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Pharm S1 > EX2 Lecture 8: CNS > Flashcards

EX2 Lecture 8: CNS Flashcards

1
Q

What are the characteristics of a classic migraine?

A

Aura (may include any of the following: nausea, vomiting, visual scotomas, or even hemianopsia and speech abnormalities)

+

Severe throbbing/pulsing UNILATERAL headache for 1 hour to a 1-2 days.

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2
Q

what does the CNS do

A

integrates sensory information and generates motor output and other behaviors necessary to interact with the environment

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3
Q

what are neurons

A

electrically excitable cells that process and transmit information via electrochemical processes

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4
Q

what is neuroglia

A

nonneuronal support cells that perform a variety of functions in the CNS such as maintaining extracellular ion concentration, providing nutrients to neurons, and insulating/controlling the speed of conduction in neurons

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5
Q

what is the blood brain barrier (BBB)

A

protective separation of the circulating. blood from the extracellular fluid in the CNS that limits penetration of substances including most medications

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6
Q

What is the difference between a classic and a common migraine?

A

Common migraines do not have the aura but the headache is similar

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7
Q

What is the common treatment for migraines?

A

NSAIDs

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8
Q

What is the more pharmacologically advanced treatment for migraines?

A

Triptans

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9
Q

what are triptans

A

serotonin neurons involved with numerous functions in the body such as mood, sleep, appetite, temperautre regulation, perception of pain, regulation of blood pressure and vomitting
(5-HT)

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10
Q

What is 5-HT?

A

Serotonin

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11
Q

What are the two 5-HT receptors we care about in migraines?

A

5-HT1B, which is the serotonin receptor found in the substantia nigra and globus pallidus (cheese of the pizza)

5-HT1D, general serotonin receptor in the brain.

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12
Q

What is the Mechanism of Action (MoA) for a triptan?

A

Act on intracranial blood vessels and peripheral sensory nerve endings, resulting in vasoCONSTRICTION and DECREASED release of inflammatory peptides.

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13
Q

What is the clinical indication for sumatriptan?

A

Migraines (First-line therapy for severe migraine attacks)

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14
Q

What are the contraindications for sumatriptan?

A

CAD
Angina (via coronary vasospasms)
Stroke (induce coronary vasospasm stroke)
(Note: All are related to the vasoconstriction aspect)

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15
Q

If I need sumatriptan ASAP, what formulation should I take?

A

Injections or nasal (faster onset than oral)

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16
Q

What is the first-line therapy for severe migraines?

A

Triptans

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17
Q

What are the other medications used for migraines besides triptans?

A

Ergot alkaloids, such as ergotamine

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18
Q

What is the MoA for ergotamine?

A

Vasoconstriction of smooth muscle working mostly at the alpha receptors.

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19
Q

What is the difference between ergotamine and sumatriptan?

A

Triptan is more effective for acute migraine attacks.

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20
Q

When is ergotamine most effective?

A

Very early in a migraine attack. Often combined with caffeine.

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21
Q

Why should I be wary using ergotamine and what are some side effects to be concerned about?

A

Frequent usage can cause rebound headaches.
Side effects can include Cyanosis, Ischemia, and prolonged vasospasms.

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22
Q

what is the dose of ergotamine to stay under to avoid vasospasm risk

A

no more than 6mg per attack or 10mg weekly

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23
Q

What are some prophylactic treatments for migraines?

A

None that have achieved notable success. (for acute migraines)
BUT
some common ones used still (shown to be effective in prevention in some pts but NO value in acute migraine):
propranolol (non-selective BB and lipophilic), topiramate (anticonvulsant), and valproic acid (Anticonvulsant)

Uncommon: Amitriptyline (TCA)
verapamil (CCB)

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24
Q

How fast is sumatriptan’s onset?

A

1.5 hours orally, 0.2 hours SubQ.
This means I can take another one within 1-2 hours if I really need to.

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25
Q

what is neurodegeneration

A

progressive loss of structure or function of neurons, including death of neurons

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26
Q

list diseases that occur as a result of neurodegenerative processes

A

ALS, parkinsons, alzheimers, huntingtons

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27
Q

what is a tremor at rest characteristic of

A

parkinsonism, when it is often associated with rigidity and an impairment of voluntary activity

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28
Q

What is chorea?

A

Chorea consists of unpredictable, irregular, involuntary muscle jerks that occur in different parts of the body and impair voluntary activity.

Huntington’s disease is also known as Huntington’s Chorea

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29
Q

What is athetosis?

