Exam Three Flashcards
What is GHB metabolized to?
GABA
Which two benzoes yield inactive, water-soluble glucoronide metabolites?
Lorazepam and oxazepam
What drug is used to treat an OD of benzodiazepines?
flumazenil
Which benzo is an antispasmodic?
Diazepam
What is the exact MOA of benzodiazepines?
increase frequency of chloride channel opening of GABA-A receptor
What two subunits of the GABA receptor do benzodiazepines bind?
alpha1
gamma2
What effects do the α1 subunits of the GABA receptor mediate?
sedation/amnesia/ataxic
Which two benzos are weakly active and short lived?
Alprazolam and triazolam
Which two benzodiazepines undergo Phase I metabolism that yields two relatively long-lasting metabolic products?
diazepam and flurazepam
Which two benzos kinetics are not influenced by age? Which benzo is influenced by age?
lorazepam and oxazepam
diazepam
Flumazenil may induce seizures in patients taking what other three drugs?
TCA
alcohol
barbiturates
What are the two newer benzodiazepine hypnotics?
Eszopiclone
Zolpidem
The newer benzodiazepines used for sleep only interact with what subunit of the GABA receptor?
α1
What CYP enzyme metabolizes the newer benzodiazepines?
3A4
Name three barbiturates. What are their functions?
Pentobarbital = medically induced coma
Phenobarbital = anti-convulsant
Thiopental = anesthesia
What is the difference between benzos and barbs regarding their metabolsim?
barbs dont have active metabolites
Are barbiturates weak acids or weak bases?
weak acids
What is the specific MOA of barbiturates?
increases open time of GABA chloride channel
What is the function of MT1?
sleep onset
What is the melatonin receptor agonist?
Ramelteon
What is the function of MT2?
circadian pattern
Where in the brain does Ramelteon work?
suprachiasmatic nuclei
What two CYP enzymes degrade Ramelteon?
2C9
1A2
Does Ramelteon produce dependence?
no
What is the 5HT agonist Anxiolytic? Which specific isoform? Agonist or antagonist?
Buspirone
5HT1A
agonist
What is an advantage of buspirone compared to benzodiazepines for treating anxiety?
Buspirone is only an anxiolytic
Which specific serotnin receptor isoform is Buspirone known to activate? What does activation of this receptor do to serotonin release?
5HT1A
decrease serotonin release
What are the two anti-histamine hypnotics?
diphenhydramine and hydroxyzine
Does Buspirone potentiate the effects of other CNS depressants?
no
What is the function of BDNF? What disease state can a decrease in BDNF be seen?
promote neural growth and survival
depression
What is the main adverse effect of 5HTreuptake blockade?
GI disturbances
What are the two non-selective MAO-A and MAO-B inhibitors? Reversible or irreversible?
phenelzine and Tranylcypromine
irreversible
What is the selective MAO-B inhibitor? What disease is treated at low dose? What disease is treated by high dose?
Selegiline
LOW = parkinsons
high = depression
What does MAO-A degrade?
serotonin
norepinephrine
dopamine
What does MAO-B degrade?
dopamine
Which MAO is preferentially used to treat Parkinsons?
Selegiline
What are the three tricyclics?
Imipramine
Amitriptyline
Desipramine
What two compounds does Imipramine inhibit the reuptake of?
5HT and NE
Why can TCAs cause lethal cardic arrhythmias?
blockade of sodium and calcium channels
Withdrawl of what drug can cause Discontinuation Syndrome?
SSRIs
What are the two main symptoms of Discontinuation Syndrome?
dizziness and paresthesias
What two compounds do the SNRIs inhibit the re-uptake of?
5HT and NE
What is a non-depressive symptom that SNRIs are used to treat?
chronic pain
What is the main 5HT2 antagonist? Which other receptor can trazodone block?
Trazodone
H1
What is the most common use for trazodone?
insomnia
What two compounds does Bupropion inhibit the re-uptake of? What is bupropion used to treat?
DA and NE
smoking cessation
What receptor does Mirtazapine block?
α2 antagonist
What two compounds Mirtazapine increase the release of?
5HT and NE
Other than α2, what three receptors can Mirtazapine block?
5HT2 and 5HT3 and H1
What is the treatment of choice for Bipolar disorder?
