Term
| Too much and too little of dopamine and Norepi in the CNS can cause what symtpoms/diseases? |
|
Definition
Too much Norepi -> anxiety, panic, anorexia, insomnia
Too Little Norepi -> depression, ADHD
Too much serotonin -> psychoses, tourettes and chorea
Too little serotonin -> parkinsons, ADD, depression |
|
|
Term
| What are the two ways in general that we cause anesthesia and treat seizures |
|
Definition
Enhance GABA
stop propagation of signals down an axon or nerve fiber |
|
|
Term
|
Definition
| Converts GABA into succinic semialdehyde or a-ketoglutarate or backwards to create GABA. Primary way GABA is synthesized though is through Glutamic Acid Decarboxylase |
|
|
Term
| What converts glutamate into GABA? |
|
Definition
| glutamic acid decarboxylase |
|
|
Term
| Name 3 ionotropic glutamate receptors and their actions |
|
Definition
AMPA - responsible for background activity
Kainate
NMDA - prolonged depolarization by AMPA removes the Mg from NMDA and activates in causing further depolarization
All are ligand gated Na and Ca channels that are excitatory. |
|
|
Term
| What is the difference between GABAa and GABAb receptors and where are they found? |
|
Definition
GABAa is found on postsynaptic cells and when active opens chloride channels -> hyperpolarization and inhibition
GABAb can activate K channels on the postsynaptic cell to inhibit and it can also feedback to auto-inhibit its own release or the release of glutamate from presynaptic glutaminergic cells. |
|
|
Term
GABAa receptor
Type of receptor?
binding characteristics?
effected by what drugs? |
|
Definition
an ionotropic receptor that when activated by GABA increase chloride influx.
Barbiturates and benzos bind allosteric sites to increase Cl conductance |
|
|
Term
GABAb receptor
type of receptor?
consequences of activation?
what is Balcofen? |
|
Definition
it is a metabotropic receptor (G protein coupled)
Either increase K efflux or decrease Ca influx -> inhibition
Baclofen is a GABAb agonist used as a muscle relaxant. |
|
|
Term
| Name 4 voltage gated sodium channel blockers |
|
Definition
| Local anesthetic lidocaine anti-seizure: carbamazapine, phenytoin, and valproic acid. |
|
|
Term
what is thought to cause anxiety, stress, and insomnia?
What is the problem with this theory? |
|
Definition
decreased serotonin levels and increased norepi levels
The problem is that both SNRI and SSRI help treat the disease. |
|
|
Term
What is the monoamine theory of depression?
What is the flaw in the theory? explanation of the flaw? |
|
Definition
depression results from pathologically decreased serotonin and/or norepi neurotransmission.
If true, SSRI and SNRI should cause immediate relief. But this is not seen. Why? initially, drug causes down regulation of natural drug secretion. Over time though, leads to down regulation of autoregulatory receptors and natural secretion resumes boosting NT levels in the synapse. |
|
|
Term
What structures release norepi in the brain?
What are the general actions of norepi in the brain? |
|
Definition
Locus cereleus projects to all of the brain.
wakes us up, keeps us awake, regulates mood and CV system. If decreased release of Norepi -> depression |
|
|
Term
What brain structure releases serotonin?
What does serotonin do? |
|
Definition
raphe nuclei: 3 divisions
midbrain project to brain
pons project to brainstem
medulla project to spinal cord
excitatory, controls feeding, body temp, mood/emotion, nociception, sleep and wake cycles
In depression there is a lack of 5-HT release |
|
|
Term
| describe the synthesis of Epinephrine |
|
Definition
| made from tyrosine ->DOPA->dopamine -> Norepi (occurs w/in vesicle) -> epi (via PNMT - phentolymine n methyltransferase) |
|
|
Term
| describe the synthesis of serotonin |
|
Definition
| starts with L-trytophan. Need Vit B6 to convert to serotonin. MAO and aldehyde dehydrogenase then reduce to 5-HIAA which can be detected in urine |
|
|
Term
| What are the intracellular signals for all the norepi (adrenergic) receptors? |
|
Definition
a1 -> increase IP3 and DAG -> increase calcium
a2 -> decrease cAMP
b1 and b2 -> increase cAMP |
|
|
Term
| What are the 5-HT1 receptors and what do they do? |
|
Definition
They are Gi coupled -> inhibit AC.
