Neuro and Psych Drugs

2.1 – “You’re getting sleepy… sleepy…”” IV anesthetic anestheticss (Propofol, eto etomidate, midate, ketamine) • IV anesthetics are used for rapid induction of anesthesia (lots of ivy in the picture). Preferred over inhaled for induction in most settings. Propofol (Prospero the hypnotist) • Most frequently used anesthetic for induction of anesthesia (“Introducing”). Lipophilic; preferentially enters CNS, accounting for rapid onset. Allows for continuous infusion, so used for maintenance as well (“Maintain your sanity!”). Can be used standalone or in combination with sedatives, opioids, inhaled anesthetics. • MOA presumed to be by potentiating chloride current through the GABA-A complex (Cab-A in the background) • Profound venous & arterial vasodilation →hypotension (dilated sleeves and pants of hypnotist) Etomidate (The Intimidator) • Can be used for induction of anesthesia (“Introducing”). Lipophilic & preferentially enters CNS, accounting for rapid onset. • MOA presumed to be by potentiating chloride current ought the GABA-A complex (Cab-A in the background) • Maintains CV stability, with minimum change to CO, HR, BP (person being lifted is stabilized) Ketamine (snaKE TAMING) • Used for induction (“introducing”) • MOA complex. Major effects probably d/t inhibition of NMDA receptor complex (nomadic camel tied up). Results in dissociative anesthesia. Eyes remain open with slow nystagmus (entranced men with wide eyes) • Common emergence reactions involve vivid colorful dreams, hallucinations, out of body experiences, visual/tactile sensitivity (vividly colored smoke). May induce fear and anxiety or euphoria (used recreationally) • Stimulates CV →↑BP, HR, CO (heart shaped cobra) • Other unique properties include analgesia, minimal respiratory depression, bronchodilation, convenient route of administration. Useful in mentally challenged & Peds patients Benzos (Ben’s Diner) • Midazolam may be used IV perioperatively. • Used for conscious sedation for minor procedures (e.g. colonoscopy) (colonic pump) Barbiturates • Occasionally used for induction (Introducing the Barber). Have been largely replaced as induction agents by propofol • Thiopental used for induction (Sweeney Pentol) • Highly lipid soluble, acts rapidly & finishes quickly (“the Ol’ Quick Shave”) 2.2 – “Laughin “Laughingg gas”: inhaled anesthetics, dantr dantrolene olene Properties • Inhaled anesthetics are taken up by gas exchange through the alveoli of the lungs, with consequences for pharmacokinetics, uptake, and distribution and partitioning. • Solubility of gas in the blood is also referred to as the blood:gas partition coefficient (partition in the ball pit); the higher the coefficient, the higher the solubility. Solubility determines speed at which blood becomes saturated, and ergo uptake and duration in the CNS. o Less soluble → more rapid saturation → more rapid onset & offset of CNS effects (e.g. N2O) (Kid sleeping in vascular ball pit; immediately getting pulled to safety). Takes less anesthetic to saturate the blood (only one kid in the ball pit rather than 2). o More soluble inhaled anesthetics have a slower onset and longer duration (e.g. halothane) (kid moving freely in the ball pit; KO’d by the end; long tapering flag)) • Arterial tension curves correlate to solubility (side of ball pit) o steeper arterial tension curve = lower blood:gas partition coefficient o Less steep arterial tension curve = higher blood:gas partition coefficient • MAC (minimum alveolar concentration) (mac & cheese) is the percentage of anesthetic needed in inspired gas mixture that renders 50% patients unresponsive (1 kid awake, 1 kid asleep). Corresponds to ED50 on dose-effect curve. o The lower the MAC, the more potent the drug (i.e. potency of the inhaled gas is inversely proportional to MAC) (inverted bowl of mac’n’cheese). The potency for inhaled anesthetics is the minimal concentration that reaches the brain that results in sufficient anesthesia. Inversely proportional to MAC. • Solubility of anesthetic in peripheral tissues is a major factor in onset/offset as well as it affects how much of the anesthetic will make it to the brain. Can be measured by the arteriovenous concentration gradient; if tissue