Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Advanced Pharm- Test 1 > Neuropharmacology > Flashcards

Neuropharmacology Flashcards

1
Q

How many neurotransmitters exist in they body?

A

21

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are some reasons why we don’t know why or how drugs work?

A
  • We have an incoplete understanding of CNS physio
    • mech of human/behavior/thought proceses/ consciousness - hard to determine in animals
  • We usually have limited understanding of the patho phys
  • Research presents many ethical/technical challenges
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the amine hypothesis around depression?

A
  • Involves major brain amines:” NE, 5HT, Dopa
  • hypothesis: functional decrease in amine dependent synaptic transmission–> results in depression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Common treatments for depression?

A
  • Psychotherapy
  • ECT
  • Pharmacology: all current antidepressants primarily act on either NE or serotonin (Except ketamine) by affecting:
    • metabolism
    • reuptake
    • selective receptor antagonism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Ketamine treatment for depression?

A
  • found to be almost similar to ECT
  • Blocks NMDA receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

MOA SSRI?

A
  • Selectively inhibit the reuptake of serotonin into the presynaptic neuro
  • higher index of safety than other classes of antidepressants
  • takes several weeks to work; not only relying on decreased reuptake of 5-HT, may have other process involved
  • Each agent has different side effect profiles
    • examples:
    • Fluoxetine (prozac)
    • Sertraline (Zoloft)
    • Paroxetine (Paxil)
    • Citalopram (Celexa)
    • Escitalopram (lexapro)
    • fluvoxamine (lexiva)
  • While efficacy is the same for each drug (Between all classes), one drug has a safety profiel to work best for one pt vs another. some patients also don’t respond to one drug in class but may respond to another
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Adverse effects SSRIs?

A
  • CNS excitation (agitation/insomnia/EPS (rare)/sleepiness, lightheadedness
  • sexual dysfunction
  • GI distress (nausea)
  • Suppression of PLT aggregation (GI bleeding 3Xrisk)
    • will often keep pt on antidepressants because long half-life, long time to restart, with potential risk of suicide
  • Bruxism - griding of teeth
  • Rash
  • short term weight loss/long term weight gain
  • hyponatremia (especially older adults and pts on diuretics)
  • prolonged QT- only citalopram
  • orthostatic hypotension
  • withdrawal if stopped abrupty
  • black box warning- suicide
  • pregnancy category C
    • late pregnancy use small risk: infant withdrawl symptoms and pulm hypotension
  • Serotonin syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is SSRI pregnancy category?

A

C

late pregnancy has small risk: found infant witdrawal symptoms and infant pulmonary hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is serotonin syndrome?

Symptoms? precaution in ssri?

A
  • Symptoms
    • Hyperthermia
    • diaphoresis
    • muscle rigidity
    • rapid fluctuations in VS
    • rapid fluctuations in mental status (confusion, agitation, anxiety, hallucinations)
  • rare with SSRI but can be fatal
    • never combine SSRI with MAOI’s or any other drug that affects serotonin levels, causes bad outcomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Drug interactions SSRIs?

Contraindications?

A
  • Use in caution in pt taking drug that impair PLTs or coags
  • inhibits multiple p450 enzymes (especially 2D6)–> potential for drug interactions
    • fluoxetine- most potent inhibitor of CYP450
    • Will increase levels of warfarin, TCAs, and lithium
  • Contraindications:
    • MAOI are ABSOLUTELY contraindicated
    • other drugs that work via serotonin system (TCA, St John’s wort, etc)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

MOA SNRIs?

A
  • Block reuptake of serotonin and NE (weak blockade of dopamine reuptake)
  • Agents
    • prototype: venlafaxine (effecor)
    • duloxetine (cymbalta)
    • desvenlafaxine (prestiq)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Drug interactions/adverse effects SNRIs?

A
  • Not many drug interactions, however, MAOIs contraindicated
  • Adverse effects (similar to SSRIs)
    • GI distress, sexual dysfunction, insomnia, diastolic BP elevation 5-7%
    • pupil dilation (caution in glaucoma/increase IOP)
    • Withdrawl symptoms (do not discontinue abruptly)
      • neonatal withdrawal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is buproprion MOA? Class?

