Term
| how are seizures classified? |
|
Definition
| by clinical manifestations not biological processes |
|
|
Term
| How does PCN cause seizures? |
|
Definition
|
|
Term
| What is the link between fevers, kids, and seizures? |
|
Definition
|
|
Term
| What is the difference between convulsions and epilepsy? |
|
Definition
convulsion = movement
epilepsy = recurrent spontaneous seizures |
|
|
Term
| What is status epipepticus |
|
Definition
30+ min of continuous seizure activity or a series of seizures without return to full consciousness between episodes
Can cause brain injury |
|
|
Term
| what is the pathophysiology of seizures? |
|
Definition
excessive excitation / no inhibitory signal --> failure of surround inhibition
bursts of AP and hypersynchronization of a population of neurons |
|
|
Term
| What are the three types of focal seizures? |
|
Definition
- simple = no AMS
- complex = AMS
- secondary generalized = becomes tonic clonic with LOC |
|
|
Term
| What are the three types of primary generalized seizures? |
|
Definition
- absence = sudden, brief LOC
- myoclonic = brief muscle contraction
- tonic-clonic = sustained --> intermittent muscle contractions and LOC |
|
|
Term
| Describe the pathophysiology of a absence = petit mal = nonconvulsive seizure |
|
Definition
| - hyperpolarization of relay neuron --> opens T-type Ca channels --> depolarozation --> activates glutamenertic neurons from the cortex --> GABA interneurons in the thalamus that further hyperpolarize the relay cell and the cycle continues |
|
|
Term
| Which drug inhibits T type Ca channels on relay neurons? |
|
Definition
|
|
Term
| What is the first choice drug for uncomplicated absence seizures? |
|
Definition
|
|
Term
| What is the difference between tonic and clonic? |
|
Definition
tonic = sustained contractions
clonic = contraction alternating with periods of relaxation |
|
|
Term
| Describe the pathology of a tonic-clonic seizure |
|
Definition
| Loss of GABA medicated surround inhibition --> rapid AP (tonic) --> GABA inhibition starts to come back (clonic) |
|
|
Term
| What three drugs enhance Na channel inactivation? Which two have another function? What is that function? |
|
Definition
- carbamazepine
- valproate (2)
- lamotrigine (2)
* inhibits voltage gated t-type Calcium channels |
|
|
Term
| What drug is the first choice for focal seizures and primary tonic-clonic? |
|
Definition
|
|
Term
| Which drug is first line for patients with absence w/ general tonic clonic attacks? |
|
Definition
|
|
Term
| What is the ADR for valproate? |
|
Definition
|
|
Term
| What types of seizures does valproate help prevent? |
|
Definition
* ALL :)
- absence (with generalized tonic clonic attacks)
- myoclonic
- focal
- tonic-clonic |
|
|
Term
| What type of seizures is lamotrigine good at preventing? |
|
Definition
- focal
- generalized tonic clonic seizures
- absence |
|
|
Term
| which anti-seizure medication is just as effective as carmanazepine but better tolerated? |
|
Definition
|
|
Term
| What 3 drugs enhance GABAenergic function for anti-seizure drugs? |
|
Definition
- BZD
- Barbituates
- gabapentin |
|
|
Term
| Describe how BZD work to help prevent seizures? |
|
Definition
| - GABA induced influx of Cl- via GABAa r --> facilitates surround inhibition |
|
|
Term
| Diazepam and midezolam prevent what seizures? |
|
Definition
|
|
Term
| What are some ADR for BZD? |
|
Definition
- tolerance
- dizziness and drowsy |
|
|
Term
| Clonazepam = which seizure? |
|
Definition
- absence seizures (can inhibit T type Ca channels)
- 4th choice |
|
|
Term
| What four drugs can be used for absence seizures and what order? |
|
Definition
| Ethosuxsamide --> valproate --> lamotrigine --> clonazepam |
|
|
Term
| Phenobarbitol prevents what type of seizures? |
|
Definition
- focal and tonic clonic (alternative treatment)
- ineffective for absence and may even make worse |
|
|
Term
|
Definition
| - very narrow window = dose close to effective dose --> hypnosis and resp depression |
|
|
Term
| Which of the drugs is said to have a rational drug design? |
|
Definition
|
|
Term
|
Definition
- mainly blocks HVA Ca chanels but designed to increase packaging of natural GABA
- enhanced GABA function |
|
|
Term
| Gabapetin anti seizure activity |
|
Definition
- less effective in controlling seizures
- limited to alternative treatment |
|
|
Term
| Describe the four types of chronic anxiety disorders |
|
Definition
- generalized = no event
- social = self-conscious
- panic = unexpected and repeated
- PTSD = ongoing emotional reaction to trauma |
|
|
Term
| What is the actue anxiety disorder? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| LC and DR interact with which brain structures? |
|
Definition
LC and DR --> H/A --> glutamate
LC and Dr --> BNST --> contributes to anxiety |
|
|
Term
| A lesion to the hippocampus and LC --> |
|
Definition
|
|
Term
| Besides 5HT and NE what else regulates glutamate release from the H/A? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What are the three types of sedatives? |
|
Definition
-BZD
-Barbituates
-Non- B/B hynotics |
|
|
Term
| Which BZD is long acting (>24 hours) |
|
Definition
|
|
Term
| Which BZD is intermediate acting? (6-24 hours) |
|
Definition
|
|
Term
| Which BZD is short acting? |
|
Definition
|
|
Term
| Describe th pathway of sedation with stages |
|
Definition
| Anxiolytic --> sedation --> hyponosis --> anesthesia --> death |
|
|
Term
| Describe the two types of GABAa receptors and which drugs generally act on those? |
|
Definition
a1 = sedation/hypnosis (short acting)