5-HT1a -> contributes to inhibition of anxiety, depression and pain
5HT1d -> activation of this receptor relieves acute migraine via constriction of cerebral vessels. |
|
|
Term
| What are the 5-HT2 receptors and what do they do? |
|
Definition
Gq coupled -> increase DAG and IP3
5-HT2a -> overactivity causes hallucinations
5-HT2c -> overactivty causes increased appetite |
|
|
Term
| what does the 5-HT3 receptor do? |
|
Definition
| it is the only ionotropic serotonin receptor and stimulates emesis. |
|
|
Term
|
Definition
| prevents the transport of NTs serotonin and norepi into the vesicle. |
|
|
Term
|
Definition
| prevents the reuptake of NE and serotonin into the presynaptic terminal |
|
|
Term
What structure in the brain secretes dopamine?
Dopamine effects? |
|
Definition
ventral tegmental nucleus supplies most of the cortex, and nucleus accumbens
Substantia nigra projects to the striatum
dopamine is excitatory. controls emotion, reward and motor movements
decreased SN dopamine to striatum -> parkinsons
Increased dopamine from VTN -> mesolimbics -> schizo |
|
|
Term
| name the two dopamine receptors and their characteristics |
|
Definition
both are metabotropic.
D1 are excitatory. increase cAMP and PIP2 hydrolysis
D2 are inhibitory. Decrease cAMP and Ca influx and increase K efflux |
|
|
Term
|
Definition
| histidine is made into histamine by histidine decarboxylase |
|
|
Term
| What are the histamine receptors? what is the main purpose of histamine in the cns? |
|
Definition
H1, H2 and H3 are Gq, Gs, and Gi.
Main use is to maintain awake state |
|
|
Term
| name 3 agents that can sensitize a nerve |
|
Definition
| bradykinin, histamine, PGE2 and NGF |
|
|
Term
| What is the mechanism by which you get central descending modulation of signals such as pain? |
|
Definition
| when a vesicle is released, it contains glutamate to transmit the signal but also contains GABA, norepi, or possible opiods to feedback and inhibit Ca influx into presynaptic terminial to prevent further release and stimulation |
|
|
Term
| what seems to be the cause of alzheimers disease? |
|
Definition
| destruction of cholinergic centers in the cortex. will see amyloid plaques and neurofibrillary tangles |
|
|
Term
| What structures in the brain produce Ach? what does Ach do in the brain? |
|
Definition
Produced by the basal forebrain nucleus of meynert and project to all cortex. Ach is excitatory in arousal, short term memory, and learning.
in AD, over 50% of cholinergic projections are lost |
|
|
Term
|
Definition
| acetlycholinesterase inhibitor |
|
|
Term
| What is occuring with the neurotransmitters in anxiety? |
|
Definition
| overactivity of norepinephrine circuits with deficiency of GABA and serotonin nerve activity. |
|
|
Term
| What is the difference between sedation and hypnosis? |
|
Definition
sedation - reduced anxiety, motor activity and mental activity
Hypnosis - drowsiness and increased tendency to sleep (big SE for benzos) |
|
|
Term
| What drugs can induce anxiety? |
|
Definition
theophylline, lithium, and anti-cancer drugs.
also from cocaine and amphetamine withdrawal. |
|
|
Term
| What diseases can cause anxiety? |
|
Definition
| angina, CHF, cancer, hyperthyroidism, pheochromocytoma, hyperparathyroidism |
|
|
Term
| What are the diagnostic criteria for GAD? |
|
Definition
three or more of the following for more than half the time over 6 months
1. restless or edgy
2. Trouble concentrating, mind goes blank
3. Irritability
4. Increased muscle tension
5. Trouble sleeping |
|
|
Term
| First line therapy in the long term treatment of anxiety disorder? |
|
Definition
| TCAs. Have broad specturm efficacy and improve GABA function. |
|
|
Term
| Name 3 drugs FDA approved and used for anxiety |
|
Definition
| venlafaxine, paroxetine, and escitalopram |
|
|
Term
| What SSRI can be used to treat anxiety? |
|
Definition
| Fluoxetine (prozac), Sertraline (Zoloft), Citalopram (Celexa), Paroxetine (Paxil) |
|
|
Term
| name 2 SNRI's used for long term treatment of GAD |
|
Definition
| Venlafaxine (Effexor) and Duloxetine (Cymbalta) |
|
|
Term
| What are some side effects of SNRI and SSRIs |
|
Definition
loss of libido and grinding teeth are common. Others include GI distress, headaches, sedation, weight gain.