A
  • Class: atypical antidepressant
  • Primarily an inhibitor of Dopa and NE reuptake
    • also used to prevent seasonsal affective disorder, smoking cessation aid
    • off label: neuropathi pain and ADHD
    • Coontraindicated with MAOI, dopamine agents
    • Avoid drugs that inhibit CYP2D6 such as SSRIs (increase seizure risk)d
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Adverse effects of buproprion?

A
  • Nervousness, HA, insomnia, N/V/constipation, dry mouth, tremor, weight loss, small risk fo psychotic symptoms
  • Increased risk of sz (0.4%)
    • useful in pt not tolerating other antidepressants (ie weight gain SSRI)
    • Used in hypoactive sexual desire disorder
    • good for when pt having issue with decreased energy levels as symptoms of depression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is mirtazapine (Remeron) MOA?

A
  • Presynaptic alpha antagonist
    • blocks negative feedback= increased release of NE and serotonin
  • 5HT2 5HT3 serotonin antagonist
    • fewer GI effects, more pronounced effect on co morbid anxiety (will decrease anxiety more)
    • E1/2 life= 20-40 hours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

S/E mirtazapine (remeron)

A
  • Sedation (>50%)
  • constipation
  • increased appetitie
  • weight gain
  • increased cholesterol
  • less sexual S/E
  • less GI s/e
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Drug interactions Remeron?

A

MAOI contraindicated

CNS depressants- go slow with anesthetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

TCAs MOA?

A
  • Blocks reuptake of serotonin and/or NE at presynaptic terminals
    • tertiary amines- inhibit serotonin and NE reuptake
      • amytriptyline (elavil)
      • imipramine (tofranil)
      • clomipramine (anafranil)
    • secondary amines- inhibit NE reuptake
      • despiramine (norpramin)
      • notriptyline (pametlor)
  • Severeal other receptors are antagonized by TCA
    • Alpha adrenergic- orthostatic hypotensiob
    • Histamine- sedative
    • cholinergic- tachycardia, dry mouth, constipation
    • cardiac conduction system affected (QT prolongation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Use of TCAs?

A
  • Treatment of depression and bipolar d/o (during depressive epidodes)
  • chronic pain syndroms in lower doses
    • chemical structure similar to LA and phenothizines
    • inhibits overactive inflammatory response systmes
    • potentiation of endogenous opioids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Adverse effects TCA?

A

Narrow therapeutic index

  • anticholinergic effects
    • sedation, dry mouth, tachycardia, urinary retention, ileus, slow gastric emptying
  • weakness and fatigue
  • orthostatic hypotension
  • modest increase in heart rate
  • cardiotoxicity
    • arrhythmias via vagal and bundle of his cell conduction inhibition
  • lowers seizures threshold
  • hypomania
  • overdose often fatal (CNS depression, anticholinergic and direct cardiac toxicity
    • suicide risk (1 week supply at time)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are some pharmacokinetics of TCA?

A
  • Highly protein bound
    • acidsosi may increase unbound drug–> more dysrhythmia
  • metabolized in liver- all have active metabolites (worry clearing in liver dx)
  • tricyclics should be weaned to prevent withdraw syndrome
  • high lipid solubility–> easily crosses BBB
  • Metabolized by CYP 450 enzymes–> prone to drug interactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Drug interactions with TCAs?

A
  • MAO- contrindicated (can lead to severe HTN (NE) and serotonin syndrome
  • direct and indirect acting sympathomimetic drugs
  • anticholinergic drugs
  • sedating drugs
    • ETOH, barb, antihistamines, opioid, inhaled agents, IV induction agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Anesthetic considerations for TCA?

A
  • Volatile anesthetic agents- may need higher MAC
  • Opioid and barbiturates- decrease dose
  • Anticholinergics- more likely to have postop delirium and confusion (central anticholinergic syndrome)
    • S/S central anticholinergic syndrome- flushing, dry mouth, myrdiasis
    • pysostigmine for anticholinergic psychosis
    • if you MUST give anticholinesterase, give glycopyrrolate- doesn’t cross BBB
  • Sympathomimetics
    • unpredictable
    • indirect acting- exaggerated responses d/t larger amounts of NE available to stimulate post synaptic adrenergic receptors (because we’re increasing NE reuptake with TCA)
      • ​go with direct instead!!
    • acute vs chronic txmt with tricyclics
      • acute: use lower dosages of sympathomimetics
      • chornic: may need potent direct acting drug
        • receptor desensitization
        • depleted catechol stores
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is MAOI MOA?

