misc neuro pharm Flashcards
CNS organization: integration of sensory relays?
thalamus
CNS organization: temp, appetite, emotional, hormonal regulation?
hypothalamus
CNS organization: respiration and CV fxn?
pons and medulla
CNS organization: control of consciousness, arousal, alertness?
reticular formation
do barbituates & alcohol follow a linear or non-linear slope?
linear slope: higher doses need for hypnosis can lead to anesthesia, and can ultimately repress respiratory and vasomotor centers
are barbituates or benzos safer?
benzos; b/c have non-linear slope
for benzos to be effective sedative-hypnotics, where must the electronegative substituent be?
EN substituent must be in the 7 position (ie. halogen or a nitro group
which benzos are not affected by age?
lorazepam, oxazepam
are eszopicolone and zolpidem considered to be benzos?
NO, they are benzo-like
which anxiolytic is non-sedating?
buspirone
MOA of buspirone?
5HTA1 partial agonist
which benzo is the date rape drug?
flunitrazepam
which drugs are contraindicated with benzos?
those that create additive CNS depresiion (EtOH, opioids, anticonvulsants, phenothiazine, antihistamines, TCA)
which drug is a melatonin receptor agonist?
ramelteon
main issues with initiation of antidepressants?
- delay of therapeutic response (can take 2-4 weeks)
2. side effects can limit usage (high risk of AE)
what are the hypotheses of depression?
- Monoamine/biogenic amine hypotheses
2. Neurotrophic hypotheses
what is the monoamine/biogenic amine hypothesis?
deficiency in the level of 5-HT, NE & DA projecting from pontine & midbrain–>cortical&limbic
what is the neurotrophic hypothesis?
loss of brain derived neurotrophic factor (BDNF)–>loss of brain fertilizer
MAO-A targets what?
tyramine, NE, 5HT, DA
mAO-B targets what?
DA
which class of antidepressants are termed “hip breakers” of elderly?
TCA
what are the early sx of serotonin syndrome?
lethargy, restlessness, mental confusion, flushing, diaphoresis, tremor
if a SSRI is suddenly discontinued, how long may it take serotonin syndrome to present?
1-7 days
are ssri or snri preferred for tx of chronic pain?
snri (specifically, duloxetine)
MOA of trazadone?
5HTA2 blocker
which types of antidepressants must you avoid mixing?
MAOI, TCA, SSRI
which antidepressants are potent inhibitors of CYP2D6?
paroxetine, fluoxetine, fluvoxamine
definition of a seizure
abnormally excessive, synchronous, and rhythmic firing
what are the 3 main causes of seizures?
- CNS injury
- congenital abnormalities
- genetic factors
when the underlying cause of epilepsy is unk, what is it termed?
primary (idiopathic) epilepsy
majority of seizures fall into what type?
complex partial (temporal lobe) & tonic clonic (grand mal)
types of partial (focal) seizures
simple partial, complex partial, partial becoming generalized
(they all start in a specific portion of he brain, remain there)
name that seizure: minimal spread of abnormal neuronal discharge, no LOC
simple partial seizure
name that seizure: starts in small brain area–>quickly spreads to other ares that affect awarness; altered consciousness, automatisms (lip smacking)
complex partial seizure
name that seizure: partial seizures that spread throughout brain and progresses to a generalized seizure
partial becoming generalized
types of generalized seizures (7)
- absence (petit mal) 2. tonic clonic (gran mal) 3. tonic 4. atonic 5.clonic and myoclonic 6. infantile spasms 7. status epilepticus
name that seizure: involve entire brain with global EEG change & bilateral manifestation, sudden onset & abrupt cessation, brief LOC, children
absence (petit mal)
name that seizure: tonic spasms and major convulsions of entire body (bilateral), LOC, aura, tonic phase w/ muscle tensing/tremor, clonic phase with convulsions, sleep
tonic clonic (gran mal)
name that seizure: continuous or very rapid recurring seizures, usually tonic clonic; medical emergency requiring immediate tx
status epilepticus
what are the 3 stages of epileptic seizures
- initiation
- synchronization of surrounding
- propagation–>recruitment of normal neurons
how successful are antiepileptic meds in eliminating seizures?