With venlafaxine -> increased BP
With Duloxetine -> urinary retention and liver effects thus CI'd in BPH. |
|
|
Term
|
Definition
| alprazolam (xanax), clonazepam (klonopin), diazepam (valium), lorazepam (ativan) and oxazepam (serax) |
|
|
Term
| What two benzos are used for acute relief of panic symptoms |
|
Definition
alprazolam and clonazepam
DO NOT USE DIAZEPAM. too long a half life |
|
|
Term
| What are the long acting benzos? How long do they last? |
|
Definition
| Diazepam (valium) is the most important |
|
|
Term
| what are the intermediate acting benzos |
|
Definition
|
|
Term
| What are other non-anxiety uses are there for benzos? |
|
Definition
| sedation, anticonvulsant, muscle relaxant, alcohol detox, anesthesia adjunct |
|
|
Term
| what substance can be a GABA mimetic? |
|
Definition
|
|
Term
| how are benzos metabolized |
|
Definition
by the p46\50 system. so don't give inhibitors with them
same reason why you CAN NOT DRINK ALCOHOL ON BENZOS.
Inhibitors of 3A4 -> erythromycin, clarithromycin, ritonavir, itraconozole, ketoconazole, grapefruit juice. |
|
|
Term
| How do benzos cause long lasting effects? |
|
Definition
| they are highly lipophilic and rapidly absorbed after oral administration and distributed well. including BBB and the adipose --> slowly leak out and extend action. |
|
|
Term
| in an elderly pt or post menopausal women, what benzos will be used and why? |
|
Definition
| because of the possible cognitive and psychomotor impairment, you don't want the falling. Give oxazepam or lorazepam b/c they don't undergoe the activation step or accumulation that causes the dizziness |
|
|
Term
| What is an indication for Triazolam? |
|
Definition
| rapid onset benzo facilitates sleep w/ no hangover effects |
|
|
Term
| what are the two serious side effects of high doses of benzos |
|
Definition
| anterograde amnesia and respiratory depression |
|
|
Term
| How do you treat an overdose of benzos |
|
Definition
| flumazenil - a competitive antagonist for the benzo receptor |
|
|
Term
| Is pregnancy an absolute contraindication to benzos? what if it is used? |
|
Definition
| no. but only use if necessary. If given in the third trimester -> floppy baby syndrome. it is CI'd in nursing mothers. |
|
|
Term
| how do you get a pt off the benzos? |
|
Definition
| gradual taper dose off over several weeks. Do not stop abruptly -> can be fatal. and monitor for 3 weeks after it's discontinued |
|
|
Term
|
Definition
partial 5-HT1a agonist. does not cause sedation, no abuse potential, no CNS depressant affects, Safe for use in pregnancy and lactation
not related to benzos
slow onset.
Metabolized by 3A4. decreased levels by rifampin and increased by erythroymcin and ketoconazole |
|
|
Term
|
Definition
BZ receptor agonist. fast onset of action. no anxiolytic, relaxant, or anticonvulsant effects
Just used for short term treatment of insomnia.
CI'd in elderly pts because it can increase confusion. |
|
|
Term
|
Definition
| a drug with addictive properties that can cause a analgesic and sedative effect. |
|
|
Term
|
Definition
| opiate is derived from the opium plant while a opioid is synthetic |
|
|
Term
| what are the four indications to use an opiod? |
|
Definition
| analgesic, anti-tussive, sedation, and anti-diarrheal |
|
|
Term
|
Definition
| heroin, oxymorphone, mepiridine, oxycodone, fentanyl, hydromorphone, methadone, morphine |
|
|
Term
| what are the combination opiod medications? |
|
Definition
tylenol 2, 3, and 4
Vicodin/Lortab
Percocet |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Diphenoxylate, loperamide, tramadol, and dextromethorphan |
|
|
Term
| what do the mu receptors do? |
|
Definition
REAP
respiratory depression, euphoria, analgesia, physical dependence |
|
|
Term
| What do the kappa receptors do? |
|
Definition
SAM
sedation, analgesic, miosis |
|
|
Term
| what do endorphins, dynorphins, and enkephalins do? |
|
Definition
they are all endogenous opiods
Endorphins bind mu recetpors
Dynorphins bind kappa receptors
Enkephalins bind delta receptors |
|
|
Term
| what are the three primary sites of action for opiods? |
|
Definition
Spinal cord - inhibit NT release in afferents
Thalamus/Limbic system - block perception of pain
Brainstem - activate descending inhibitory systems |
|
|
Term
| what are the CI to giving morphine? |
|
Definition
| respiratory compromise, asthma, increased ICP, paralytic ileus. |
|
|
Term
| what are the cardiovascular effects of morphine? |
|
Definition
vasodilation, decreases BP some decrease ionotropy
- do not give to MVA pts w/ suspected head trauma |
|
|
Term
| what does morphine cause in the lungs? |
|
Definition
| bronchospasm - so don't give with asthma. |
|
|
Term
| what does morphine cause in the urinary system? |
|
Definition
| increased tone of the detrusor along with increased tone of the urinary sphincter --> want to pee but can't pee. |
|
|
Term
| how is morphine metabolized and excreted? |
|
Definition
| metabolized via conjugation w/ glucoronic acid and excreted by the kidney. 2-3 hour half life |
|
|
Term
|
Definition
opioid. very strong. mc used as patch and epidurals. rapid onset < 5 min but lasts only 30 min.