solubility is high, a large amount of anesthetic is taken up from arterial blood, resulting in low venous concentration and larger AV concentration gradient. • Gaseous anesthetics may be used to deepen anesthesia after induction with IV agents. Precise MOA not known; may involve glycine, GABA, or antagonism of NMDA receptors. • All can cause myocardial depression → ↓CO & ↑arterial & ventricular pressures (clown with heart balloon). May cause hypotension (kid passing out) • Can cause respiratory depression, leading to decreased minute ventilation & hypercapnia (deflating lung balloons). Also decrease mucociliary clearance which may contribute to pos-op atelectasis. Agents • Gaseous: Nitrous oxide = laughing gas (N2O) o Lowing boiling point, gaseous at room temperature (gas canister). o Physically impossible to overdose. o Fairly benign. • Volatile anesthetics o Include enflurane, isoflurane, halothane. All are fluorinated. End in -thane or -flurane (kid in pool holding flower) o High boiling point, liquid at room temperature (Air tank getting wet in pool) o Can decrease cerebral vascular resistance → increased cerebral blood flow →↑ICP (crown with red brain wig) o Halothane rarely used d/t hepatotoxicity with massive hepatic necrosis (liver with cracked piñata). Presents within 2d – 4w. Will have widespread centrilobular necrosis and up to 80% mortality. o Enflurane: nephrotoxicity (guy getting hit in the kidney with bat). Convulsions (shaking) o Malignant hyperthermia (Magnificent birthday) ▪ Life threatening. Presents with fever and muscle rigidity soon after surgery with inhaled anesthesia (flame hat) ▪ Muscular hypersensitivity to volatile anesthetics or succinylcholine (SUCKS poster). Results in excess Ca2+ release from defect in ryanodine receptors (RyR) in the sarcoplasmic reticulum (Ryan sign falling). Causes excessive ATP-dependent reuptake by the sarcoplasmic reticulum, resulting in heat production (flame theme) and consequent muscular damage (bitten drumstick) ▪ May see potassium, CK, myoglobin released into circulation on labs (chicken legs) ▪ Treatment: Dantrolene (mm relaxant) (trampoline). Blocks RyR and prevents further release of calcium into muscle fibers (adult blocking Ryan from getting on trampoline). 2.3 – “Utop “Utopia ia resort”: Opiates, naloxone, naltre naltrexone xone Physiology • An opioid is any compound that that acts on at an opioid receptor (utopia resort). 3 endogenous receptors, all expressed throughout the central & enteric nervous systems (colon shaped table): o μ (mu-ssage parlor): major analgesic receptor (pain relieving massage); also responsible most adverse effects including sedation, constipation, respiratory depression, miosis, physical dependence??. Exist in high density in the GI tract & modulate enteric NS. Stomach, SI, LI decrease motility & increase tone → delayed passage of stool & increased H2O absorption oκ oΔ • At the molecular level, activated opiate receptors interact with G i proteins and open ion channel. In nn, open K+ channels → hyperpolarization of the membrane (open banana barrels). Also close VG Ca channels on presynaptic nn terminals (calci-YUM ice cream; unplugging presynaptic wire) →↓transmitter release (glutamate, ACh, Ne, serotonin, substance P). These effects combines to stop transmission of pain signals to brain Opioid withdr withdrawal awal • Tolerance is accompanied by physical dependence. Stopping abruptly can cause withdrawal (“withdraw to the spa” sign). Referred to as abstinence syndrome when occurs abruptly d/t stoppage of analgesics or illegal substances; also in neonates with opioid withdrawal. • Presentation: “anxious, hot, & moist” – anxiety, hyperventilation, hyperthermia, muscle aches, rhinorrhea, lacrimation, yawning, nausea/vomiting, diarrhea, mydriasis. • With Morphine or heroin: withdrawal SSx start within 6-10 h of last dose, peak 36-48 h, slowly decrease over a few days. • Detox involves curbing withdrawal SSx and minimizing symptoms using a long-acting opioid agonist (white tapering flag) o Methadone is a long-acting opioid full agonist used to attenuate withdrawal symptoms (done timer). Once tapered off, effects slowly subside with much less intense withdrawal. Patient can be slowly weaned off