Lithium
What severe condition are valproic acid and carbamazepine used to treat?
acute mania
What is the most common side effect of lithium?
tremor
Other than tremor, what are three side effects of lithium?
nephrogenic diabetis insipidus
hypothyroidism
skin issues
What two drugs are contraindicated in lithium use? Why?
loop and thiazide
increase lithium absorption
Where in the kidney is the primary site of lithium absorption?
PCT
What is the most common site for the origination of a seizure?
temporal lobe
What are the two MOAs of valproic acid?
blocks GABA transaminase
blocks Na+ channels
What is the MOA of vigabatrin?
blocks GABA-transaminase
What are the two MOAs of gabapentin?
block L-type
increase GABA release
What is the MOA of tiagabine?
blocks GABA re-uptake
What drug do most anti-seizure drugs interfere with the synthesis of? Why?
oral contraceptives
induction of p450
What neurotransmitter can phenytoin enhance the release of?
GABA
What are the two main side effects of phenytoin?
nystagmus
gingival hyperplasia
Why can phenytoin cause anemic issues?
decreases folate levels
What is the drug of choice for trigeminal neuralgia?
carbamazepine
What are the two major side effects of carbamazepine?
leukopenia
SIADH
What is the drug of choice for seizures in infants?
phenobarbital
Other than treating seizures in infants, what condition is phenobarbital used to treat?
status epilepticus
Primodine is similar to what drug? What does primodine get converted into?
phenytoin
phenobarbital
What is the drug of choice for petit mal seizures? What patient population are petit mal seizures most often seen?
ethosuximide
children
What are the two MOAs of valproic acid?
inhibits Ca2+ influx
blocks GABA-T
What type of seizure is valproic acid used to treat?
petit mal
According to Duric, what are the two toxicities of valproic acid?
hepatotoxic
teratogenic
What is the preferred initial drug for status epilepticus?
Diazepam
What are the two MOAs of lamotrigine?
block Na+ and Ca2+ channels
What specific antiseizure drug does Duric say can cause Steven-Johnson Syndrome?
Lamotrigine
What is the MOA of tigabine?
block reuptake of GABA
What are the two MOAs of topiramate?
block AMPA
What is the MOA of baclophen?
GABA-B agonist
What is the BG Coefficient?
a measure of a drugs solubility in blood
What is anesthetic potentcy correlated to?
fat solubility
Will increased cardiac output increase or decrease the induction of anesthesia?
decrease
What is the MAC?
[anethetic] in the inspired air at equilibrium when 50% of patients do not sense noxious stimuli
What is the most adverse side effect of halothane during anesthesia?
malignant hyperthermia
What is the most adverse side effect of halothane during postop?
hepatitis
What is the most adverse effect of enflurane?
CNS induced seizuring
What are the two constituents of the diencephalon?
thalamus and hypothalamus
What are the three monoamines in the brain?
NE, 5HT, dopamine
Which benzo can be used as a date drug? Why?
flunitrazepam
induction of amnesia
Is selegilie reversible or irreversible?
irreversible
What condition is high dose selegiline used to treat?
depression
What are the two main side effects of all MAOIs? Antagonization of which receptor mediates these effects?
orthostatic hypotension and weight gain
H1
Which class of drug can be used to treat neuropathic pain?
TCAs
What two transporters do TCAs block?
SERT and NET
What three receptors can TCAs directly antagonize?
cholineric, histaminergic and α-adrenergic
What is Imipramine used to treat? Why?
enuresis
Imipramine is anti-cholinergic
What is the result of TCAs antagonizing cholinergic receptors?
GI issues
What is the result of TCAs antagonizing histamine receptors?
sedation
What is the result of TCAs antagonizing α1-adrenergic receptors?
orthostatic hypotension
What can TCAs produce in elderly patients?
delirium
What ion channels can TCAs effect? What can this lead to?
Na/K ATPase
arrhythmias
What are the three C’s of TCAs?
coma
convulsion
cardiac arrhythmias
What is the short term side effect of SSRIs?
GI disturbances
What is the long-term effect of SSRIs?
sexual dysfunction
Which SSRI is most likely to produce Serotonin Syndrome?