CI'd in cognitive impaired pts b/c if they double up -> overdose |
|
|
Term
|
Definition
metabolized to active normeperidine. CI'd in renal pts b/c it can accumulate -> seizures. may also inhibit 5-HT reuptake -> serotonin syndrome
does not constrict sphincter of Oddi. Does not cause miosis (large doses -> mydriasis)
not fully reversible w/ nalaxone |
|
|
Term
|
Definition
strong. long half life of up to 24 hours
well absorbed PO
used for maintenance in narcotic recovery program |
|
|
Term
|
Definition
a tenth as potent as morphine
the best anti-tussive
low abuse potential (low euphoria)
usually combined w/ acetaminophen |
|
|
Term
|
Definition
has low mu, kappa, and sigma activity
used as antitussive |
|
|
Term
| name three opioid agonst/antagonists? |
|
Definition
pentazocine, nalbuphine, and butorphanol
antagonist at mu and agonist at kappa |
|
|
Term
|
Definition
synthetic w/ modest mu activity
also is a mixed SSRI and SNRI -> CI'd w/ antidepressants
only partially antagonized by naloxone |
|
|
Term
|
Definition
administered IV push. displaces all opioids on mu, kappa, and delta.
Short duration - 1-2 hours |
|
|
Term
|
Definition
oral form of naloxone that has a high half life and can be used in outpatient setting.
highly hepatotoxic |
|
|
Term
| Name 3 psychiatric diseases that may present with depression? |
|
Definition
| bipolar, major depressive disorder, dysthymia, or anxiety disorders |
|
|
Term
| What two NT's are involved in controlling mood? |
|
Definition
|
|
Term
| what nucleus gives rise to the NE in the brain? |
|
Definition
locus coeruleus
lateral tegmental area projects to the diencephalon. |
|
|
Term
| What receptor changes are seen in long term treatment w/ anti-depressants? |
|
Definition
| downregulation of a2, b1, 5-HT1d and 5-HT2 receptors. |
|
|
Term
|
Definition
| imipramine, desipramine, amitriptyline, and Nortriptyline |
|
|
Term
|
Definition
block the reuptake of 5-HT and NE by competitive inhibition at the reuptake transporter.
chronically --> downregulation of a2, b1, 5-Ht receptors |
|
|
Term
| What other receptor effects to TCAs have? |
|
Definition
| mostly have antimuscarinic effects but can have some antihistaminic and antiadrenergic. |
|
|
Term
| what are some side effects of TCAs? |
|
Definition
| anticholinergic, orthstaic hypotension, sedation (amytriptyline), cardiac conduction delays, weight gain and sedxual dysfunction |
|
|
Term
| what are some common drug interactions of TCAs? |
|
Definition
w/ alcohol --> CNS depression
w/ insulin or other hypoglycemics -> hypoglycemic effect (via sympathomimetic actions)
If combined w/ MAOI --> toxic therapeutic effects. |
|
|
Term
| What are some concerns in acute toxicity w/ TCAs? |
|
Definition
used in suicides so assess the suicide risk before you prescribe
at toxic levels -> cardiac dysrhythmias |
|
|
Term
| what are the pharmacokinetics of TCAs? |
|
Definition
| rapidly absorbed, highly bound to albumin, metabolized by the p450 system and excreted by the kidneys. Have long half lives, use w/ caution in pts w/ BPH and Cardiac arrythmias |
|
|
Term
|
Definition
| venlafaxine, duloxetine, and desvenlafaxine |
|
|
Term
| What are the side effects of SNRI? |
|
Definition
similar to TCAs except reduced in severity.
