CNS disorders Flashcards

Question

Latuda 3 clinicals

Answer 1

take with food - increased absorption Avoid strong CYP inducer and inhibitor Less sedating, less EPS and Less risk of metabolic sydnrome compared to other antipsychotic

Answer 2

partial D2 agonist - dopamine stabilizer SE: activating - not sedating --> partial dopamine agonist Dose once daily in the morning - max 30 mg

Answer 3

latuda - take with FOOD Latuda - sounds like TUNA Lunch

Answer 4

**Abilify has the ability to stimulate D2 - partial agonist** **Abilify is a DOPAMINE stabilizer** Partial agonist: stimulates or works like an agonist but provide partial responsive, not FULL responses In abundance of DA, abilify actually works like a dopamine antagonist because it is taking up the receptor site but providing only partial response. When DA is low, Abilify's ability as a partial agonist provides dopamine activiting instead of blocking. **Antipsychotics block dopamine receptor - but abilify is a partial agonist**

Answer 5

Lower risk for metabolic syndrome * Fat man with ice cream - diabetes, weight gain and cholesterol Targets 5HT7 - great for helping negative symptoms of schizophrenia * Depression * Cognition Take with Food - latuda sounds like tuna for Lunch

Answer 6

**highest risk for metabolic syndrome** **Sedating - high affinity for anti-histamine receptors** **shows greater improvement and insight in understanding patient's mental status** Remember: * bullsfighter shouting o'le (olanzapine) with clothespin (clozapine) taking to Fat Man outside * olanzapine and clozapine have highest risk for metabolic syndrome

Answer 7

Extended Release Technololgy - providing steady drug level Invega Sustenna - monthly injection * same as Abilify maintena Higher risk for Hyperprolectinemia * gynecomastia ## Footnote paliperidone - active metabolite of risperdal

Answer 8

paliperidone - the active metabolite of risperidone * more purified Both drugs are associated with high risk of prolectinemia * **BUT - paliperidone causes more prolectinema** Paliperidone clear by kidney * check creatinine clearance

Answer 9

No OROS - osmotic release oral system Drug release through a laser drill hole

Answer 10

Lower EPS --> does not bind tightly to dopamine receptors Sedating Goldilocks dosing * lower dose = sedation * moderate dose = bipolar * high dose = schizophrenia So, how well you remember? * quetiapine is very sedating - small dose cause sedation already * need high dose for schizophrenia

Answer 11

800 mg per day

Answer 12

Higher risk for hyperprolectinemia * Raspberry milking cow Metabolic syndrome (weight gain) * **less than olanzapine & clozapine** Dose dependent * lower dose - more 5HT2 blockade - helps negative symptoms * higher dose - more Dopamine blockade - helps with schizophrenia

Answer 13

highest risk for **QT prolongation** * sQuirrel with long Tail * inhibits NE reuptake - more norepinephrine to stimulate the heart Less metabolic syndrome (NE reuptake) FOOD - need at less 500 calories * more than latuda (tuna for lunch) NOTE: Z in Ziprasidone - looks like * Cardiogram - heart beat graph ## Footnote Pelican - with zipper (ziprasidone). sQuirrel with long Tail (QT)

Answer 14

**May cause severe liver toxicity** SL dosage forms Very low anti-muscarinic - less atropine like side effects (less BUCD) A-senna * A = without * senna * don't need senna - less constipation (less antimuscarinic)

Answer 15

**Raybow afro grandma** D3 partial agonist (not dopamine blocker) * similar to abilify * Abilify is a D2 partial agonist * partial agonist - provides partial response * **partial dopamine stimulation - more akathisia (restlessness) - both abilify and vraylar** CARI-prazine - makes you more CARING * more motivated - helps with negative sx * more motivated to loose weight - less metabolic sydrome (wt gain) After Raybow grandma takes vRAYlar - it makes her more caring (cariprazine) and thinking about takin care of a third doberman (D3 agonist).

Answer 16

A copy cat of aripiprazole (abilify) but * **enginerred for better tolerability** * less restlessness (akathisia), less ESP, less metabolic syndrome (weight gain) * A better side effect profile compared to aripiprazole * **like abilify - partial agonist at D2 and 5HT** Decrease **prolactin level** * most antipsyhotic increase prolactin level Brexpiprazole - aims for the Goldilocks zone of dopamine modulation * not too much and not too little

Answer 17

Remember: on the TV is an episode of antipyschotic idol. A Fan of the show is watching. Fan (fanapt) is watching antipsychotic idol (idoperidone) Idoperidone = Fanapt

Answer 18

QT prolongation High alpha-1 antagonist = orthostasis * slow titration to decrease OSH **Trade-off** * antipsychotic is known for metabolic syndrome and EPS * idoperidone has less metabolic syndrome and EPS - **but higher risk for QT prolongation required ECG monitoring** The antipsychotic idol show crazing to watch, it almost gave the Fan (Fanapt) a heart attack (QT).

Answer 19

Works on 3 NT (dopamine, serotonin and Glutamate) * glutamate - excitatiory NT --> binds on NMDA receptor (post-synaptic) * works like SSRI - inhibits serotonin reuptake inhibitor - good for depression, negative sx Unique action on Dopamine compared to other antipsychotic * partial agonist at presynaptic D2 receptors --> provides negative feedback --> less dopamine release into synapses * also blocks post-synaptic D2 receptors (like most antipsychotics) Helps positive (hallucination, delusion) and negative symptoms (lack of motivation, cognition) and depression. * **good for bipolar depression and schizophrenia**

Answer 20

42 mg daily

Answer 21

little brother to aripiprazole But copied and engineered for better side effect profile

Answer 22

Day 1: Injection + PO dose Take PO dose for 14 days, then can discontinue 2nd injection: * 30 days from 1st injection * **window: no sooner than 26 days after 1st dose** NOTE: * Established oral abilify tolerability prior to injection * make take 14 days to establish oral tolerability

Answer 23

Abilify is not a prodrug - it is the active drug metabolized by CYP 2D6 and 3A4 Poor metabolizer 2D6 * needs lower dose to prevent drug toxicity * pt on 3A4 inhibitor -- need lower dose to prevent abilify toxicity

Answer 24

NO oral overlap **Invega - has an initiation phase (2 shots in 7 days)** Day 1: 234 mg Day 8: 156 mg Monthly dose: (5 weeks after 1st dose) * **to make it less confusing --> consider day 8 as your last dose** * **monthly injection will be 4 weeks from last dose** Other way to look at it: * Monthly dose --> Day 36 (35 days - 5 weeks) plus or minus 7 days to prevent missed dose Schedule: Day 1: 234 mg Day 2: 156 mg Day 36: monthly injection --> see equivalent po dose

Answer 25

You have a 7 days window 7 days before or 7 days after

Answer 26

Day 1: Risperdal Consta + continue taking PO risperidone for 3 weeks Day 15 (every 2 weeks): Risperdal consta * continue PO risperdal for 1 more week and taper per doctor's preference Then give Risperdal Consta every 2 weeks

Answer 27

Risperdal Consta - takes 3 weeks to ready steady state Bridge or continue PO risperdal for 3 weeks, the taper per provider's preference ## Footnote YES - continue PO risperdal for 3 weeks

Answer 28

Thorazine = chlorpromazine IM chlorpromazine - takes 15 minutes Thorazine PO --> max 1,000 mg per day * usual dose: 300 to 1000 mg per day

Answer 29

Typical antipsychotic Mid Potency 1st generation antipsychotic max dose: 250 mg per day

Answer 30

Perphenazine = mid potency 1st gen antipsychotic Max: 64 mg per day divided up to 4 times a day

Answer 31

Initiation phase: * take patient's daily haldol dose x 20 * **First injection: do not exceed 100 mg** * if dose exceed 100 mg - give remaining dose in 3 to 7 days --> then continue with monthly injection * **monthly injection can be 200 mg --> can be over 100 mg** PO haldol * can continue for 2 to 4 weeks - needed for IM to reach state Example: patient takes haldol 10 mg daily * initial dose: 10 x 20 = 200 mg * First injection: 100 mg im --> then given remaining dose in 3 to 7 days * montly injection: 200 mg IM monthly

Answer 32

DECA in decanoate * Deca = 10 = decade (10 years) * long time Lactate = L = Little * short acting

Answer 33

Highes QT risk * **First Generation has the highest QT risk** * Haldol --> H for Heart * Thioridazine and chlorpromazine --> lower potency 1st gen (magazine with the thigh and prom dress) 2nd gen: **ziprasidone has the highest risk** * Ziprasidone - sQuirrel with Tail Zipper * Ziprasidone = QT * Z - in ziprasidone - looks like a heart rhthym upside down Highest Risk for EPS * Risperdal and its active metabolite Paliperidone have the highest risk for EPS * Quetiapine --> low risk for EPS * Quetiapine makes you quiet - resting (no movement) * Risperdal - sounds like restlessness (unable to rest or sit still --> movement disorder * Risperdal - raspberry milk cow - highest risk for hyperprolactinemia Highest risk for metabolic syndrome * olanzapine and clozapine * Bullsfighter fighter shouting o'le with a clothespin (clozapine) taunting the fat man eating ice cream * Quetiapine: remember, lowest EPS, makes you rest, no movement = weight gain NOTE: drugs with less weight gain * abilify - aripiprazole * ziprasidone - geodon * lurasidone - latuda * asenapine - saphris

Answer 34

Ziprasidone sQuirrel with the Zipper Tail (ziprasidone) QT = ziprasidone **just remember - first gen haloperidol, chlorpromazine and thioridazine are associated with QT** **just associate 1st gen with QT and EPS** **just remember the 2nd gen ziprasidone**

Answer 35

Risperdal and its metabolite Paliperidone Quetiapine = quiet please, no talking and moving * less EPS - prefer in patient with Parkinson **Quetiapine - quiet please, no talking no moving (librarian) = MORE WEIGHT GAIN** Gain weight from NO movement

Answer 36

o'le with clothespin on his cape talking to fat man eating ice cream o'le - olanzapine clothespin - clozapine Quetiapine = quiet please, no talking no moving * no moving means no exercise = weight gain

Answer 37

Pimvanserin - treats psychosis in with parkinson's psychosis * psychosis due to parkinson's disease Significant SE: **QT prolongation** Takes psychosis but does not block dopamine * **psychosis is related to TOO much dopamine**

Answer 38

Inverse = opposite inverse agonist = think of it as opposite of agonist --> antagonist inverse agonist vs antagonist then? * produce a more POTENT antagonist effect * an antagonist - basically blocks the receptor sites, does not affect baseline function * **inverse agonist - blocks and reduce its baseline function. Opposite of what a agonist would do** **pimavanserin - blocks serotonin receptors, treats psychosis this way. does not affect dopamine - so no effect on motor symptoms**

Answer 39

Quetiapine (seroquel) Quetiapine - quiet please, no talking and no moving - **treats psychosis with less EPS side effects**

Answer 40

paliperidone - is cleared by the kidney Risperdal - is clear by metobolism by the liver * CYP interaction

Answer 41

Seizure risk Clozapine also increase risk for: * agranulocytosis * Weight gain

Answer 42

Clozapine blocks dopamine receptors **metoclopramide (reglan) - treats nausea by blocking dopamine receptors also** **increased risk for EPS** Chemoreceptor Trigger Zone CTZ in brain - when stimulanted, sends signal to vomiting center of brain to induce vomit * CTZ has receptors for dopamine and serotonin * **reglan works by blocking the dopamine in the CTZ to reduce vomiting signaling** **Reglan and clozapine BOTH blocks DOPAMINE** **Risk EPS and NMS** NMS - is too little DOPAMINE Serotonin Syndrome - TOO much Serotonin ## Footnote md cancel clozapine dose for tonight

Answer 43

Pima = sounds like primate (crazy monkey) pimavanserin = psychosis

Answer 44

Tardive dyskinesia - a side effects (not mental condition) from psych meds Tardive dyskinesia - late (developing) abnormal movments (lip smacking) Tardive dyskinesia is causes by too much dopamine * dopamine is for movement

Answer 45

TD - due to too much dopamine * **TD = Too much Dopamine = TD** When you take antipsychotic meds (blocks dopamine) too long: * body compensate by making more dopamine receptors * these receptors are extra-sensitive * Even a small amount of dopamine can cause brain to over react causing abnormal movement. | Body's compensatory mechanise to make more dopamine receptors = TD