A
  • MAOI form a stable irreversible complex with MAO–> nicreasing availability of these neurotransmitters in CNS and peripheral ANS
    • dopamine
    • serotonin
    • epinephrine
    • norepinephrine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is monoamine oxidase?

A

An enzyme found in rpesynaptic nerve endings, the liver and intestinal wall that metabolizes biogenic amines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What neurotransmitters does MAO A metabolize?

A
  • Serotonin
  • Norepinephrine
  • Epinephrine

MAOI A- depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What neurotransmitters does MAO B metabolize?

A
  • Phenylethylamine
  • Dopamine

MAOI B used more for parkinsons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are drug examples of MAOIs?

A
  • Phenelzine (nardil)
  • Isocarboxazid (marplan)
  • Tranylcypromine (parnate)
  • Selegiline (eldepryl)- seletive for MAO B, but at higher doses, becomes non selective.
  • in class, Bowman said we needed to know individual names for this class*
  • From health assessment:*
  • Iproniazid
  • moclobemide
  • befloxatone
  • brofaromine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are some side effects of MAOIs?

A
  • Most common is orthostatic hypotension
    • especially prominent in elderly
  • anticholinergic like effects
    • dry mouth, urinary retention, constipation, etc)
  • Impotence/anorgasmy
  • Weight gain
  • Sedation or mild stimulant effects
  • MAO A enzyme present in liver, GI tract, kidneys, lungs
    • metabolizes dietary tyramine (need to watch out for tyramine in diet)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the reason why patients have to watch tyramine intake when taking MAOIs?

What are some symptoms to watch out for because of this interaction?

A

Causes massive release of endogenous catecholamines/serotonin–> HTN crisis, hyperpyrexia, CVA

Symptoms:

  • Serious HA
  • Vomiting
  • Chest pain
  • tachycardia
  • HTN
  • Hyperthermia
  • CNS excitation
  • delirium
  • Seizure
  • Death

Examples of food with tyrmaine: cheese, fava beans, wine, avocado, liver, cured meats

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What drugs/ foods have interaction with MAOIs?

A

Drugs (anything that increases endogenous catecholamine levels)

  • Antidepressants (TCAs, SSRI, etc)
  • Opioids
    • NO MEPERIDINE!
  • Cold- allergy drugs
  • Sympathomimetics
  • Nasal decongestants (ex- afrin is alpha 1 agonist, hidden sympathomimetics)

Foods

  • Cheese
  • fava beans
  • wine
  • avocado
  • liver
  • cured meats
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the 2 types of serotonin syndrome seen with MAOIs and meperidine?

A
  • Excitatory response (Type I)- enhances serotonin activity in the brain
    • Agitation
    • Skeletal muscle rigidity
    • hyperpyrexia
  • Depressive response (Type II)- Slowed breakdown of meperidine
    • hypotension
    • respiratory depression
    • coma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How do MAOIs affect our VA?

What is another major drug class that has interactions with MAOIs?

A
  • May need higher MAC with volatile agents
  • Sympathomimetics
    • May ge exaggerated response from indirect acting drugs NO EPHEDRINE (also avoid dopamine)
    • use direct acting agnest if absolutely needed (phenylephrine)
      • ​​decrease dose by 1/3 and titrate to effect!
  • Minimize possiblity of sympathetic nervous stimulation or drug induced hypotension
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What are some antidpressant discontinuatuion syndromes?

A
  • Can get dizziness
  • myalgias
  • parasthesai
  • irritability
  • insomnia
  • visual disturbances
  • tremors
  • lethargy
  • N/V/D

psychiatrist needs to be on board for taper if determined necessary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is MOA for benzodiazepines?

A
  • Facilitates the action of gamma aminobutyric acid (GABA) (causing increase Cl conductance, hyperpolarizing the cell)
    • GABA- major inhibitory neurotransmitter in CNS
      • sometimes we can see opposite effect in some patients, where benzos make patients more “wild” from inhibiting the inhibitor
  • Widely prescribed for anxiety and insomnia
  • panic disorder
  • muscle relaxation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is alprazolam?

A
  • Benzodiazepine
  • High potency, short acting
  • significant anxiety reducing effect
  • used for primary anxiety and panic attacks
  • can depress cortisol secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is clonzepam?

A

longer acting benzo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is ambien?