all opiates. o Buprenorphine is another long acting mu-opioid partial agonist (blueprint). Safer than methadone. Effects slowly subside as tapered. • Neonatal abstinence syndrome (irritable, moist, tachypneic baby in pool). Occurs when a newborn undergoes withdrawal from transplacental transmitted opiates. o Treatment: full mu-agonist, usually morphine or methadone. Pure μ agonists • Morphine & derivatives (hydromorphone) (“More fun, less pain”) o Prototypic drugs o μ receptor agonist o Used in management of chronic pain • Fentanyl (“make your pain a fantasy”) o μ receptor agonist o Used for post-operative & chronic pain • Tramadol (tram) o Weak μ receptor agonist (in the background). Used for management of chronic pain. o Centrally acts on blockade of 5-HT & norepinephrine reuptake (N/S compass), making effective for neuropathic pain specifically. • Loperamide (lop-eared rabbits), diphenoxylate (dolphins) o Don’t cross BBB; work on enteric system. o Increase colonic phasic segmental activity (i.e. tract squeezes down on stool rather than moving it along) (dolphins back & forth between haustra) o Antidiarrheals (muddy footprints) • Codeine (barcode), dextromethorphan (coughing orphan on package) o Opioid antitussives (coughing patron). MOA is poorly understood as the physiology of coughing is complicated. o dextromethorphan also antagonizes NMDA receptors (Nomadic camel on package) • Shared adverse effects o Direct extensions of pharmacologic action and may be utilized clinically in certain situations: ▪ Because principal effects are in CNS, can cause significant sedation & respiratory depression (lady with towel on head). Drowsiness & clouding of mentation are common adverse effects especially in the elderly, or in combo with other sedatives ▪ ↓brainstem respiratory mechanisms. Dose dependent. May initially be seen as ↑PCO2. Can be fatal with underlying respiratory disease (deflating lung vest). ▪ Constipation. Major problem with chronic use or ↑↑dosing, as in the case of managing cancer pain (plunger for clogged bathroom). ▪ Miosis (constricted hoodie) ▪ Biliary colic d/t contraction of biliary smooth muscle (biliary tree with seagull) o Side effects that are always undesirable ▪ Tolerance (“All are welcome” sign). Repeated doses have decreasing analgesic effect. After only a few days of exposure, high tolerance for euphoric, sedating, and respiratory effects. • No tolerance develops to miosis and constipation (“Out of order” bathroom). Anyone on prolonged opiates should be on prophylactic bowel regimen. ▪ LT use (chronic) activation of opioid receptor on nociceptive nn can cause ↑ pain sensitivity; this is referred to as opiate induced hyperalgesia (masseuse hurting client). Not known how this phenomenon occurs. May be due in part to downregulation of opiate receptors and/or upregulation of glutamatergic pathways. Partial agon agonists ists (partial foo foott massage) • Include buprenorphine, nalbuphine, butorphanol (-buphin = bluefin) • Used as analgesic. o Exception is in patients who have developed tolerance to full agonists and still have full agonists onboard. Giving such patients a partial agonist has the same effect as giving a direct antagonist & may precipitate withdrawal (waiter tripping into withdrawal spa) Pure antagoni antagonists sts • Naloxone (“No Lax Zone” trainer) o Used to reverse acute opioid toxicity. Completely & dramatically reverses OD effects within 3-5 minutes. Will virtually instantaneously precipitate withdrawal. o IF you suspect someone of OD’ing on opiates, IMMEDIATELY administer Naloxone!!! ▪ No ill effects of administering naloxone when someone has OD’d on something else. • Naltrexone (“No Tricks” trainer) o helps maintain abstinence in addicts. Blocks virtually all the effects of heroin, so useful in rehab. o May also reduce craving for alcohol & nicotine (trainer with XXX beer). o When combined with bupropion, can provide synergistic approach for weight loss (guy working out). 