Fluoxetine
What are the two SNRIs?
venlafaxine and duloxetine
What other drug is the side effect profile of SNRIs similar to? What is the difference
TCAs
not as severe
What is the side effect profile of 5HT2?
GI disturbances
Which two classes of anti-depressants should never be combined?
TCAs and SSRI
Which two drugs can be added to lithium to treat Bipolar Disorder?
valproic acid
carbamazepine
Which lobe of the brain is most susceptible to developing a seizure?
temporal lobe
What three drugs are used for partial seizures?
Carbamazepine, Phenytoin, Valproate
What three drugs are used to treat tonic clonic seizures?
carbamazepine, phenytoin, valproate
What two drugs are used to treat Petit Mal seizures?
Ethosuximide and valproate
What two drugs are used to treat myoclonic seizures?
Clonazepam and valproate
What four drugs are used to treat status epilepticus?
lorazepam, diazepam, phenytoin, fosphenytoin
Which anti-epileptic is considered safest during pregnancy?
Phenobarbital
What is the difference between phenytoin and fosphenytoin?
fosphenytoin is more water soluble
Which antiepileptic possesses zero order elimination kinetics?
Phenytoin
What neurotransmitter does phenytoin promote the secretion of? Decrease the release of?
GABA
glutamate
What are the CNS defects in phenytoin?
ataxia and nystagmus
Which anti-epileptic is a teratogen?
Phenytoin
What are the two MOAs of carbamazepine?
sodium channel blocker
GABA receptor agonist
What is the new metabolite of carbamazepine?
Oxacarbazepine
What is the drug of choice for trigeminal neuralgia?
carbamazepine
What drug can cause SIADH?
carbamazepine
What three drugs can carbamazepine have potential interactions with?
Phenytoin,
valproate
phenobarbital
What drug is metabolized into phenobarbital?
Primidone
What is the MOA of Ethosuximide?
block T-type Ca2+ channels
What are the two main side effects of valproate?
liver damage and teratogen
Which anti-epileptic can prevent neuropathic pain?
Gabapentin
What is the MOA of pregabalin?
functions similar to GABA
What is the MOA of baclofen?
GABA-B agonist
How does diazepam reduce spasticity?
increases descending inhibition of α-MNs
What is the MOA of ketamine?
NMDA receptor antagonist
Does ventilation rate effect the drugs more with higher or lower soluibilities?
higher
Does a lower solubility make a drugs concentration in the blood rise faster or slower?
faster
Does a higher cardiac output mean a drug will reach the brain faster or slower?
slower
Does being less soluble mean a drug is eliminated faster or slower?
faster
What are the three side effects of halothane?
decreased CO/hypotension
hepatitis
What is the side effect of enflurane?
jerking/twitching
What is the advantage of sevoflurane?
can be used in those with airway disease
When is ketamine contraindicated?
pt’s with psychiatric history
Where is a spinal block injected? Is a spinal block reversible?
subarachnoid space
No
Where is an epidural block injected?
extradural space
Do amides have one or two I’s?
two
Do ester have one or two I’s?
one
Are all local anesthetics weak bases or acids?
bases
Which has a shorter half life, ester or amides?
esters
Where are amides metabolized? By what enzyme?
liver
p450
Where are esters metabolized? By what enzyme?
blood
butrylcholinesteras
Which are more sensitive to local anesthetics, myelinated or unmyelinated nerves?
myelinated
Does a higher pH means more or less of a local anesthetic is needed?
higher = less is needed
What does calcium do to local anesthetic dose?
high calcium requires more local
Would a LA ester or amide more likely cause an allergic rxn?
ester
Which metabolite of local anesthetics can cause an allergic reaction?
PABA
Which preservative used in local anesthetics can cause an allergic reaction?
methylparaben
Which local anesthetic can cause systemic allergic reaction with particular cardiac toxicity?
Bupivicaine
Which drug is used to treat an allergic reaction to a local anesthetic?
IntraLipid
What is the clinical use of bupivacaine?
labor analgesia
Which local anesthetic is used in its topical form only? Why?
benzocaine
methemoglobinemia
What is the only use of chloroprocaine?
epidural
What is contained in Exaprel-Liposome? Why is this special?