A

Abnormal movements that are slow and writhing in nature.

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30
Q

What is dystonia?

A

Abnormal posturing, muscle rigidity

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31
Q

What are tics? Most notable disease?

A

Sudden, coordinated abnormal movements that occur repetitively. Usually in the head/face area, such as shoulder sniffing or sniffing in children.

Gilles de la Tourette syndrome or Tourette’s (chronic multiple tics)

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32
Q

What are some of the most notable signs of parkinson’s? first symptom and declining ability during disease?

A

Combination of rigidity, bradykinesia, tremor, and postural instability. Bradykinesia often comes before the diagnosis can be made. (first)
cognitive decline occurs as disease advances

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33
Q

What is the pathology of Parkinson’s?

A

Loss of dopamine neurons in substantia nigra.
Dopamine normally inhibits GABA, which is an INHIBITORY NT.

Ach will bind to the GABAergic neuron to activate it, but dopamine normally inhibits it.

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34
Q

other non motor symptoms of parkinsons

A

affective disorders (anxiety, depression)
confusion
cognitive impairment
personality changes
apathy
fatigue
abnormalities of autonomic function (sphincter or sexual dysfunction, dysphagia and choking, sweating ab., sialorrhea, distubrances in BP regulation)
sleep disorders
sensory complaints or pain

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35
Q

What are the two goals of treatment of Parkinson’s based on the pathophysiology?

A

Increase Dopamine levels.
Inhibit Ach.

( dopamine from substantia nigra usually inhibits the gabaergic output from striatum but dopamine loses ability to do so in parkinsons)

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36
Q

What is the special characteristic of Levodopa vs dopamine?

A

Levodopa is a prodrug/metabolic precursor that CAN cross the BBB via an L-amine transporter (LAT). It is then decarboxylated to dopamine.

Dopamine cannot actually cross the BBB, therefore injecting or eating dopamine does nothing for Parkinson’s

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37
Q

how much administered levadopa actually gets tot he brain when given by itself? why is that?

A

1-3%
the remainder is metabolized extra cerebrally, predominantly by decarboxylation to dopamine which does not penetrate the BBB

levadopa must be given in LARGE amounts when given alone

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38
Q

Why do we add carbidopa to levodopa?

A

Carbidopa is an inhibitor of the decarboxylating enzyme, so more Levodopa can get into the brain. Carbidopa DOES NOT penetrate to the BBB.
so, peripheral metabolism of levadopa is reduced, plasma levels of levadopa are higher, plasma half life is longer, and more available to enter the brain

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39
Q

Concomitant adminstration of carbidopa and levadopa can reduce the daily amount of levodopa required by up to _____. Carbidopa acts as levadopas _____

A

75%, bodyguard

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40
Q

What are some common side effects of levodopa and carbidopa?

A

Dizziness, Nausea, dyskinesia, constipation.

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41
Q

how is combination levadopa/carbisopa treatment initiated? with or without food?

A

small doses eg carbidopa 25mg levadopa 100mg three times daily and gradually increased

take with food for delayed absorption, without food if need more immediate absorption

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42
Q

what is the average patient carbidopa levadopa regimen

A

25mg carbidopa, 250mg levadopa three or four times daily

43
Q

What does food do to levodopa?

A

Delays the appearance of levodopa in our bloodstream.

44
Q

What is the most common side effect of levodopa and how/why do we have issues treating it?

A

Dyskinesa, occuring in up to 80% of pts over a 10 year span of taking levodopa.

Development is dose-dependent and going off levodopa reduces the dyskinesia, BUT then the parkinson’s motor symptoms worsen.

45
Q

does mild dyskinesia require treatment? what is used for it?

A

We do not treat mild dyskinesia. We use amantadine (antiviral) to reduce more troublesome dyskinesia.

46
Q

If I have a patient having clinical fluctuations in their clinical response to levodopa due to the timing of their intake, what is this called?

A

Wearing-off reactions OR end-of-dose akinesia

47
Q

If I have a patient having fluctations in their clinical response to levodopa regardless of the timing of their intake, what is this called?

A

on-off phenomenon. This generally occurs in patients who responded to treatment well initially.

off periods have marked akinesia and on periods have improved mobility but marked dyskinesia

alternate over course of a few hours

48
Q

What does on-off phenomenon present as clinically?

A

Off-periods of marked akinesia alternate over the course of a few hours with on-periods of improved mobility but often marked dyskinesia.

49
Q

What is a drug holiday for Parkinson’s?