Added warning of serotoinin syndrome.
higher doses can precipitate hypertension |
|
|
Term
|
Definition
SNRI. Boxed warning of serotonin syndrome.
Avoid this drug in hepatic or renal disease pts.
can be used to treat mood disorders or also neuropathic pain. |
|
|
Term
|
Definition
| phenelzine, tranylcypromine and selegiline |
|
|
Term
| MAOI mechanism of actions |
|
Definition
| irreversibly inhibit both A and B forms of MAO. However inhibiting just MAO-a is more effective. |
|
|
Term
|
Definition
inhibitor of MAO-B used to treat parkinsons.
if high doses --> inhibit MAO-b |
|
|
Term
| what are some side effects of MOAI |
|
Definition
| orthostatic hypotension, insomnia, weight gain, sexual dysfunction, anticholinergic effects, overdose -> convulsions, and phenelzine can --> hepatotoxicity. |
|
|
Term
| What is tyramine induced hypertensive crisis? |
|
Definition
| tyamine causes NT to leak from storage vesicles. the MAO-A in the synapse usually inactivates these NTs. tyramine itself is usually inactivated in the synapse by MAO-b. inhibition of both MAOs-> significant rise in blood pressure. B/c of this, pts on MAOIs should not eat a lot of cheese. |
|
|
Term
| what drug interactions should you be concerned about with a pt on MAOIs? |
|
Definition
CNS stimulants such as appetite suppressants, decongestants, ephedrine, or levodopa. May cause HTN crisis.
Don't use w/ agents that increase serotonin levels -> serotonin syndrome |
|
|
Term
|
Definition
citalopram, escitalopram, fluoxetine, paroxetine, and sertraline
MC prescribed antidepressant |
|
|
Term
| Adverse effects of SSRIs? |
|
Definition
| N/V, sexual dysfunction, akathesia, slight increase risk of suicide in children, may induce mania in undiagnosed bipolar disorder |
|
|
Term
| drug interactions with SSRIs? |
|
Definition
increase concentration of clozapine --> seizures
Do not use w/ TCAs
do not use w/ MAOI -> serotonin syndrome
used with lithium -> seizures |
|
|
Term
| half lives of SSRIs? Which one has the longest? |
|
Definition
usually around 24 hours.
fluoxetine has 96- 10 days. |
|
|
Term
|
Definition
block reuptake of NE and dopamine. antidepressant effect from increased NE.
SE - CNS effects (hallucinate, delusion, catatonia, delirium). CI'd w/ MAOI b/c of HTN crisis
unlike other antidepressants, doesn't cause weight gain, drowsiness or sexual dysfunction |
|
|
Term
|
Definition
5-HT2 and 5-HT1 autoreceptor antagonist
SE - orthostatic hypotension, dizziness, hepatotoxicity
Strong inhibitor of 3A4. |
|
|
Term
|
Definition
antagonist at a2 autoreceptor. increases NE and 5-HT.
SE - muscarinic effects. mostly weight gain. Rare agranulocytosis and elevated LFTs |
|
|
Term
| when do you put a pt on MAOIs? |
|
Definition
| when they have failed SSRI, TCA and atypicals |
|
|
Term
| what is the pathophysiology of bipolar disorder? |
|
Definition
monoamine oxidase theory.
deficient catecholamins -> depression
excess of NE and DA -> mania
both bipolar and depression have low levels of 5-HT |
|
|
Term
| what is the preferred drug for bipolar disorder? |
|
Definition
|
|
Term
|
Definition
mimics Na. can't be pumped back out -> depolarization. also depletes inositol phosphates in the brain
secreted in the urine but reabsorbed in proximal tubules. Na depletion promotes lithium retention and thus toxicity
May induce nephrogenic diabetes insipidus (SIADH)
major SE is weight gain
toxicity -> confusion, seizure, arrhythmias, coma, death |
|
|
Term
|
Definition
| valproic acid and carbamazepine |
|
|
Term
|
Definition
unclear MOA
less symptoms than lithium
only effective for the first few weeks. |
|
|