A
  • Benzo that promotes sleep side but doesn’t work on anti-anxiety
  • still get anterograde amnesia- do things in sleep they don’t remember
39
Q

What is buspirone?

A
  • Non benzodiazpeine
  • partial agonist at serotonin receptor
  • No direct effect on GABA, so no cross reactivity with benzo, barbs or ETOH
    • good safety profile
  • used for treatment of generalized anxiety di/o but not panic d/p
  • E 1/2 t= 2-11 hours

not many anesthesia impliactions…

40
Q

What are some examples of first generation “typical” antipsychotics?

A

Class- phenothiazines, thioxanthenes

  • Chlorpromazine (low potency)
  • Thioridazine (Mellaril)
  • Perphenazine (trilafon)
  • Trifluoperazine ( navane)
41
Q

What are some examples of second generation typical antipsychotics?

A

Class: butyrophenone

  • Haloperidole (high potency)
  • Droperidol (D2 antagnoist)
42
Q

Where do first and second generation (typical) antipsychotics work?

A
  • Mesolimbic tract (which deals with behavior, mood)<– most have therapeutic effect here, antagonize D2 receptors
  • Nigrostriatal tract (which deals with movement)<– also have D2 receptors. antagonize here
43
Q

What is MOA of typical antipsychotics?

A
  • Dopamine antagnoists at D2 receptors (high potency) in the basal ganglia and limbic portions of forebrain
  • also muscarinic, hcolinergic, antihistamine and alpha-blocking properties
    • Sedation (H1 receptor blockade)
    • Anticholinergic effects (dry mouth, constipation, urinary hesitancy)
    • Anti-adrenergic effects: alpha blocking effect usually seen as orthostatic hypotension
    • interference with dopamine–> extrapyramidal side effects)
    • blockade of dopamine receptors in chemoreceptor trigger zone of medulla–> antiemetic effects
      • beneficial effect
44
Q

What are some movement side effects seens with typical antipsychotics?

A
  • Extrapyramidal symptoms/Neurologic effects
    • parkinsonianism: bradykinesia, rigidity, tremor, akinesia (difficulty starting movement)
    • Dyskinesia: spasms of muscle groups
  • Acute Dystonia (reversible): acute skeleton muscle rigidity and cramping of muscles of eyes, tongue, face, larynx, neck, and back ( can be severe enough to cause jaw dislocation)
    • respiratory distress form laryngeal dyskinesia (laryngospasm)
    • responds well to diphenhydramine 25-50 mg IV
  • Tardive dyskinesia (permanent)
    • involuntary jaw or oral musculature movmement expanding over tiem to include muscles in extremities and trunk (smacking lips, involuntary mvmt in mouth)
    • results of long term therapy (15-20%) and diagnosed only after 6 month exposure to antipsychotics
45
Q

What is neuroleptic malignant syndrome?

s/s?

development?

treatment?

A
  • Develops over 24-72 hours after dose typical agent
  • (may be related to dopamine antagonism)
  • S/S
    • hyperthermia
    • hypertonicity of skeletal muscle
      • myogloinuria
    • instability of autonomic NS
    • Fluctuating LOC
  • 4% fatality with early intervention; 30% mortality with delayed intervention
  • r/t respiratoyr failure, CV collapse and dysrhythmia
  • Treatment
    • supportive
    • includes dantrolene (will produce flaccid paralysis) and doapmine agnoists
46
Q

What are some other adverse effects (non movement related) of 1st generation, typical antipsychotics?

A
  • Severe dysrhythmias: QT prolongation (rare) leading to torsades de pointes and ventricular fibrillation
  • Decrease in BP
    • due to depression of vasomotor reflexes/peipheral alpha adrenergic blockade
    • relaxant effects on vascular smooth muscle
    • direct cardiac depression
  • Agranulocytosis (rare) check WBC
  • Pregnancy 3rd trimester babies may develop w/d symptoms and EPS
  • Sedation: similar to TCA
    • alpha 1, muscarinic, histamine receptors
    • tolerance to sedation devleops with chornic therapy
  • seizure threshold is decreased/
    • EEG pattern as seen with sz d/o
  • skeletal muscle relaxation
    • ​by CNS action not NMJ
47
Q

What are drug interactions with 1st generation (typical) antipsychotics)?

