamide (Vimpat)

A

hepatic disease or CrCl <=30 then max daily dose is 300mg instead of 400

121
Q

side effects Lacosamide (Vimpat)

A

increased SI
dizziness
ataxia

DRESS ( drug reaction with eosinophilia and systemic symptoms)

PR interval prolongation

122
Q

Drug interactions Lacosamide (Vimpat)

A

Substrate CYP2C19

123
Q

pregnancy risk Lacosamide (Vimpat)

A

C

124
Q

Levetiracetam (Keppra) indications

A

partial seizures
tonic clonic
myoclonic
status epilepticus (off label)

125
Q

MOA Levetiracetam (Keppra)

A

inihibit voltage dependent N type Ca++ channels

Facilitate GABA ergic inhibitory transmission by displacing negative modulators

binding to synaptic vesicle proteins 2A ligand (SV2A) that affect neurotransmitter release

126
Q

dosing Levetiracetam (Keppra)

A

reduce dose once CrCl <80mL/min

127
Q

Side effects of Levetiracetam (Keppra)

A

behavior problems (shows up in preexisting neuropsychiatric conditions)

weakness

n/v
headache

128
Q

Brivaracetam (Briviact) works on

A

partial seizures

129
Q

Vigabatrin (Sabril) indications

A

monotherapy for infantile spasms

add on to adults with partial complex seizures refractory to other anticonvulsants

130
Q

why does Vigabatrin (Sabril) have strict access

A

toxicity to retina
(irreversible concentric peripheral visual field deficits) associated with retinal dysfunction

SHARE program

requires vision testing baseline and testing every 3 months

131
Q

MOA Vigabatrin (Sabril)

A

thought to be related to being an irreversible inhibitor of GABA -T which is responsible for the metabolism of GABA

132
Q

Vigabatrin (Sabril) drug interactions

A

Inducer of CYP2C9

can lower levels of phenytoin (Dilantin)

increase clonazepam through unknown mechanism

preg risk C

133
Q

Zonisamide (Zonegran)indication

A

adjunct therapy in adults with partial seizures

134
Q

Mechanism of Zonisamide (Zonegran)

A

blockade of Na and CA

135
Q

Side effects Zonisamide (Zonegran)

A

dizziness and drowsiness

Hyperthermia (heat stroke in children)

Nephrolithiasis (encourage hydration)

136
Q

drug interaction Zonisamide (Zonegran)

A

dont take with Sulfonamide allergy

Substrate CYP2C19 and 3A4

137
Q

Perampanel (Fycompa) indication

A

Partial seizure and generalized tonic clonic

138
Q

Perampanel (Fycompa) metabolism

A

Avoid if CrCl <30ml/min

major substrate of CYP3A4

139
Q

Black box warning Perampanel (Fycompa)

A

dose related serious and life threatening psychiatric events - aggression, anger, HI, hostility in the first 6 wks of use

140
Q

Rufinamide (Banzel) indication

A

Lennox-Gastaut syndrome

141
Q

notes on Rufinamide (Banzel)

A

weak inhibitor of CYP2E1 and weak inducer of CYP3A4

known to cause dose related shortening the QT interval

142
Q

what drugs inhibit Na channels

anticonvulsant

A
Carbamazepine
Eslicarbazepine
Lamotrigine
Lacosamide
OxCBZ
Phenytoin
Rufinamide
143
Q

what drugs increase GABA activity (anticonvulsant)

A
Benzodiazepine
Phenobarbital
Primidone
Tiagabine
Vigabatrin
144
Q

What anticonvulsant drugs work on synaptic vesicle protein 2A ligand

A

Brivaracetam

Levetiracetam

145
Q

what anticonvulsant drugs work on inhibit Na and Ca channels

A

Zonisamide

146
Q

what anticonvulsants inhibit Na channels and increase GABA levels

A

Topiramate

Valproic acid

147
Q

What anticonvulsants decrease glutamate

A

Felbamate

Perampanel

148
Q

non-opioid cox 3 inhibitor

A

Acetaminophen

149
Q

max daily dose for tylenol

A

4,000mg/d however some limit to 3,000mg/d

150
Q

Iv formulation of tylenol is approved for what age

A

2 yrs and older

151
Q

antidote for acetaminophen tox

A

N-acetylcysteine (mucomyst; acetadote) best if given within 8-10 hrs of APAP ingestion/overdose