A

Discontinuance of a drug for 3-21 days.
- may temporarily improve responsiveness to levadopa and alleviate adverse effects but usually of little help in management of the on-off phenomenom

50
Q

what are possible side effects of drug holiday of levadopa in parkinsons? should you reccomend?

A

MANY SIDE EFFECTS POSSIBLE: Aspiration pneumonia, venous thrombosis, pulmonary embolism, and depression resulting from immobility.

DO NOT RECOMMEND!

51
Q

What is pyrixidone (Vit B6) for?

A

Enhances extracerebral metabolism of levodopa, inhibiting its therapeutic effect.
( would need to adda peripheral decarboxylase inhibitor like carbidopa)

52
Q

Why are MAO inhibitors a concern in a patient with Parkinson’s?

A

Combination of MAO inhibitors with Levodopa (or within 2 weeks of their discontinuance) can cause hypertensive crises (via increased dopamine and/or NE).
Levodopa alone can already cause hypotension frequently or sometimes hypertension.

Always do a drug interaction check for any patient on a MAO inhibitor!

53
Q

What two things break down dopamine?

A

MAO-B
COMT

54
Q

examples of dopamine receptor agonists

A

pramipexole, ropinirole
bromocriptine, pergolide

55
Q

How do COMT inhibitors work?

A

Prolong effects of Levodopa by diminishing its peripheral metabolism.

Decreases levodopa clearance and increases bioavailbility of levodopa.

56
Q

Why do we like COMT inhibitors?

A

Might help with patients receiving Levodopa who have response fluctuations.

Can help with smoother responses, prolonging on-time, and reducing daily dosage of Levodopa.

57
Q

Why do I use entacapone over tolcapone? what are these drugs classified as

A

Both are COMT inhibitors

Tolcapone is associated with hepatotoxicity, entacapone has not been shown to be

(entacapone does not cross BBB)

58
Q

What is Stalevo?

A

A COMT inhibitor consisting of combination of levadopa, carbidopa, and entacapone

59
Q

effects/ side effects of stalevo

A

simplifies drug regimen, consumption of fewer tablets

May provide greater symptomatic benefit than just carbidopa+levodopa, but associated with earlier occurrence and increased frequency of dyskinesia.

60
Q

what are the three dose strengths of stalevo

A

stalevo 50 ( 50levadopa, 12.5 carbidopa, 200 entacapone)

stalevo 100 (100 levadopa, 25 carbidopa, 200 entacapone)

stalevo 150 (150 levadopa, 37.5 carbidopa, 200 entacapone)

stalevo strenth is same mg as levadopa, always 200 mg entacapone, and 1/4 of stalevo is carbidopa

61
Q

What is a seizure and what is epilepsy? does everyone that has a seizure have epilepsy?

A

Seizures are finite episodes of brain dysfunction caused by abnormal discharge of cerebral neurons.

Epilepsy is a chronic disorder involving recurrent seizures.

not everyone who has seizure has epilepsy

62
Q

What are some common causes of seizures?

A

Infection, tumor, head trauma, hypocalcemia, degenerative diseases, genetic mutations, and epilepsy.

63
Q

What can cause too much neuronal excitation/ more excitable?

A

Increase in the intracellular flow of Na or Ca. Causes earlier depolarization.

OR

Increase in glutamate NT release. Glutamate is an excitatory NT.

64
Q

What can cause too little neuronal inhibition?

A

Decrease in intracellular flow or Cl or efflux of K.

Decrease in release of inhibitory NTs like GABA.

65
Q

What are some clinical pearls (mainly for epilepsy)?

A
  • Start low, go slow
  • When DCing a med, taper off slowly (bc of breakthrough seizures) unless life-threatening toxicity(rare).
  • The longer the therapy, the more extended the tapering should be. - Write it out for patients!
66
Q

how should you taper a therapy that has been <8 weeks, >= 8 weeks, >= 6 months

A

<8 weeks - 25% per week reduction in dosage for two weeks then taper remaining dosage over next 7 days

> = 8 weeks, taper over 3-4 weeks

> = 6 months, taper over 6-8 weeks

(make dosage manageable for patient with their formula, write out schedule for them)

67
Q

What are the two categories of seizures and their subtypes?

A

Generalized: Tonic, Clonic, Myoclonic, Atonic, and Absence

Partial/Focal: Simple (Without dyscognitive features), Complex (With dyscognitive features) (sub cat of secondary generalized)

68
Q

What meds should be given for a tonic clonic seizure and what is a tonic clonic seizure?

A

Also known as a grand-mal seizure, characterized by muscle rigidity (periods of stiffness) and jerking motions.