3.1 – “Ser “Serotonin otonin sitcom”: SSSRIs, SRIs, SNRIs, cyprohe cyproheptadine ptadine • Major depressive disorder (MDD) has 17% lifetime prevalence in US & is one of the major causes of disability in the developed world. While mechanisms are not clear, is thought to be related to a deficiency of CNS serotonin, NE, dopamine. There is a clear role for increasing available serotonin to address disease (serotonin smiley faces; 5H-TV). SSRIs, SNRIs are some of the most prescribed meds in the US. • Clinical indications: o MDD (comedy/tragedy masks): Acute episodes may last 6-14 months if untreated. About ⅓ of patients will achieve remission on treatment with a new med. Treatment is continued for at least 6 mos., and may be used for maintenance therapy. SIGECAPS for diagnosis criteria. o long-term treatment of anxiety disorders are the second most common indication, Benzos provide much more rapid anxiolytic effects, but SSRI/SNRIs at least as effective for maintenance therapy, without many of the Adverse effects. Include many of the major anxiety disorders, including ▪ GAD (anxious coworker). ▪ Panic disorder (same deal with the benzos) (Scream-saver) ▪ PTSD (dog tags). Usually require therapy as well ▪ OCD (obsessively organized desk) o Note that neither are for the management of acute symptoms of anything (depression, anxiety, pain). On average, 2 mos. before onset of efficacy (2-month calendar). SSRIs (selective serotonin reuptake inhibitors) (Express Trips) • Include fluoxetine (Fly out poster), paroxetine (parrot air poster), sertraline (desert airline poster), citalopram (Celexa®) (The City poster) • Inhibit presynaptic serotonin reuptake transporter (SERT) →↑ concentration at the synapse (Smiley face pad not kept in drawer) • Increased availability of monoamines at the synapse responsible for many of the beneficial and detrimental effects. • Clinical indications where SSRIs are preferred: o Bulimia (binge snack drawer with lady bending over). Not useful for anorexia. o Social anxiety disorder (shy guy) • adverse effects o Rare: SIADH → hyponatremia (guy sweating and spilling water while replacing bottle) o Diminished sexual function & interest in up to 50% of patients (girl rejecting guy’s advances) o Weight gain (rotund dude) o Drowsiness (sleeping on the job) o Rapid cessation can cause discontinuation syndrome, particularly with drugs with a short half-life (e.g. paroxetine or sertraline) ▪ Presents with flu-like symptoms (dizziness, fatigue, headache, nausea) 1-2 days after stopping meds (“Out with the Flu” note) ▪ Avoid by tapering o Serotonin syndrome (excessive smiley-face post-it notes in corner office). Potentially fatal. ▪ Presentation: Hyperthermia, hypertension, hyperreflexia & clonus (flushed angry boss tapping foot) ▪ Can look like the neuroleptic malignant syndrome precipitated by dopamine blocking agents (e.g. antipsychotics). Differentiation: Hyperreflexia & & clonus (NMS characterized by hyporeflexia & rigidity) ▪ Can occur with OD of a single drug or combos with other serotonergic drugs (e.g. TCAs, MAO-Is) (mousetraps & trike in corner office) ▪ Management: discontinuation of all serotonergic agents, stabilization of vital signs, ± serotonin antagonist (e.g. cyproheptadine, a 5HT-2 blocker) (“Silly Pranks Prohibited” for cyproheptadine) SNRIs (serotonin-norepinephrine reuptake inhibitors) (Compass rose on wall map) • Include Venlafaxine (fax), duloxetine (dual copier, scanner), sibutramine, milnacipran, levomilnacipran, and other derivatives • Inhibit presynaptic reuptake of norepinephrine & 5-HT, increasing availability of monoamines at the synapse. • Clinical indications where SNRIs are preferred: o Drugs that have 5-HT & norepinephrine reuptake blocking are helpful in pain management, particularly of neuropathic pain (frayed wire). Examples include diabetic neuropathy (venlafaxine, duloxetine) (hand stuck in Diasweeties vending machine). o Duloxetine has been found effective in many other pain conditions including lower back pain (guy bent in really uncomfortable position), osteoarthritis, & fibromyalgia (fiber bars) • Adverse effects o ↑noradrenergic transmission →HTN, ↑HR, CNS activation (insomnia, agitation) (angry coworker) o Discontinuation syndrome o Serotonin syndrome 3.2 – “I want to ride my tricycle tricycle”: ”: Tricyclic anti antidepressants depressants • Depression is thought to be related to a deficiency of CNS serotonin, NE, dopamine. There is a clear role for enhancing availability of synaptic monoamines to address disease. TCAs are 2nd or 3rd line in treatment of depression because of adverse effects, and are generally reserved for patients with treatment resistant depression (student struggling with resistant door to drama room, marked by comedy/tragedy masks) Tricyclic antidepressants (TCAs) (tricycle) • Include imipramine & derivatives desipramine, clomipramine (imprint of ball on girl’s face); amitriptyline, nortriptyline (girl tripping over trike) • Inhibit presynaptic norepinephrine & 5HT reuptake by blocking NET & SERT (blocked uptake of compass & smiley-face balls) • Off label uses: o Pain disorders, neuropathic & otherwise; notably diabetic neuropathy (kid stuck in Diasweeties machine) & chronic pain (frayed wire) o Migraine prophylaxis, especially Amitriptyline (school bell). o Clomipramine may be used to treat OCD, although SSRIs first line (child very neatly arranging marbles). o Central blockade of H1 histamine receptors, so may be used with allergies (bee ball) • Adverse effects o Many effects are a direct result of anticholinergic activity d/t inhibition of muscarinic acetylcholine receptors (child playing Mad Hatter’s tea party). ▪ Amitriptyline has most potent anticholinergic effect ▪ Less prevalent with secondary amines (e.g. nortriptyline & desipramine) (kid hiding under Secondary School sign) o Sexual dysfunction (rejected advances) o Relatively contraindicated in elderly patients d/t severe anticholinergic & antihistamine effects (just like dodgeball) (older man holding head) ▪ Urinary retention can be a clue to anticholinergic toxicity in delirium (bladder shaped tea kettle) o Central block of H1 histamine receptors can cause ↑appetite & weight gain (bee ball; heavy kid eating) o Can block α-1 receptors (extinguished α-1 candle). Can cause peripheral vasodilation & orthostatic hypotension, especially in the elderly (fainted girl) o CV toxicity ▪ Fatal cardiac arrhythmias are the most common cause of death in OD d/t blockage of fast Na channels (broken heartshaped peanut cookies; peanut butter jar). Causes ↓cardiac conduction → QRS & QT prolongation & arrhythmias (QRS shaped crack in bake sale sign; torsades streamers). ▪ Contractility depression can cause fatal hypotension. ▪ When a patient on TCAs presents with widened QRS or ventricular arrhythmia, treat with sodium bicarb (girl throwing baking soda). Alkalinizes serum, favoring non-ionized form of the drug which decreases affinity for Na channels. Also increases extracellular Na, allowing outcompetition of TCAs. o Seizures, probably d/t antagonist effect of TCAs on GABA-A receptor (kid in convulsions) o Serotonin syndrome (stack of smiley faced balls) o Can cause coma (kid sleeping it off) o *3 C’s: Cardiac, coma, convulsions 3.3 – “Of Mice & MAOIs” Physiology • Monoamine oxidases (MAO) breaks down monoamines (serotonin, NE, dopamine) (MAO = mouse). Two forms: o MAO-A deaminates dopamine, serotonin, and norepinephrine (albino mouse nibbling from smiley-faced & compass cheeses as well as dopamine rope). Usually breaks down tyramine in the GI tract (albino mouse eating meat) o MAO-B preferentially metabolizes deaminates dopamine (black mouse eating rope) • MAO-inhibitors (MAOIs) (mousetraps) o Include tranylcypromine (“Try a sip of wine!”), phenelzine (funnel in bottle), isocarboxazid (boxed wine) o Selegeline is a selective MAO-B inhibitor(sledgehammer hitting black mouse) ▪ inhibits breakdown of dopamine, increasing CNS levels. Useful in management of motor SSx of Parkinson’s as adjunct therapy to levodopa (cogwheeled clock). Especially useful with fluctuating or decreasing response to levodopa. o Block monoamine oxidase, decreasing breakdown of monoamines and thereby increasing their availability & increasing serotonin, NE, & dopamine transmission in CNS & periphery, enhancing activity of all of these. Irreversible (dead rat). o Historically used for depression & anxiety, but out of favor d/t adverse effects (comedy/tragedy masks) ▪ Not first line. Like TCAs, have potential lethal OD, require careful titration, many drug interactions & many adverse effects. Reserved for treatment resistant depression (bottle resistant to opening). ▪ May be useful in treating atypical depression with traits like