Answer 46

Psychosis * DA stimulation * TOO much dopamine = causes hallucination, delusion * TOO much dopamine = Tardive dyskinesia Parkinson * Too little dopamine * Dopamine = movement

Answer 47

**Dopamine receptor super sensitivity** Chronic dopamine blockade from antipsychotic meds --> body compensate by producing super sentive dopamine receptors (or producing more) So even in the presence of little dopamine, it can cause the brain to over-react causing TD. **Thus tx for TD - we need to deplete dopamine so it cannot stimulate these supersensitive dopamine receptors** **TD - is due to hyperdopaminegic state (excessive dopamine signaling)** **Austedo (deutetrabenazine) - lowers the amount of dopamine release - so system is not over stimulated causing TD**

Answer 48

Deutetrabenazine = involuntary movement disorder (tardive dyskinesia) Mechanism of Action * blocks the monoamine transporter on vesicle * less monoamine (dopamine, serotonin, NE) entering vesicle for release into synapse * monoamine that do not enter vesicle gets destroy by mono-amine oxidase enzyme **net result - less dopamine in synapse to overstimulate dopamine receptors - helps with Tardive Dyskinesia** Dose: twice a day

Answer 49

QT prolongation NMS - to little dopamine * muscle stiffness * coma * hyperthermia * hypo-reflexia Dopamine regulates muscle movement, temperature, alertness, motivation

Answer 50

Ingrezza = valbenazine indication: tardive dyskinesia Mechanism of Action: * inhibits a protein called found inside the presynaptic neuron called VMT2 * VMT2 = vesicular monoamine Transporter * **blocks the transport of dopamine into the vesicle to package for release into the synapse** * **result - less dopamine release into synapse** * **dopamine not package into vesicle are broken down by mono-amine oxidase** ## Footnote Same as Austedo = Deutetrabenazine

Answer 51

Ingrezza = In Grace (of motion) * **helps with graceful movement** Focus on the double ZZ **ZZ - think dizzy** **dizzy = involuntary movement**

Answer 52

Astute - means sharp, clever and highly perceptive A = opposite = someone who is not sharp or precise (uncontrolled) AUSTEDO * Abnormal Uncontrolled Sudden Twitching * TD in name = tardive dyskinesia

Answer 53

Anti-psychotic used to be called **neuroleptics** NMS = neuroleptic malignant syndrome Too little dopamine --> muscle contraction (rigidity)

Answer 54

Relax the muscle * use benzodiazepine, dantrolene * dopamine agonist: bromocriptine Quetiapine and clozapine - lower risk for NMS

Answer 55

quetiapine - seroquel clozapine - clozaril

Answer 56

Muscle rigidity - lead to respiratory failure * Suffocation and death Intense muscle contraction can lead to acute renal injury * due to RHABDOmyolysis ## Footnote NMS = death

Answer 57

in the spinal cord (CNS), there are ALPHA MOTOR NEURONS * **sends signal to muscle for muscle contraction** Benzodiazepine * Binds to GABA - receptor at a diferent site * Allows Cl- to enter - makes the neuron more negative --> LESS action potential or firing * **benzo reduces the activity or firing of the alpha MOTOR neurons** Note: only valium (diazepam) is approved for muscle spasms Others are use off-label

Answer 58

Diazepam (valium)

Answer 59

Works directly on the muscle Muscle gets a signal to contract Calcium release inside muscle cells to contract **Dantrolene - binds to the receptor (gate-keeper) - prevents Ca+ movement --> no muscle contraction**

Answer 60

NMS - is too little dopamine Bromocriptine is a dopamine agonist * **has high affinity for dopamine receptors** * can out-compete or displaced dopamine blocking agent * **restore normal dopamine function: temperature, muscle function**

Answer 61

Prolactin - a hormone produce by the pituitary gland * regulates milk production and breast development (gynecomastia) **dopamine - a NT that naturally inhibits prolactin release from the pituitary gland** **when psych meds block dopamine - there's NO dopamine to block secretion of prolactin ---> leads to milk production and gynecomastia** ## Footnote Risperdal - highest risk for gynecomastia

Answer 62

Fluctuations between extreme sadness and elevated, overexcited or irritatable moods So - goal of treatment is to stabilized the fluctuation = **mood stabilizers**

Answer 63

stabilize mood = **mood stabilizer** without inducing mania or depression Note: * classic mood stabilizer = lithium

Answer 64

Anti-depressant when alone in bipolar treatment can **induce mania** **must be used in combination with a mood stabilizer**

Answer 65

Antipsychotic (olanzapine, risperidone), lithium, OR valproate Preferred: * a combo of anti-psychotic + lithium or valproate Can you use lithium with valproate? * Yes - standard * may provide synergistic effect

Answer 66

**Anti-psychotic = quetiapine, lurasidone** NOTE: anti-psychotic is actually first line in treatment acute depressive episode in patient with bipolar and NOT anti-depressant **Anti-depressant = can induce a mania episode** **lithium, valproate or lamotrigine - can be added or used as alternative** * notice = carbamazepine is not for acute depressive episode

Answer 67

Valproate Lamotrigine Carbamazepine **all 3 meds are Na+ channel blocker - prevents Na+ entering presynaptic neurons --> less action potential**

Answer 68

Lithium is cleared by kidney Monitor kidney function

Answer 69

1,800 mg per day divided BID to TID

Answer 70

Twice a day to 3 times a day

Answer 71

0.6 to 1.2 mEq/L **Think: 0.6 then double up**

Answer 72

Therapeutic level is 0.6 to 1.2 Acute mania episode = may required up to 1.5 mEq/L initially Okay to verify as is and advised to monitor lithium level

Answer 73

kidney absorbs too little water --> causing the body increase urine output = **polyuria** polyuria (frequent urination) --> less water in the blood --> body compensate by increasing thirst --> drink more **polydipsia** Nephrogenic diabetes insipidus * frequent urination * frequent thirst Cause: problem with anti-diuretic hormone ADH (usually vasopressin) * vasopressin - concentrate urines --> body can retain fluid (water balance) **Lithium blocks ADH from binding to its receptor --> no Anti-diurectic activity** * no preservation of water - polyuria * to compensate for water loss - polydipsia (frequent drinking)

Answer 74

lithium blocks TSH (thyroid stimulating hormone) from binding to its receptors TSH --> stimulate **thyroid hormone release** NO TSH stimulation --> no thyroid hormone release

Answer 75

Body can't distinguish salt vs. lithium Body see lithium and salt as the same so: * lithium level up --> Na level is down * Na level down --> lithium level up Hyponatremia - can cause lithium toxicity

Answer 76

lithium level 0.6-1.2 Renal function Thyroid (TSH) level - lithium blocks TSH receptors, no thyroid hormone release Sodium * Hyponatremia - means lithium level can be up and lead to toxicity * need a balance between sodium and lithium **Balance bar between Li and Na** **lithium up means Na Down Na up means lithium Down**

Answer 77

Seizure, coma, arrhythmia **Death can occur**

Answer 78

A large LITHIUM battery was trying to break into a house through a narrow window. * narrow therapeutic window * lithium range 0.6 to 1.2 Inside the house, there's a two headed polar bear staring at the lithium battery. There's a sad, crying man with a forcefield bouncing medications away. * bipolar - 2 headed polar bear * resistant major depression - forcefield bouncing medications away Opposite the man is Einstein holding a baby wearing a heart T-shirt. There's 3 leaves on Einstein pant cuff. Next to them is a GIANT sippy cup for the baby. A bunch of white blood cells are trying to climb up the sippy cup. The sippy cup is wearing a GIANT FROZEN BOWTIE. * Einstein - Ebstein's anomaly * Heart T-shirt = congenital heart defect * 3 leaves = tri-cuspid valves are displaced downward. * GIANT sippy cup = diabetes insipidus * white blood cell = leukocytosis (high count) * giant frozen bowtie = hypothyroidism A taxi driven by a BRAIN crashes through the wall by the window. The car hit and killed a KIDNEY. The driver's hands was shaking. * to help remember the dangerous side effects * Brain - cns toxicity * shaking hand - fine hand tremor produce by Li * Kidney - can cause acute kidney failure * high level = can cause death (kill a kidney)

Answer 79

influence the re-uptake of serotonin and/or norepinephrine or by modulating (fine-tune) GLUTAMATE Glutamate - excitatory NT High glutamate level - can cause mania

Answer 80

Yes. Lithium is thought to inhibit reuptake of serotonin Serotonin sydnrome - caused by TOO much serotonin Symptoms: * hyper-reflexia NOTE: NMS - is no reflex -- muscle rigidity

Answer 81

be concern if lithium is > 1 Lithium is like Na+ (salt) * can enter renal cells and damage normal cellular process * lithium can cause NMS. NMS can cause rhabdomyolysis - muscle proteins can clog kidney tubules * lithium can cause polyuria - if patient can drink enough - reduce blood flow to kidney and cause damage

Answer 82

broken down muscle proteins can clog kidney fitration system Broken muscle proteins (myoglobin) contains IRON * iron is toxic to renal cells The damage muscle is soaking up all the water - less water to kidney

Answer 83

Motrin -blocks prostaglandin Prostaglandins are potent vasodilators * dilate afferent arterioles - leading to filtration Motrin - blocks prostaglandin * causing afferent arterioles to narrow decreasing nutrient and oxygen to kidney causing damage When prostaglandins are inhibited, there's less blood flow to the kidney (afferent arterioles are narrow) * kidney thinks need more blood * reabsorb more sodium - water follows sodium to increase blood volume * **however, lithium and sodium - body can't tell the difference. In absorbing sodium, it also reabsorb lithium** * can increase lithium level

Answer 84

COX-1 and COX-2 are enzymes found in kidney also these enzymes produce prostaglandin - a potent vasodilator * keeps afferent arterioles open Motrin inhibits cox-1 and cox-2 * prevents production of prostaglandin

Answer 85

lithium syrup is lithium **citrate** Lithium tab/cap = lithium **carbonate** 5 ml lithium citrate syrup = 8 mEq of lithium ion = 300 mg lithium carbonate tabs/caps **Basically - easy conversion** * **300 mg lithium carbonate is 5 ml of lithium citrate**

Answer 86

Acetylcholine - tells muscle to contract **too much = shaking, contracting** Dopamine = muscle movement **smooth** **too little = slow movement = parkinson** **too much = psychosis**

Answer 87

Blocks acetylcholine receptors Helps with movement disorders: * parkinson * EPS

Answer 88

anti-psychotic blocks dopamine - for movement body compensate by increasing NE NE - causes restlessness or akathisia Propranolol - blocks NE --> drug of choice for akathisia cause by antipsychotics

Answer 89

Dystonia is painful, prolong muscle contraction (involuntary) Acetylcholine is a NT for muscle movement Benadryl - is an antihistamine but has strong anticholinergic (blockes acetylcholine) properties. * blocks acetylcholine --> helps muscle contraction relax

Answer 90

increase activity of inhibitory inhibitory neurons GABA - inhibitory NT

Answer 91

Cells becomes more positive **Think: north pole** * cold - negative temperature * dePOLAR: de (down or away) --> move away from POLAR --> more positive temperature **dePOLARization --> Action potential**

Answer 92

cell relax or rest sending K+ out (inside cells becomes more negative)

Answer 93

excitatory glutamate opens allow Na and Ca to enter cells Cells become postive --> action potential

Answer 94

inhibitory Open and allows Cl- ions to enter cells (becomes more negative) Negative cells --> relax and rest (no action potential)

Answer 95

both sides of the brain are affected Types of generalized seizures: Tonic clonic * Tonic = muscle tense * clonic = muscle contract and relax * jerking Absense Seizure * impaired awareness or responsiveness * spaced out

Answer 96

seizures lasting more than 5 minutes without stopping or multiple seizures without returning to normal in between seizures

Answer 97

Too much excitation in the brain Too much neuronal activity (no inhibition)

Answer 98

status - a "state" or "condition" * a condition where seizure are continuous epilepticus - an adjective for epilepsy or sz Together: a continuous seizure * seizure lasting more than 5 minutes without stopping or multiple seizures without returning to normal in between

Answer 99

**TOO much excitation or TOO little inhibition** Increase GABA NT * inhibitory NT Decrease or block glutamate * excitatory NT **seizure is due to much excitation in the brain**