A
  • many of these agents are metabolized by CYP450 enzymes, others are inhibitors of CYP450
  • Intesnsification of effect: anticholinergics, CNS depressants
  • Reduction of effect: levodopa and dopamine agonists
  • Avoid drugs that prolong the QT interval (amiodarone, erythromycin, quinidine)
48
Q

What is neuroleptanalgesia?

A
  • Using combination droperidol/fentanyl
  • prolongs action of fentanyl, intense analgesia
  • ptoentiation of opioid side effects
    • sedative, ventilatory, analgesic
  • used in procedural sedation (ie burn)
49
Q

Metabolism of droperidol?1

A
  • Second generation (Typical)
  • clearance is perfusion dependent- hepatic metabolism opposed to hepatic enzyme activity
  • accumulation of drug with decreased hepatic blood flow
  • maximal excretion of metabolites in first 24 hours
50
Q

CNS effects of droperidol?

A
  • Extrapyramidal reactions
  • cerebral vasoconstrictor (decreased cerebral blood flow but not CRMO2)
  • dysphoria
51
Q

What are CV efffects of droperidol?

A
  • Decrease in systemic BP from alpha blockade- usually minimal (droperidol)
  • antidysrhythmic- protects against epinephrine induced dysrhythmia
  • large doses decrease conduciton along accessory pathways, responsible for tachy dysrhythmias WPW syndrome
  • Prolonged QT interval
  • torsades de pointes
    • have occured at low doses
    • poatients with no risk factors
    • no precise cause
    • some have been fatal
52
Q

What is droperidol’s black box warning?

A
  • All patients get 12 lead prior to administration of droperidol
  • must be monitored prior to and continued for 2-3 hours
  • caution with patients at risk for devleoping QT syndrome
53
Q

What is atypical MOA?

A
  • Multi-receptor antagnoists, less potent dopamine blcoker than typical agents
  • potent serotonin receptor antagonist
  • also blocks receptors for alpha-1, histamine and acetylcholine
  • These drugs were developed with purpose of reducing extrapyramidal symptoms (EPS)
    • decreased risk of EPS and tardive dyskinesia
    • increased risk of metabolic disease
54
Q

What are atypical antipsychotics? What is cloazapine (cloazril)?

Serious side effects?

common side effects?

A
  • Prototype agent (indicated for schizophrenia- especially high suicide risk and bipolar d/o)
  • serious side effects
    • clozapine only- agranulocytosis : decrease WBC, increases risk of serious fatal infections. contraindicated WBC is less then 3500
    • all agents: neuroleptic malignant syndrome (NMS)
    • tonic clonic sz
    • myocarditis
  • Common side effects:
    • weight gain–> leading to metabolic syndrome (prematurely ages CV system), sedation, orthostatic hypotension, anticholinergic s/e
55
Q

What is lithium?

A
  • Mood stabilizer
  • treatment of bipolar d/o (gold standard)
    • bipolar d/o: recurrent extreme mood fluctuations- pattern vary considerably b/w individuals
      • euphoria mania
      • hypomania
      • depression
56
Q

MOA of Lithium?

A
  • Unknown despite considerable research (italics more promising)
    • altered distribution of certain ions )calciu, sodium, Mg?)
    • serotonin receptor blockade?
    • altered glutamate signaling
    • inhibiton of glycogen synthase kinase 3 beta
      • ​glycogen synthase kinase 3 beta normally signals apoptosis
    • promotion of neuronal survivial factors and reversal of atrophy
  • MRI shows increase density of brian matter when on lithium
57
Q

Pharmacokinetics of Lithium?

A
  • Distributed throughout total body H2O and excreted by the kidneys
  • filtered by glomerulus and reabsorbed by the proximal renal tubules
  • proximal reabsorption of lithium and Na is competitive
    • Na depletion can increase plasma concentration of drug by 50%
  • Elimination 1/2 timeis 24 hours
  • Narrow therapeutic index
    • 1.0-1.2 mEq/L for acute mania
58
Q

What are some lithium side effects?

A
  • kidney– evaluate renal fxn every 6 months
    • polydipsia and polyuria >3 L /day
    • impaired renal concentrating ability
      • amiloride (potassium sparing diuretic) can decrease urine volume
  • EKG- Twave changes, flattening or inversion
    • no related clinical effects and reversible
  • Heart block (rare)
    • contraindicated in pateitns with SA node dysfunction
  • Hypothyroidism can develop- more common in females
  • New onset psoriasis/acne
  • fine tremor
  • sedation
  • memory distrubances/cognitive slowing
59
Q

What are signs of mild lithium toxicity?