152
Q

what organ does acetaminophen overdose effect

A

liver

153
Q

opioid analgesics are all prototypes of

A

heroin

154
Q

the net effect of opioid analgesics

A

a reduction in the ascending pathways for pain stimuli

155
Q

opioid poisoning symptoms

A
coma
pinpoint pupils
respiratory depression (apnea)
156
Q

Oxygenation vs ventilation

A

Oxygenating is inhaling (oxygenating)

ventilation is exhaling (blowing off Co2)

157
Q

symptoms for opioid sedation

A

confusion with lack of rest from inadequate pain control
change dose

Can consider stimulant in certain patients

158
Q

Resp depression from opioid overdose - antidote

A

Narcan

159
Q

Rapid Sequence intubation

A

Pre-oxygenation (3-5 min at 100% O2)

cricoid pressure

sedative

paralytic

intubate

post intubation sedation

160
Q

what drug class for Dexmedetomidine (precedex)

A

Sedative/hypnotic

selective CNS A-2 agonist

161
Q

what sedative is used in ICU for weaning off ventilator since it doesn’t depress resp drive

A

Dexmedetomidine (precedex)

162
Q

Autoimmune destruction of the beta-cell thereby leading to absolute insulin deficiency

A

type I DM

163
Q

A metabolic disorder resulting from the body’s inability to make enough or properly use insulin

A

Type II DM

164
Q

when would a hypothyroid pregnant woman need a dose increase

A

1st trimester

165
Q

thyroid gland primarily secretes what?

A

T4

166
Q

the most potent form of the thyroid hormone on metabolic influence is ____ is primarily derived by ____ being converted to ___ at the tissue level

A

T3

T4->T3

167
Q

It takes about _____ weeks for the TSH to reach steady state after changes in the T4/T3

A

6-7 weeks

168
Q

TSH low

T4 WNL

A

subclinical hyperthyroidism

usually asymptomatic

169
Q

Low TSH

High T4

A

Overt hyperthyroidism

symptomatic

170
Q

Very low TSH

Very high T4

A

thyroid storm

hyperadrenergic state

171
Q

high TSH

High T4

A

secondary hyperthyroidism

usually tumor from pituitary

172
Q

excess thyroid hormone with thyroid storm being the more extreme presentation of hyperthyroidism

A

thyrotoxicosis

173
Q

what herb can cause increase TSH secretions via thyroiditis

A

St. Johns Wort

174
Q

what drugs can increase TSH secretion/release via thyroiditis

A

Amiodarone
Amphetamine
metoclopromide

175
Q

what drugs increase T4/T3 synthesis

A

Amiodarone

Iodine ingestion

176
Q

What drugs increase T4/T3 free fraction (inhibit protein binding)

A
ASA
carbamazepine
heparin
lasix
NSAID
phenytoin
177
Q

if a pt with hyperthyroidism develops fever what would you NOT give because it can make it worse

A

ASA
NSAID

they increase T4/T3 free fraction (inhibits protein binding)

making them more hyperthyroid

178
Q
Anxiety
nervousness
dyspnea
weight loss
heat intolerance
N/V
menstrual irregularities
weakness (proximal muscles and pelvic girdle)
Agitation
Tachycardia +- a-fib
tremor
fever
diffuse goiter
ophthalmopathy
lid retraction or lag
A

Hyperthyroidism

179
Q

if someone presents with A-fib, what should you check for

A

Hyperthyroidism

180
Q

Hyperthyroidism management

A

Assumes no thyroitoxicosis or thyroid storm

Thioamides (meds)
Thyroidectomy
Thyroid replacement therapy

181
Q

Meds for Hyperthyroidism

A

Methimazole (MMI) (Tapazole) - basically stop synthesis of T4/T3 in the thyroid gland - dosing initially high (30-60mg daily divided into 3 doses for an adult then taper to 5-15mg daily single dose…half life is 6 hours) - not protein bound - so always working bc not protein bound with long half life. Not good for a breastfeeding mom due to no protein binding. liver tox
Agranulocytosis - side effects. No in pregnancy