Answer 100

blocks voltage (electrical) gated Na+ channel prevents Na+ channel from opening **decrease release of GLUTAMATE** **when Na+ enters cell ---> cells become more positive resulting in an ACTION potential** Other drugs that affected Na channel * valproic acid * phenytoin * Lamotrigine * topiramate **CAR hitting the shelf containing only Salt - for sodium channel blocker**

Answer 101

Seizure Nerve pain Bipolar

Answer 102

Increase GABA activity and inhibits Na channel Increase GABA activity * inhibits the enzyme GAB transaminase (breaks down GABA) * increase GABA activity (inhibitory NT) --> less firing of neuron Blocks Na+ channel * prevents Na entering cells * **decrease pre-synaptic release of glutamate** * Na+ entering cells cause cells to be more positive leading to ACTION * keeps cell at resting or relaxing state

Answer 103

inhibits Na+ gate ion channesl prevents Na+ entering cells **when Na+ enters cells, cells become more positive --> ACTION potential**

Answer 104

inhibitors Na+ ion channel inhibits release of Glutamate (an excitatory NT) inhibits Na+ ion channesl * when Na+ enter cells - cells become more positive --> action potential inhibit release of glutamate * Glutamate - an excitatory NT --> action potential **lamotrigene may increase release of GABA (inhibitory neurons)**

Answer 105

inhibits Na+ channel Inhibits Ca+ channel increase effect of GABA Carbonic anhydrase inhibitor Inhibits Na channel * when Na+ enters cells, cells become more positive --> action potential Inhibits Ca+ channel * prevents presynaptic neuron from releasing NT Increase effect of GABA * binds to GABA receptor (a different site) - causing changes in the receptor to increase affinity for GABA (inhibitory - opens Cl-) * **increase GABA level** Carbonic anhydrase inhibitor * lead to mild acidosis - decrease seizure activity

Answer 106

mood stablizer

Answer 107

Carbamazepine is indicated for * seizure * mood stabilizer (bipolar) * nerve pain (trigeminal neuralgia)

Answer 108

mood stabilizer (bipolar) Migraine prophylactic Only as adjunct to psychosis

Answer 109

mood stabilizer (bipolar) migraine prophylactic

Answer 110

Same as Carbamazapine Blocks Na+ channel Prevents release of Glutamate into synaptic cleft

Answer 111

Blocks Na+ channel Prevents release of glutamate from presynaptic neuron Glutamate - excitatory neurons

Answer 112

Blocks Na+ channel Prevents release of glutamate in presynaptic neurons

Answer 113

DUAL mechanisms Blocks Na+ channel * prevents depolarization - prevents release of glutamate GABA-A receptor Agonist * when gaba binds to gaba-a receptor, channel opens --> allow Cl- to enter * more Cl- (more negative) --> decrease action potential

Answer 114

Blocks Na+ channel * prevents depolarization and prevents release of glutamate * same as phenytoin Inhibits GABA Transaminase (enzyme) * enzymes breaks down GABA after GABA reuptake * more GABA in vesicle to release into synpatic cleft again * **increase GABA in presynaptic neurons to fuse with vesicle**

Answer 115

Blocks Na+ channel * prevents release of glutamate into synpatic cleft

Answer 116

Blocks the Ca++ channel in presynaptic neurons Prevents depolarization --> action potential

Answer 117

In presynaptic - ca+ needs to bind to receptor on vesicle for vesicle to fuse with presynaptic membrane to release stored glutamate **inhibits binding of Ca to receptors (SV2) on vesicle** SV2 - synpatic vesicle protein

Answer 118

blocks NMDA receptors NMDA receptors (post-synpatic receptors) for glutamate Glutamate binds to NMDA receptors What happens when glutamate binds to NMDA * Na and Ca enters cells - making inside of cells more positive --> action potential

Answer 119

perAMPAnel - **blocks AMPA receptors (allosteric site - different site) - keeps channel closed (Na and Ca+ can't dePolarized neurons)** Glutamate binds to AMPA receptors * allows Na and Ca to enter cells * becomes more postive --> action potential Perampanel - blocks Glutamate binding to AMP-A receptors novel moa - can be use with other seizures meds

Answer 120

GABA (NT) analogs - but do not interact with the GABA receptors on postynaptic neurons Activation of GABA receptors * allow Na and Ca influx to make neuron more positive --> action potential **binds to Ca+ channel (presynaptic) - a different site than ethosuximide** * reduces Ca+ entering cells - preventing release of glutamate into synpase Site: alpha-2-delta-1 subnit of the Calcium channel

Answer 121

Blocks the transporter in presynaptic neurons responsible for re-uptake of GABA into neurons for release or metabolize **blocks reuptake of GABA - more GABA in synpase --> inhibitory neurons good for seizure**

Answer 122

Inhibits GABA Transaminase **no longer use due to permanant vision loss** **vegan bat with patches over eyes - increase gaba by preventing gaba metabolism**

Answer 123

Binds to GABA-A receptors (post-synpatic neurons). Increase FREQUENCY of channel open Allow Chloride Cl- ions to flow in * more negative * harder for cell to reach ACTION potential BEN wants it more FREQ BAR(biturate) wants it LONGER (duration)

Answer 124

Binds to GABA-A receptors Allows influx of Chloride Cl- ions Makes cells more negative --> less excitated (less action potential) **primidone is metaboized to phenobarbital**

Answer 125

Dual Mechanism Blocks Na+ and Ca+ channel * prevent Na+ and Ca+ to enter cells * Cells can't depolarize - no action potential

Answer 126

Benzodiazepine Barbiturate Propafol

Answer 127

Ethan, Carl, Larry Ethosuximide Carbamazepine Lamotrigine

Answer 128

valproate Carbamazepine

Answer 129

barbiturate * phenobarbital * primidone Phenytoin Carbamazepine

Answer 130

Ethan - vacum the section of the store that only stores MILK for Ca+ Ethan - Ethosuximide * Calcium channel inhibitor * prevents ca+ entering pre-synpatic cell * prevents action potential and release more glutamate * decreases glutamate in synpases

Answer 131

Valproate ## Footnote Carbamazapine and phenytoin - cyp inducer

Answer 132

CAR runs into the store and hits the shelf that contains **SALT (Na+)**. The driver comes out and a baby he rescue. He wears a **fanny pack (Phenytoin)**. His **loco (lacosamide) wife** is still inside the car alert and conscious trying to take care of the other baby. (lacosamide - more favorable mental side effects) Outside there's a shock **Valet (valproate)** holding a cabagge (also increase GABA) who is bald (alopecia) There's a pirate (topiramate) who was got scared and broke a lamp (lamotrigine) with 3 bulbs. CAR - carbamazepine and oxcarbazapine driver with Fanny pack - phenytoin loco wife - lacosamide Pirate with top hat - topiramate broke a lamp - lamotrigine valet - valproate

Answer 133

Valproate * decrease folic acid synthesis - neural tube defect * Valet man holding a baby with his spine showing Phenytoin * fetal hydantoin syndrome * Fanny man holding a baby with spine and heart showing Carbamazepine * cleft lip * baby inside with cleft lip

Answer 134

Valproate * pancreatitis Carbamazepine * SIADH --> hyponatremia Phenytoin * gingival hyperplasia Topiramate * metabolic acidosis * kidney stone * glaucoma

Answer 135

CAR-bamazepine - other car hitting the silo (grains coming out) * agranulocytosis - a deficiency in neutrophils (granulocytes) * Liver and diaper on top of the silo - for liver toxicity and SIADH * Chromo cell battery pops out of the hood - cyp inducer Phenytoin - fanny pack man * mustache - hirsutism (hair growth) * blowing bubble gum - gum hypertrophy * folder with important file coming out of his fanny pack - folic acid deficiency * holding a baby with cleft lip and visible heart - teratogenic and cardiac defect * other hands, holding a leash to his pet wolf - Lupus like syndrome Lacosamide - loco wife * laco wife is inside car alert taking care of the other baby - lacosamide has more favorable side effects Topiramate - pirate with TOP hat * holding a kidney stone - kidney stone * eyes popping out - glaucoma Lamotrigine - lamp with 3 (tri) bulbs * RASH - attack by zombie Steve and John Valproate - valet eating cabbage (increase gaba) * valet is bald - alopecia * Eating the cabbage - increase GABA level - inhibits the enzyme the breaks down GAB (gaba transaminase) * Blowing a broken chrom whistle - CYP inhibitor * Carrying a baby with spine showing - contraindicated in pregnancy * Next to him are piles of broken dishes with dead WBC and liver on top = decrease platelet, WBC and hepatotoxicty

Answer 136

In the part of the store that stores MILK - Ca+ Ethan vacuming = ethosuximide Artist painting on a lever = levetiracetam The artist was painting a Cabbage = gabapentin and pregabalin * gabapentin and pregabalin - binds to different site on the Ca+ channel --> prevents depolarization (ca entering cell and making cells more positive for action potential) * Gabapentin and pregabalin are GABA NT analog **but does not bind to GABA receptors on post-synaptic neurons** levetiracetam works on preventing Ca+ binding to synaptic vesicle receptors inside presynaptic neurons. **does not block ca+ channel**

Answer 137

Vegan bat sitting on the pile of cabagge (gaba) Increases GABA level in the brain **Ties GABA to the synpases --> blocks the reuptake of GABA into the presynaptic neurons**

Answer 138

prevents Ca+ from binding to the synpatic vesicle (containing glutamate NT) This inhibition prevents vesicle from fusing with presynaptic neurons to release glutamate NT

Answer 139

Inhibits GABA Transaminase An enzyme inside presynaptic neurons that breaks down GABA NT NOTE: * valproate - also inhibits gaba transaminase

Answer 140

Valet outside blowing a broken chrome whistle and holding onto a cabbage when the car run into the store and hit the shelf containing sodium sodium channel blocker holding the cabbage - prevents the breakdown or car from smashing the cabbage * inhibits enzyme that breaks down GABA in the presynaptic neurons * GABA Transaminase inhibitor broken chrome whistle * Cytochrome P450 inhibitor (inhibit - broken)

Answer 141

hyperpolarization - increase negative charge inside the cell Depolarization - increase positive charge inside the cell Negative charge (Cl-) --> NO action potention Positive charge (Na+, Ca+) --> positive is ACTION POTENTIAL

Answer 142

Think: POLAR - polar bear or COLD north pole Hyper - more cold Hyperpolarization - too make inside of cell more cold (more negative temperature) More negative (Cl-) --> NO ACTION potential Depolarization * De - oppositive of POLAR * more Positive (Ca+, Na+) * Positive inside cell --> Action potential

Answer 143

GABA - inhibitor neurons * GABA binding - cause influx of Cl- ion into post synaptic neurons * Cells become hyper-POLARIZE (more cold - more NEGATIVE) * LESS firing and ACTION potential Glutamate * excitatory NT * influx of Na+ and Ca+ * Inside cells become dePOLARIZE (de - less POLAR = less cold = more positive) * positive charge = action potential

Answer 144

Carbamazepine * Car - ran into SALT shelf Oxcarbazapine * sister of carbamazapine Phenytoin * driver with Fanny Pack = phenytoin Lacosamide * Loco wife inside car Lamotrigene * Zombie who got scare and dropped 3 light bulbs Topiramate * Pirate with a TOP hat Valproate * Valet man outside the store ## Footnote prevent release of glutamate

Answer 145

Ethosuximide Plus 2 drugs not use in seizures as much * Gabapentin * Pregabalin Gabapentin - binds to an allosteric site on the calcium channel * prevents influx of Ca+ * prevent dePOLARization and release of glutamate from post synaptic neurons

Answer 146

NO: gabapentin and pregabalin are structural analog of GABA but does not bind to GABA-A receptors. Bind to a subunit of the Ca Channel * blocks Ca+ influx into cell * cell can't dePOLARIZE (become positive) * prevents release of glutamate

Answer 147

Binds to SV2A (synpatic vesicle protein 2A) This is found on membrane if secretory vesicle in neurons. Binding to this SV2A protein - decrease the rate vesicle release glutamate into the presynaptic cleft. **levetiracetam - unique MOA, can combine with other seizure meds**

Answer 148

DUAL: reduce excitatory signals and enhance inhibitory signals Affects both glutamate and GABA NT NMDA receptors - receptors for gutamate * To activate this receptors: you need glutamate and glycine binding * Felbamate binds to glycine site (antagonist) * So, even in presence of glutamate, receptor is not activated without glycine binding * **NMDA receptors open - allow influx of positive ion Ca+, Na+ and K+** This dePOLARize (less polar - less cold = more positive) --> action potential Felbamate affects on GABA * binds to GABA-A receptors (allosteric site). a site different than the active site but activates the receptor * Opens - allow Cl- ion influx * Cl- hyperPOLARizer (more polar = more cold = more negative) -- negative is less action potential