Significant toxicity?

A

Mild

  • sedation
  • nausea
  • skeletal muscle weakeness
  • Wide QRS
  • AV heart block
  • hypotension
  • dysrhythmia
  • seizure

Significant toxicity

  • >2.5 mEq/L
  • medical emergency
  • aggressive Rx
  • hemodialysis
  • osmotic diuresis and IV Na Bicarb
60
Q

Lithium anesthesia considerations?

A
  • Preoperative labs and EKG (especially Na level!)
  • Anesthetic requirements may be decreased
    • esp CNS depressants
  • Action of neuromuscular blocking agents may be prolonged
  • drug interactions
    • diuretics increase litihium levels/risk of toxicity by lowering Na levels
    • NSAID increase lithium level 60%
    • ACE inhibitors increase litihium levels
    • anticholinegic- urinary retnetion with polyuria can be uncomfortable
61
Q

What are some targets for epilepsy management?

A
  • Inhibit the eizure focus (silence neurons generating abnormal discharge)
  • inhibit spread of the discharge through the CNS

Pharmacotherapy- suppress neuronal firing by:

  • Inhibiting voltage activated ion channels (Na, Ca)
  • Promote the efflux of K= hyperpolarization
  • Antagnoize glutamate (primary excitatory NT of CNS)
  • Enhance the function of GABA-inhibitory NT
62
Q

What are sodium channel blockers’ role in preventing seizures?

A
  • During neuronal firing, Na chennels open to allow Na influx, but pass through an inactive state before truning to resting state
    • Na channel blocker drugs hold Na channel in inactive state slightly longer
  • slowing recovery from this inactive state, can suppress the high freqeuency repeititve firing characteristic of epilepsis
63
Q

What is phenytoin MOA?

A
  • Regulates neuronal excitabiliyt and thereby the spread of seizure activity from a seizure focus by regulating Na and Ca ion transport across neuronal membrane
  • ATYPICAL PHARMACOKINETICS
    • non-linear pharmcokinetics; metabolism is saturable
      • low dose= 1st order kinetics, large dose= zero order kinetic
    • narrow therapeutic window, therapeutic drug monitoring required
64
Q

Pharmacokinetics phenytoin?

A
  • IV formulation- very basic product–> phlentiis, extravasation are concerns
    • pH of 12 and precieptiates in solution with pH of <7.8
  • Not recommended for Im injection- precipitates at site
  • INFUSION NO FASTER THAN 50 MG /MIN IN ADULTS to prevent hypotension and cardiac dysrhythmias
    • 1-3 mg/kg/min in peds or 50mg/min; whichever is slower
  • Highly protein bound0 90% to albumin
    • this matters because of narrow therapeutic window and effect of albumin level
65
Q

What are some dose dependent and non dose dependent side effects of phenytoin?

A
  • Dose related
    • CNS toxicity- nystagmus, ataxia, diplpia
    • vertigo
    • peripheral neuropathy
    • drowsiness
    • cognitive impairement
  • Non-dose related
    • Allergic rash–> Steven johnson syndro
    • hirsutism
    • acne
    • measles like rash
    • hepatotoxicity
    • purple glove syndrome
    • severe congenital malformation
  • GI irritation
  • hepatotoxicity
  • induces CYP450 system- burns thorugh drugs, esp NMB
    • increases metabolism of other antiepileptics, BCP, warfarin, corticosteroids
66
Q

Overview fosphenytoin?

A
  • acts on Na ion channel blockade
  • highly protein bound
  • water soluble phenytoin pro drug
  • used in hospitals for status epilepticus and in neurosurgyer to prevent/treat seizures
    • 10-20 mg /kg IV loading dose
67
Q

What is Tegretol MOA?

A

AKA- Carbamezapine

  • MOA- sodium channel blocker
  • Drug interactions: enzyme inducer, autoinduciton
    • accelerated metabolism of warfarin and OCP are of particular concern
    • grapefruit juice can increase levels
    • phneytoin and phenobarb can decrease levels
68
Q

Adverse effects Tegretol?