Propylthiouracil (PTU) -> Half life 1-2 hours
adults give 300-400mg/day in 3 divided doses then taper to 100-150mg/day in divided doses. 60-80% protein bound so technically better for breastfeeding. However, still not good bc it will still get into milk and your newborn needs those thyroid hormones. liver tox, Agranulocytosis - side effects. no in pregnancy

meds are only used in the interim until definitive treatment for hyperthyroid state

182
Q

Thyrotoxicosis not yet decompensated symptoms

A

Weakness
weight loss
palpitations

still functioning

183
Q

Decompensated thyrotoxicosis symptoms

A

fever
tachycardia
tremors

184
Q

CV effects of thyrotoxicosis

A

Sinus tachycardia (most common)

A-fib (2nd most common)

Reduced filling times ->high output heart failure

185
Q

what do you use to diagnose thyroid storm

and what tool?

A

clinical diagnosis

Burch & Wartofsky tool

  • Thermoregulatory dysfunction
  • CNS effects
  • GI-hepatic dysfunction
  • CV system

score -
<25 unlikely
25-44 - suggestive of impending storm
>45 - highly suggestive

186
Q

Thyroid workup

A

Labs - TSH, T4, T3
T3 resin uptake
-assess thyroxine binding globulin levels ->if high means, TBG levels are low
+/- thyroid-stimulating antibodies

CXR
ECG

Differentials:
-Infection, heat exhaustion/stroke, delirium tremens (alcohol withdrawal), malignant hyperthermia, neuroleptic malignant syndrome, pheochromocytoma, cocaine, amphetamine ingestion

187
Q

Steps in managing thyroid storm

A

Supportive care - oxygenation (metabolic demand is increased - may need oxygen), fluid resuscitation - if glucose is low use D5NS due to glycogen depletion, temp control (no NSAID or ASA) - ONLY Tylenol

Inhibit new hormone synthesis - usually PTU (this is because it also inhibits T4-T3), can also use Methimazole.

inhibit thyroid secretion - be careful - give the methimazole and PTU first so it can get into the gland. Then you give SSKI (super saturated potassium iodide) - possible to increase but when you give this large of a dose it should inhibit. if pt has iodine allergy- lithium carbonate
Dopamine, Octreotide and steroids

inhibit T4-T3 peripheral conversion (T3 is more potent and biologically active) - PTU, propranolol will also do this
Dexamethasone, Hydrocortisone

inhibit Beta receptors - causing tachycardia and hypertension - propranolol most commonly studied but overall a Beta blocker. Propranolol used frequently bc it also inhibits T4->T3 conversion (also decrease pulse, increase ventricular filling, decreases high output HF)

Thyroid hormone removal - cholestyramine binds enterohepatic reabsorption of thyroxine (can also use plasmapheresis, charcoal hemoperfusion, plasma exchange)

definitive treatment

  • Radioactive iodide
  • Surgery
188
Q

what drugs used in thyroid storm treatment block TSH release

A

Octreotide
Steroids
Dopamine

189
Q

What drugs used in thyroid storm work on thyroid hormone production

A

Methimazole

Propylthiouracil

190
Q

what drugs use in thyroid storm work on thyroid gland activity

A

Iodine or SSKI

Propylthiouracil
Propranolol
Steroids
these 3 also help with preventing T4-T3

191
Q

what thyroid lab can you not rely on and why

A

TSH, takes 6-7 weeks for T3/T4 to effect this number

192
Q

when you are looking at thyroid storm, what should you consider

A

differential diagnoses

especially sepsis

193
Q

In hyperthyroid, caution with giving ____ in failing to recognize high output heart failure

A

diuretics

194
Q

Wait at least _____ after thioamide before giving high dose iodine

A

1 hour

195
Q

dispo for thyroid storm

A

Admit to ICU

may take 1-2 weeks to completely recover

196
Q

TSH high

A

subclinical Hypothroidism

197
Q

TSH high

T4 low

A

overt hypothyroidism

symptomatic

198
Q

TSH VERY HIGH

T4 VERY low

A

Myxedema coma

199
Q

Myxedema coma is more common in who?