a2 = anxiolytic/muscle relaxer/anti seizure (inter-long acting) |
|
|
Term
| What is flumazenil and what is it used for? |
|
Definition
- BZD antagonist (used for OD)
- no actions along
- blocks both alpha 1 and 2 |
|
|
Term
| Describe the location of the binding sites for BZD and GABA for the GABAa receptor |
|
Definition
BZD = between a and y
GABA = between a and b |
|
|
Term
| Describe how BZD acts on GABA r |
|
Definition
| BZD binding --> conformational change --> increased affinity for GABA for the receptor |
|
|
Term
| What is the first drug of choice for generalized anxiety? |
|
Definition
|
|
Term
| Which drug can treat all anxiety disorders |
|
Definition
|
|
Term
| What are the four general functions of BZD? |
|
Definition
- insomnia
- seizures
- dependence of other sedatives
- anti anxiety |
|
|
Term
| Describe the use of BZD in situational anxiety |
|
Definition
- short term (2-3 weeks)
- ADR = sedation, abuse potential, avoid with other CNS depressants |
|
|
Term
| What are some ADR and withdrawl to BZD? |
|
Definition
- ADR = drowsy, respiratory depression, abuse potential, tolerance, amnesia, loss of coordination, confusion
- Withdrawl = anxiety, insomnia, seizures, taper down! |
|
|
Term
| In general which drugs should be avoided with BZD and why? |
|
Definition
- sedatives/CNS depressants
- ETOH
- Opiods
- general antesthetics
* further opens Cl ion channels --> shifts the curve to the left --> closer to danger zones |
|
|
Term
| What are 6 drug classes that inhibit metabolism of BZD? |
|
Definition
- Anti-d = fluxetine, fluvoxamine
- BB = propanalol
- ABX
- Anti-fungals
- CCB
- OCP |
|
|
Term
| What type of patients should not receive BZD? |
|
Definition
- pregnant
- glacoma
- sleep apnea |
|
|
Term
| What are two drug classes that increase the metabolism of BZD? |
|
Definition
- anti seizures = carbamazepine
- ABX |
|
|
Term
| Describe individual variability in BZD response |
|
Definition
- altered liver metabolism
- cross tolerance with other drugs
- drug interactions
- age (elderly more susceptible to toxicity) |
|
|
Term
| Describe the three main function of barbituates |
|
Definition
- sedative
- controls seizures
- IV anesthetics (euthanasia) |
|
|
Term
| Which has more profound CNS depression ? Barb/BZD? |
|
Definition
|
|
Term
| What are the 5 effects of barbituates? |
|
Definition
- increase activity of GABAa receptors
- high doses = can mimic GABA and open channel itself (narrow window)
- blocks Ca channels
- inhibit AMPA receptors
- low doses = facilitates GABA binding |
|
|
Term
| What are some ADR of barbituaties |
|
Definition
- decreased BP
- decreased HR
- decreased RR |
|
|
Term
| What are the two drugs used to treat insomnia? |
|
Definition
Zolpidem = Ambien
Zaleplon = Sonata |
|
|
Term
| Describe the effects of Z and Z? |
|
Definition
- alpha 1 GABAa recptor agonist
- increases sleep without changing REM sleep
- diminished effects on seizure, anxiolytic, and muscle relaxant
- no analgesia
- rapid onset, short lasting
- better tolerated after short and long term
- ok in preg |
|
|
Term
| What are some ADR to Z/Z? |
|
Definition
- amnesia
- hallucinations
- delusions
- euphoria (abuse potential) |
|
|
Term
|
Definition
|
|
Term
| what is ramelteon = rozerem? |
|
Definition
- targets melatonin receptors (M1 and M2) expressed in the suprachiasmatic nucleus
- no affinity for GABA |
|
|
Term
| ADR of ramelteon = rozerem ? |
|
Definition
- dizzy
- fatigue
- decreased testosterone
- increased prolactin |
|
|
Term
| What interactions with ramelteon = rozerem? |
|
Definition
| SSRI --> decreased metabolism |
|
|
Term
| buspirone what does it do? what class? |
|
Definition
- Azaspirone
- serotonin autoreceptor agonist --> decreases 5HT release
- Binds to LC --> NE |
|
|
Term
| What is buspirone used to treat? |
|
Definition
| - situational and general anxiety disorders |
|
|
Term
| Describe side effects and ADR of buspirone |
|
Definition
- effects take 2-3 weeks to emerge
- used in people who dont take BZD/Hx of abuse
- no side effects with anxiolynic effects (CNS depression)
- ADR (mild) = increased HR, Gi distressm paresthesia |
|
|
Term
| SSRI = MOA and acute/chronic effects |
|
Definition
- block serotonin transporter --> increased 5Ht that binds to autoreceptor --> down regulates receptor --> increased serotonin release (synaptic modeling)
- reduced clearance of serotonin
- acutely = increase in transporter and increase in anxiety
- chronic = neurotrophic changes, tx anxiety disorders |
|
|
Term
|
Definition
- first line for all anxiety disorders except generalized
- anti depressant |
|
|
Term
|
Definition
SSRI = anti-anxiety
Anti depressant |
|
|
Term
|
Definition
|
|
Term
| What is the purpose of noradrenergic agents in antianxiety disorders and what are two examples? |
|
Definition
- decrease central effects generated from the LC (NE)
- decrease peripheral effects
- Clonidine = alpha 2 receptor agonist
- Propranol = B receptor antagonist |
|
|
Term
|
Definition
|
|
Term
| What are the primary and secondary indications for clinical sedation |
|
Definition
primary = anxiety/fear
secondary = dental care, surgical procedures |
|
|
Term
| Describe conscious sedation |
|
Definition
- can respond to verbal and physical stimulation
- quick sedation
- used for mild-mod anxiety
- low amnesia
- breathing not impaired |
|
|
Term
|
Definition
- cnat respond to stimulation, verbal
- behavior suppression in kids
- most anxiety
- marked amnesia
- intermediate risk
- breathing reflexes unstable
- primary cause of death from dental sedation |
|
|
Term
| Describe general anesthesia |
|
Definition