hyperphagia, hypersomnia, leaden paralysis. o Adverse effects ▪ Most common are orthostatic hypotension, weight gain, & decreased sexual function; • Most severe sexual dysfunction effects of any antidepressant. ▪ Should be avoided with tyramine containing food (aged meats, wine, cheese). Without MAO-A activity, tyramine enterers circulation & acts as a sympathomimetic (Falling norepinephrine cheeses). May lead to tyramine toxicity, which can precipitate a hypertensive crisis. ▪ Chronic use of tyramine + MAOIs may cause malignant HTN ▪ Associated with serotonin syndrome (pile of smiley-face cheeses). Most serotonergic antidepressants should be discontinued at least 2 weeks before beginning an MAOI. 3.4 – “March Sadness”: Atypical antidepressants (Bupropion, mirtazapine, trazadone) • Atypical antidepressants are used in treatment of depression non-responsive to treatment • Bupropion o Blocks NET & DAT, leaving more NE, DA available in the synapse (“Net Dat Ball pro!”). Has no effect on serotonin. o Chemical structure similar to amphetamines. CNS activating affects, helps with hypersomnolence (kid cheering on the sidelines) o Can treat nicotine dependence; MOA unknown (“Pros don’t Smoke”) o Fewer sexual adverse effects than other antidepressants (lovebirds under net) o Less likely to cause weight gain (“Stay Fit” poster) o Adverse effects ▪ Lowers seizure threshold (player holding net). contraindicated in any patient with h/o seizures. ▪ Contraindicated with h/o bulimia (play with popcorn) ▪ Contraindicated with h/o anorexia (cachectic player) • Mirtazapine (mirth & misery cam) o Alpha-2 blocker (extinguished double-α candle) causing increased catecholamine release. o Also blocks 5HT-2 & 5HT-3 receptors (retired jerseys) o Potent H1 histamine antagonist (bee swatter). ▪ Can cause sedation (sleeping dude). ▪ May be therapeutic in patients with major depression & insomnia. May also be used to balance out effects of more activating agents. o Can cause weight gain (heavy eater drifting off while watching the game). May be preferable in elderly or with concurrent anorexia o Does not cause sexual adverse effects (kiss cam) • Trazadone (trombone) o Serotonin modulator. Antagonizes postsynaptic 5HT-2 R with some prevention of reuptake (smiley face drummer marching to the beat of his own drum with 52 jersey) o Antagonizes α-1 receptors (extinguished α lighter) ▪ May rarely cause priapism d/t α one effects (trombone; “trazabone”) • should be used with caution in conditions that predispose to priapism ▪ orthostatic hypotension (fainting dude) o H1 receptor antagonist, with major hypnotic effects (yellow team is out) ▪ Main therapeutic benefit is for patients with comorbid depression & insomnia. ▪ Should be avoided in the elderly (older man is sleep) ▪ Should not be used with other CNS depressants o Can cause sexual dysfunction (kid not getting kissed) o Serotonin syndrome (tipped over rack of balls) 4.1 – “Ski Man Mania”: ia”: Lithium • Bipolar consists of manic phases and depressive phases (two ski poles stabilize; peaks and valleys of mountains) • Lithium (lift) o Can be used to treat acute mania, or prophylactically for mania and depression. o Inhibits signal transduction pathways, including inositol triphosphate and other signaling. o Narrow therapeutic index (narrow window to get off the lift) o Urinary excreted. Anything that affects GFR will affect levels (e.g. diuretics such as thiazide may ↓ by as much as 25%; NSAIDS decrease) (kid on high dive; “low clearance” sign). o Adverse effects: ▪ Acute toxicity with GI SSx (skier on lift looks ill) ▪ Chronic → development of neuro SSx (e.g. tremor, confusion, ataxia) (trembling ski pole). ▪ Reversible thyroid inhibition in most patients (penguin with untied bow tie). Generally not symptomatic; may occasionally present with hypothyroid (e.g. weight gain) (snowboarder) ▪ Can induce diabetes insipidus (frozen fountain). Antagonizes action of ADH in collecting tubules. Polydipsia & polyuria usually resolve with cessation, but may be permanent with chronic use. ▪ Teratogenic (tarantula hats). Causes Epstein’s abnormality: arterialization of the R ventricle, ASD, malformation tricuspid (shapes of snowmen heads). Kids will present in later life