A
  • Minimla cognitive impairment: mold CNS effects can occur
  • rash mild–> SJS
  • Hematological effects: aplastic anemia, thrombocytopenia, anemia, leukopenia
  • Inappropraie ADH secretion
  • congenital defects (neural tube defects)

**Used as mood stabilizer in mania and biopolar disorder and in treatment of neuralgias**

69
Q

What is Lamictal?

MOA?

PK?

CNS effects?

S/E?

A

Lamotrigine

  • MOA: Blocks Na channels also decreases glutamate via CCB
    • Decrease NT release
  • PK: metabolism can be induced by other anti epileptics that are inducers (phenytoin, phenobarb, carbamezapine) or inhibited by valproate
  • Braod spectrum of activity
    • can also be used as mood stabilizer
  • CNS effects: sedation, visual disturbances, HA, N/V/depression
  • Rash is major concern (SJS) MUST titrate dose slwoly
70
Q

What is phenobarbital?

A
  • Long acting barbituate
  • MOA:
    • modulation of post synaptic actions of GABA and glutamate
      • more Cl entering cell, hyperpolarization
    • prolong duration of Cl channel opening, limiting spread of Az

S/E

  • Enhances Cyp 450 system
  • Cognitive and behavioral S/E limit usefulness
  • Sedation in adults; hyperactivity in children
  • depression
  • confusion in edlerly
71
Q

What is depakote?

MOA, interaction, S/E

A

Valproate/Valproic acid

  • not seeing as often…
  • MOA:*
  • ​blocks Na channels
  • block T type calcium currents
  • promotes synthesis of GABA

Interactions

  • not metabolized by CYP 450 but inhibits cyp450!
  • when administered with topiramte; high levels of ammonia can accumulate and cause CNS toxicity

S/E

  • N/V, Weight gain, alopecia, thrombocytopenia
  • fatal hepatotoxicty
  • fatal pancreatitis- rare
  • MAJOR congenital malformation- Cat D
72
Q

What are topiramate’s MOA?

A
  • Blocks Na channels
  • enhances GABA
  • blocks Calcium channel
  • sglutamate (excitatory NT) antagnoist
73
Q

What are topiramate’s interactions and adverse effects?

A

Interactions

  • Phenytoin and carbamazepine can increase levels of drug
  • topiramate can increase phenytoin levels

Adverse effects

  • drwosiness, impaired cognition, ataxia, weight loss
  • serious: psychomotor slowing, renal stones, metabolic acidosis, glaucoma, congenital malformation

has FDA indication for migraine prophylaxis

74
Q

What is keppra?

MOA?

Adverse effects?

Pregnancy?

A

MOA: unknown

  • not known to affect GABA receptors
  • may have affects on voltage gated ion channels

Chemical structure and pharmacologic action unique

Adverse effects MUCH less significatn compared to other AEDs

very few drug interactions, not metabolized by CYP 450

Pregnancy safety unclear- cat C, so far no issues

75
Q

Pharmcotherapy for parkinsons?

A
  • Treatment is palliative
    • therapy does not stop preogression of neuronal degeneraiton
  • Goals of therapy- restore dopamine loss1
    • incrase dopamine synthesis
    • increase dopamine release
    • dopamine receptor agnoism
    • decrease dopamine reuptake
    • decrease dopamine metabolism
76
Q

Overview parkinson’s disease?

A
  • Movement d/o with chornic progression, some gneetic risk factors
  • Characterized by
    • dyskinesias
    • muscle rigidity
    • tremor at rest
    • cognitive impairments
  • D/T loss of dopaminergic neruons in substantia nigra at basal ganglia
    • degeneration of nigrostriatal pathway leads to dpeletion of inhibitory NT dopamine
77
Q

What is levodopa/carbidopa?

A
  • Dopamine does not cross BBB
  • immediate precursor, levodopa, does via active transprot
  • carbidopa does not cross BBB but does inhibit peripheral conversion of levadopa to dopamine by blocking peripheral dopamine decarboxylase; therfore, levadopa is available to cross BBB
78
Q

What would have to happen to levodopa dose if we didn’t give it with carbidopa?

A

would have to increase dose significantly because of peripheral conversion dopamine

79
Q

Levodopa Side effects?

A
  • N/V- due to dopamine induced stimulation of chemoreceptor trigger zone
  • CV- alpha, beta responses evoked by higher plasma levels of dopamine result in transient flushing of skin, ST, PVC, PAC, orhtostatic hypotension
  • abnormal involuntary movmt
    • hard to set apart from parkinsons
  • Psychiatric disturbances

Lab measurement

  • urinary metabolites can give false positive for ketoacidsosi
  • transient increase in BUN
  • increase in liver enzymes
80
Q

Levodopa drug interactions?