Carbamazepine, Lamotrigine, Levetiracetam (Keppra), Phenobarbital, Perampanel, Phenytoin, Topiramax (Topamax), and Valproic acid (Sodium valproate)
( also oxcarbazepine, zonisamide)

69
Q

What meds should be given for an Absence seizure?

A

Ethosuximide, valproic acid
(also lamotrigine, zonisamide)

70
Q

What meds should be given for a myoclonic seizure?

A

Lamotrigine & Levetiracetam (Keppra)

(also maybe topiramate, valproic acid, zonisamide)

71
Q

What meds should be given for atonic seizures?

A

None that are FDA approved. Refer to non-pharmacological therapy.

(but possibly lamotrigine, valproic acid, zonisamide)

72
Q

What is measured drug level inclusive of?

A

drug unbound + drug bound.

73
Q

What are Michaelis-Menten kinetics and what drug does it affect?

A

Phenytoin.

Michaelis-Menten kinetics means that a drug relies on a finite number of molecules that can metabolize it.
Phenytoin requires a certain transporter, which the blood does not have that many of. Once the amount of transporters is maxed out, the metabolism is maxed out

74
Q

What is phenytoin subject to kinetic wise?

A

Michaelis-Menten kinetics
Protein Binding
Narrow therapeutic range

** it is a highly protein bound, only free non bound portion will give effects– have to be careful if you have decreased albumin bc you will have increase in unbound phenytoin levels

75
Q

what is another name for michaelis menten and the example she gave in class

A

saturable kinetics

think of conveyer belt- if youre wrapping chocolates and more chocolates keep coming faster than what you can wrap you will have more unwrapped (unmetabolized or bound in blood) because the liver cant take them all out fast enough

76
Q

phenytoin levels (dilantin)

A

narrow TI
10-20 mu/mL total serum phenytoin

can also measure free phenytoin (free/unbound) -less common $$$
0.75-1.25 mu/mL

77
Q

if albumin is low what should you do? what is the equation?

A

if albumin levels are low, phenytoin levels can look. low so you may need to adjust total serum phenytoin after calculation

phenytoin (corrected)= (phenytoin(measured) / ((0.2 x albumin) + .1)

78
Q

adjustment levels for phenytoin forumla if CrCl is > and < 25 mL/min

A

> 25 is .2
<25 is .1

79
Q

what does normal v low albumin look like in blood

A

normal is most of phenytoin is bound, less than half is free/unbound

low labumin is only some phenytoin is bound, more than half is unbound

80
Q

what level is indicitative to increase/ decrease phenytoin regarding its corrected dose?
why is a corrected dose needed?

A

corrected dose needed because low albumin can make drug levels look low

below 10 - increase dose
above 10-12- decrease dose

81
Q

What is an example of an auto-inducer drug and what does this mean?

A

Carbamazepine
It is both a substrate and inducer of 3A4.
Has induction of its own metabolism occuring over a period of 3-4 weeks when starting drug
stabalizes with long term therapy

82
Q

What are the 4 big inducers and what do they induce?

A

Carbamazepine: 2C9, 3A4, 1A2, and 2C19
Oxcarbazepine: 3A4
Phenobarbital: 2C9 & 3A4
Phenytoin: 2C9 & 3A4

83
Q

What is the one main inhibitor of 2C9?

A

Valproic acid/sodium valproate.

84
Q

what one of the 4 main inducers also has an inhibition effect- what does it inhibit

A

oxcarbazepine inhibits 2C19

85
Q

what are the 4 main inducers metabolized by

A

carbamazepine by 3A4+ 1A2+ 2C9

oxcarbazepine not metabolized

phenobarbital by 2C9+ 2C19

phenytoin by 2C9+ 2C19+ 3A4

86
Q

What side effect categories are most antiseizure meds?

A

Category A: Sedative effects

(A-> E sx usually get worse)

87
Q

What are the two stimulant classes and which one is more effective at MAO inhibition?

A

Amphetamines and methylphenidates.
Amphetamines work better at MAO inhibition, also releasing catecholamines.