Answer 149

Lennox-Gastaut syndrome a rare and severe form of epilepsy usually in children

Answer 150

Benzodiazepine - binds to GABA-A receptors * lorazepam * Midazolam * Clonazepam * Clobazam Barbiturates * Phenobarbital * primidone **propofol** **Topiramate - dual mechanism** * Na+ channel blocker and GABA-A receptor agonist

Answer 151

Binds to different site on the GABA-A receptors Receptors for GABA NT - an inhibitory neurons * allows influx of Cl- into cells * hyperPOLARizae (more POLAR - more negative) - less action potential Benzo binding to GABA-A receptors also cause changes that makes the receptors more sensitive to GABA NT

Answer 152

Valproate - the bald valet man outside the store that saw the car drove into the store and crashing into the SALT shelf * SALT = Na channel blocker * this eventually decrease release of glutamate Valproate also inhibits * GABA Transaminase (an enzyme inside the presynaptic neurons that breaks down GABA once it is reuptake) * This action allow more GABA to be package into vesicle for release Thus: Valproate decreases glutamate and increases GABA

Answer 153

Topiramate = this the pirate with a TOP hat inside the store. He saw the CAR ran into the SALT shelf. * SALT = Na channel blocker Topiramate also binds to GABA-A receptors * Makes GABA-A receptor more sensitive to GABA NT * opens and allow influx of Cl- into cells * hyperPOLARize = more POLAR = more negative --> NO action potential

Answer 154

perAMPAnel spell this way so you know it works on the AMPA receptors AMPA receptor - receptor for glutamate Glutamate is an excitatory NT Blocks excitatory NT glutamate to bind to AMPA receptors in the post synpatic neurons

Answer 155

omnicell Controlled substance CIII

Answer 156

GABA-A receptor agonist * allows Cl- to enter cells * hyperPOLARize = more POLAR or more cold more NEGATIVE = no AP propofol * generally use for general anethesia or sedation what is anethesia? * a controlled medical treatment that prevents pain and sensation during surgery by blocking nerve signal from reaching the brain

Answer 157

1:1 conversion Example: Depakote DR 500 mg twice a day (1000 mg per day) Valproic acid (depakene): 250 mg QID or 500 mg BID **valproic acid is usually 3 to 4 times a day** **divalproex can be once or twice a day**

Answer 158

Reduce new dose by 10-20% Depakote ER is less bioavailable

Answer 159

Yes. Valproic acid is a narrow therapeutic index med (like lithium) level above 150 mcg/ml --> toxic Keep level below 150

Answer 160

metabolic syndrome bulls figher with clothespin on cap shouting ole (olanzapine) and taunting FAT man eating ice cream Olanzapine - metabolic syndrome clozapine (clothespin) - metabolic syndrome Metabolic syndrome * weight gain * cholesterol * glucose

Answer 161

movement disorders Benztropine is anti-cholinergic * too much acetylcholine stimulation --> dystonia Main USE: * Parkinson's Disease * EPS - from antipyschotic

Answer 162

Anti-cholinergic (centrally acting) Inhibits reuptake of DOPAMINE

Answer 163

Tardive - late developing dyskinesia - bad or involuntary movement **late developing (from long term psych meds use) involuntary muscle movements**

Answer 164

Valbenazine treats: * involuntary movements of TD * TD - hyperdominergic state (excessive dopamine secretion) - due to chronic blockade of dopamine receptors from psych meds Mechanism: * Blocks a protein call: VMAT2 * Vesicular Monoamine Transporter 2 VMAT2 - normal function * protein found in presynaptic neurons * Packs Dopamine to vesicle for release into synpatic cleft * DA not package will be broken down by MOA (monoamine oxidase) **Valbenazine moa** * blocks VMAT2 protein * prevents Dopamine package into vesicle for release * NET result: less dopamine release into synpatic cleft **Connection** * Ingrezza works like Keppra * Keppra prevent exocytosis of glutamate vesicel into synaptic cleft

Answer 165

VMAT2 * v = vesicular (vesicle) * MA = monoamine (DA, NE) * T2 = transporter 2 (transport) VMAT2 - found on the membrane of synpatic vesicle that stores monoamine * function = pumps DA into vesicle for release SV2A * SV = synaptic vesicle * membrane bound protein in synaptic neurons * Function: budding or exocytosis * exocytosis - fusion with membrane and releases into synaptic cleft

Answer 166

TD - primarily due to dopamine receptor upregulation (more productive of dopamine receptors) These new receptors are more sensitivite to even a small amount of dopamine Thus - Valbenazine (ingrezza) is use in TD to decrease the packaging and release of dopamine into synaptic cleft.

Answer 167

Bipolar I and II Schizophrenia

Answer 168

Weight neutral - less metabolic syndrome Less EPS

Answer 169

Dopamine - blocks dopamine receptors 5HT2A receptor antagonist * receptor for sertonin * when serotonin binds --> excitation of neurons * when caplyta binds --> reduces excitation. stabilize moods and thoughts SERT - sertonin reuptake inhibitor Glutamate - upregulate

Answer 170

blocks dopamine in the mesolimbic and mesocortical pathway Avoid nigrostriatal pathway Mesolimbic pathway function * addiction, psychosis * DA blocks - help psychosis Mesocortical pathway function: * cognition * negative symptoms (schizophrenia) Nigrostriatal pathway function: * motor control * blocked by antipsychotics Tuberoinfundibular pathway: * regulate prolactin * dopamine inhibits release of prolactin * blocked by antipsychotic --> increase prolactin

Answer 171

MENT Mesolimbic - reward, pyshosis (hallucinaton and delusion) Extracortical (Mesocortical pathway): * cognition, negative symptoms (flat affect) Nigrostriatal * movement * Parkinson if blocked Tuberoinfundibular pathway * increase prolactin * Dopamine inhibits release of prolactin * if dopamine receptor is block --> increase prolactin release

Answer 172

nigrostriatal pathway Midbrain to center Striate = refers to muscle straite

Answer 173

All starts from midbrain (center of brain) Mesocortical pathway * center to outer cortex of the brain Mesolimbic * center to just before prefrontal cortex Tuberoinfundibular pathway * center to pituatary gland area Nigrostriatal pathway * center and move up to more center of the brain * brain's movement center

Answer 174

movement disorder * TD, parkinsonism, akathisia Hormonal changes * increase prolactin Metabolic changes * metabolic syndrome * wt gain, cholesterol, increase glucose Sedation Caridac * QT prolongation **Orthostasis** **Anticholinergic**

Answer 175

Blocks K+ channel in the heart Blocks: K+ moving out of cells * rePOLARization after heart has dePOLARize This delay of repolarization shows up as QT interval prolongation

Answer 176

ACTION potential or cell firing Repolarization - coming back to resting state HyperPOLARization - past resting state (sleep) * hard to wake up

Answer 177

decrease GABA or decrease 5HT (serotonin) GABA - inhibitory NT 5HT - feel good and sleep * serotonin is a precursor to melatonin

Answer 178

Pineal gland * secrets melatonin * melatonin inhibits SCN Suprachiasmatic nucleus (SCN) * master switch * **technically - the SCN is on the ON switch all the time until supppress by hormone like melatonin** * SCN function is to keep us awake * To keep us awake, SCN suppress the sleep center **VLPO** * once SCN activity is decrease by melatonin, it can no longer suppress VLPO * VLPO - "sleep switch" - promotes sleep Ventrolateral preoptic nucleus (VLPO) * when no longer suppress --> promotes sleep * to promote sleep - vlpo has to suppress the ascending arousal systems * to sleep - it has to suppress arousal * releases GABA to suppress arousal system Ascending arousal system * if not suppress by VLPO --> promotes wakefulness and arousal * to promote arousal - it has to suppress sleep center VLPO * releases Orexin and histamine * orexin and histamine - suppress or inhibts VLPO (can't promote sleep) * orexin and histamine thus keep us awake Bottom line: SCN - master switch --> sends signal to keep us awake (suppress the VLPO) VLPO - promotes sleep when no longer suppress by SCN and arousal system Ascending Arousal System - keeps us awake but suppressing VLPO

Answer 179

melatonin is a hormone produced by the pineal gland in response to darkness melatonin - binds to melatonin receptors on the SCN suprachiasmatic nucleus and suppresses the SCN SCN functions * sends signal to keep us up * suppresses the sleep center VLPO ventrolateral preoptic nucleus **melatonin inhibits SCN - thus SCN no longer can inhibt VLPO. VLPO becomes activated and promotes sleep**

Answer 180

Orexin * known as master stabilizer * prevents suddenly involuntary transition between wakefulness and sleep **narcolepsy - sudden sleep attack** Histamine * essential for high-level alertness and wakefulness * **antihistamine - blocks histamine --> can stimulate wakefulness. antihistamines thus make you sleepy and drowsy** * released by TMN Histamine and Orexin relationship * Orexin stimulates the TMN to release histamine * histamine neurons then alert the rest of the brain to stay awake * without orexin, the histamine neuron systems cannot stay active long enough to maintain wakefulness.

Answer 181

low melatonin low GABA high orexin high histamine Explain

Answer 182

Buspar * partial agonist at postsynaptic 5HT1A * K+ move out = inside of cell becomes MORE negative = less AP Viibryd * partial SSRI * potent partial agonist at 5HT1A Vortioxetine (Trintellix) * full agonist at 5HT1A

Answer 183

5HT1A - stimulated * K+ move out = cell becomes more negative * hyperPOLARize - less action potential Other Serotonin-receptors (for now) * influx of Na+ and Ca+ * cells become more positive -depolarize * action potential --> neuron to release GABA (inhibitory NT) * GABA - binds to post synaptic receptors * allows Cl- to move in --> more negative is less action potential

Answer 184

happiness hormone GI tract * causes peristalsis - motility * n/v - overstimulation --> helps body get rid of toxin * digestion --> increase acid secretion but too much stimulation can cause ulcer Sleep * precursor to melatonin --> helps suppress SCN (brain's master clock) Clotting * stored in platelet * released during injury to cause vasoconstriction and promote platelet clotting

Answer 185

Platelets use serotonin as a messenger to cause vasoconstriction and signal other platelets for clot formation. Platelets cannot make its own serotonin. Platelets must absorb serotonin from bloodstream. SSRI blocks platelet ability to reuptake serotonin into platelet - depleting platelet's stored serotonin, thus cannot signal clot formation = bleedings.

Answer 186

Barbiturates Benzodiazepine NOTE: barbiturates are not use for anxiety due to toxicity use mainly in seizures, anesthesia, and to induce coma

Answer 187

Short: * midazolam, triazolam Intermediate: * Lorazepam, Oxazepam, Alprazolam, Temazepam Long-Acting: * Diazepam, Chlordiazepoxide, clonazepam Which one is used in anxiety in practice? * lorazepam * oxazepam * alprazolam * diazepam * clonazepam Chlordiazepoxide - first benzo * mainly used in alcohol withdrawal

Answer 188

Ramelteon (Rozerem) Melatonin

Answer 189

mimic natural hormone melatonin binds to melatonin receptors on the suprachiasmatic nucleus (master clock) Suppress the SCN so it can't suppress the VLPO (sleep center) - ventrolateral preoptic nucleus Helps you fall asleep - **helps you fall asleep faster**

Answer 190

Benzodiazepine * Temazepam and Flurazepam - benzo use in insomnia Barbiturates * NOT use in insomnia Z-drugs * Zolpidem * Zaleplon (sonata) * Eszopiclone (Lunesta)

Answer 191

Temazepam Flurazepam

Answer 192

Zolpidem (ambien) * high affinity - sedating Zaleplon (Sonata) * short half-life --> for sleep initiation Eszopiclone (Lunesta) * intermediate half-life 6 hours * maintain sleep

Answer 193

Histamine release promotes alert and wakefulness Thus --> antihistamine blocks this activity and histamine cannot promote wakefulness and alert Anti-histamine makes you sleepy **this is how anti-histamine like benadryl and vistaril work to promote sleep**

Answer 194

Doxepin (TCA) * at low dose: 3 to 6 mg - highly selective for H1-histamine receptors (antagonist) * histamine release by arousal system keeps you awake * **at high dose - doxepin acts as a TCA (selective for 5HT and NE) - inhibits reuptake of 5HT and NE** Mirtazapine * at low dose (15 mg) - high affinity for H1 histamine receptors (antagonist) * blocks histamine (histamine keeps you up) * at low dose - causes sedation * at high dose - for major depression (increase NE release - think SNRI) Trazodone * at low dose - helps sedation and sleep * at high dose - becomes like an SSRI - for depression

Answer 195

Orexin - released by arousal system suppress the VLPO and promotes wakefulness and alert

Answer 196

suvorexant = Belsomra Orexin receptor antagonist orexin promotes wakefulness and alert by suppressing the VLPO suvorexant blocks orexin activity * orexin cannot stimulate wakefulness anymore - thus you sleep

Answer 197

Suvorexant (Belsomra) suvOREXANT = orexin

Answer 198

narcolepsy - a neurologic disorder characterized by excessive daytime sleepiness and sleep attack primarily causes of narcolepsy * loss of neuron producing orexin * autoimmune disorder - attacking neurone producing orexin orexin * a neuropeptide responsible for maintaining wakefulness Suvorexant - blocks orexin action In narcolepsy - you already have low orexin level, thus with suvorexant, you are only making narcolepsy worse.

Answer 199

Female: start at 5 mg (unless obese than can use 10 mg) Male: can start at 10 mg WHY? * belsomra concentration is higher in female, thus lower dose can have the same affect as higher dose in male

Answer 200

Trazodone low dose = sleep * blocks 5HT2A * 5HT2A: 2 = have stuff 2 to do (need to stay alert and awake) * block this receptor = sleep Trazodone low dose also * H1-receptor antagonist = sleep * alpha-1 adrenergic receptor antagonist = calms the fight or flight response Trazodone at high dose * works like an SSRI * inhibits reuptake of serotonin * helps depression and anxiety **trazodone and mirtazapine have different affect at low and high dose**

Answer 201

Mirtazapine low dose < 15 mg * selective for H1-histamine receptor (antagonist) * causes sedation and helps insomnia Mirtazapine high dose - for depression * selective for alpha-2 adrenergic receptors (presynaptic - negative feedback) **think clonidine** * NE normally binds to this receptor and act as a negative feed - **tells neuron that there is enough NE in the synpase and to stock releasing NE** * mirtazapine blocks this negative feedback **also think SNRI - increase NE helps depression**

Answer 202

Class: SPARI * serotonin **partial** agonist reuptake inhibitor serotonin partial agonist: * stimulates 5HT1A --> depression serotonin reuptake inhibitor * works like SSI 5HT1a - stimulation is most beneficial for depression Similarilty: * SSRI + Buspar --> buspar stimulates 5HT1a Closest cousin: * Vortioxetine -- BUT * Full agonist and stimulates more serotonin receptors

Answer 203

similar NAME but works differently Vilazodone - SPARI * serotonin partial agonist + SSRI Trazodone * serotonin **antagonist 5HT2A** + weak SSRI Difference: * Vilazodone is partial agonist * Trazodone is antagonist at 5HT2A How does antagonist at 5HT2A - helps depression? Is it more serotonin (like SSRI) beneficial for depression? * Trazodone - blocks specifically 5HT2A (not as important for depression) * This blockade benefits surrounding or available serotonin in synapse to bind to 5HT1A (helps depression)

Answer 204

Trazodone - SARI * serotonin antagonist and reuptake inhibitor * Also inhibits: histamine and alpha-1 receptors Serotonin antagonists at 5HT2A * funnels availalbe serotonin to stimulate 5HT1A (helps depression) Histamine - keeps you up (suppress the VLPO - sleep center) * antihistamine (trazodone) = sleepy Alpha-1 blockers * dilates or cause vasodilation = OSH * alpha-1 stimulation = vasoconstriction (EpiPEN)

Answer 205

partial agonist at 5HT1A (serotonin) receptors **note: partial** * think serotonin stabilizer - like Abilfiy is a dopamine stabilizer * in low serotonin - it activates the receptor enough to produce response * in high serotonin - it works like a serotonin block because it occupies the receptors without producing a full response **simplify: works like natural serotonin NT - but produce partial response**

Answer 206

**blocks alpha-2 presynpatic autoreceptors** * blocks the negative feedback mechanism * **under normal condition - negative feedback tells neuron to stop firing because there's enough NT in the synpase** * by blocking this negative-feedback (autoreceptors) - neurons keeps releasing NE and 5HT **BLOCKS negative FEEDBACK** Other receptors: * Blocks 5HT2A and 5HT3A post-synpatic receptors --> funnels available serotonin to bind to 5HT1A receptors (beneficial in depression) - since in depression there's low serotonin * Histamine-1 blocker: sedation (histamine keeps you awake and alert by suppressing the sleep center in the brain) Connection: * clonidine - stimulates the pre-synaptic alpha-2 receptors * **clonidine - works like a negative feedback - telling neurons there's enough NE or SE and stops neuron firing and reducing BP**

Answer 207

compete for same pre-synaptic alpha-2 autoreceptors (negative feedback receptors) Mirtazapine * **blocks - tells neuron to keep release NE and 5HT** Clonidine: * **stimlates - acts like the negative feedback is turn on --> tells neurons there's enough NE and 5HT in synapse and stops neuron releasing NT**

Answer 208

Mirtazapine - low dose * anti-histamine predominate leading to sedation (helps with sleep) Mirtazapine high dose * alpha-2 antagonist (blocker) predominate * Neurons keep releasing NE and 5HT * Helps depression mirtazapine - confusing * low dose - sedationg but * high dose - not as sedating due to NE predominate (since alpha-2 blockage predominate at higher dose)

Answer 209

class: NDRI * norepinephrine and dopamine reuptake inhibitor * inhibits NE and DA transporter enzyme * thus - higher concentration of NE and DA in synapse Antagonist at **nicotinic-acetylcholine receptors** * helps prevent wdl from smoking cessation NOTE: lower seizure's threshold * how? * high level of DA and NE?

Answer 210

Thought process: buproprion blocks NE and DA reuptake transporter - thus increase NE and DA in synpase This increase in excitatory NT - increase neuronal firing and increase seizure **seizure is thought to be too much excitation**

Answer 211

Trintellix SMS - serotonin modulator and stimulator

Answer 212

SMS = serotonin modulator and stimulator Serotonin Stimulator: * activates 5HT1A - good for dep/mood Serotonin modulator: * inhibits other 5HT receptors subtypes * inhibits reuptake of 5HT - works like SSRI How is it different? * affects at least 6 NT: main serotonin * affects: DA, NE, glutamate, acetylcholine, histamine * **very different from plain SSRI**

Answer 213

5HT1A - stimulation (agonist) * helps with depression/mood inhibitions of 5HT2A - helps dep/mood * funnels available serotonin to bind to 5HT1A

Answer 214

Serotonin - mood and sleep * emotional stabilizer - formally called the happiness NT * Calm state of alertness not like NE Dopamine - Reward/Focus, motivation * suppress VLPO (sleep center) * **activated wakefulness - too much is pyschosis** NE - Energy/Attention * Fight or Flight response * urgency, focus, stressed induced wakefulness * suppress VLPO (sleep center) Glutamate - learning and memory * excitatory * fast acting --> triggers neurons firing Acetylcholine - learning and memory * **more refine - resolution and clarify in learning and memory** Histamine - Wakefulness * makes you stay awake * suppress the VLPO * Hunger = low glucose --> promotes histamine release = stay awake Orexin - state stabilizer * stabilize wake and sleep * orexin reinforce wakefulness * orexin prevents the brain from accidently flipping to sleep during the day - **thus state stabiizer**

Answer 215

prazosin is an alpha-1 blocker blocks alpha-1 in brain - blocks NE * NE - stress induced wakefulness, fight or flight response **blocks NE function in the brain** What does NE do in the brain? * Fight or flight response * stress induced wakefulness * urgency * focus

Answer 216

Quviviq = daridorexant * blocks orexin 1 and orexin B receptors Orexin - released by ascending arousal system (in brain) to suppress VLPO * VLPO - promotes sleep * Orexin - suppress VLPO so it cannot promote sleep * Orexin - promotes wakefulness * Quviviq blocks orexin - so you can sleep **Quviviq is for insomnia** * blocks orexin (wakefulness) - so you can sleep

Answer 217

closest cousin: Vilazodone (Viibryd) Works like vilazodone * both are SERT - works like SSRI * both stimulates 5HT1A - good for dep * but vortioxetine - modulates many other subtypes of serotinin receptors and NT's

Answer 218

**Trintellix + SSRI + Mirtazapine** Trintellix and trazodone * both inhibits 5HT2A receptors * allows available serotonin to bind 5HT1A (beneficial in dep) - good receptor SSRI and Trazdone * Trazodone is a weak SSRI Trazodone and Mirtazapine * both inhibits H1 receptors and * inhibits alpha-1 receptors * trazodone - has much higher affinity for alpha-1 blockade = more OSH * trazodone and benadryl = trazodone provides a deeper more natural sleep

Answer 219

main: alpha-2 presynaptic (autoreceptors) * blocks the negative feedback * neurons keep releasing NE and 5HT H1 blocker - antihistamine * similar to benadry or trazodone * much better at helping you stay asleep compare to benadry or trazodone Alpha-1 blockade: * cause OSH - vasodilation Serotonin receptors antagonist: * 5HT2A and 5HT2C = bad receptors b/c when stimulated causes insomnia and sexual dysfunction (side effects of SSRI) * Not all serotonin receptors produce good effects * **5HT3 - gut and chemo zone** = helps nausea * works similar to Zofran

Answer 220

mirtazapine BLOCKS 5HT3 receptors ZOFRAN blocks 5HT3 to help with nausea 5HT3 receptors located in the vagus nerve GI tract * when irritated - nerve releases serotonin and binds to 5HT3 receptors to sign vomit sign to brain CTZ 5HT3 - the 3 looks like intestine

Answer 221

Vilazodone (Viibryd) * SPARI * serotonin partial agonist = works like buspar at 5HT1A * serotonin reuptake = SSRI Vortioxetine (Trintellix) * SSRI - inhibits serotonin reuptake * FULL agonist at 5HTA = good * antagonist at other serotonin receptors

Answer 222

Tryptophan Why is this important to know? * pt taking MAO-Inhibitor = avoid food high in tryptophan

Answer 223

GI (n,v): +5HT3 = nausea and vomiting * link: Zofran - blocks 5HT3 Decrease Libido * +5HT2 decreases libido Bleeding risk * Platelet uses serotonin for platelet aggregation * Platelet cannot make its own serotonin, it needs to reuptake serotonin from bloodstream * SSRI - blocks this reuptake Serotonin Syndrome - dead knight * overstimulation of serotonin

Answer 224

Citalopram - more Escitalopram Why is this important? * avoid in pt taking other QT drugs

Answer 225

fluOXetine fluvOXamine parOXetine Look - OX - in name * OX - inhibts CYP450

Answer 226

Serotonin Syndrome * MAOI-inhibitor (washout 14 days) * **linezolid** * Opioid - tramadal, fentanyl, methadone Bleeding * NSAID * Apixaban, Warfarin, Plavix Cardiac - QT prolongation * citalopram - highest risk * escitalopram CYP450 inhibition (OX meds) * fluoxetine, paroxetine, fluvoxamine * Fluoxetine and metoprolol - can increase metoprolol level by 500% * sertraline - less cyp inhibition * Atenolol - bypass liver metabolism Which pain meds can increase serotonin level? * Tramadol * Fentanyl * Methadone

Answer 227

Tramadol - inhibits SERT * increase serotonin level Tramadol at high dose * inhibit GABA-A receptors * GABA NT cannot bind to receptor * GABA is an inhibitory NT - open channels and move Cl- in to become more negative (less AP) **Serotonin level** * moderate level with SSRI -- therapuetic * high serotonin - seizure. * **serotonin sydrome (seizure) is cause by excess serotonin** * TOO much serotonin is NOT good

Answer 228

Inhibits SERT * works like SSRI Fentanyl is an agonist at some serotonin receptors: 5HT1A and 5HT2A (good for dep) * mimics sertonin - excess serotonin stimulation is not good Risk of Fentanyl induce serotonin syndrome is less than 1%