A

women >60yrs old

200
Q

TSH low

T4 low

A

secondary hypothyroidism

may be hypothalamus-pituitary axis problem or
sick euthyroid syndrome

201
Q

autoimmune hypothyroidism

A

Hashimoto’s Thyroiditis

202
Q

drugs that decrease TSH secretion

A

Dopamine
Glucocorticoids
Octreotide
Opiates

203
Q

Drugs that decrease T4/T3 synthesis

A

Amiodarone
Lithium
Methimazole (MMI)
Propylthiouracil (PTU)

204
Q

Drugs that decrease T4/T3 secretion

A

Amiodarone
Lithium
SSKI

205
Q
Fatigue
weight gain
depression
constipation
shortness of breath
cold intolerance
infertility
Macroglossia
periorbital puffiness
hoarseness
decreased bowel sounds
dry skin
delayed relaxation of ankle jerks
A

Hypothyroidism

206
Q

Myxedema coma symptoms

A
AMS
bradycardia
hypotension
hypoventilation
hypothermia

metabolic and multi organ dysfunction

207
Q

what can precipitate myxedema coma

A

uncorrected hypothyroidism or noncompliance

Infection

trauma

MI

HF

CVA

metabolic problems

208
Q

Myxedema Coma diagnosis

A

hypothyroid based on labs (TSH may not be accurate)

Myxedema coma/crisis is a clinical diagnosis

209
Q

labs for Myxedema

A

TSH
T4/T3
cortisol level (can be +/-)

BMP - risk of hyponatremia due to increase ADH and risk of hypoglycemia due to decreased gluconeogenesis, decreased insulin clearance and +/- adrenal insufficiency

VBG/ABG - metabolic & resp acidosis - d/t hypotension, hypoventilation, tissue hypoxia

210
Q

managing hypothyroidism

A
synthetic T4 (levothyroxine) - gets converted to T3 by the body
-99% protein bound
-half life depends on thyroid status (euthyroid = 6-7 days, hypothyroid=9-10 days, Hyperthyroid =3-4 days)
(pregnant patients have dose increase in 1st trimester)
211
Q

what factor needs to be taken into consideration when giving levothyroxine for hypothyroidism (pt history)

A

Cardiovascular disease

If <50 and with or without CVD = 1.6mcg/kg

If > 50 +/- CVD = 12.5-25mcg daily (more conservative approach - too much thyroid hormone can cause sinus tachycardia which can be bad on a diseased heart. This can cause A-fib - could cause a stroke)

212
Q

Bioavailability of levothyroxine is higher on a empty or full stomach?

A

empty (however the most important is that they are consistent)

213
Q

drug interactions with levothyroxine

A

Decrease Absorption -
-Di- and Tri- valent cations will reduce absorption (Al, Ca, Fe, Mg)

  • Cholestyramine (Questran) - can bind to it.
  • Sucralfate (carafate) - can chelate with charges
  • Fiber supplements - increases peristalsis so transit time changes

Increase Clearance (enzyme inducers)

  • Rifampin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
214
Q

If you have to change manufacturer for Levothyroxine what do you need to do

A

re-check TSH, T3, T4 in 6-7 weeks to see if they need dose adjustments

215
Q

If not able to make T3 in the periphery, what med

A

Desiccated thyroid (Armour thyroid, Westhroid) (animal brain)

-seen in Congenital hypothyroidism

these are fixed doses of T4 and T3

216
Q

Liotrix (Thyrolar)

A

another T4/T3 replacement
Congenital hypothyroidism

not animal sourced

217
Q

Liothyronine indications

A

T3 therapy

Hypothyroidism (congenital)
Myxedema
Myxedema coma 
cadaveric organ recovery
antidepressant augmentation
218
Q

myxedema coma management

A

ABC support

Dextrose for hypoglycemia

Free water restriction for hyponatremia

Vasopressors (treat hypotension first with fluids)

Passive warming for hypothermia

Glucocorticoid replacement for stress

IV synthetic T4 (levothyroxine) (onset is 6-8 hours) - don’t wait for labs - high morbidity rate

if initial dose T4 fails, give T3

219
Q

what happens in pregnancy that a hypothyroid pt needs a dose adjustment

A

the increase in estrogen increases the thyroid binding globulin secondary to a reduction in its catabolism -> leads to an increase in T4 (bound and free) and T3. Since there is an increase in both, the free fraction and TSH is normal in a euthyroid patient. -> not the case in someone who gets pregnant - need large dose increase in thyroid replacement to avoid problems