A
  • Butyrophenones and phenothizines
    • antagnoize effect of dopamine- avoid them!
    • metaclopramide- worsens effects of disease and antagonizes levodopa
    • Droperidol- skeletal muscle rigidity and pulm edema d/t suddent antagonism of dopamine
  • MAO inhibitors
    • interferes with inactivation of catacholes including dopamines
  • Anticholinergic
    • Act synergisitically with levodopa to improve tremor
81
Q

What are COMT inhibitors?

A
  • Prevent breakdown of dopamine–> more levodopa to cross BBB
  • Incease amt of dopamine aviable to CNS (prolongs half life 50-75%)
  • Agents
    • protype: entacapone
      • used with levo/carbidopa
      • AE: similar ot levodoap as it intensifies effects, urine discoloraiton (orange) hallucination
82
Q

What are direct dopamien agonists?

A
  • FOr parkinsons
  • Agents:
    • protoype: pramipexole(mirapex)
    • bromocriptin
    • pergolide
    • ropinirole (requip)
  • Started with dx before levodopa (try to hold off using levodopa because it only works about 5 yrs)
  • MOA: selectively binds to D2 and D3 receptor subtypes; delayed onset of effect 2-3 weeks
  • A/E: N/V. posutral hypotension, hallucinations, vivid dreams, sleepiness, dyskinesias (less than levodopa) impulsvie, high risk behaviors
83
Q

What are some anticholinergics used with parkinson’s D/O?

A
  • Trihexyphenidyl (artane) and benztorpine (cogentin)
  • BLunts effects of excitatory NT acetylcholine correcting blanace b/w dopamine and Ach
  • s/e - confusion, hallucination, urinary retention
84
Q

What is amantadine (for parkinsons)

A
  • Symptomatic improvement of parkinsonian symptoms
  • enhance dopamien rleease into synapse and delay re uptake into nerve endings

(antivrial)

85
Q

What is selegiline?

A
  • Highly selective irreversible inhibitor of MAO b
  • used as adjunct to carbidopa-levodopa
  • drug interactions
    • don’t have to worry so much about meperidine/ephedrine admin, but still avoid them
86
Q

Non pharmacologic rx of parkinsons?

A
  • Deep brain stimulation
    • contorls symptoms if resistant to drug therapy
  • stem cell transplantaiton and other therapeutic mechanisms are under investigation
87
Q

Pathology of alzheimer’s dx?

A
  • Amyloid plaques (amyloid beta)
  • neurofirillatory tangles
  • cholinergic neuron loss
  • current drug therpay not effective
88
Q

Cholintesterase inhibitors and role in alzehimers?

A
  • MOA: inhibits acetycholinesterase, therby increasing acetycholine concentraitons in synapse
  • s/e:
    • Nausea, diarrhaea
    • dizzines
    • HA
    • Bronchoconstriction
  • Examples
    • donepezil (aricept)
    • rivastigmine (exelon)
89
Q

What is memantine role in alzheimers?

A
  • MOA: NMDA receptor antagonist
    • blocking leaky channels to help reduce calcium induced excitotoxicity
    • blocking bleaky channels helps reduce backgorund noise, making signals relatively stronger
  • indicated for moderate to sever AD
  • very modest benefits
  • S/E
    • dizziness, HA, fatigue, sedation, HTN, rash, diarrhea, weight gain, urinary frequency, anemia
90
Q

What are some drugs that induce CYP 450?

A

Phenytoin

Carbamazepine (Tegretol)

Phenobarbital

91
Q

What drug inhibits CYP450?

A

Valproic acid (Depatkote)

92
Q

Which drugs also antagnoize “HCA” receptors (histamine, cholinergic, adrenergic)

A

TCA

Typical antipsychotics

atypical antipsychotics

93
Q

Which drugs are highly protein bound?

A

Fosphenytoin

TCA

Phenytoin

“foster trains (with) protein

94
Q

Which drugs prolong QT?

A

Fluoroquinolones

Typical antipsychotic

Celexa (SSRI)

TCA

Erythromycin

“QT” flamingos typically can’t talk everyday

Advanced Pharm- Test 1 (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions