This diagnosis is characterized by feelings of intense sadness and despair, mental slowing, loss of concentration, pessimistic worry, agitation and self-deprecation - what is it?
Major Depression
- an affective disorder, ie altered mood
What does the acronym SIGECAPS stand for?
changes noted in depression
S - sleep I - interest G - guilt E - energy C - concentration A - appetite P - psychomotor disturbance S - suicidal ideation
a chemical family including - dopamine - norepinephrine - serotonin what family is this and which drugs act on this family?
Monoamine neurotransmitters
- most antidepressants work on metabolism of these neurotransmitters and their receptor sites
All anti-depressants carry an increased risk of what?
Suicide*
black box warning on all antidepressants
can also lower the threshold for seizure
(especially in combination with alcohol)
These are:
- used less commonly than other anti-depressants (d/t serious side effect profile of: weakness, dizziness, severe HA, tremors and HYPERTENSIVE CRISIS)
what are they?
Monoamine Oxidase Inhibitors
- tranylcypromine / parmate
- phenelzine / nardil
- isocarcarboxazid / marplan
- selegiline
This amino acid has the ability to enter presynaptic terminals and inhibit serotonin, it can also do this in the blood vessels - it’s thought to displace NE from neuronal storage vesicles - which amino acid is it and why is this important?
tyramine
- MOAIs prevent breakdown of this AA which causes marked HTN with MAOIs
- found in all the good foods: cheese, soy, dried fruits, meat, wine - anyone on MAOIs must avoid these foods!
- fatal HTN emergencies have been reported when patients reported intake of tyramine containing foods with their MAOIs
Tyramine is thought to act directly as a neurotransmitter, through which recently discovered receptor?
TA1
a G protein-coupled receptor (high affinity for tyramine)
found in
- brain
- peripheral tissue
- kidney
The MOA is thought to
- diminish re-uptake of monoamine neurotransmitters, sp. Serotonin and NE (increasing amt of neurotransmitter in the synaptic cleft)
with subsequent down regulation of post-synaptic receptors (potentially the main action) - which drug class is this?
tricyclic antidepressants (TCAs)
amitriptyline / elavil
- generally taken at bedtime due to sedative effects.
- takes approx. 4 weeks to meet therapeutic dose (will not see results until this time)
The chief side effects of these are anti-cholinergic in nature - DRY MOUTH being one of the best known SEs, ALL have potential to be CARDIOTOXIC - which class is this?
tricyclic antidepressants (TCAs)
anti-cholinergic reminder:
- dry mouth
- constipation
- urinary hesitancy
- orthostatic hypotension
- sedation
What is most disconcerting about tricyclic and tetracyclic antidepressants?
dangerous in OVERDOSE
- 10x daily dose can be fatal
- generally due to prolongation of QT interval.
- a week’s supply taken at once can be fatal for many individuals.
this tricyclic antidepressant works primarily on the serotonin transporter, moderately on the NE transport to effectively increase both in synapse.
Generally taken PO or IM. Which drug is this and can it be stopped abruptly?
Amitriptyline/Elavil
- stopping treatment abruptly causes withdrawal-like symptoms:
N, HA, dizziness, lethargy, flu-like sx
ie - discontinuation syndrome
This tetracyclic is a potent antagonist of
- 5-HT2, 5-HT3 and Histamine (H1) receptors
- creates prominent sedative effects.
A moderate antagonist of peripheral alpha-1 adrenergeic receptors explaining a common side effected noted with it’s use - what drug is it and what’s the side effect?
Remeron / Mirtazapine
S/E: occasional orthostatic hypotension
Another common SE of TeCAs is WEIGHT GAIN
this tetracyclic works as a serotonin reuptake inhibitor and partial antagonist (decreases serotonin at pre-synaptic and increases at post-synaptic R sites)
- it’s an ANXIOLYTIC and induces sleep - which drug is this?
Trazodone / Desyrel
This TeCA has off-label indications for use with:
fibromyalgia, complex regional pain syndrome, control of nightmares, panic disorder, diabetic neuropathy, bulimia nervosa, OCD, alcohol withdrawal and - best yet - ERECTILE DYSFUNCTION - what drug is this and what significant SEs should be noted?
Trazodone / Desyrel
- HYPOTENSION - fatalities are rare
- possible MANIA in patients w/ bipolar
Appears to be safer than TCAs and MAOIs
This class of drugs has been helpful in 50-70% of patients with major depression, it’s the most commonly prescribe anti-depressant - their full effect takes 3-8 weeks or more before a patient finds relief - what drug class is this and what two neuro-protective proteins increase as the hypothesized “downstream” effect of their action?
SSRIs
increases in serotonin lead to increased neuro-protective proteins:
- Brain-Derived Neurotrophic Factor (BDNF) and
- Bc1-2
Many users of SSRIs complain of apathy, lack of motivation, emotional numbness, feelings of detachment and indifference to surroundings - SSRIs, SNRIs and serotonergic TCAs can all cause this to varying degrees - what is the term for this notorious side effect?
mood anesthesia
- ie emotional blunting
- All SSRIs also come with the side effect of
sexual dysfunction
This SSRI decreases serotonin re-uptake at presynaptic cleft allowing for increased serotonin in the synapse and at post-synaptic R sites
- it is the antidepressant drug of choice for CHILDREN and TEENS. This drug is generally given PO, with a half life of 48-72 hours - what drug is this?
Fluoxetine / Prozac
- kid friendly, mother approved?
- SE: Serotonin syndrome (fever, agitation, diarrhea, HTN)
Painkillers of what family may interfere and reduce the efficiency of SSRIs and may compound the increased risk for GI bleed caused by SSRI use - these agents are?
NSAIDs
- aspirin
- ibuprofen
- naproxen (aleve)
The effects of this SNRI drug are dose-dependent
- low dose (<150 mg/day) acts on serotonergic transmission
- moderate dose (>150mg/day) acts on serotonergic and noradrenergic systems
- high doses (>300mg/day) they affect dopaminergic neurotransmission
What drugs is this?
venlafaxine / effexor
- first and MC used SNRI
This SNRI is C/I for use in patients with heavy alcohol use OR chronic liver disease (can cause ACUTE HEPATITIS**) - used mainly for major depressive disorder, general anxiety disorder, painful peripheral neuropathy and fibromyalgia.
- approved in Canada and Europe for stress urinary incontinence, not approved by the US due to concern of liver toxicity and suicidal events.
What drug is this?
Duloxetine / Cymbalta
(SNRI)
- don’t forget
antidepressants increase the risk of suicidal thinking and behavior in children, adolescents and young adults (Black Box)
This SNRI the active metabolite of venlafaxine - evidence suggests a lower efficacy when using this compared to venlafaxine and duloxetine - what drug is this?
Desvenlafaxine / Pristiq
This NDRI (NE and dopamine) and nicotine receptor antagonist - is indicated for depression, bipolar disorder and ADD - however, under a separate brand name it also aids in smoking cessation. What drug is this? What is its separate brand name?
Bupriopion / Wellbutrin
As a smoking cessation drug:
Bupriopion / Zyban
- approved for up to 6 months to prevent relapse for those quitting.
Takes 5-7 days to reach steady state blood levels
- 150mg/day x 3 days
then bid each day to follow
This drug is
- a partial nicotine agonist indicated for smoking cessation
- has a serious SE profile of neuropsychiatric events such as mood disturbances, psychosis and hostility - occurring in those W and W/OUT PRE-EXISTING psychiatric disease.
In combination with nicotine withdrawal - incidence of neuropsychiatric events increases - what is the name of this drug that is NOT recommended, ever.
Varenicline / Chantix
“No chance you’ll prescribe Chantix” (cheesy, deal with it)
Marketed in the US as a “medical food.”
- indicated for management of suboptimal folate levels in depressed patients
- assumed MOA w- acts as a trimonoamine modulator (TMM) enhancing synthesis of:
dopamine, NE and serotonin
- boosts efficacy of antidepressants.
What is the name of this active form of folic acid, and what is the medical food brand name?
Levomefolic acid / Deplin
Activated name:
Levomefolic acid / methyltetrahydrofolate / 5-MTHF
Medical food name: Deplin
- substantial evidence suggests deficiency in folic acid is associated with depression
When sedative or hypnotic agents are used for their anesthetic effects - how are they usually administered?
IV administration
Fun fact:
- when used to induce sleep, doses of sedatives are generally higher than when used for anxiety
What are the 5 things that can cause FATAL withdrawal syndromes?**
- alcohol
- barbituates (NO reversal agent)
- benzodiazapines (reversal agent
- chloral hydrate
- miltown / meprobamate
Both of these drug classes
- bind GABA receptors
- increasing affinity for GABA, prolonging the action of the receptor
- although, the locations of binding for these drug classes are not the same - what drugs are these?
Barbituates (low TI)
Benzodiazapines (High TI)
- could be seizure protective (blocking GABA induces seizure)
There are two classes of GABA receptors - GABAa and GABAb, that bind the chief inhibitory neurotransmitter of the CNS - what is the difference between these two receptors?
GABAa - ligand-gated ion channels (ionotropic Rs)
GABAb - G protein-coupled receptors (metabotropic)
These drugs can cause sleep followed by anesthesia at high doses (IV) can cause retro- or antero-grade amnesia, however, they DO NOT RAISE PAIN THRESHOLD therefore have NO analgesic properties - what drug class is this?
Barbituates
- low therapeutic index
- cause resp. and CV depression
- suppress REM sleep
- neuronal depression
History Buff?
- Bayer created the first barbituate by combining urea and malonic acid
this ultra-short acting barbituate, reaches the brain in 3-45 seconds following IV administration, causing unconsciousness. Dose peaks at one minute in the brain (60%)
- with NO analgesic property
- most commonly used as “truth serum” (makes patients chatty and cooperative with interrogators, confessions may be unreliable)
- With ability to depress the CV and respiratory system, it is the first of three drugs administered for LETHAL INJECTION in the US - what is this drug?
Thiopental / Pentothal
- largely being replaced with propofol (milk of amnesia) surgically
- SE - nocturnal emission
This category of barbituate is administered either orally or IV, produces effects in 15-30 mins with a DOA of 6-8 hrs. Primarily used to treat insomnia and pre-operative sedation, they also have been used for physician assisted suicide in Oregon (orally) - which category is this and what is the most common drug used in this barbituate category?
SHORT-ACTING barbituates
SCHEDULE II**
Pentobarbital / Nembutal
- also used for anesthesia and euthanasia by veterinarians
These drugs are primarily used for insomnia and pre-operative sedation - with onset of 20-40 mins and DOA of up to 6 hrs. They can be combine with analgesics (aspirin or acetaminophen) to treat migraine and cluster headaches - what are these drugs and what is a common example of these drugs?
INTERMEDIATE-acting barbituates
Butalbital / Fiorinal
Fiorinal is a combination analgesic medication (with aspirin and caffeine) used to tx migraine HA
long acting barbituates
- effects are generally realized in 1 hour, lasting approx. 12. They are primarily used to treat what?
Seizure disorder
This is the most widely used anti-convulsant worldwide and the oldest medication for seizure control. It has sedative and hypnotic properties, but is generally superseded by benzodiazepines - which drug is this?
Phenobarbital / Luminal
Barbituate, Schedule IV
SE profile is too rough with low TI
This class of drugs works by binding GABA R site that triggers opening of Cl channels - influx of chloride causes hyper-polarization making it difficult for excitatory neurotransmitters to depolarize the nerve cell and cause an AP - what class of drug is this and aside from anxiety, what else can this drug class treat?
Benzodiazepines
can also be used for
- MUSCLE RELAXATION
There are short-acting and long-acting benzodiazepines - when is each indicated?
Short-acting: Sleep ONSET insomnia
Long-acting: insomnia, anxiety
This short-acting benzodiazepine is used for sedation and anxiety prior to upper and lower GI endoscopy - gen. administered IV but can be available in a syrup form
- use of this drug via nose or buccal route as an alternative to rectal diazepam is becoming increasingly useful in the emergent treatment of childhood seizures - what is it?
Midazolam / Versed
long term use for seizure disorder is not recommended - tolerance is easily achieved and marked SE of sedation makes it unfavorable.
This benzodiazepine has gained popularity due to its use as a “date rape” drug - when it is mixed in alcohol and administered to an unsuspecting victim
Flunitrazepam / Rohypnol
this long-acting benzo binds to receptors in the CNS to enhance GABA activity
- rapidly absorbed PO and metabolized in the liver to active metabolites prolonging clinical duration of action
- largely been replaced by shorter acting agents (xanax and halcion) - which drug is this?
Diazepam / Valium
- rebound insomnia may occur if discontinued
- withdrawal can be severe for chronic users
This is a short-acting, non-benzodiazepine hypnotic that potentiates GABA by binding to GABAa receptors at the same location as benzos - works within 15min w/ a short half life (2-3 hrs).
Effective in INITIATING sleep, no evidence for maintenance. If given in 10-20x the dose, it can act as an anti-convulsant and muscle relaxant - but has not been approved for either seizure prevention or muscle relaxation. What drug is this?
Zolpidem / Ambien
Chamberlainism:
these are “the work of the devil”
this benzo-like hypnotic is indicated for insomnia
- works by potentiating the effect of GABA on Cl ion channels, binds to a specific R site not involved with the binding of benzos. Taken PO.
- Rapid onset of action (15-30 mins) w/ minimal reports of drowsiness upon waking - seems good, however - full side effect profile may not be fully appreciated until its been on the market for at least 5 years, this is a newbie - what is it?
Eszopiclone / Lunesta
SE - impaired mentation prior to sedation
This new class of sedative hypnotics, act as melatonin receptor agonists - high binding affinity at MT1 and MT2 receptors - mimicks and enhances endogenous melatonin action - associated with maintaining circadian rhythm. The drug that represents this class has no appreciable binding activity on the GABAa receptors (associated with muscle relaxation, anti-anxiety and amnesia effects) - what is the name of this drug?
Ramelteon / Rozerem
Melatonin Agonist
- no published studies have indicated whether Ramelteon is more or less safe or effective than melatonin
Is gastric lavage with activated charcoal beneficial in benzo overdose? When is charcoal lavage recommended?
No
although charcoal absorbs the benzos due to risk of adverse effects that outweigh the potential benefit
Recommended ONLY
if benzo was taken with other drug that may benefit from gastric decontamination
This is a benzo-R antagonist
- can rapidly reverse effects of benzodiazepines.
It is ONLY administered IV with a rapid onset of action (1-2mins) w/ half life of only 1 hour (therefore repeat dosing is necessary, esp with long acting benzos).
- VERY effective in reversing CNS depression
- LESS effective at reversing RESPIRATORY DEPRESSION. It has the ability to abruptly precipitate withdrawal syndrome in patients who are benzo dependent* - what is this drug? And what CIs does it have?
Flumazenil / Romazicon
C/I:
- history of seizure d/o (can precipitate seizure)
- tachycardia
- WIDENED QRS COMPLEX ON ECG*
- hx of long-term benzo use (precipitates acute withdrawal)
antipsychotic drugs are also referred to as what?
neuroleptic
anti-schizophrenic drugs
tx:
delirium
mania
agitated states
Which antipsychotic drug is used to treat Tourette’s Syndrome?
Haloperidol / Haldol
psychosis - a mental state where the perception of reality is distorted and is particularly associated with schizophrenia, bipolar disorder (manic depressive disease) and severe depression - has been traditionally linked to which neurotransmitter?
Dopamine
What is the dopamine hypothesis of psychosis? In what pathway is this hypothesis active?
psychosis results from overactivity of dopamine function
- esp. in the mesolimbic pathway
- dopamine antagonists (antipsychotics) reduce psychotic symptoms
- dopamine boosting drugs - amphetamine and cocaine - trigger psychosis
Dopamine is the neurotransmitter traditionally linked to psychosis, however a dysfunction in this recently hypothesized excitatory neurotransmitter and its receptor can also create psychosis?
what is the neurotransmitter and what is the receptor name.
glutamate
action with NMDA receptor
NMDA Receptor antagoinsts (kteamine, PCP, detromethorphan) in large overdose induces psychosis more readily than dopinergic stimulates - even at recreational doses
As with primary and secondary diseases - psychosis that is not psychological is known as secondary psychosis - what are 4 causes of this type of psychosis?
- neurological disorders
- electrolyte disorders
- multiple medical conditions
- Drugs - use, abuse, withdrawal
There are several drugs whose use, abuse or withdrawal have been associated with psychosis
- withdrawal from these 2 can be particularly dangerous - leading to delirium, psychosis or potential lethal withdrawal - what are these two?
barbituates
alcohol
- additional drugs whose use, abuse and withdrawal are associated with psychosis
- amephtamines
- cannabis
- cocaine
- LSD
- MDMA (ecstasy)
- Mescaline
- PCP
- Psilocybin
What is the MOA of a first generation (typical) neuroleptic?
what is it for a second generation (atypical) neuroleptic?
TYPICAL
First gen. antipsychotic
- D2 Antagonism
ATYPICAL
Second gen. antipsychotic
- 5HT2A/D2 Antagonism
Atypical antipsychotic medications include which 4 classes as an example?
Butyrophenone class Dibenzodazepine class Thenobenzodiazepine class Benzisoxazole class
what is the main MOA of both the typical and atypical neuroletic drugs?
blockade of dopamine receptors in the brain
This group of neuroleptics is
- first line tx for schizophrenia
they are a heterogeneous group of otherwise unrelated drugs united only by the fact they work differently from typical antipsychotics - what are they?
atypicals
- some believe MOA to be D2 and 5-HT2A receptor antagonists
- atypical neuroleptics also serve to antagonize fully or partially the serotonin receptors
what are the two decreased propensities of an atypical antipsychotic and therefore among its most defining characteristics?
- extrapyramidal side effects (less likely to cause tardive dyskinesia)
- absence of sustained prolactin elevation
(making them superior)
Five dopamine receptors have been identified, which of these is the chief receptor of neuroleptic action?
D2 receptors
- stimulation associated with tardive dyskinesia*
- evidence suggests atypicals have less an affinity for D2, and more affinity for D4 receptors
excess release of dopamine in which region of the brain has been linked to psychotic experiences?
mesolimbic pathway
- blockage here is thought to control psychotic experiences
dopamine can be further processed into norepinpehrine by which enzyme?
dopamine beta-hyrdoxylase
Which two enzymes break down dopamine?
- catechol-O-methyl transferase (COMT)
- monoamine oxidase (MAO)
Antipsychotics are often antagonists of this, while psycho-stimulates are indirect agonist of these receptors - which ones are they?
dopamine receptors
This is a neuro d/o characterized by involuntary movements of the face and jaw
tardive dyskinesia
- often caused by medications
- COMMON S/E OF ANTI-PSYCHOTICS*
This is a state of abnormal muscle tone resulting in muscular spasm and abnormal posture
dystonia
- either inherited or acquired due to underlying dz such as Parkinson’s
generally speaking, these are hoped to have lower likelihood of developing tardive dyskinesia when compared to what?
atypical antipsychotics lower likelihood of developing tardive dyskinesia than typical antipsychotics
- generally occurs after long-term use
many of the atypical neuroleptics block 3 additional receptors aside from dopamine?
- cholinergic
- alpha adrenergic
- histamine (H1) Rs
NO ATYPICALS ARE APPROVED FOR CHILDREN
In 2003, the FDA required all manufacturers of atypical antipsychotics to change their labelling to include these two warnings - what are they?
hyperglycemia
diabetes
- greatest negative effect
Clozapine
olanzapine
(assoc. with inc. weight gain and insulin resistance) - Least negative effect
Ziprasidone
Aripiprazole
this rare side effect of neuroleptics is likely caused by the blockade of D2 receptors characterized by catatonia, fluctuating blood pressure, dysarthria and fever. Muscle cramps, fever and blood pressure instability are the first signs to show up. Removal of the antipsychotic drug is recommended immediately. What is this side effect and what is used to treat this unfortunate, but rare side effect?
Neuroleptic Malignant Syndrome
(lasts 8-40 hours)
TX with
- Bromocriptine (dopamine agonist)
what lab values will be increased with neuroleptic malignant syndrome?
- WBC count
- Creatine Phosphokinase (CPK)
due to increased muscular activity and rhabdomyolysis (destruction of muscle)
Most neuroleptics have anti-emetic effects mediated by blockage of which receptors in which aspect of the brain?
anti-emetic effects mediated by D2 receptor blockage
in
chemoreceptor trigger zone (CTZ) of the medulla
This typical neuroleptic works by blocking D2 receptor sites as well as alpha-adrenergic and H1 receptors.
Chlorpromazine / Thorazine
What commonly happens as a result of blocking dopamine?
increased prolactin release*
this can result in
- galactorrhea (F)
- amenorrhea
- infertility (M and F)
this typical neuroleptic works by
- antagonizing the H1 receptor as well as
- alpha adrenergic and D2 receptors.
Characterized by having less orthostatic HYPOtensive responses and fewer extrapyramidal signs (only seen at high doses over long duration) than others.
Better anti-emetic than other neuroleptics as well.
Prochlorperazine / Compazine
10-20x more potent that chlorpromazine*
SE
- drowsiness
- dry mouth
- constipation
- urinary retention
this typical neuroleptic is indicated for various things, sp. acute agitated behavior - it works chiefly as a D2 receptor antagonist
- side effects are parkinsonian-like - extrapyramidal effects that may be very dramatic.
- significant potential for FATAL neuroleptic malignant syndrome - which neuroleptic is this?
Haloperidol / Haldol
“Vitamin H”
- less blockade of muscarinic and alpha adrenergic Rs when compared to others such as Chlorpromazine
On the slides - also listed as ATYPICAL - not sure which it is.
this atypical neuroleptic
- indicated for schizophrenia when others have failed
- blocks multiple receptors, most noted are D2 and 5-HT2 R sites.
- administered PO.
- first atypical approved by the FDA (1989), has been shown to be superior to typicals in tx-ing schizophrenia (and reducing suicidal behavior).
However, it’s a third-line neuroleptic due to it’s RARE but LETHAL SEs of AGRANULOCYTOSIS (1-2% of pts) and MYOCARDITIS
clozapine / clozaril
- safe use requires weekly blood monitoring x5 mos (moves to every 4 weeks there after)
- echocardiograms rec. q6mo
- DISCONTINUE if granulocyte ct is less than 1500
this atypical neuroleptic has an unknown moa, perceived to work as
- dopamine and serotonin antagonism.
Metabolized by the p450 enzyme to active metabolites (decreased dose in liver impaired pts)
- side effects are all those common to neuroleptics with the added “benefit” of weight gain, hyperglycemia and diabetes and an increase risk of stroke in the elderly - which neuroleptic is this?
Respiradone / Riperdal
- black box warning:
increased mortality in elderly patients with dementia-related psychosis
this atypical neuroleptic is structurally similar to clozapine - it’s indicated for schizophrenia when other meds haven’t worked
- blocks multiple receptors, largely D2 and 5-HT2 Rs with higher affinity for 5-HT2
- administered PO, rapidly absorbed
- has relatively diminished extrapyramidal s/e’s but comes with increased WEIGHT GAIN, hyperglycemia, diabetes and INCREASED RISK OF STROKE IN THE ELDERLY
Olanzapine / Zyprexa
30% of pts gain approx 22 lbs after a year of use*
like most atypical antipsychotics lower affinity for the following receptors
- histamine
- cholinergic muscarinic
- alpha adrenergic
citing an increased risk of stroke, in 2004 the committee on the safety of medicines (CSM) in the UK issued a warning that these two atypical antipsychotics should NOT be given to elderly patients with dementia - which drugs are these?
- Olazapine / Zyprexa
- Risperidone / Riperdal
This second gen. atypical anti-psychotic is a partial dopamine agonist with additional anti-depressant properties used to tx schizophrenia, bipolar disorder and clinical depression - what is it?
Aripiprazole / Abilify
these are used prophylactically in treating bipolar disorder and manic episodes.
- widely distributed in the CNS, interacts with multiple neurotransmitters
- specifically decreases NE release (dampening transmission) and increases Serotonin synthesis.
- may diminish response to glutamate (an excitatory neurotransmitter)
lithium salts
- lithium levels should be checked after EACH dose increase
- steady state gen. reached after 5 days of dose adjustment.
this lithium salt is administered PO, cleared by the kidneys with a small therapeutic index and side effects of weight gain, cognitive impairment and short-term memory deficits - what is this salt?