- unconscious/unresponsive
- loss of protective reflexes
- need breathing assistance
- all anxiety and phobias
- total amnesia
- significant risk
- slow recovery |
|
|
Term
| Regarding conscious sedation = which is the most frequent means? |
|
Definition
|
|
Term
| What are the 5 types of oral conscious sedation |
|
Definition
- BZD = triazolam
- non-B/B = zolpidem = ambien
- anti-histamine
- barbituates
- chloral hydrate |
|
|
Term
| What is the type of inhalation conscious sedation |
|
Definition
|
|
Term
| what types of conscious sedations can be given through IV |
|
Definition
- BZD
- barbituates
- opiates
- propofol |
|
|
Term
| what are some advantages and disadvantages to oral sedation |
|
Definition
advantaes = decrease OD/allergic reaction, effective, cheap, easy to use
disadvantage = variable response, cant titrate, slow onset, prolonged duration of action, no analegsia |
|
|
Term
| What is the drug of choice for oral conscious sedation? why? |
|
Definition
BZD
- anxiolytic
- no analgesia
- sedative but more anxiolytic actions |
|
|
Term
| What BZD drugs are used in oral conscious sedation. What are their onset and duration? |
|
Definition
- Diazepam = slow onset long acting
- Triazolam = short acting (2 hours) rapid onset (15 min)
- Midazolam = rapid onset (15 min) short (1-6 hours) |
|
|
Term
| What is the MOA of anti-histamines in oral conscious sedation? |
|
Definition
| - 1st generation H1 receptor antagonist |
|
|
Term
| What is MOA of barbituates in oral conscious sedation? |
|
Definition
| SHOULD NEVER BE USED! increased abuse potential and directly opens channel = dangerous |
|
|
Term
| Chloral hydrate - MOA, ADR, uses |
|
Definition
- alcohol that binds to GABAa recptor
- trichloroethanol is an active metabolite that inhibits alcohol dehydrogenase --> alcohol cannot be broken down (mickey)
- frequently combined with NO = reduces doses of both (safer)
- liver toxic, and carcinogenic
- very small therapeutic window
- dentist, peds, |
|
|
Term
| NO = dose? max? onset and recovery? |
|
Definition
- start at 20% --> 70%
- rapid onset (minutes) and rapid recovery |
|
|
Term
|
Definition
- analgesia!
- anxiolytic
- sedative |
|
|
Term
| Sequence of events for NO |
|
Definition
| (1) tingling in extremitis (parastesia) --> warm sensation --> euphoria --> (4) dream stage (sleepy with sense of dreaming) --> nausea, dysphoria, sometimes flashbacks |
|
|
Term
| NO disadvantags and contraindications |
|
Definition
- can develop tolerance
- some people dont respond
- avoid in preg, head colds, severe respiratory disease, and patients who cannot breathe through their noses |
|
|
Term
|
Definition
| - adjunctive with surgical procedures |
|
|
Term
| Muscle relaxant advantage = |
|
Definition
| reduced risk for cardioresp depression |
|
|
Term
| depth of paralysis with muscle relaxant monitored with? |
|
Definition
- electrical stimulation
- observation |
|
|
Term
| two types of muscle relaxnts |
|
Definition
- NM blockers = paralysis for surgical procedure
- spasmolytics = control chronic pain |
|
|
Term
| Which muscle is most resistant to NM blocks |
|
Definition
- diaphragm and other large muscles :) good!
- last effected and first to recover |
|
|
Term
| What are the two types of NM blockers? |
|
Definition
Non-depolarizing
- majority
- competitive antagonist with Ach at low doses
- blocks ion channels opened by Ach at high doses
Depolarizing
- nicotinic Ach receptor agonist
- drug mimics Ach and opens channel --> depolarizes MEP --> muscle contraction unable to repolarize --> flaccid paralysis because drugs not metabolized at synapse
- prolonged exposure eventually repolarizes but with lingering resistance |
|
|
Term
|
Definition
| NM blocker - depolarizing |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
- spinal injury
- cerebral palsy
- MS
- Stroke |
|
|
Term
|
Definition
| - modify hyperexcitability of stretch reflex arc and interfere with skeletal muscle |
|
|
Term
| What four drugs are spasmolytics |
|
Definition
- BZD = diazepam (facilitates GABA actions)
- Baclofen
- Tizanidine
- Dantrolene
- |
|
|
Term
|
Definition
- GABAb receptor agonist --> increases K conductance --> hyperpolarizes cell
- as effective as BZD with spasm but causes decreased sedation
- can develop tolerance |
|
|
Term
| MOA of tizanidine and ADR |
|
Definition
- alpha 2 agonist
- pre and post syn to decrese NT release and activity
- as effective as BZD with sedation but reduced sedation
- ADR = hypotension, dry mouth, asthenia |
|
|
Term
| MOA of dantrolene and ADr |
|
Definition
- acts at muscle fibers
- binds to RyR channel rectpro --> inhibits Ca release from SR
- ADR = muscle weakness and sedation |
|
|
Term
| What are affective disorders? |
|
Definition
- mood disorders
- most common of all mental disorders |
|
|
Term
|
Definition
| - 5+ symptoms present most of the day and persist nearly every day for 2 weeks |
|
|
Term
| What is the difference between typical and atypical for MDD? |
|
Definition
- typical = decreased appetite and insomnia
- atypical = increased appetite and oversleeping (more common) |
|
|
Term
| Bipolar affective disorder what is it? |
|
Definition
| - depression interrupted by mania (increased mood, more energy, grandiosity, need for sleep, disorganized racing thoughts) |
|
|
Term
| What is the amine hypothesis |
|
Definition
| - depression is due to decreased monoamine neurotransmission (DA,NE,5HT) |
|
|
Term
| What are some side effects of SSRI? |
|
Definition
- n/v
- HA
- sex dys
- insomia
- non fatal acute toxicity |
|
|
Term
| What is serotonin syndrome |
|
Definition