effective in 2/3 patients; but 20% do not respond
anticonvulsant drugs bind to Na channels during which state?
inactive state—>prolong Na channel inactivation
result of inhibiting VG Na channel?
decr in sustained, high frequency, repetitive discharge
result of reducing activity of Ca channels?
reduce Ca influx–>decr NT release
name the drugs that have interactions with phenytoin
barbituates, warfarin, carbamapazine, saliclyates, valproic acid
what is the drug of choice for absence seizures?
ethosuximide or valproic acid
what is the anti seizure drug of choice for pregnancy?
phenobarbital
what limits the use of lorazepam and diazepam to tx status epilepticus?
tolerance, sedative effects
which anticonvulsant can create stevens johnson syndrome?
lamotrigine
what drugs can be used for status epilepticus?
phenytoin, benzodiazepines, phenobarbitol
what is the triad of anethesia?
asleep, pain free, still
in addition to CV issues, respiratory disease, and allergies, what hx must you know before doing anesthesia?
famhx of malignant hyperthermia
anesthetics with higher or lower solubility are more affected by ventilation rate?
partial pressure of anesthetics with higher solubility are affected by vent rate (ie. halothane vs NO)
what is the ostwald coefficient?
blood: gas partiton coefficient (solubility in blood)
lower ostwald coefficient = lower solubility in blood = what?
more rapid rise in partial pressure of blood–>faster induction, lower potency (ex. NO)
how to determine an anesthetics agents solubility in lipid?
brain: blood partition coefficient
high blood flow/solubility of an anesthetic agent mean what type of induction?
low induction–> slower onset (b/c gets more rapidly disseminated everywhere)
if an anesthetic agent is less soluble, will it be faster or slower to eliminate?
faster elimination (faster induction)
lower MAC = what potency anesthetic?
more potent anesthetic
what type of drugs can decrease the MAC of inhaled anesthetics when admin together/?
CNS depressants
why use NO for fast induction with other general anesthetics?
decr general induction time, decr req’d conc of primary agent, decr toxicity of primary agent
halogentated inhalables are used for what?
maintenance anesthesia
which anesthetic is assc’d with post-op hepatitis?
halothane
why is enflurane not as popular as other halogenated agents?
CNS stimulation effects–>EEG convulsive pattern, jerking, twitching
which halogenated agent has a lower toxicity and can be used in sick patients with impaired kidneys/liver?
isoflurane
which halogenated agent has teh fastest onset & recovery?
desflurane
what is the most commonly used halogenated agent?
sevoflurane
into what space do you inject a spinal block??
subarachnoid space
into what space do you inject an epidural block?
extradural space
all local anesthetics are……..?
weak bases
what forms can local anesthetics take?
cationic form–>active at Na receptor
uncharged form–>lipid penetration of membranes
what does a larger fiber size indicate for the minimum anesthetic concentration (Cm)?
incr Cm (requires larger amt local anethesia to block)
list the order that fibers would be blocked by local anesthesia?
B fibers 1st, then C-fibers, A delat, A gamme, A beta, A alpha
does a lower or higher pH correlate with a lower Cm?
more alkaline will require less LA
does a lower or higher Ca conc correlation with a higher Cm?
higher Ca concentration = higher Cm
what is the most important factor that affects reversal of LA?
absorption into circulation
what is a potential issue with admins of an ester LA?
ppl may be prone to PABA allergic rxn (PABA is what esters is metabolized into)
what is the tx for LAST (local anesthetic toxicity)?
IV lipid emulsion or intralipid–>forms a lipid sink to absorb circulating lipophilic toxin
what would be considered negative sx in schizophrenia?
flat affect, socially withdrawn, inattentiveness
what is the dopamine hypothesis of schizo?
hyperactivity of mesolimbic/mesocortical DA system–>excessive limbic DA activity
what is the glutamate hypothesis of schizo?
hypofxn of NMDA receptors on GABAergic interneurons
what are neuroleptics/direct antipsychotics associated with?
extrapyramidal side effects
what are some extrapyramidal sx?