Lithium carbonate / Eskalith
- incidence of polyuria d/t nephrogenic diabetes insipidus is approx. 20% for patients on chronic tx
What is the most common effect of lithium on the renal system? and what condition may occur in 5-35% of patients on long-term lithium therapy?
impaired concentration capacity
due to reduced renal response to ADH (antidiuretic hormone)
- HYPOTHYROIDISM may occur in 5-35% of patients on LT lithium therapy
What is the acronym for lithium side effects?
LITH leukocytosis inispidus tremor / teratogenic hypothyroisim
Lethargy, confusion, diarrhea, abdominal pain, nausea and vomiting, ataxia and severe tremors - These are signs that what could be too high?
lithium.
as lithium levels increase
- seizures develop
- cardiotoxicity can occur
these are seizures that frequently occur during sleep or at transition between sleep and wakefulness - what are these called?
hypnogogic seizures
What are examples (5) of certain environmental factors that can lead to increased likelihood of seizures in someone with epilepsy
flashing lights sleep deprivation alcohol consumption stress/anxiety illness
these are potential causes of what? space occupying lesions head trauma drug s/e's fever meningitis, encephalitis metabolic / electrolyte abn
non-epileptic seizures
Which imaging option for MRI will show water as white?
T2 weighted
small, numerous lesions in the brain are generally what? (2)
metastatic or
infectious
Seizures are classified as either simple or complex - what differentiates these two classifications?
change in level of consciousness
simple - no change
complex - change
seizures can also be classified as partial / focal OR generalized - what’s the diff?
partial / focal - one part or side of body is affected
generalized - entire body affected
How are anti-epileptic drugs generally chosen?
according to TYPE of seizure experienced
60% of people with epilepsy have what type of seizure?
focal seizure
- eeg is used to determine origin of aberrant activity
In this type of seizure a person
- remains conscious
- experience unusual feelings/sensations of differing forms
- sudden unexplainable feelings of fear, joy, anger or sadness out of context
- may also involve - hallucination (sight, sound, smell, taste, skin sensation)
simple partial seizure
Drugs
Carbamazepine / Tegretol
Phenytoin / Dilantin
Diazepam / Valium
in this type of seizure a person
- experiences change in or LOC
- strange, repetitious behaviors (blinks, twitches, mouth movements, motions - walking in a circle)
- these repetitious movements have a name - what type of seizures are these and what is the term for the repetitious movements lasting a few seconds?
complex partial seizures
automatisms
- repetitious movements lasting just a few seconds during seizure
this type of generalized seizure holds the highest chance of outgrowing the condition, a person gen. experiences - interrupted consciousness - unresponsive for approx 30s - slight muscle twitching may occur What are they?
Absence seizures
- aka petit mal seizures
3Hz spiking wave appears over entire spectrum of EEG
drugs:
Ethosuximide / Zarontin
Valproic acid / Depakote
This type of seizure causes a mix of symptoms
- stiffening of the body
- repeated jerks of the arm and or legs as well as LOC
- initial contraction of the muscles (tongue biting, urinary incontinence, absence of breathing)
- followed by rhythmic muscle contractions
Generalized seizures
- aka Tonic Clonic Seizures
- aka Grand Mal Seizures
can also be referred to as:
epileptic fit*
drugs:
Valproic acid / Depakote
this refers to continuous seizure activity with NO recovery between successive seizures - What is the preferred tx??
Status Epilepticus
tx’d with Lorazepam / Ativan OR Diazepam
should be considered a MEDICAL EMERGENCY
- a tonic-clonic seizure lasting longer than 5 minutes (or 2 mins longer than a persons N time)
- risk of CEREBRAL ISCHEMIA
what is the goal of therapy with seizures and how do anticonvulsant/antiepilepsy drugs generally work?
MONOTHERAPY is goal - cyp450 issues if multiples used
nearly all work by blocking sodium or calcium channels or potentiating inhibitory effects of GABA
what are third-line seizure meds generally used
benzodiazepines
- status epilepticus occurs because pt does not have ativan or phenobarbitol (benzos)
What is used to treat epilepsy in children and adults - but also approved for prevention of migraine, tx of bipolar disorder, counter weight gain of antidepressants and potentially useful in txing
- tremor, bulimia, OCD, alcoholism, smoking cessation, neuropathic pain
Topiramate / Topamax
also being studied for treatment of OBESITY when combined with phentermine
- Qsymia*
for head injury assoc. with status epilepticus - which drug is preferred?
phenytoin / dilantin
this barbituate anticonvulsant works by enhancing GABA activity - it’s administered generally IV/PO with a slow onset (30 + mins) and very long half life (50 + hours).
It may be the initial drug of choice for children with seizures - it CAN be used to stop acute convulsions or status elipticus, however - that’s reserved for the benzos - what is this drug?
phenobarbital / phenobarb
S/E
CNS depression, associated with LOWER IQ in KIDDOS undergoing chronic tx
- metabolized by p450
stimulation of these enzymes can increase metabolism of other drugs and concurrent phenobarbital use can lower serum conc. of multiple drugs*
this barbituate anticonvulsant likely works by GABA mediated inhibition - it’s given PO, metabolized in the liver, with a half life of 10-12 hours for the drug itself and greater than 48 hours for its metabolites. Which drug is this?