with fatigue, tricuspid regurgitation. ▪ If patient on lithium presents with new onset neuro or psych SSx while on lithium, take a break from treatment. • Valproate therapy (“Festival” on violet banner) o Antiepileptic that can be used first line for acute mania or maintenance therapy. Can be combined with lithium for treatment refractory to either agent alone. • Carbamazepine (classic carved car) o Antiepileptic that can be used first line for acute mania or maintenance therapy • Lamotrigine (llama outfit) o Antiepileptic that can be used first line for maintenance therapy; can prevent depressive cycles. • Both first- & second-generation antipsychotics can treat acute mania (paintings on the peak) o Include haloperidol (halo in starry sky) 4.2 – “Seize the land”: Broad spectru spectrum m anti-ep -epileptics ileptics (valproate (valproate,, topiramate, lamotrigine, levetiracetam) Physiology • Epilepsy is a chronic disorder characterized by seizures (cerebral dysfunction caused by abnormal discharge of cerebral nn) (seizures = seizure, in this case of land). Can be from a variety of causes, but have characteristic patterns. • Focal: attack begins in a specific locus & typically involves only 1 part of the body (person dodging cannonball with one arm shaking). Multiple types, although treatments generally the same. o Simple: no LOC + clonic jerking of extremity or other sensory, psych, or motor symptom. o Complex: loss of consciousness; often associated with automatisms (e.g. lip smacking, swallowing) • Generalized involve both hemispheres at onset (trembling person falling off wall). Most common type is generalized tonic-clonic (historically grand mal)characterized with diffuse muscle contraction, rhythmic jerking, often have post-ictal state. • Partial seizures may also become generalized and turn into tonic-clonic • Juvenile myoclonic epilepsy is a type of generalized seizure disorder (kid making chicken wings) • Absence seizure • Others Manageme Management nt • Valproate (Festival) o Effective for all seizure types discussed above. One of the go-to agents o Binds VG Na channels, preventing sustained high-frequency firing and sustaining inactivation phase of neurons (open basket of sodium peanuts, with open lid “gates”) o Also affects other channels, ions, and neurotransmitters, notably elevating levels of inhibitory neurotransmitter GABA (taxicab colored palanquin elevated in the air) o Metabolized by CYP450 (ship with CYP 450 nameplate). o Adverse effects: ▪ GI adverse effects (ill emperor Atahualpa) ▪ Increased appetite & wight gain (Emperor’s girth) ▪ Tremor (trembling weapon) ▪ Rare but potentially fatal hepatotoxicity (cow with liver spot) ▪ Pancreatitis (pancreas sponge) ▪ Teratogen: causes neural tube defects and increases risk of spina bifida (tarantula shields; mother playing on pipe flute) • Topiramate (toupee) o Effective in many of the seizure types discussed above; not as effective as valproate or lamotrigine o Binds VG Na channels, preventing sustained high-frequency firing and sustaining inactivation phase of neurons (open basket of sodium peanuts, with open lid “gates”) o Allosterically binds to the GABA-A receptor (directly binding hands) o Metabolized by CYP450 (ship with CYP 450 nameplate). o Adverse effects ▪ Dose related somnolence & fatigue (tired soldiers) ▪ Confusion & cognitive slowing (soldier scratching head) ▪ Wight loss (cachectic soldier) ▪ Urolithiasis (kidney shaped wheel and cannonballs) ▪ Acute myopia & angle-closure glaucoma (closing angle on high-pressure tea-kettle). Must stop medication immediately. • Lamotrigine (llama) o Effective against many seizure types, including absence. o Binds VG Na channels, preventing sustained high-frequency firing and sustaining inactivation phase of neurons (open basket of sodium peanuts, with open lid “gates”) o Metabolized by CYP450 (ship with CYP 450 nameplate). o Adverse events ▪ Skin rash in up to 10%. ▪ 1%, especially children, may have SJS/TEN (red mask) ▪ Diplopia (cross-eyed llama) • Levetiracetam (Keflex) (elevator) o Effective against many seizure types; not used much against absence o Metabolized by CYP450 (ship with CYP 450 nameplate). o Adverse effects: ▪ Somnolence (sleeping person on elevator)