Answer 229

inhibits SERT * weak SSRI Agonist at serotonin receptors * agonist at 5HT1A - acts like serotonin * similar to Fentanyl * too much serotonin stimulation is not good --- serotonin sydnrome

Answer 230

Des-venlafaxine is the active metabolite of venlafaxine Venlafaxine --> Desvenlafaxine

Answer 231

Venlafaxine Desvenlafaxine Duloxetine

Answer 232

Stressed urinary incontinence Fibromyalgia NOTE: Stressed urinary incontinence vs overactive bladder * stressed urinary incontinence - weak urethral sphincter. Stressed (coughing, sneezing) causes leakage * overactive bladder - bladder muscle contract involuntary

Answer 233

**A disorder of CENTRAL sensitization** **CNS becomes over-sensitive and amplified pain signals** widespread musculoskeletal pain Results in: **Hyperalgesia** - feeling more pain than expected from a stimulus **Allodynia** - Feeling pain from things that shouldn't hurt Core symptoms * Profound fatigue * Mental Fog - impaired memory and focus

Answer 234

Fibro - fibrous tissue * refers to tendons & ligaments My - muscle Algia - pain **muscle and fibrous tissue pain**

Answer 235

Substance P and glutamate - transmit PAIN signal Serotonin and NE --> NT the inhibits pain signal * these level are decreased in patient with Fibromyalgia Connection: **duloxetine - increase serotonin and NE --> inhibits pain signal thus help with fibromyalgia**

Answer 236

Opens the CHANNEL - allows Ca+ to influx (flow in) Cells become more POSITIVE - depolarized --> Action Potential

Answer 237

Substance-P binds to NK1 these complex gets taken inside cells --> causes INTRAcellular Ca+ to be release Cells becomes more positive --> more action potential

Answer 238

Pain signal - sensitive neurons (more active) * cause release of intracellular Ca+ * cell becomes more POSITIVE - AP * **capsaicin cream - depletes substance P - desensitive neurons** Inflammation - vasodilation * creates the wheal and flare response GI motility * Key driver for vomiting reflex * **Aprepitant - NK1 receptor antagonist for n/v with chemo**

Answer 239

NE binds to alpha-2 presynaptic receptors * prevents release of Substance P and glutamate Serotonin * when bind to 5HT1 receptors -- trigger release of body's natural pain killer (enkephalin) **just know - serotonin and NE inhibits pain signal** **substance P and glutamate amplify pain signal**

Answer 240

Hyper - excessive or above Alges - pain or sense of pain ia - a state or condition Hyperalgesia - abnormally sensitive to pain, making a painful stimuli feel more intense than it normally should

Answer 241

Allo - other, differen, strange odynia - pain Allodynia - "other pain" - referring to a pain response cause by a pain stimuli that normally does not cause pain

Answer 242

Allodynia * something that is not painful (like a light touch) causes pain Hyperalgesia * something that is painful (like a needle) hurts way more than it should

Answer 243

Class side effects: Insomnia - NE will cause insomnia N/V - serotonin stimulation in the gut Sexual dysfunction * stimulation of some 5HT receptors - decrease sex-drive * 5HT2A and 5HT2C - antisex receptors * excess stimulation inhibits DA release * DA - driver for libido (reward and pleasure) * **+5HT1A - improve sexual function (buspar, vilazodone)** Increase BP = NE Serotonin syndrome = overstimulation of serotonin receptors Drug Specific Duloxetine - liver toxicity * extensively metabolize in the liver * thought process - one of its' metabolite is a reactive metabolite damaging liver cells (assumption only) Venlafaxine and Desvenlafaxine * CYP 450 inhibits

Answer 244

Duloxetine - is approved for stress urinary incontinence **nerve that sends send to external urethral sphincter is strength with more serotonin and NE --> thus nerve tells muscle to squeeze more tightly**

Answer 245

5HT1A --> 1A (excellent grade) * stimulation is good for mood and anxiety * **buspar and vilazodone** 5HT1B --> B = feedback (presynaptic) * stimulation --> decrease serotonin release (initially bad) but * it **desensitize** overtime and not work as well --> this is why it takes 4 to 6 weeks for SSRI to work 5HT7 ---> think 007 - james bond - ACTION * proarousal * when you block it --> improve sleep and focus * **vortioxetine (trintellix) - blocks this receptor**

Answer 246

SSRI --> SNRI --> mirtazapine --> bupropion

Answer 247

Sertraline and escitalopram * preferred Paxil - x - in drug name * avoid in pregnacy * heart problem

Answer 248

phenelzine - nardil Tranylcypromine - Parnate Isocarboxazide - Marplan (brand only, no generic available)

Answer 249

Nardil MAO-I inhibitor (non-selective)

Answer 250

Parnate MAO-I inhibitor

Answer 251

Marplan MAO-Inhibitor Only Brand name available

Answer 252

Lithium Helps transport L-tryptophan into the brain L-tryptophan is the precursor to serotonin **increase raw material for serotonin synthesis** Lithium also help enhance release of serotonin into synpase Lithium also desensitize 5HT1B autoreceptors * 5HT1B - works as a break to stop serotonin firing **bottom line:** * increase production * increase release

Answer 253

Buspar partial 5HT1A agonist (good receptors for mood and anxiety) Desensitize 5HT1A autoreceptors (presynaptic) * **deSENSITIZE negative feedback - eventually more serotonin release** **Bottom LINE - simplify** * buspar - agonist at 5HT1A * desensitize negative feedback - eventually more serotonin release

Answer 254

Triptans are structural analogue of serotonin NT Triptans - design specifically to mimic serotonin * but binds to different serotonin receptors (although some triptans will still bind to 5HT1A - the main receptors for serotonin syndrome) Thus - triptans (suma, riza, zolmitripta) are metabolized by MAO * if you take with MAO-inhibitor --> have more triptans available to stimulate serotonin receptors = serotonin syndrome **Triptans were designed to mimic serotonin - pretend to be serotonin** **Think: triptan = serotonin NT**

Answer 255

Migraine - vasodilation of brain blood vessels Triptans - mimic serotonin * binding to receptors (5HT1B) - causes vasoconstriction * reduces throbbing sensation Remember: Serotonin (duloxetine) * blocks transmission of pain signal * Prevents the release of substance P and CGRP * Substance P - amplify AP * substance P - cause release of intracellular Ca --> cells become more positive - more AP * CGRP - calcitonin Gene-Related Peptide Calcitonin Gene-Related Peptide CGRP * a powerful PROTEIN function as the primary messenger of pain during a migraine attack * causes vasodilation - throbbing, pulsating pain * transmit PAIN

Answer 256

Prozac - due to long half-life active metabolites - takes about 1 to 2 weeks (half-life) **prozac can be stop immediately, it will self-taper due to long half-life**

Answer 257

SERT * transport serotonin * SSRI - blocks this to increase serotonin level NET * transport NE, but * Sloppy - will transport DA also * Cymbalta or Strattera DAT * transport Dopamine * wellbutrin and stimulants Strattera moa: * blocks NET - but NET is sloppy, it will reuptake DA also, thus strattera also blocks DA * Increase NE --> focus and alert * **in prefrontal cortex - DAT are scarce (limited) - NET will transport both NE and DA** * Thus - strattera increases NE and DA (in prefrontal cortex) --> improve cognitive function * strattera - does not affect DA in reward center

Answer 258

Wellbutrin - NDRI norepinephrine dopamine reuptake inhibitor * inhibits NET and DAT * NO SERT - **unique - no sexual dysfunction, no weight gain** * blocks Nicotinic receptors - blocks nicotine binding to its nicotinic acetylcholine receptors --> once stimulated --> causes release of DA rush What happens: * blocks DAT --> more DA --> more energy, motivation and pleasure * blocks NET --> more NE --> more alert, focus and physical energy **wellbutrin increases NE and DA by blocking reuptake transporter, DOES NOT affect serotonin**

Answer 259

Two mechanisms Blocks NET and DAT, no SERT * blocks reuptake of NE and DA - works similar to bupropion Adderall - also enters the neuron and FLIP this transporter * so instead of reuptake NE and DA * NET and DAT now pumps out NE and DA into synapse - **incredible** Inhibits VMAT2 - vesicle monoamine transporter 2 * function: transport monoamine (NE, DA, 5HT) cytoplasmic NE, DA, 5HT into vesicle * Adderall interferes with VMAT2 - causing the vesicle to burst and dump NE and DA into cytoplasm --> DAT and NET pumps the monoamine into synapse since it works in reverse now with adderall on board (it does not pull instead it pumps)

Answer 260

VMAT2 - vesicle monoamine transporter 2 * monoamine: NE, DA, 5HT VMAT2 - transport cytoplasmic monoamine into synaptic vesicle for release into synaptic cleft VMAT2 - **controls how much monoamine is store and release** In tardive dyskinesia - Dopamine receptors becomes supersensitive from chronic blockade with antipsychotic drugs * Body produce more D2 receptors - making these supersensitive to dopamine * these receptors overreact even with a small amount of dopamine * DA - for movement --> but in this case --> causes jerky movement assoc with tardive dyskinesia VMAT2 inhibitors * Tetrabenazine * Deutetrabenazine (Austedo) * Valbenazine (Ingrezza) Connections: * VMAT2 vs SV2

Answer 261

VMAT2 - the pump * moves monoamine into vesicle - acts as a vacuum that sucks monoamine from cell cytoplasm into the vesicle for storage and release SV2 - synaptic vesicle 2 - the gate keeper * ensure vesicle is ready to fuse with membrane to release into the synapse **VMAT2 pumps into vesicle and SV2 dumps into synapse** Keppra - inhibits SV2 * binds to sv2 --> prevents the vesicle from release their NT (glutamate) too quickly or too often

Answer 262

OCD Obsessive-compulsive disorder NOTE: dose > 100 mg per day * divided BID

Answer 263

40 mg elderly > 60 yo: 20 mg daily

Answer 264

20 mg per day Elderly > 60 yo: max 10 mg

Answer 265

citalopram is a mixture or S and R enantiomer R-enantiomer --> no clinical benefit --> and causes QT prolongation * K channel blockade * prevents - repolarization (becoming more negative - prevents efflux of K+) escitalopram - is the s-enantiomer

Answer 266

max: 80 mg per day Unique: * long half-life ~ 7 days * No need to taper off - no withdrawal sx because of life half-life, it self-taper

Answer 267

60 mg per day Unique: NIOSH drug * paxil = x = pregnancy category X drug

Answer 268

200 mg per day Unique: **prefer in patient with cardiac risk QT**

Answer 269

Sertraline (Zoloft) Zoloft is soft or safe for heart

Answer 270

5 weeks fluoxetine + thioridazine interaction: * thioridazine - highest risk for QT prolongation * thioridazine is metabolize by cyp2D6 * thioriDazine = 2D6 * fluoxetine is the most potent 2D6 inhibitor known * increase thioridazine level = QT prolongation * combo - is contraindicated **Note: if wanting to start thioridazine - must wait 5 weeks washout period**

Answer 271

Fluoxetine - Prozac

Answer 272

SIADH * syndrome of inappropriate antidiuretic hormone * TOO MUCH ADH Anti-diuretic hormone (vasopressin) * anti = against * diuresis - excretion of urine * body retents water SSRI increases 5HT * 5HT stimulates release of vasopressin (ADH) from hypothalamus * tells your body to hold onto water What happen when too much ADH? * body holds onto water --> this dilute the Na+ --> we got hyponatremia * Inside cell (normal Na level) * Outside cell (low sodium) - water follows sodium - there's more sodium inside the cell * Water flows into cell --> cell swells --> brain swells and cause confusion What happen when too little ADH? * You don't have hormone to block diuresis (urination) * thus - you urinate alot but pale and watery urine * you lose a lot of water - thus you need to drink a lot of water - you get extreme thirst * but you can't drink enough water to compensate for the water loss * you get hypernatremia --> confusion and seizure * this condition is called Diabetes Insipidus Diabetes insipidous - loss more water than Salt ADH - helps balance osmolarity * Salt and water balance * Helps in dehydration - to hold onto water

Answer 273

loss more water than Salt LOW ADH level (vasopressin) you get extreme thirst - but can't drink enough to keep up with water loss You get hypernatremia - loss more water than SALT Hypernatremia risk * brain damage * Water leaves brain cells to balance outside cells * Cells shrink --> as brain shinks and pull away from skull, this can cause intranial bleeding (tears) * Seizure and coma * Permanant brain damage