88
Q

does lack of response to one chemical class mean lack of response to antoher? give example

A

no, lack of repsonse to one chemical class (methylphenidate or demethylphenidate) doesnt mean lack response to another (dextroamphetamine, lisdexamfetamine, or amphetamine salts)

89
Q

what are the short acting stimulants and their duration

A
  • dexedrine zenzedi (dextroamphetamine)tablet 4-6 hours
  • procentra (dextroamphetamine) oral soln 4-6 hours
  • adderall (dextroamphetamine sulf- saccharate (mixed salts)- cap -4-6 hour
  • focalin (dexmethylphenidate HCL) tab 4-6 hours
  • methylin (methylophenidate HCl) chew tab soln 3-4 hours
  • ritilan ( methylphenidate HCl)-tab 3-4 hours
90
Q

what are the intermediate acting stimulants and their duration

A
  • dexedrine spansule (dextroamphetamine sulfate) sprinkle cap- 6-8 hours
  • **evekeo (amphetamine sulfate) tab 6 hours (1:1 racemic mix)
  • metadate ER (methylphenidate HCl) 6-8 hours ER tab
  • ritalin SR (methylphenidate HCl) 4-8 hours ER tab
91
Q

what are the long acting MPH/DMPH stimulants and their durations

A
  • aptensio XR (methylphenidate HCl) 10-12 hours
  • concerta (methylphenidate HCl) 8-12 hours
  • daytrana transdermal (methylphenidate) up to 10 hours
  • focalin XR (dexmethylphenidate HCl) 6-10 hours
  • metadate CD, equasym XL (methylphenidate HCl) 8-10 hours
  • ritalin LA (methylphenidate HCl) 8-10 hours
    -contempla XR-ODT (methylphenidate) 4 hours
    -quillivant (methylphenidate HCl) 12 hours
92
Q

what are the long acting DXA/MXA stimulants and durations

A

-adderall XR (mixed amphetamine salts) 8-12 hours
- mydayis (mixed amphetamine salts) 12-16 hours
- adzenys XR (amphetamine base) 10-12 hours
- dyanavel XR (amphetamine base) 10-12 hours
-vyvanase (lisdexamphetamine) 10-12 hours

93
Q

what is the delayed release stimulant and duration

A

jornay PM (methylphenidate) delexis delivery system delays medication release for 10 hours- inner layer controls rate of release throughout the day
dosed at NIGHT!

94
Q

What is the treatment protocol for ADHD?

A

Begin with a long-lasting stimulant of either class. If first trial fails, switch to a different formulation.
We typically start with methylphenidates (less effect on growth)- those who fail one class usually good w another
2nd failure would involve using a 3rd formulation or using a 2nd line non-stimulant.

Each trial should be 3 months. (including dose titration and balance of side effects)

95
Q

What is the PK of methylphenidates?

A

De-esterified prior to elimination, resulting in LESS metabolic drug interactions vs mixed amp salts.

Males usually have increased bioavailability.

Metabolized via 2D6. The bioavailability and half-life can be increased 4-8x greater via Bupropion (atypical anti-depressant)
Fluoxetine, and Paroxetine. (SSRIs)

96
Q

What is the difference in dosing timing for long acting and short acting stimulants?

A

Short acting is taken usually in the morning due to its quick onset. It can also be given in the evening for coverage of afternoon activities.

Long-acting takes 60-90 minutes for onset, intended for once daily dosing, takem only in the morning.

97
Q

What is the effect of food on stimulants?

A

Delays therapeutic effect by 30 mins -1 hr for IR
1-2 hrs for ER

Decreases bioavailability from 10-30%, even more so for beaded forms.

Capsule formulations can be sprinkled on semisolid food to help absorption.

98
Q

What are the common stimulant adverse effects and treatment options?

A

Reduced-appetite, weight loss (give high-calorie meal)
Stomachache (eat on a full stomach or lower dose)
Insomnia (take it earlier or sedate at bedtime)
Headache (divide dose, give analgesic)
Rebound (use long-acting, use antidepressant to inhibit)
Irritability/jittery (reduce dose or mood stabilizer or antipsychotic)

99
Q

What are the rare adverse effects for stimulants?

A

Dysphoria (reassess dx)
Zombie-like state
Tics/abnormal movements
Hypertension/pulse fluctuations
Hallucinations (reassess dx)

Reduce dosage or discontinue or change.

100
Q

What is the one kind of patient you should never give a stimulant to?

A

Schizophrenic patients.

101
Q

Which stimulant class has more pronounced effects on growth?

A

Amphetamines. (more than methylphenidate)

102
Q

What are the general adverse event classes for stimulants?

A

Psychosis/mania
Aggressive/violent behavior
Severe anxiety/panic attacks

Reduce or discontinue med.

103
Q

when to start stimulants if pt has other dx

A

treat side diagnoses like depression/anxiety before stimulants- get balance in body and if they still have ADHD sx you can try stimulants now

Pharm S1 (18 decks)

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