Bupivicaine
time-released
What two drugs are contained within EMLA?
lidocaine and prilocaine
What three drugs are contained within TAC?
tetracaine, adrenalin and cocaine
What two regions in the brain have profound loss of neurons during Alzheimers disease?
cortical and hippocampal neurons
What type of neurons and where are lost during Huntingtons Disease?
dopaminergic from basal ganglia
What type of neurons and where are lost during Parkinsons Disease?
dopaminergic from basal ganglia
What two proteins accumulate during Alzheimers?
β-amyloid
Tau
What is the precursor protein for β-amyloid?
β-amyloid precursor protein
What protein accumulates during Parkinsons?
α-synuclein
What neurotransmitter is hypothesized to be deficient during Alzheimers? What is the significance of this?
acetylcholine
loss of acetylcholine correlates to severity of disease
What chromosome is β-amyloid precursor protein located on?
21
Does β-amyloid accumulation correlate to disease severity?
no
What two proteins are defective during early Onset Alzheimers? What is the consequence of this?
PSEN1 and PSEN2
overproduction of β-amyloid
What protein is defective during Late Onset Alzheimers? What is the consequence of this?
ApoE
accumulation of β-amyloid
What is the post-translational modification made to tau proein during Alzheimers?
hyper-phosphorylation
Current treatments for Alzheimers aim to slow down the activity of what two enzymes?
acetylcholinesterase and butrylcholinesterase
What is another name for Donepizil?
aracept
Which Alzheimers drug inhibits AchE and ButE?
Rivastigmine
What is the advantage of Rivastigmine over Donepezil?
rivastigmine has less GI issues
What is the MOA of Galantamine?
potentiates nAchR
What is the MOA of memantine? What disease?
non-competitive antagonist of NMDA
Alzheimers
What disease is Memantine used to treat?
Alzheimers
What anti-depressant should be used in Alzheimers?
SSRIs
Which anti-depressant should be avoided in Alzheimers?
TCAs
What are the two characteristics of Psychosis?
delusions and hallucinations
Rearding Schizophrenia, what is a positive symptom?
manifestation of abnormal behavior
Rearding Schizophrenia, what is a negative symptom?
absence of normal behavior
What three other receptors are implicated during Schizophrenia?
5HT2A
5HT2C
NMDA
In addition to D2, what other two receptors are inhibited by atypical antipsychotics?
5HT2A
5HT2C
Which endocrine disorder can antipsychotics produce?
Hyperprolactinemia
Which two antipsychotics can cause weight gain?
Clozapine and Olanzapine
Which antipsychotic is known to cause the most Extra-pryamidal syndrome side effects ?
risperidone
Which two antiepileptics are associated with the least effect on EPS?
clozapine and quetiapane
Which cytochrome enzyme works on most opiates?
CYP2D6
Which Phase II metabolism is done tomost opiates?
Glucoronidation
Which G-protein are most opioid receptors coupled to?
Gi
Which type of interneuron can opioids block?
GABAergic
Where in the body can opiates can reflexive cerebral vasodilation? What situation would make their use contraindicated?
reflexive cerebral vasodilation
head trauma
What part of the brain do opiates activate that can suppress the cough?
CTZ
Why can opiates cause urticaria?
degranulation of mast cells
Opiates used in combination with MAOIs can cause what two severe reactions? Which opiate specifically?
HTN and hyperpyrexia
Meperidine
Which opiates metabilite can act as a convulsant?
Meperidine
Which opiate can also inhibit the reuptake of 5HT/NE?
Tramadol
Which opiate is 7-10x more potent than morphine?
hydromorphone
By causing inhibition of GABAergic interneurons, opioids lead to the enhanced release of what neurotransmitter? What can this lead to?
dopamine
dependence
What is the clinical use of doxapram? What two factors does doxapram increase?
respiratory stimulant
rate and tidal volume
What is the main clinical use of Theophylline?
bronchial smooth muscle activator
What two drugs should be avoided if taking amphetamines?
SSRIs and MAOIs
How do analeptic drugs function?
decrease inhibitory neurotransmitter release
How do methylxanthines function?
decrease release of adenosine
What three neurotransmitters does Cocaine inhibit the reuptake of?
DA/5HT/NE
What part of the brain is activated by cocaine?
Ventral Tegmental Area
Which stimulant can cause Steven Johnson Syndrome? What patient population is this drug not FDA approved for?
modafinil
kids
What percent of ADHD is hyperactive predominant?