Answer 274

Diabetes insipidous * loss more water than SALT * Hypernatremia * Brain cells shrink -- water moves out SIADH * body holds onto water * Hyponatremia * Brain cell swells - water moves in **NOTE: to help remember** Diabetes insipidous - in diabetes, you have frequent thirst and urination * more water loss than salt SIADH * inappropiate TOO much ADH * ADH = no diuresis * Retain water - dilutes Na - hyponatremia * occurs in SSRI

Answer 275

Diabetes - "pass through" * refers to the massive amount of urine passing through the pt's body * Frequent URINATION Insipidous * IN = not * Sapidus = not tasty * Tastelss or flavorless **urine was tasteless - too diluted, not salt --> hypernatremia** Diabetes Mellitus * Mellitus = honeyed * Urine was sweet like honey **Before modern era - doctors diagnosis by tasting patient's urine** * diabetes insipidous - tasteless * diabetes mellitus - honeyed - sweet

Answer 276

Escitalopram * S-enantiomer of citalopram * Potent Citalopram * S and R-enantiomer R-enantiomer = non therapeutic THUS: max dose citalopram = 40 mg escitalopram = 20 mg (1/2 of escitalopram) R-enantiomer = cardia risk (QT) * citalopram has a higher QT risk

Answer 277

Diabetes Insipidous - urine is tasteless (no salt) * body retain's SALT * HYPERNATREMIA SIADH * Against diuresis - body retain's water * dilute sodium * HYPONATREMIA

Answer 278

fluOXetine parOXetine fluvOXamine OX - in name = cyp inhibitor FluOXetine - most potent 2D6 inhibitor known Interaction: * Tamoxifen and fluoxetine or paroxetine * Tamoxifen is a prodrug --> metabolized by 2D6

Answer 279

Tamoxifen Tamoxifen is a prodrug - needs to be metabolized by 2D6 to active metabolite Paroxetine and Fluoxetine - blocks 2D6 * making tamoxifen ineffective Connection: omeprazole and clopidogrel * clopidogrel --> prodrug * metabolized by CYP2C19 * omeprazole blocks this metabolism Omeprazole and esomeprazole * POTENT 2C19 inhibitor **do not use fluoxetine with thioridazine also - explain?**

Answer 280

SSRI (sert) + 5HT1A partial agonist * buspar - 5HT1A agonist **blocks SERT and partial stimulate 5HT1A receptors**

Answer 281

SSRI + 5HT3 receptor antagonist + 5HT1A agonist * vilazodone + 5HT3 receptor antagonist NOTE: vilazodone does affect other 5HT receptors - for now keep it simple with above

Answer 282

5-HT3 receptors * mainly in gut - block = relief N/V - **Zofran** * In brain - 5HT3 receptors locate on GABAnergic neurons (inhibitory neurons) When 5HT3 is stimulated * GABA release - inhibits neuron firing * inhibits release of NE, DA, 5HT and Acetylcholine Vortioxetine - inhibits this receptor. It is 5HT3 antagonist, so it's benefit: * stops GABA release --> thus excitatory neurons are free to fire NE, DA, 5HT and acetylcholine * thus increasing NE, 5HT --> good for depression and mood and cognitive * **this is why vortioxetine has seizure risk and warning. Vortioxetine stops GABA release**

Answer 283

Serotonin is mainly located in the gut * 95% of serotonin are located in the gut produced by specialized cells called Enterochromaffin cells (EC) * Serotonin is the main driver for peristalsis * Serotonin causes nausea, vomiting and diarrhea * Zofran - blocks 5HT3 receptors - helps nausea and vomiting **Serotonin also located in** * Brain < 2% - helps regulate mood and awake * Platelets - signals platelet aggregation * SSRI increase bleeding risk

Answer 284

Serotonin - **one of the most potent natural vasoconstrictor** * increased 5HT stimulates release of vasopressin (more vasoconstriction) * Excessive serotonin - can cause hypertensive crisis Triptans * mimics serotonin - acts like serotonin * for migraine - **in migraine - get vasodilation (pulsing and throbbing)** * Triptan blocks these serotonin receptors - **vasoconstriction** * Triptans decreases blood flow --> **you get side effects like numbness in hands and fingers and chest pain** High serotonin levels increase blood vessel senstivity to other pressors (vasopressin and angiotensin II) --> more hypertension Binds to 5HT2A receptors (on nerves that controls smooth muscles)

Answer 285

Pain pathway - ascending and descending pathway Ascending pathway - send signals to brain (3 neurons involve - called 1st and 2nd and 3rd order neurons) 1st order neuron (sensory fibers) * transmit pain (cut) to the dorsal horn of the spinal cord * injury causes PG release --> sensory neurons respond to PG and carries signal to dorsal horn of spinal cord * 1st order neurons send signal to 2nd order neurons by releasing substance-_ 2nd order neurons: * crosses the spinal cord to the opposite side and ascend to the thalamus * located in dorsal horn * crosses spinal cord (**stimuli from right side goes to left side of brain)** 3rd order neurons * located in thalamus (relay center) * sends pain signal to cortex for perceptions Descending pathway (top-down) * Function: controls and inhibits communication between 1st order and 2nd order neurons * Descending neuron (serotonergic and noradrenergic neuron) from brain meets 1st order and 2nd order neurons. * Release NE and 5HT --> bind to presynaptic neuron (1st order neuron) and inhibits 1st order neuron from releasing substance-P to stimulate 2nd order neurons * descending neurons also stimulate interneurons (another neuron - where 1st, 2nd and descending neuron meets in the dorsal horn) * Interneurons (when stimulate) --> releases enkephalins **endogenous opioid** * Enkephalin has dual action in this meeting: **inhibts 1st order neuron from releasing substance P thus cannot transmit signal to 2nd order neurons** * **enkephalin also inhibits 2nd order neurons (can depolarize) = no action potential** * STOPS pain signal up to the brain **This convergence of the 1st order neuron, 2nd order neuron, descending neurons and interneuron is refer to the the gateway for pain** In fibromyalgia (duloxetine treats) * not enough NE or 5HT from descending neurons to stop 1st order neurons from releasing substance P and continue pain signal to 2nd order neurons * NE and 5HT stimulates interneurons to release enkephalins (endogenous opioid) * enkephalin also inhibits 1st order neuron and 2nd order neurons * **in fibromyalgia - this gateway is wide open - allowing even tiny stimuli to reach the brain** Dorsal horn is packed with interneurons * intrathecal injections

Answer 286

Reach the brain **body to react to danger without the brain** not all pain needs to reach the brain * have you notice there are times when you got injury but didn't felt it

Answer 287

Yes - opioids work extensively in the dorsal horn of the spinal cord To feel pain - pain signal has to reach brain Opioid stops pain signal - how? * Stops communication between 1st order neurons and 2nd order neurons in the dorsal horn of spinal cord opioid - binds to mu receptor of the terminal neurons (1st order neurons) * blocks Ca+ channel * Ca+ can't depolarize cells = no AP * prevents release of substance P and glutamate * pain is stop before reaching 2nd order neurons Opioid - also inhibit 2nd order neurons * Opens K+ channel * K+ flows out --> hyperPOLARize the neurons -- becomes more negative * more negative --> NO AP

Answer 288

Venlafaxine --> 2D6 --> Desvenlafaxine Desvenlafaxine is the active metabolite of venalafaxine Indications are different: Venlafaxine * approved for multiple indications: depression, anxiety, panic, social anxiety disorder * **Desvenlafaxine - is only approve for depression**

Answer 289

50 mg per day * no clinical benefits > 50 mg per day * Studies show higher dose does not produce significant improvement **Dose can be as high as 400 mg per day**

Answer 290

No Extended release tablet - uses a matrix-base ER system Absorbs moisture and slowly dissolve over 24 hours Does not use a a laser drill hole

Answer 291

Venlafaxine - can prolong QT interval **However, it's metabolite - desvenlafaxine DOES NOT - not clinically significant anyway**

Answer 292

Primary: NET and SERT * NE and 5HT reuptake inhibitors * increased NE and 5HT --> mood improvement and energy Secondary Targets (side effects) * (-) Muscarinic Acetycholine Receptors * Blocks Histamine Receptors * Blocks Alpha-1 Receptor Anti-muscarinic Side Effects: * BUCD Anti-histamine * Sedation, weight gain * **Histamine - keeps you up --> suppress the VLPO (sleep center) so it cannot promote sleep** Alpha-1 Blocker * Relaxes smooth muscle --> vasodilation --> OSH * Alpha-1 agonist --> vasoconstriction * **Doxazosin --> alpha1 blocker - relaxes smooth muscle so you can pass urine easier** * **Epipen - alpha1 agonist --> vasoconstriction to increase BP in anaphylaxis**

Answer 293

Ami**triptyline** --> Nor**triptyline** Im**ipramine** --> Des**ipramine**

Answer 294

Amitriptyline * Nerve pain * Migraine Nortriptyline * Depression **TCA - called tricyclic antidepressant** * But --> only nortriptyline is commonly use for depression

Answer 295

Nerve pain = neuropathic pain * a direct malfunction or direct injury to the nerve itself Damage: physical compression or trauma * herniated disc Metabolic * Long term high blood sugar poisons nerve fiber Shingle infection * can leave nerve permanently inflam

Answer 296

spinal disc has 2 layers * outer layer (tough) * soft center (jelly like) Hernia - means rupture or protrusion * occurs when an internal part of organ pushes through a weakness or tear in the surrounding Herniated disc - thus means * Jelly like center - pushes through a creak or tear in the outer tough layer * This hernia can compress on nearby nerve fiber

Answer 297

High sugar swells the nerve, stiffens it with glue, starves it of oxygen, and melts its insulation. * swells * stiffens * starves * melts **just know that high sugar damage nerves**

Answer 298

the virus lives inside the neurons Damage neurons from inside out Where does the virus live? * Dorsal root ganglia - stays asleep until active Where is the dorsal root ganglia? * junction box before 1st order neuron terminate in the dorsal horn * dorsal root ganglia is not inside the spinal cord - it is part of the peripheral nervous system

Answer 299

Cardiac Infarction (MI) * Blocks Na+ channel (stops influx of Na+ into heart cells) * Delay heart conduction or signal Glaucoma * Antimuscarinic - blocks fluid from back of eye to front of eye due to pupil dilation and pressing against the lens * Fluid buildup --> increase intraocular pressure Urinary Retention * antimuscarinic - causes urinary retention

Answer 300

in most clinical settings - the terms are use interchangeably To understand the difference, you need to understand the neurotransmitter Acetylcholine Acetylcholine - has two receptors * muscarinic receptors * nicotinic receptors Anti-cholinergic (agents) * drugs that can block any acetylcholine receptors (muscarinic and nicotinic) Anti-muscarinic (agents) * drugs that block only muscarinic receptors **Anti-cholinergic is the broad term** Where are these receptors mainly? Muscarinic * Rest and Digest of Parasympathetic NS * Eyes, Heart, Gut and Sweat Glands Nicotinic * Between nerves and muscle **For almost all practical purpose - the two words mean the exact same thing - don't OVERTHINK**

Answer 301

ABCDs of anti-cholinergic A - anhidrosis B - blurry vision C - constipation D - Dry mouth S - stasis (urinary retention) or Anticholinergic are anti-SLUD S - salivation - dry mouth L - lacrimation - dry eye - blur vision U - urinary retention D - defecation - constipation

Answer 302

Anti-cholinergic dilates the pupil - by relaxing the eye muscle **to constrict the pupil - you need muscle to contract to pull and close the pupil (make the pupil smaller** Thus - anticholinergic works opposite --> it dilates the pupil This dilation - blocks the drainage Fluid bluids up --> increase intraocular pressure **Connections:** * antimuscarinic - relaxes the smooth muscle of the bladder for overactive bladder * Think of your hand - when it relaxes, you hand opens (pupil dilates). When you constrict - your hands become smaller

Answer 303

Movement (nicotinic receptors) * physical messenger that makes muscle contract or squeeze * Binds to nicotinic receptors * causes muscle to squeeze Muscarinic receptors - Rest and Digest * Heart - slows down - rest * Gut - speeds up - digest * Glands - secretion (saliva, tears, sweats, stomach acid * Bladder - relax muscle and urinate * Eye (focus) - constrict pupils to allow focus - see closer