- drug interaction with MAOI and SSRI
- hyperthermia, muscle ridigity, tremors, seizures
- can --> coma
- can occur weeks after SSRI administration |
|
|
Term
|
Definition
- block NE and 5HT transporters
- variable blockage of muscarinic, histamine, and adnergic receprots (alpha 1)
- takes 2-3 weeks |
|
|
Term
| What do first generation secondary amine TCA's do? |
|
Definition
|
|
Term
|
Definition
| 1st gen secondary amine TCA's |
|
|
Term
| What do 1st gen tertiary amine TCA's do? |
|
Definition
| block Ne and 5HT transporters |
|
|
Term
|
Definition
| - tertiary amine TCA (1st gen) |
|
|
Term
| Wat are the side effects of the three main types of receptors that TCA's exert effects on? |
|
Definition
- anti cholinergic = n/v, dry mouth, blurred vision, increased HR
- anti hist = sedation, weight gain
- anti adrenergic = orthostatic hypotension, increased HR, drowsy, dizzy, sex dys |
|
|
Term
| What might happen in an acute toxicity reaction with TCA? |
|
Definition
- coma
- respir depression
- delirum
- seizures
- cardiac arrhythmias
- can be fatal |
|
|
Term
|
Definition
- Inhibit MOA = prevents breakdown of NT
a = serotonin and NE
b = dopamine
- most irreversibly block so it takes to stop showing effects (need to generate new) |
|
|
Term
|
Definition
- sleep disturb
- weight gain
- risk of orthostatic hypotension |
|
|
Term
|
Definition
- agitation
- hallucination
- convulsion
- potentially fatal |
|
|
Term
| Sympathomimetics taken with MAOIs --> |
|
Definition
HTN crisis
- Increased BP
- HA
- fever
OTC = ephedrine, pseudoephedrine, phenylpropanylamin
Tyramine = food and wine (metabolized by hepatic MAO --> promotes NE release |
|
|
Term
|
Definition
| - reversible and selective MAOIa with few interactions |
|
|
Term
|
Definition
| - blocks Ne and serotonin transporters |
|
|
Term
|
Definition
|
|
Term
|
Definition
- nausea
- dry mouth
- sex dys
- constipation
- insomnia
- sweating
- HA |
|
|
Term
| drug interactions with SNRI |
|
Definition
| - serotonin syndrome (MAOI) |
|
|
Term
| Atypical anti depressant = ? |
|
Definition
|
|
Term
|
Definition
| weak blockage of NE and DA transporters |
|
|
Term
|
Definition
- seizures
- dry mouth
- nausea
- insomnia
- tremor
- dizziness
- arrhythmias |
|
|
Term
| drug interactions with bupoprion |
|
Definition
- theophylline
- anti psychotics |
|
|
Term
| Efficacy of anti-d = acute vs. LT |
|
Definition
- acute = not effective
- LT = >3 weeks --> decreased symptoms, decreased relapse |
|
|
Term
|
Definition
- both effecive
- exercise decreased relapse and decreased symptoms |
|
|
Term
| What drug do you choose for depression? |
|
Definition
- no class is best
- based on ADR and toxicitiy
- SSRI and SNRI = 1st line for MDD
- MAOI = last treatment option |
|
|
Term
|
Definition
- neuroendocrine and neurotrophic factors modulate affective state
- may explain why it takes a long time to work
- BDNF and VEGF modify synaptic activity , neural structure, and neurogenesis
- effective anti-d increase neurotrophic support in the cortex and hippocampus |
|
|
Term
| what is plasticity and down regulation |
|
Definition
- down regulation of presynaptic serotonin autoreceptors and increased post syn expression of serotonin receptors
- change in # of adrenergic receptors
- increased cAMP --> increased BDNF
- change in function of GCC receptors
- change CRF
- GCC may change synaptic connections and neurogenesis |
|
|
Term
| What are 5 features of PD |
|
Definition
- bradykinesia
- Muscular rigidity
- resting tremor
- stooped posture and instability
- cognitive defects |
|
|
Term
| what are the 4 dopamine projections? where do they start and stop |
|
Definition
1. mesolimbic = VTA --> limbic (amygdala and n.accumb)
- motivation, arousal, and memory
2. mesocortical = VTA --> frontal cortex
- cognition and communication
3. tuberoinfundibular = hypothalamis --> pituitary
- prolactin regulation
4. nigrostraital = SN --> striatum
- voluntary mvmt (through thalamus, motor cortex, and LMN) |
|
|
Term
|
Definition
- dopamine neurons die in the SNc
- lewy bodies in SNc and other cells |
|
|
Term
| To generate MVMT you must ? |
|
Definition
- inhibit the indirect pathway
- activate the direct pathway |
|
|
Term
| Describe the difference between teh direct and indirect pathways |
|
Definition
Direct
- D1 receptor (and D5)
- activates Gs --> AC --> cAMP --> PKA
Indirect
- D2 - D4 r
- activates Gi --> inhibits AC --> decreased cAMP --> decreased PKA |
|
|
Term
| Describe the synthesis of dopamine |
|
Definition
- tyrosine -(tyrosine hydroxylase)-> LDOPA -(LAAD)-> DA
- DA cannot cross the BBB
- Tyrosine hydroxylase is the rate limiting step
- LDOPA can cross BBB |
|
|
Term
| Describe the metabolism of dopamine |
|
Definition
| - DA -(MAOb)-> DOPAC + H2O2 |
|
|
Term
| Describe actions of LDOPA |
|
Definition
- doesnt stop progression but decreases symptoms
- intense side effects
- best results in the first few years
- most metabolised in periphery before gets to brain |
|
|
Term
|
Definition
- inhibits COMT which converts LDOPA --> 3-OMD
- Increases LDOPA avilable to DA neurons by decreases metabolism in periphery and brain
- helps prevent on/off syndrome
- reduces level of LDOPA needed |
|
|
Term
|
Definition
|
|
Term
|
Definition
- alternative therapy
- fatal hepatotoxic
- COMT inihibitor |
|
|
Term
|
Definition
- inhibits LAAD
- blocks LDOPA --> DA in periphery
- cannot cross BBB |
|
|
Term
|
Definition
Peripheral (carbidopa can decrease)
- GI = anorexia, nausea, constipation and vomiting
- CV = arrhythmias
Central
- beh/cog = depression, anxiety, insomnia, confusion, delusion, hallucination, nightmares, euphoria