10%
What percent of ADHD is Inattentive predominant?
30-40%
What percent of ADHD is combined predominant?
50-60%
What two lobes of the brain are particularly effected during ADHD?
frontal lobe and temporal lobe
Which specific part of the frontal lobe is particularly affected during ADHD? Where does this part of the brain project?
Dorsolateral prefrontal cortex
ACC
What is the MOA of atomoxetine?
NE reuptake inhibitor
What is the MOA of Modafinil?
releases histamine from Tuberomamillary Body of the hypothalamus
Where does the VTA project to in order to produce drug addiction?
Nucleus Accumbens
What is the relative risk of CNS depressants?
3
What three organs are responsible for elimination of alcohol?
Liver, Kidneys and Lungs
What is the difference between women and men in the processing of ethanol?
women have lower first pass effect
What enzyme is inhibited by Fomepozil?
alcohol dehydrogenase
When is MEOS activated?
chronic alcohol consumption
What does ethylene alcohol get oxidized to? What enzyme?
oxalate crystals
Alcohol Dehydrogenase
What enzyme does Disulfarim inhibit?
Aldehyde Dehydrogenase
What are the two CNS MOAs of ethanol?
potentiates GABA-A
inhibits NMDA
Which receptor does alcohol inhibit that produces its amnesiac effects?
antagonize NMDA
What drug can ethanol potentiate? What compound is created?
cocaine
cocaethylene
What drug can reduce the risk of alcohol relapse? What type of drug is this?
Naltrexone
mu-opioid antagonist
What three benzos are most likely to be abused?
Alprazolam/Diazepam/Flunitrazepam
How can benzos produce dependence? Which GABA receptor?
disinhibition of dopaminergic neurons of VTA
GABA-A
What is the MOA of GHB?
same as benzo but via GABA-B
Which receptor does MDMA block?
SERT
What are two major side effects of MDMA?
hyperthermia and dehydration
What neurotransmitter does LSD increase the release of? Where is this accomplished? Via what structure?
glutamate
cortex
thalamus
What receptor is activated by LSD? Activation of this receptor is correlated to what property of the drug?
5HT2A
potentcy
Does LSD stimulate dopamine release?
no
What receptor does ketamine block? What two areas of the brain does ketamine decrease activity?
NMDA
cortex and limbic system
How do opiates produce euphoria? Which isotype?
inhibition of GABAergic neurons onto VTA
mu
How do opiates produce dysphoria? Which isotype?
inhibition of VTA dopaminergic neurons
kappa
How is morphine formed from codeine?
demethylation
How is morphine formed from heroin?
de-acetylated
What is the MOA of cannabinoids to produce euphoria?
disinhibits VTA dopaminergic neurons
What is the MOA of nicotine to produce euphoria? What two parts of the brain?
NAchR on VTA dopaminergic neurons
Nucleus accumbens and PFC
What two drugs have been known to aid in smoking sessation ?
Bupropion
Varenicline
Which TCA is used to treat neuropathic pain?
Desipramine
What is the side effect of Imipramine?
sedation
Which two SSRIs are at the greatest risk of Discontinuation Syndrome?
Paroxetine and Sertraline
Which SNRI has mixed affinity? Which has a higher affinity for NE?
Duloxetine = balanced
Venlafaxine = higher affinity for SERT
Which SNRI can be used for chronic pain?
Duloxetine
Which two p450 enzymes do anti-depressants particularly effect?
2D6 and 3A4
Which three antidepressants are potent inhibitors of 2D6?
Paroxetine
Fluoxetine
Fluvoxamine
What is Primary Epilepsy? Secondary?
Primary = idiopathic
Secondary = identifiable
What is a Complex Partial seizure ?
seizure that starts in one part of the brain and moves to others
Atonic seizures are most often seen in what patient population?
children
Which antiepileptic can cause hirsutism?
phenytoin
Which antiepileptic can cause osteomalacia?
phenytoin
Which antiepileptic is a potent inducer of p450?
carbamazepine
What two drugs should lamotrigine not be administered with ?
Valproate
Carbamazepine
Which benzo is used for pre-op anxiolysis?