PD-like syndrome, akathesia, dystonia, tardive dyskinesa
besides EPS effects, what are some other anti-D2 effects?
antiemetic, hyperprolactemia, weight gain, anticholinergic effects, antihistaminic (Sedation), anti-adrenergic (postural hypotension)
metabolic syndrome is higher risk in typical or atypical antipsychotics?
atypical
tops reasons that ppl stop antipsychotics?
lack of efficacy, cannot tolerate SE, weight gain, EPS, sedation, sexual SE
how many ppl re affected with PD?
1% of ppl >65
how many ppl are affected with AD?
10% of ppl>65
how long does it take for death to ensue after onset of AD?
6-12 yrs
key pathological findings of AD?
- neuronal degeneration, cortical atrophy
- neuritic plaques
- neurofibrillary tangles
what is the cholingic hypothesis of AD?
degeneration of subcortical cholinergic neurons–>deficiency of Ach–>affects memory formation areas
does accumulation of beta amyloid plaques correlation well with neuronal loss?
no
what is the MT-assc’d tau hypothesis of AD?
hyperphosphorylation of tau–>neurofibrillary tangles–>MT disintegration & instability–>collapse of neuronal transport system
what are the 3 AchE inhibitors used for AD?
donepezil, galantamine, rivastigmine
which AchE inhibitor has a long half life (70-80 hrs)?
donepezil
which AchE inhibitor also inhibits butyrylchlinesterase?
rivastigmine
which AchE inhibitor is admin via transdermal patch?
rivastigmine
cholinesterase inhibitors all ave what SE?
N/V, diarrhea + SLUDGE (salivation, lacrimation, urinary incontinence, diarrhea, GI cramps, emesis)
which AD drug is a non-competitive antagonist of NMDA glutamate receptor?
memantine
best drugs to give to AD patients with psychosis?
atypical antipsychotics
best drugs to give to AD patients with depression.anxiety?
SSRI (esp setralin, citalopram)
which antidepressants should you def avoid in AD?
TCA due to anticholinergic effects + orthostatic hypotension
aggregation of misfolded proteins is what disease?
PD
PD can affect what brain regions?
basal ganglia, brainstem, hippocampus, cerebral cortex
what are the cardinal signs of PD?
bradykinesia, muscular rigidity, resting tremor, postural instability
pathophysiology of PD?
- loss of DA neurons in substantia nigra that project to striatum (putamen + caudate nucleus)
- incr activity of Ach in basal ganglia
what are some of the genetic factors that characterize PD?
alpha synuclein accumulation, lewy body formation, incr production of free radicals
which motor pathway becomes more dominant in PD?
indirect pathway
adverse effects of levodopa
dyskinesias, response fluctuations, on-off phenomenon, drug holiday, GI disturbance, postural hypotension, tachycardia, behavioral disturbance
what class of PD drugs is assc’d with lower incidence of the response fluctuations that are associated with L-dopa?
DA-receptor angonists
what type of drug can you start a PD patient on once they start having a diminished response to levodopa?
rasagiline, selegiline (MAO-B inhibitors)
what drug increases DA release?
amantidine
livedo reticularis
SE of amantidine
benztropine and trihexyphenidyl have what tx effects for PD?
reduces tremor and rigidity
NOT bradykinesia
what are opioids generally used for?
euphoria, analgesia, sedation, diarrheal relief, cough suppression
what are the 2 naturally occuring opioids?
morphine + codeine (opium)
when a drug is extracted from the exudate of the poppy?
opiate
which opioids are endogenous?
endorphins, enkephalins, dynorphins
what are the opioid receptors?
mu 1, mu 2, kappa, delta
which opioid receptor is located outside the spinal cord?
mu 1; central interpretation of pain
which opioid receptor is located in the CNS?
mu 2
what is disinhibition?
when opioids block inhibitory GABAergic interneurons–>enhanced inhibition of nocioceptive processing
what are the sites of action of opioids?