Primidone / Mysoline
- Category D
- DO NOT USE IN PREGNANCY
unless life threatening condition*
this benzodiazepine anticonvulsant works by increasing sensitivity to GABA by increasing chloride influx (therefore inhibiting CNS APs) - its acts as a Ca channel blocker and significantly inhibits depolarization-sensitive calcium uptake - which drug is this that works so well for status epilepticus?
Diazepam / Valium
This long-acting benzodiazepine anticonvulsant works by sensitizing GABA in the CNS (via Cl and Ca - inhibiting APs) it is indicated for absence seizures and status epilepticus - however it has a marked abuse potential. What is it?
Clonazepam / Klonopin
- clinicians hesitate to rx this due to increased likelihood of benzos decreasing IQ in kiddos
This anticonvulsant reduces sodium and calcium currents across neuronal membranes - it works prophylactically for all seizures EXCEPT ABSENCE seizures - administered PO/IV/IM with short onset, but long half life - what is it?
Phenytoin / Dilantin
When treating with Phenytoin / DIlantin - what MUST be monitored? (3)
CBC
drug levels
LFTs (metab via LV)
this is because many drugs alter the metabolism and binding of dilantin
What are the adverse effects noted with Phenytoin (using PHENYTOIN as the acronym)
P - 450 interactions H - hirsuitism E - enlarged gums (GINGIVAL HYPERPLASIA*) N - NYSTAGMUS Y - yellow-browning of skin T - teratogenicity O - osteomalacia I - interferes with B12 metab N - neuropathies
This anticonvulsant works by reducing Na and Ca currents across neuronal membranes - it’s a prophylactic for all seizures except absence, administered PO - what drug is it? What does it commonly treat and what should NEVER be prescribed with this drug?
Carbamazepine / Tegretol
- Tegretol treats Trigeminal Neuralgia
- NEVER RX W/ MAOIs (increases risk of hypertensive crisis)
What must be monitored when treating a patient with Carbamazepine / Tegretol?
CBC
LFTs
SE - vertigo, N/V, bone marrow suppression, ANEMIA, HEPATITIS
this broad-spectrum anticonvulsant has an unknown MOA (but may increase GABA concentrations by inhibiting GABA transaminase while also blocking Na channels and T-type Ca channels) - can be used in ALL seizures but recommended for GRAND MAL*, generally administered PO or IV - and is safe to give with other anticonvulsants with added benefit of anti-seizure effects - what is it?
Valproic acid / Depakote
- could be alt. tx to bipolar over lithium salt
remember grand mal seizure tx* along with
Lamotrigine / Lamictal
Valproic acid / Depakote seems great with it’s universal abilities in the seizure world, however - it has serious potential for what? meaning we should monitor what? and - should it be used in pregnancy?
SEVERE HEPATOTOXICITY
- monitor blood levels!
- known folic acid antagonist, therefore when taken by pregnant women, increases IRREVERSIBLE birth defects by 3-10x - NT defects, anencephaly :(
- NOT OK IN PREGNANCY
this anticonvulsant is THE DRUG OF CHOICE for ABSENCE seizures - may work on T-type Ca ion channels - what is it and why is it preferred?
Ethosuximide / Zarontin
- drug of choice due to decreased hepatotoxicity (when compared to Valproic acid)
** increases phenytoin levels, bc metab in liver
Ethosuximide/Zarontin is less toxic than other anticonvulsants, but that doesn’t mean it’s without a SE profile of it’s own, what are the two biggies for this on and should we monitor blood levels?
SE - gingival hyperplasia, lupus-like syndrome
- DOES NOT need frequent blood level monitoring
This anticonvulsant, atypical analgesic may potentiate GABA while affecting N-type Ca channels, halting formation of new synapses - can be added to monotherapy due to low SE profile. It’s used for chronic pain syndrome such as post-herpetic neuralgia - what drug is this?
Gabapentin / Neurontin
This drug can be used for reduction of withdrawal symptoms/desire associated with methamphetamine and or cocaine use - what is it?
Gabapentin / Neurontin
- 1200mg at bedtime for40-60 days
In other countries - this is combined with Flumazenil to successfully stop cocaine and methamphetamine habits
this anticonvulsant may stabilize neurons by decreasing excitatory effects of glutamate and aspartate. It’s given PO, metab by the liver - it was the first drug approved (since lithium) for TX of type I bipolar disorder and is the preferred drug for PARTIAL SEIZURES*- what is it?
Lamotrigine / Lamictal
Preg. Cat. C*
SE
dizziness, HA, rash, diplopia, somnolence, ataxia
remember - partial seizures*
can also be used for grand mal*
this anticonvulsant may stabilize neurons by inhibiting Ca movement through presynaptic Ca channels - is it generally well tolerated, given PO and metabolized by that there liver - what is it?
Levetiracetam / Keppra
*safe to add to monotherapy
What anticonvulsants can also be used for neuropathic pain?