Answer 304

Acetylcholine does the movement (work) and dopamine gives the command (manager) Worker vs manager Dopamine * resides in the brain * decides when to move and how much effort (coordinate movements) to use * Without dopamine - you are frozen Acetylcholine * reside in the neuromuscular junction * takes command and physical forces the muscle fiber to contract * Without the workers - the muscle stays limp (myasthenia gravis)

Answer 305

TCA can block GABA-Receptors * Under normal conditon when GABA-A receptor is activated --> influx of Cl- ions to make inside more NEGATIVE - no AP * GABA - inhibitory NT TCA - blocks Na+ channel in heart * Beside HEART - **TCA also blocks Na+ channel in the brain** * Under normal conditon --> Na channel allows influx of Na+ and activated the Ca+ channel to open and influx Ca+ ions * makes inside more POSITIVE = AP * Some neurons releases GABA - inhibits too much excitation (in seizure)

Answer 306

buproprion - TID bupropion SR - BID bupropion XL - Once daily Max: 450 mg daily * seizure risk

Answer 307

NO - only affects DA and NE Does not affect 5HT (sexual dysfunction)

Answer 308

Seizure risk Risk increase 10X

Answer 309

monoamine oxidase enzyme * breaks down: serotonin, NE, Epi, and DA **Bottom line: increases these NT** **Depression is thought to be due to low serotonin level**

Answer 310

Tyramine is structurally similar to NE Our gut wall has MAO - which breaks down tyramine from food before it can reach the bloodstream MAO-Inhibitors (drugs) block MAO. Tyramine not broken down, enters blood stream and gets taken up by our nervous systems: * Tyramine uses NET to enter our nerve Once Tyramine enters our neurons * Reverse the NET - it pumps out NE intsead of reuptake into neurons * Enter vesicles and displace NE * More NE --> gets pump into system * Flood of NE causes HYPERTENSIVE crisis **Bottom Line:** * **Tyramine not broken down by MAO due to inhibitor** * **Tyramine causes a massive release of NE from neuron**

Answer 311

Norepinephrine NE Can get inside neurons by using NET Can displace NE in vesicle --> causes hypertensive crisis

Answer 312

L-Dopa --> Dopamine --> NE Why is this important to know? * **we have drugs that are use to treat OSH --> by increasing NE level** * **Droxidopa (Northera) - use specifically to increase NE for treating OSH**

Answer 313

Levodopa --> dopamine * precusor to dopamine Carbidopa * C = Convert = prevents the conversation or breakdown of levodopamine so levodopa can reach the brain and gets converted to dopamine

Answer 314

Cardiac QT risk * sertraline preferred * avoid citalopram and escitalopram Smoker: * buproprion Peripheral Neuropathy * Duloxetine Seizure disorder * avoid buproprion - lower Sz threshold Pregnant * Sertraline - soft on baby preferred * avoid Paxil - x - category X Daytime sedation * Avoid sedating drugs early in the day * paroxetine, mirtazapine, trazodone Insomnia * buproprion and fluoxetine - take in the morning (activating) Sexual dysfunction * bupropion and mirtazapine - lower risk

Answer 315

Anti-psychotics are use in treatment resistant depression. * depression that does not respond to standard antidepressants **We call this augmentation** Which drugs are approved * aripiprazole (abilify) * olanzapine (zyprexa) * quetiapine (Seroquel) * brexpiprazole (Rexulti) * cariprazine (Vraylar) * **lithium - augmentation**

Answer 316

Anxiety -> worry or fear First line drug: * SSRI + SNRI * snri - duloxetine, venlafaxine ER 2nd line: * Buspar - takes 2 to 4 weeks * TCA - ami and nortrip * Vistaril - short term * Pregaba and Gaba Special situation - stage freight * propranolol - take 1 hr prior

Answer 317

Ami = a mom - the mother gives birth to Nortript = the daughter (more energetic) Amitriptyline - a mom - puts you to sleep and calms you down * migraine prophylaxis * sleep Nortriptyline - daughter (more energy) * more NE --> better for nerve pain * less drowsy - daughter has more energy

Answer 318

LOT drug Lorazepam Oxazepam Temazepam Lorazepam - anxiety Temazepam - insomnia Why is the LOT drug preferred? * Most BZD are metabolized by CYP * **LOT bypass this metabolism** * **MOST will interact with CYP Inducers or Inhibitors** * Exception: Valproate can increase concentration of Lorazepam

Answer 319

BZD - sedating and safety concern (dependence) Why not preferred? * Most anxiety is due to depression * **SSRI and SNRI --> this is why SSRI and SNRI (antidepressant) are the preferred first line**

Answer 320

Valproate inhibits phase 2 * glucuronidation - adding a sugar molecule so drug can be excreted in urine Valproate and lorazepam * Valproate - blocks the enzyme that glucuronidate lorazepam (add a sugar molecule) * lorazepam - less get excreted in urine and level can build up

Answer 321

Insomnia * can't fall asleep * can't stay asleep --> wake up too early Restless Leg Syndrome * **irresistable urge to move the legs** Narcolepsy * **sleep attack** * excessive daytime sleepiness or suddent sleep attack

Answer 322

neurological * your brain fails to turn off the wake signal * Low GABA or high orexin (wake NT) VLPO (sleep center) --> release GABA to inhibit Arousal Center * this promote sleep Arousal Center * release histamine or OREXIN to suppress VLOP sleep center * **STAY ALERT and AWAKE**

Answer 323

Thought process: * Dopamine - movement (manager) * Neuron excitation Treatment: Gabapentin, pregabalin, horizant * binds to a subunit of the Voltage gated calcium channel (presynaptic) * **stops influx of Ca+ ** * hyperPOLARization (more ++) NO AP * specific: gabapentin is an alpha-2 delta ligand of the calcium channel blocker * **ligand = a molecule that binds** Dopaminergic Agonist * Ropinorole (Requip) and Pramipexole (Mirapex) * **why use dopaminergic agonist for RLS?** * dopamine - stops the urge to move the legs 2nd line: clonidine * decrease NE --> decreases the fight or flight response * calms down the nervous system to move

Answer 324

narke = numbess, stiffness (sleeping) * **narcotic = numbness. also comes from this root word** -lepsis = attack or seizure **connection: epilepsy** Together: a seizure of numbness what is a seizure? * A sudden uncontrolled electrical disturbance in the brain

Answer 325

Seizure * a **single** sudden, uncontrolled electrical disturbance in the brain Epilepsy * chronic condition, unprovoke reoccuring seizures * frequent seizure (a single event) * Epilepsy is multiple

Answer 326

**Z-drugs are called NON-Benzo because they are not benzo but works like BENZO** Both binds to GABA-A receptors * just different sites (allosteric site) Z-drugs mechanism (how different) * binds to gaba-a receptor (allosteric site) * **binding does NOT open Cl- channel to hyperPOLARIze neuron** * binding ONLY makes GABA-A receptors more sensitive to GABA NT

Answer 327

CYP 3A4 Inhibitors * G-PACMAN * SICKFACES.COM exception: * zaleplon (sonata) - cyp3A4 is a minor pathway - only 9% Connection: Review G-PACMAN and SICKFACES.COM

Answer 328

Melatonin is the **dark signal** for your brain Tells your brain it is dark and prepares the body for sleep * It does NOT force your brain to sleep like sedative Melatonin --> suppress the SCN (master clock) to calm down and prepare for sleep * SCN - suprachiasmatic nucleus **Review and connection** * serotonin --> melatonin --> suppress the SCN

Answer 329

Ramelton - a synthetic analog of melatonin * made in lab * more lipophilic - penetrate cns faster and has a longer half-life * melatonin - is natural Thus - mechanism of action: * binds and activate M1 and M2 receptors on the SCN to calm down and prepare body for sleep What is an analog? * a drug that is structurally similar to another compound but with a small tweak

Answer 330

Doxepin - at low dose * **potent-highly** selective for H1 histamine receptor antagonist (blocker) * **histamine - keeps you up** Review of TCA mechanism: * H1 blocker - antihistamine * SERT - serotonin reuptake blocker * NET - NE reuptake blocker * Anticholinergic Which other TCA helps sleep? * Amitriptyline - at low dose --> function mainly as H1 blocker **Connection: Doxepin vs benadryl** * Doxepin - design to be highly specific for H1 receptor (antagonist) * more potent **800X compare to benadryl**

Answer 331

**TCA - can act as a GABA-A receptor antagonist** * prevents GABA binding to its receptor Remember: TCA can block Na+ channel in the heart --> cause Cardiac Toxicity * Blocking Na+ in CNS is good for seizure --> **however this Na+ channel blockade can destablize the neuron** * **Seizure meds - blocks Na channel -- HMM - counterintuitive**

Answer 332

Temazepam Why is Temazepam preferred? * ideal half-life: 8 hours * no active metabolite --> less hangover * takes about 1 to 2 hours to work --> good to help you maintain sleep

Answer 333

movement dopamine agonist - dopamine is for movement * dopamine is the manager for movement * acetylcholine is the worker - contracts the muscle **RLS is an urge to move the lower legs. RLS is relieved with MOVEMENT. RLS is THOUGHT to be due to a dysfunction of dopamine**

Answer 334

Sleep attack - can last a few seconds to a few minutes * can occur at anytime Tx: we use stimulants * modafinil * armodafinil * sodium oxybate * ADHD drugs: Adderall and concerta

Answer 335

Sodium oxybate - analog of natural GABA NT * sodium oxybate - more potent How it treats narcolepsy? Though process: * Narcolepsy is excessive DAYTIME sleepiness * **The idea is to give patient a good night sleep --> maybe this can help with DAYTIME sleepiness** * Given with stimulant

Answer 336

**Mo**dafinil * Mother - mixture R and S A**R**modafinil * R - enantiomer * A - active version Thus --> Armodafinil is more potent Mechanism: * **Inhibits --> DAT** * Increase DOPAMINE --> dopamine is for AROUSAL and wakefulness * **modafinil can directly inhibit the VLPO - sleep promoting** Dopamine role in Arousal * stimulates the Ascending Arousal System * Thus - **modafinil - indirectly stimulates release of orexin and histamine via more dopamine** **Connection:** * Orexin - inhibits VLPO so it cannot promote sleep * Histamine -- same action on VLPO How to remember modafinil moa? * **Mo-da-**finil --> look at the drug name * Mo = more * Da = DA = dopamine * more dopamine * How you get more dopamine? * Block dopamine reuptake - block the transporter DAT

Answer 337

Narcolepsy Mechanism: * blocks H3 autoreceptors (presynaptic neurons) * Blocks the negative feedback --> thus neuron keeps releasing histamine * Highly designed to be specific to H3 --> does not bind to H1 and H2 receptors **Connections:** * Histamine - promotes wakefulness by suppressing the VLPO

Answer 338

**LOOK at the name** **MO-DA**finil MO = more DA = dopamine Together: more dopamine How do you get more dopamine? * Block DAT - block the transporter that reuptake dopamine

Answer 339

Solriamfetol (Sunosi) Mechanism: DNRI * dopamine and NE reuptake transporter inhibitor

Answer 340

GABA and pregabalin binds to the same receptors * alpha-1 Delta-1 subunit of the calcium channel (presynaptic) * prevents influx of Ca+ to dePOLARize * Inhibits **release of excitatiory NT: glutamate, NE and substance P** Same moa - can a patient take both? * consider therapeutic duplication **however - exception** * pt can't tolerate high dose * cross-taper to prevent **seizure**

Answer 341

Patient can't tolerated high dose of each ingredient Cross-taper to prevent seizure

Answer 342

Thought process: * GABApentin - 1st version - or first generation * PreGABALIN - analog of gabapentin (2nd version or gen) --> improved version * more potent, more predictable absorption **Pregabalin - is 2nd version of gabapentin.** **Pregabalin is an analog of GABApentin**

Answer 343

Carbamazepine --> is not metabolize into oxcarbazapine * **carba has a toxic metabolite --> side effects** * think: carbamazepine - 1st gen Oxcarbazepine (Trileptal) * analog of carbamazepine * does not convert to a toxic metabolite (less side effects) * **gets converted into licarbazepine * oxcarba is a mixture of R and S licarbazepine Eslicarbazepine (Aptiom) * you would think it is an enantiomer but it is NOT an enantiomer * **design to be metabolize into only S-licarbazepine --> thats how you get the name es-licarbazepine** NOTE: oxcarba is metabolized into both R and S licarbazepine * S-licarbazepine is therapeutic

CNS disorders Flashcards

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