Midazolam
What kind of complications can Nitrous Oxide produce in a female?
pregnancy complications
What is a potential drawback to Isoflurane? WHat is the good thing about Isoflurane?
long duration of action during post-op
can be used in pt’s with poor liver/kidney function
Does desflurance have a fast or slow onset?
fast
Does desflurance have a fast or slow recovery?
fast
What is the potential drawback to desflurane?
bronchial irritant
Which anesthetic can cause a macrocytic anemia?
Nitrous oxide
Which drug can replace propofol as an induction agent? When?
Midazolam
pt’s with CV of pulmonary issues
What is the MOA of most local anesthetics?
blockade of voltage gated Na+ channels
Where do most toxins bind voltage gated Na+ channels?
extracellular
What is the clincal use of articaine?
dental anesthetic
What is the clinical use of cocaine?
ENT anesthetic
What is exaprel?
long lasting bupivicaine
Is lidocaine an injectable or topical?
both
According to Duric, what three parts of the brain can Parkinsons spread to?
brainstem
cortex
hippocampus
Where does the substantia nigra project?
striatum
What are the two parts of the striatum?
caudate and putamen
During Parkinsons, there is a reflex increase in what neurotransmitter?
acetylcholine
Which pathway is overactive during Parkinsons?
indirect
What neurotransmitter is released in excess during Parkinsons? What part of the brain?
glutamine
Subthalamic Nuclei
What drug is L-dopa coadministered with? What is the MOA of this drug? What two symptoms does L-DOPA treat?
Cardidopa
inhibits DOPA decarboxylase in periphery
bradykinesia and rigidity
What B vitamin is a cofactor for DOPA decarboxylase?
B6
What three drugs are dopamine receptor agonists?
Pramipexole
Ropinirole
Apomorphine
What are the two MOA-B Inhibitors used to treat Parkinsons?
Rasagline
Selegiline
What is the peripheral COMT Inhibitor?
Entacapone
What is the central and peripheral COMT Inhibitor? What is the toxicity of this drug?
Tolcapone
liver toxicity
Which antiviral has anti-PD effects?
amantidine
What is the side effect of amantidine?
Livedo Reticularis
What are the two anti-muscarinics to treat PD?
Benztropine
Trihexyphenidyl
What two effects are reduced by Benztropine and Trihexyphenidyl?
tremor and rigidity
What effect of PD is not reduced by Benztropine and Trihexyphenidyl?
Bradykinesia
Excessive activity of the of brain system is hypothesized to cause psychosis? Which neurotransmitter?
excessive limbic activity
dopamine
Which type of antagonist can exacerbate the psychosis of schizophrenia?
NMDA antagonist
What are the two serious consequences of Neuroleptic Malignant Syndrome?
HTN and hyperthermia
Which two CV effects do opioids produce?
bradycardia
hypotension
What is the medical use of caffeine?
apnea of prematurity
What is the MOA of atomexitine?
NE reuptake blocker
What drug has the fastest onset and recovery of the general anesthetics?
Desflurane
Are higher frequency or lower frequency nerves more sensitive to local anesthetics?
higher
What are the thre anti-psychotics used to treat Alzheimers?
Risperidone, Clonzapine, Quietapine
Atypical
What do Lewy Bodies contribute to the formation of?
free radicals
What is the #1 main adverse effect of L-DOPA?
GI disturbances
Which two antipsychotics are least associated with EPS?
clonzapine and quietapine
Which beverage can contain tyramine?
chianti
What is venlafaxine used to treat?
severe depression
What is duloxetine used to treat?
neuropathic pain
Which anesthetic can produce strange dreams?
ketamine
What is the use of apomorphine?
rescue drug for L-dopa induced dyskinesia
Which two drugs are contraindicated in pt’s suffering from psychosis? Why?
ketamine and phenylcyclidine
NMDA antagonists
What is the main side effect of neuroleptics?
extra-pyrimidal symptoms
Why are atypicals used more than typicals?
atypicals have less EPS syndromes
Atypical antipsychotics antagonize what receptor?
5HT2A and D2
Do opioids reduce or increase the threshold for seizures?
reduce
How is fentanyl administered? How long does it last?
transdermal patch
72 hours
Which amphetamine carries a potential suicide risk in children?
atomexitine
Which general anesthetic has excellent minute to minute control?
Desflurane