Gabapentin / Neurontin
Levetiracetam / Keppra
this was approved in 1997 as an adjunctive therapy for partial-onset epilepsy - what is it?
vagus nerve stimulator
- sends electrical signals down L vagus nerve in neck via lead, implanted under skin
What is the chief neurotransmitter used by the basal ganglia to initiate and stop movement?
dopamine
In Parkinson’s
75-90% must be destroyed before sx present
What system connects communication between the brain and skeletal muscle?
extra-pyramidal
Where are the dopamine-secreting neurons located?
substantia nigra
What pathway is notable for the development of Parkinson’s?
Nigrostriatal pathway
Dopamine disruption along the non-striatal pathways lead to ___, ___, and ___ associated with Parkinson’s.
Depression
Dementia
Psychosis
Major notable PD symptoms include: (4)
Tremor at rest (pill roll)
Rigidity
Bradykinesia or akinesia
Postural instability
What is the characteristic gait of PD?
Slow and reduced in amplitude with small, rapid, stutter-steps with stooped or flexed posture
PD may also impair nerve endings in the heart regulating the release of _____ leading to what?
Norepinephrine
Abrupt hypotension when standing
Alzheimer’s is a disease of _____ loss while PD is primarily a disease of _____ loss although they may overlap in picture.
AD: memory loss
PD: motor loss
What may be found in AD, PD, and other dementias? What is found in AD specifically?
Lewy bodies found in both!
Plaques and tangles found in AD.
What is the mean age of onset in Parkinson’s and what is often the first symptom to occur?
58-60 years
first sx: TREMOR - “pill-rolling” in nature. - decreased with intention - does not occur during sleep - rhythmic (4-5/sec)
starting in upper extremities and gen UL
When you think Parkinson’s what is the first medication that SHOULD come to mind?
Levadopa!
dopamine itself cannot cross BBB - that’s why we use Levadopa
What is a major potential side effect of L-Dopa?
Severe, protracted nausea
- due to activation of the chemoreceptor trigger zone in the medulla oblongata and the dopamine receptors in the GI tract
Levodopa is no longer used without combination therapy. What is it usually combined with? Why?
Combined with:
Carbidopa (a peripheral dopa-decarboxylase inhibitor)
To prevent peripheral breakdown, increasing availability for central utilization
- without - only 1% reached CNS
- when doing this, can drop levo dose by 75%*
- If need to increase dose, increase carbidopa first, then levo.
With combination therapy of L-dopa, you can _____ (decrease/increase) the overall dosing.
DECREASE!
Sinemet is a combination of Levodopa with ___? How long is treatment with Levodopa effective?
Carbidopa
tx with levodopa generally effective for 5 years.
Levodopa in the first 2-5 years provides a sustained effect, but slowly loses it’s ability to create sustained relief - lack of response is inevitable
- signifies complete loss of dopamine-producing cells in substantia nigra
Entacapone inhibits what enzyme?
COMT (catechol-o-methyltransferase)
The most frequent adverse effects caused by Entacapone relate to the increased effects of L-dopa, leading to what?
dyskinesia
- beginning of tx, later diminishes
Never combine levodopa with what?
MAOI
- leads to hypertensive crisis
This medication is used to treat prolactin-secreting adenomas and acromegaly - as well as Parkinson’s - what is it and what class is it in?
Bromocriptine
dopamine agonist
- must titrate up in 4-6 weeks, max dose 100mg/day
SE: N, Hyper/hypo-tension, confusion, hallucinations, H/A, depression, DYSKINESIA, pulmonary fibrosis, galactorrhea
There is a secondary effect to bromocriptine that can be beneficial - what is this?
decreased insulin resistance
Anticholinergics may treat some of the symptoms of PD and are also used as an antidote to _____ poisoning.
Treats organophosphate poisoning
Symptoms of PD tx’d:
- drooling
- tremor (not bradykinesia)
- incontinence, etc.
this anticholinergic, used to treat symptoms of PD can cause confusion and nervousness, therefore it’s best taken before bed - it can also lead to toxic psychosis (take caution in patients under antipsychotic care) if too large a dose - what drug is this and what drug can reverse it’s OD?
Benzotropine / Cogentin
- CI in seizure, lowers threshold
Physostygmine reverses anticholinergic intoxication
What antiviral for Influenza A may be indicated in Parkinson’s? What receptor is blocked for the MOA?
Amantadine/Symmeterel
NMDA receptor antagonist
- diminishes dopamine re-uptake
- only effective x 6 months*
This AA binds allosterically to the NMDA receptor causing what?
glutamate
- diminishes dopamine re-uptake (like Amantadine)
Rate treatment efficacy from highest to lowest for: Bromocriptine Anticholinergics L-dopa Amantadine
L-dopa then
Bromocriptine
Amantadine
Anticholinergics
This is a MAO-B inhibitor used to treat PD - What distinguishes the A from B class for MAOIs?
Selegiline / Eldepryl
MAOI B class has decreased risk of hypertensive crisis with tyramine containing foods - therefore diet isn’t AS large an issue
Given in the AM due to it’s amphetamine like effect (upper)