- periaqueductal gray area (midbrain)
- rostral ventral medulla (brainstem)
- locus coerulus (pons in brainstem)
what are the analgesic effects of opioids (2)?
sensory and affective
what do opioids do to respiratory system?
inhibits brainstem respiratory mechanisms–>less sensitive to pCO2 tension
what can occur in opioid OD when brainstem not responsing to incr pCO2?
reflexive cerebral vasodilation
how do opioids suppress the cough center?
via the brainstem chemoreceptor trigger zone
how do opioids stimulate emesis?
via the brainstem chemoreceptor trigger zone
how do opioids stimulate constipation?
decr gut motility, incr tone of intestinal smooth muscle
CV effects associated with opioids?
hypotension, bradycardia
receptor down regulation and desensitization is what type of tolerance?
physiological tolerance
what is cross tolerance?
tolerance to one drug produces tolerance to another drug (ie. someone tolerant to morphine will also be toelrant to fentanyl)
how is the reward pathway activated by opioids?
they inhibit GABAergic inhibitory interneurons–>incr activation of dopaminergic neurons
withdrawal sx for opioids? onset of sx when?
muscular aches, chills, diarrhea, N/V, fever, insomnia, sweating, anxiety, hostility
occurs within 6-10 hrs
which stimulant is a resp stimulant used to counteract postanesthetic resp depression?
doxapram
are methylxanthines bronchodilators or bronchoconstrictors?
bronchodilators
what is the primary tx for apnea of prematurity?
caffeine
what type of stimulant can you use to tx COPD and asthma?
theophylline
what is teh main drug used to tx narcolepsy?
modafinil
what drug is used as adjunctive tx for obesity?
amphetamine
what are amphetamines approved to tx?
narcolepsy, ADHD, short term weight loss
what area of the brain does cocaine affect?
reward circuitry–>the ventral tegmental area (VTA)
which CNS stimulant has an incr risk for suicide risk?
atomoxetine; esp in children
what are the % for each subtype of ADHD?
- impusivity/hyperactivity: 10%
- inattention: 30-40%
- impulsivity/hyperactivity/inattention: 50-60%
sx of childhood ADHD
motoric hyperactivity
aggressiveness
low frustration tolerance
impulsiveness
children with ADHD have deficits in what part of brain?
frontal lobe:
- dorsolateral prefrontal cortex
- dorsal anterior cingulate cortex
- caudate + putamen
adults with ADHD present how?
shift activities, easily bored, impatient, restlessness
when incr drug metabolism results in decr in amt of available drug or duration of drug at target site?
pharmacokinetic tolerance
when CNS responds and adapts to presence of drug, resulting in desensitization, down regulation, or internalization of receptors?
pharmacodynamic tolerance
is addiction psychological or physical dependence?
psychological dependence
dependence is physical
what CNS mechanisms account for addiction?
incr synaptic plasticity and DA release in the mesolimbic reward pathways
why is it that you get more drunk when drinking on an empty stomach?
drinking on an empty stomach reduces the time EtOH is susceptible to 1st pass metabolism—>incr BAC
metabolism of alcohol includes?
- alcohol dehydrogenase (ADH)
- microsomal ethanol-oxidizng system (MEOS)
- aldehyde dehydrogenase (ALDH)
is rate of elimination of alcohol dependent on time and concentration of alcohol?
no it is independent.
constant amt eliminated per unit time
what does disulfuram inhibit?
aldehyde dehydrogenase (step 2 of alcohol metabolism)
chronic alcohol use leads to upregulation of what type of receptor?
glutamate NMDA receptors–>responsible for withdrawal sx
what is a benzodiazepine receptor antagonist used to tx benzo OD?
flumazenil
what is the date rape drug used to induce amnesia (not flunitrazepam)?
GHB
what sympathomimetic effects can amphetamines induce?
mydriasis, tachycardia, HTN
due to vesicular release of NE
MOA of MDMA?
inhibs SERT to release 5HT from presynaptic terminals–>depletes 5HT
what are the most commonly abused opioids?
codeine, morphine, heroin, oxycodone
what can be used to tx nicotine addiction
transdermal nicotine patch, buproprion, vareniclin