- MVMT = dyskinesia
- wearing off syndrome = rigidity, akinseia at end of dosing
- on-off syndrome
Withdrawl --> severe akinetic state
* neurons left stop responding - think there is enough |
|
|
Term
|
Definition
- prevent metabolize DA
- increases effects of LDOPA and side effects
- use for mild disease symptoms (monotherapy)
- used with LDOPA to control motor fluctuations
-* can also --> HTN in presence of LDOPA by inhibiting NE |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Which drug may slow PD progression? |
|
Definition
|
|
Term
|
Definition
- anticholinergic for PD Tx
- muscarinic antagonist to inhibit cholinergic hyperactivity |
|
|
Term
|
Definition
- D2 like = dopamine r agonist
- monotherapy for mild diseases
- adjucant to LDOPA --> decreases On/Off adn reduces dose |
|
|
Term
| what are some advantages and disadvantages of Ropinirole |
|
Definition
advantages
- selective
- duration
- lack free radical production from Da metab
Disadvant
- poor efficacy
- increased risk psychosis
- dizziness |
|
|
Term
| Amantadine = Tx? MOA? Use? |
|
Definition
- antiviral for PD Tx
- blocks NMDA r --> prevent excitotoxic of alter activity of basal ganglia
- modest effects, short lived
- reduces tremor early in the disease
- reduces LDOPA induced dyskinesia |
|
|
Term
| What are some environmn. factors linked to schizo |
|
Definition
- maternal HTN
- Prenatal markers of folate metabolism (HCY)
- urban environm |
|
|
Term
| Describe the pre-psychotic and psychotic events |
|
Definition
Pre-psychoic
- negative symptoms = social withdrawl, hygeine, loss of interest, prior to psychotic event
Psychotic
- persists at least 1 month --> full recovery (rare), episodic, and continuous |
|
|
Term
|
Definition
A - 2+ for at least 1 month / 1+ with delusion or hall
[del, hall, disor speech/behav, negative symptoms]
B - Social/occup dys
c - duration (6 mo)
D - Symptoms not caused by meds/drugs |
|
|
Term
| Describe positive, negative, and cognitive symptoms |
|
Definition
- positive = paranoia, delusions, hall, concept disorg
* induced by dopamine adonist
- Negative = affectiv blunting, alogia (poverty of speech), anhedonia (lack of joy), anvolition (lack motivation)
- cognitive = impaired attention, working memory, executive function |
|
|
Term
|
Definition
- increased / dysregulated levels of DA
- positive = chang in mesolimbic (increased DA)
- negative = change in cortex and hippocampus (decreased DA, change in glut signal and NMDAr) |
|
|
Term
| What are the three first generation typical anti-psych? |
|
Definition
- halperidol
- fluphenazine
- chlorproamzine
* D2 DA receptor antagonists = blocks!
* decrease freq and severity of + symptoms NOT neg/cog |
|
|
Term
| Side effects of 1st gen typical antipsychotics |
|
Definition
- PD syndrome [Tx with cholinergic agents/amantadine]
- akathisia = distress, constant mvmt
- endocrine = increased prolactin
- neuroleptic malignant syndrome = fever, catatonia, antonumic dys, rigidity [from DA signaling in hypothalamus] can be fatal
- acute dystonia = muscle spasm in tongue, face, neck and back due to DAr block
- tardive dyskinesia = abn spasms, oral facial, due to prolonged admi, pot irreversible
- sedation and impaired cognition |
|
|
Term
| 2nd gen atypical antipsych drugs (3) |
|
Definition
- Clozapine
- Quetiapine
- olanzapine (more EPS) |
|
|
Term
| Clozapine = MOA, use, and ADR |
|
Definition
- most effectie (positive, negative and cog)
- not first line due to ADR
- blocks D2 r and serotonin r
- ADR = orthostatic hypo, agranulocytosis (need weekly WBC ct) and sedation
- mild motor side effects but if block >70-90% can induc more EPS |
|
|
Term
| 2nd generation anti-psychotics = use? |
|
Definition
- mimic clozapine without agranulocytosis
- 1st line treatmet
- some more effective 1st gen for + symptoms
- more effective for neg symptoms when weak NMDA agonist is added
- may be used for depression |
|
|
Term
| Which line of drugs has increased risk for metabolic syndrome? |
|
Definition
- second gen anti psychotics (75% with clozapine)
- increased risk for type II dm, CVD, adn renal toxic |
|
|
Term
| What are three types of pain? |
|
Definition
- neuropathic = nerves, severe, burning, tingling, lancinating, numb, stocking glove
- visceral = internal organs, poorly localized, pressure, squeezing, encapsulated body areas, due to compression, extension, or stretching is viscera
- somatic = bodily, can be deep (dull/aching and well localized) or surface (sharp, burning or prickley), cutaneous or musculoskeletal |
|
|
Term
| Describe acute vs. chronic pain |
|
Definition
- acute = well defined pattern of onset, more likely to have VS changes, responds wel to analgesia or reversal of pain, 3> months for duration
- chronic = >3 months, no VS changes (adapted autonomic NS), may have period of control and periods of breakthrough |
|
|
Term
What is breakthrough pain
Why might this happen |
|
Definition
| - transient increase in pain >moderate intensity occuring on a baseling pain of - could be worsening of pain due to end of drug, worsening condition, due to treatment (dressing change) |
|
|
Term
| What do you do for mild pain? |
|
Definition
- levels 1-3
- OTC
- acetaminophen up to 1000 mg q 6 hours (4 grams max!)
- ibuprofen 800 mg q hours with food (2400 mg max)
- can use tylenol + NSAID but not more than one NSAID |
|
|
Term
| What do you do for moderate pain? |
|
Definition
- level 4-7
- single agents = codeine (dose limited), oxycodone (no dose limit), tramadol
- combination agents = Acetaminophen/ASA + narcotic (percocet, vicodin) 4 grams max!
Oxycodone = hydrocodone > codeine = tramadol > propoxyphene |
|
|
Term
|
Definition
- 8+
- IV
- short acting = morphine, hydromorphine, oxycodone (PO), meperidine (IV/IM - limited due to seizure pot) [fast onset and short duration]
- long acting = MS contin, oramorph, oxycontinm oxycodone, kadian (sprinkled on food), transderm fentanyl (takes 24 hours to work) |
|
|
Term
| Which is the perferred method of giving pain meds? |
|
Definition
Oral
- rectal also (morphine hydromorphine) |
|
|
Term
| What is the dose escalation for pain? |
|
Definition
- 50-100% for severe/uncontrolled pain
- 25-50% for mild/moderate pain
- short acting = every 1-2 hours
- long acting = every 24 hours
- patch = every 48-72 hours |
|
|
Term
| What should you do for constipation with pain meds (opioids)? |
|
Definition
- Senna-S
- prn suppository |
|
|
Term
| what do you do about nausea and opioids? |
|
Definition
- switch med
- chlorperazine |
|
|
Term
| What should you do regarding pruritis? |
|
Definition
- morphine worst
- fentanyl least
- not a true allergy
- not a contraindiction
- H1 and H2 blockers can help or switch opioid |
|
|
Term
| What is teh difference between tolerance, physical dependence, and psychological dependence? |
|
Definition
-tolerance = expected with chronic opioid use
-phy dep = withdrawl symptoms if discontinued
-psy, dep = loss of control despite harm (addiction) |
|
|
Term
| What are the scheduling rules for wisconsin |
|
Definition
- III/IV = hydrocodone, propxyphene, codeine = telephone ok
- II = all opiods except above, no refills, 3 day supply in telephone emergencies, 7 day prescrip expires
-I = illegal |
|
|
Term
| What are some drugs for neuropathic pain? |
|
Definition
- TCA / other anti d
amitriptylne - start low --> sedation, anticholinergic effects dissipate over time, DC is no response
- anticonvulsants = gabapentin
- corticosteroids = not LT, dexamethasone, prednisone
- lidocaine patches (best for near surfaces)
- capsaicin cream = near surfaces
- non-pharm therapy = acupuncture, phy therapy, biofeed, meds, hot/cold, TENS |
|
|
Term
| What are some other therapies for somatic pain |
|
Definition
- radiation
- bisphosphonate
- NSAIDS
- steroids
- calcitonin spray
- muscle relaxant
- PT, massage, accupuntcure |
|
|
Term
| who should you avoid morphine in ? |
|
Definition
renal patients
- increased risk for sedationm seizures, and myoclonis
- hydromorphone better |
|
|
Term
| If a patient develops a mental status change or respir depression on a stable opioid dose without new renal/liver failure --> |
|
Definition
| risk that its the opioid is low |
|
|
Term
| waht are some stimuli that activate nociceptrs? |
|
Definition
- acid
- ATP (P2x and P2y r)
- Bradykinin
- mechanical
- thermal
* all are ion channels --> increased Na and Ca --> depolarization --> AP
* analgesics dont block these r --> would cause numb |
|
|
Term
|
Definition
- increase fequency and longer duration of AP
- initiate slower modulatory response
- increase conductance |
|
|
Term
| spinal cord interneurons have two types of receptors |
|
Definition
GABA (a = post) and (b = post and pre)
- A = opens Cl channel
- B = opens K channel and inhibits Ca channel
Opiod u r
- decreased calcium influx pre syn
- increased K post syn
* both lead to pain reduction |
|
|
Term
| Descending neurons have what two types of receptors |
|
Definition
Serotonin
NE alpha 2 receptors
* both --> decreased ca conduction presyn --> pain reduction |
|
|
Term
| Describe the effects of pre and post syn for pain reduction |
|
Definition
- pre = inhibits calcium channels
- post = activation of K channels |
|
|
Term
| describe the difference between a delta and c fibers |
|
Definition
a delta
- myelinated
- sharp
- immediate
- 1st pain
C
- small
- unmyelinated
- prolonged burning pain
- repetitive firing
- sensitized responses |
|
|
Term
|
Definition
- modulates sensory descriminative pain
- a delta first pain
- few opiod receptors
- more resistant |
|
|
Term
| what is paleospinothalamic |
|
Definition
- motivational affective pain
- C fibers second pain
- more opioid receptors |
|
|
Term
| What are the 2 functions of opioid r ... how does this work? |
|
Definition
- coupled to g proteins --> inhibits AC
1. suppress voltage gated ca channels
2. stimulate K channels |
|
|
Term
| Describe the three types of opioid receptors and waht tey do? |
|
Definition
U = analgesia, sedation, euphoria, constipation, resp. distress
- endogenous = endophine, enkephaline
K = analgesia, sedation, dysphoria, diuresis, hallucin
- endogenous = dynorphins
delta = analesia, siezures, euphoria
- endogenous = endorphins, enkephalins |
|
|
Term
| Describe the three locations of opioid r and why that matters |
|
Definition
1. peripheral = inhibits action of SC afferents
2. SC = inhibits action of STT
3. brain stem = increases activation of descending pathways
* cortex alters response to pain |
|
|
Term
| Describe peripheral agents and response to pain |
|
Definition
- goal is to inihibit voltge gated Na and Ca channels (pre)
- may require inflammation to be effective
- local, peripheral application
- effective for bone, dental, visceral, eye
- decreased central effects, no constipation, and red, repir, depression |
|
|
Term
| Describe the use of analgesics in the SC |
|
Definition
- pre = block Ca influx and inhibit exocytosis
- post = open K channels nad hyperpolarize |
|
|
Term
| Describe the analgesic use in teh brainstem |
|
Definition
- Activation of descending pathway by glut release and inhibit GABA
- opioids on GABA interneurons inhbits GABA release --> descending pathway is activated --> releases NE and 5HT
- opiods also make glutmate --> activates descending tracts |
|
|
Term
| What are 4 full agonists opioids (u) |
|
Definition
- morphine
- fentanyl
- codeine
- tramadol |
|
|
Term
| What are mixed/partial antagonists and agonists? |
|
Definition
- pentazoeine
- buprenorphine
- butophanol
- nalbuphine |
|
|
Term
| what are two opioid antagonists |
|
Definition
|
|
Term
| What are two phenanthrenes |
|
Definition
|
|
Term
| Describe codeine in relation with morphine, combined with?, and other uses? |
|
Definition
- increased bioavailability
- prodrug
- 1/10th of morphine
- combined wiht NSAID/acetaminophen
- anti diarrhea and tussive |
|
|
Term
| What is an exmaple of a phenylpiperidines |
|
Definition
|
|
Term
| how is fentanyl used and what is special about it? |
|
Definition
- transderm
- chronic pain
- fast = lipophilic |
|
|
Term
|
Definition
|
|
Term
| Methadone = route? duration? action? effective against? |
|
Definition
- PO
- increased duration
- D dimer can antagonize NMDA
- effective against neuropathic pain |
|
|
Term
| Describe the effects of CYP2D6 and pharmacogenetics |
|
Definition
- activates codeine and tramadol
- decreased enz activity (4 and 17) --> less abuse potential and little effect of drugs
- increased enz activity (2) --> amplification and increased risk for resp depression |
|
|
Term
tramadol
- types
- effects
- side effects
- drug interactions |
|
Definition
racemic mixture (similar effects to codeine + acetominophen)
+ = prodrug of weak opoid (converted to o-desmethyl tranadol) [peripheral]
- = increased synp NE and 5HT by inhibiting uptake and promoting release [sc]
- not reversed by opioid blockers
- fewer side effects
- increased risk of seizure esp with SSRI
- Serious effects with MAOIs |
|
|
Term
|
Definition
- butorphanol
- buprenorphine |
|
|
Term
- butorphanol
- buprenorphine
describe an advantage and disadvantge |
|
Definition
- a = decreased respi depression
- d = caution in opioid dependent people |
|
|
Term
Nalbuphine
- agonist at?
- antagonist at?
- advantage? |
|
Definition
- agonist at K receptor
- antagonist at Ur
- decreased abuse potential |
|
|
Term
| side effects of agonist opioids ? |
|
Definition
Mood alterations
- U and delta r --> indcreased DA release in NAc
- K --> decreased DA release in the NAc
Repiratory dep
- decreases medulla response to CO2 and pons and medulla respiratory activity
- morphine and sedation effects
N/V
- stimulates chemo r in medulla vomiting center
CV = vasodilation
- peripheral = directly affects histamine release
- cerebral = indirectly effects resp depression
Anticholinergic
- decreased saliva
- can use peripheral antaonists to treat side effects |
|
|
Term
| Describe the two U r antagonists |
|
Definition
|
|
Term
| Describe how naloxone and naltrexone effect? |
|
Definition
- reverses agonist ADR
- Dx dependence
- short half life - effects are short |
|
|
Term
|
Definition
- antagonist of opioid r
- doesn't cross BBB
- decreases full agnoist peripheral effects (n/v ect) |
|
|
Term
| Describe the three types of repeated agonist use? |
|
Definition
Tolerance = decreased effectiveness
- analgesia and resp depression = fast
- GI = slow (opoids increase gut motility)
Dependence
- require needed to maintain adjusted
Withdrawl
- hyperthermia
- dysphoria
- diarrhea
- vomiting
- hyperventilation
* peripheral = the more pain the more pain you can have |
|
|
Term
| describe how prostaglandings mediate pain |
|
Definition
Prostaglandins --> PGE2 r --> increased PKC and PKA --> p of ion channels and nociceptors --> decreased activation threshold --> increased chance for AP
- recruit inflamatory mediators |
|
|
Term
| Describe how prostaglandins --> sensitization |
|
Definition
| - prostaglandints sensitize sensory fibers --> increased glut and sub p release in SC |
|
|
Term
|
Definition
| not normally pain is pain |
|
|
Term
|
Definition
| - increased sensitization to pain |
|
|
Term
| Describe how central sensitization works |
|
Definition
- depolarize --> ca induced activation of PKA --> p ionotrophic r and VG ion channels
- prolonged PKA --> p transcription factors --> gne expression --> increased response to stimulation |
|
|
Term
| Describe prostaglandin synthesis |
|
Definition
- Phospholipids -(PLC/PLA2)-> AA -->
COX --> prostaglandin H2 --> TA2 (cox1) and prostacyclin (cox2)
LOX --> leukotrienes |
|
|
Term
| Describe how GCC inhibit prostaglandin synthesis |
|
Definition
- inhibits Cycloxygenase
- inhibit PLC/PLA2 |
|
|
Term
| What is the mechanism of NSAIDS and what are some examples? |
|
Definition
- inhibit the COX 1 and 2 pathway --> inhibits prostaglandin production
- decreases hyperalgesia and allodynia
- peripheral and central effects
- increase activation theshold of C fibers
- decrease recruitment of inflamm mediators
- change sensitiv of ST neurons
- aspirin
- indomethacin
- ketorolac
- ibuprofen
- celecoxib (cox 2) |
|
|
Term
|
Definition
- para aminophenol
- central affects only!
- inhibits cox2
- cannot inhibit plt aggregation
- analgesic and antipyretic as good as aspirin ecept with soft tissue injuries (inflammation)
- cannot inhibit cox in areas of inflammation (increased peroxide)
- mild ADR (no GI) except at OD |
|
|
Term
|
Definition
- covalenty modifies Cox 1> Cox2
- irreversible
- duration depends on turnover |
|
|
Term
| Cox 1 constitutive functions (3) |
|
Definition
- kidneys = electrolyte and water balance
- GI = inhibits acid secretion and stimulates mucus release
- plt = TA2 |
|
|
Term
|
Definition
- inflammation, allodynia, hyperalgesia
- kidneys = electo and water transport
- endothelium = prostacyclin |
|
|
Term
| What are the four main functions of aspirin |
|
Definition
1. analgesia
- mild to mod pain, neuropathic pain
- no tolerance/dependence abuse
- cox2 effects
2. anti-pyresis
- promotes body's set point back to normal
- cox 2 effects
3. anti-inflammatory
- Tx musculosk disorders = RA/OA
- cox 2
4. prophylaxis of CAD
- inhibits plt agg
- 325 is good - increasing doesnt help
- cox-1 effects - cox2 makes worse! |
|
|
Term
| gastric ulcers and cox inhibitors |
|
Definition
- inhibiting cox 1 --> acid secretion and decreased mucus release --> gastric bleeding, PU, GI perforation
- less with cox 2
- chronic low doses can be serious |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| two ADR to cox 2 inhibitors |
|
Definition
- kidney problems
- CV risks = inhibition of prostacyclin |
|
|
Term
| what are 6 contraindications/warnings to taking aspirin and what should you use instead? |
|
Definition
- ulcer
- asthma
- influnza/chicken pox --> reyes syndrome in kids
- hypocoag/bleeding
- hypersensitivity
- pregnant (last trimester) --> increased risk bleeding
* use acetinophen |
|
|
Term
Describe how an acetaminophen OD occurs
- with alcohol? |
|
Definition
- 20-25 grams can be fatal
- 10-15 grams can be toxic to liver
ACE -(CYP2E1)-> NAPQE -(glutathione)-> non-toxic metabolite
- high doses uses up glutathione --> increased NAPQE (toxic)
- chronic alcohol increases CYP2E and decreases glutathione --> more NAPQE!!!! |
|
|
Term
| Describe the treatment of acetaminophen OD |
|
Definition
- N acetylcystine = cysteine prodrug
- adminester within 36 hours |
|
|
Term
| What is a propinic acid derevative? |
|
Definition
|
|
Term
| Describe the uses of ibuprofen |
|
Definition
- aspirin alternative
- decreased effective in PLT agg
- inflammation disorders chronic
- decreased GI effects
- more effective than aspirin + codeine
- most common NSAID |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
- 20-50 times more potent than aspirin
- poor tolerance |
|
|
Term
|
Definition
- potent analgesic
- poor anti-inflammatry
- more COX1
- ketorolac > aspirin / aceto
- moderate to severe pain
- severe ADR (renal failure) |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
- synergistic = distant sites of action
- improve effect and tolerance |
|
|
Term
|
Definition
Anti-d
- SSRI = changes activity of descending, least effective
- SNRI = duloxetine
Antiseizure (prolonged inact Na channels)
- Valproic acid
- carbamezephine
- gabapentin
- lemotrigine
Ketamine
- NMDA r antagonist
- inhibits central sensitization by decrease Ca mediated activation of kinase
- can prevent p of AMPAr
- decrease chronic post op pain
- use is limtied due to psychomimetic effects (delusions, hall) |
|
|
Term
| Describe how addiction changes the brian and behavior |
|
Definition
- negative emotion state promotes drug seeking
- adaptive homeostatic response
- chronic drug use changes the physiology of the brain |
|
|
Term
| negative reinforcement vs. positive reinforcement |
|
Definition
negative = removing an undesirable effect
- homeostatic changes = taking drug to alleviate bad feelings
positive = producing a desirable effect |
|
|
Term
| Homeostatic responses to drugs |
|
Definition
- tolerance = decreased effectiveness
- dependence = requirements increase
- withdrawl = absense of drug
* all drugs engage the mesolimbic sys --> increased DA release in the nuc acc
* changes are typically reversible
* typically tries to moves things in the opposite direction (tolerance and dependence) |
|
|
Term
| neuroplastic responses to drug |
|
Definition
- sensitization = repeated adminiestration leads to amplification of response
* emergence of craving - loss of inhibitory control
* direction of effect may not be related to the mechanism of action
* changes are persistent/permanent |
|
|
Term
| What type of impulses affect motivation = input to Nucleus accumbens --> motivational behavior |
|
Definition
- DA
- Ach
- opioids
- glutamate
- GABA |
|
|
Term
| Describe the three Tx means to inhibit drugs |
|
Definition
- detox = inhibit homeostatic changes
- block reward = inhibit homeostatic changes and positive reinforcement
- anti-craving = inhbit neuroplasticity |
|
|
Term
|
Definition
| - central nicotinic Ach receptors |
|
|
Term
|
Definition
- nicotinic r partial agonist
- tobacco |
|
|
Term
|
Definition
- atypical antidepressant
- inhibits uptake of NE and DA
- stabilizes DA levels from tobacco withdrawl
- 22% of people 1 year |
|
|
Term
| Acutely abused opiates --> |
|
Definition
- euphoria
- analgesia
- reduced gut motility
- breathing depression |
|
|
Term
| If someone is on an opiod (heroin) what should you give them for Tx? |
|
Definition
naltrexone + general anesthesia
- U opioid r antagonist
- rapid severe detox
- shortens withdrawl period |
|
|
Term
| Describe what happens to people with opoid/heroin withdrawl? |
|
Definition
- dysphoria
- increased pain sensitivity
- hyperventilation
- net excitation |
|
|
Term
| Decribe how tolerance and withdrawl are related to PKA activity |
|
Definition
- opiods acutely reduce PKA
- tolerance = reduces effects of reduced PKA
- in withdrawl = PKA is elevated (upregulation overshoots) |
|
|
Term
|
Definition
- U oioid r agonist
- agonist approach prevents withdrawl
- long lasting
- slower and less intense euphoria
- transfer of dependence |
|
|
Term
| What can be given to help with the side effects of withdrawl fro heroin? |
|
Definition
clonidine
- decreases symp activity by stimulating alpha 2 receptors |
|
|
Term
| What three effects does alcoohol have on the body |
|
Definition
- increases levels of endogenous opioids
- inhibits glut/excit NMDA
- augments GABAa r activation |
|
|
Term
| What are the withdrawl symptoms of alcohol abuse? |
|
Definition
- hyperexcit
- anxiety
- insomia
- hyperthermia
- convulsions in severe cases
- DT = delirium tremens
* can last a week and can be fatal |
|
|
Term
| What are two drugs that be used to Tx alcohol abuse withdrawl symptoms |
|
Definition
- Diazepam (BZD) = long acting
- Carbamazepine = antiseizure (prolonged inact st. Na) |
|
|
Term
|
Definition
blocks reward
- blocks Acetaldehyde dehydrogenase
- accumulation of acetaldehyde --> flushing, HA, n/v, general dysphoria
- hepatotoxi = no liver dys pts |
|
|
Term
|
Definition
- opioid r antagonist
- blocks endogenous reward systems (alcohol releases endogenous opioids)
- hepatotoxi = no liver dys pts |
|
|
