ANTIEPILEPTIC DRUGS (AEDs) ANTIEPILEPTIC DRUGS (AEDs) Prototype: Phenytoin Prototype: Phenytoin (Dilantin) (Dilantin) Mechanism of Action Other

AEDs
Inhibits entry of sodium into neurons Suppresses action potential of neurons

Uses
Epilepsy, Cardiac dysrhythmias

Adverse Effects

Nystagmus, sedation, ataxia, diplopia, cognitive impairment Gingival hyperplasia, rash, hirsutism, liver damage Fetal harm, bleeding tendencies in newborns Narrow therapeutic range (10 to 20 mcg/mL) Inject slowly (do not exceed 50 mg/minute) Dysrhythmias and hypotension if injected too fast Use normal saline to prevent precipitation Induces the metabolism of other drugs such as: oral contraceptives, warfarin, and glucocorticoids (drug effect is decreased) Withdraw over 6 to 8 weeks to prevent seizures

Carbamazepine (Tegretol) Valproic acid (Depakene, Depakote, Depacon) Ethosuximide (Zarontin) Phenobarbital Fosphenytoin (Cerebyx), a prodrug form of phenytoin

All AEDs may increase suicidal thoughts and behaviors

LOCAL ANESTHETICS Prototype: Lidocaine

Mechanism of Action Stops axonal conduction by blocking sodium channels in axonal membrane Stops nerve conduction Uses Surgical anesthesia Adverse Effects Central nervous system excitation followed by depression, crosses placenta Convulsions, respiratory depression Bradycardia, heart block, reduced contractile force Cardiac arrest!, hypotension, allergic reactions

LOCAL ANESTHETICS Prototype: Lidocaine Other Local Anesthetics

Procaine (Novocain)esterin dentistry Bupivacaine (Marcaine)used with Lidocaine Amidevery low allergic response Benzocainecalled hurricaine, spray +Epinephrineprolongs anesthesia & reduces the risk of systemic toxicity!

GENERAL ANESTHESTICS
Mechanism of Action Enhance transmission at inhibitory synapses (GABA) Depress transmission at excitatory synapses (NMDA) Uses Surgery Adverse Effects Respiratory and cardiac depression Sensitization of the heart to catecholamines, leading to dysrhythmias Malignant hyperthermiatreat with

GENERAL ANESTHETICS Inhaled Anesthetics

Halothane (Fluothane) Isoflurane (Forane)malignant hyperthermia Enflurane (Ethrane) Desflurane (Suprane) Sevoflurane (Ultane)no Laryngospasm Nitrous oxideDont use alone. (in dentistry)

Intravenous Anesthetics

dantrolene Aspiration of gastric contents Toxicity to operating room personnel Hepatotoxicity

Thiopental sodium (Pentothal)No with seizures, called truth serum. Causes Laryngospasm. Give Succinylcholine. Diazepam (Valium)give b/f Ketalar Midazolam (Versed)anti-anxiety Propofol (Diprivan)soy/egg allergy, through away in 6hrs Ketamine (Ketalar)dissociation from environment, delirium, hallucinations. Give Valium prior to prevent side effects Droperidol plus fentanyl (Innovar)

OPIOID ANALGESICS Prototype: Morphine

Mechanism of Action Activates mu receptors Produces analgesia, euphoria, sedation Uses Relief of pain Adverse Effects Respiratory depression, constipation Orthostatic hypotension, urinary retention, cough suppression Biliary colic, emesis, elevation of intracranial pressure Euphoria, dysphoria, sedation, miosis, neurotoxicity Tolerance and physical dependence Prolonged use affects hormone and immune functions Reversed with naloxone (Narcan)

OPIOID ANALGESICS Prototype: Morphine Other Strong Opioid Agonists

Fentanyl (Sublimaze, Duragesic, Fentora, Actiq, Ionsys) Alfentanil (Alfenta) sufentanil (Sufenta) Remifentanil (Ultiva) Meperidine (Demerol) Methadone (Diskets, Dolophine, Methadose) Heroin Hydromorphone (Dilaudid) Oxymorphone (Opana) Levorphanol (Levo-Dromoran)

Moderate to Strong Opioid Agonists

Codeine Oxycodone (OxyContin, Percodan, Percocet) Hydrocodone (Vicodin, Lortab) Propoxyphene (Darvon)

ERGOT ALKALOIDS Prototype: Ergotamine (Ergomar)

Mechanism of Action Alters transmission at serotonergic, dopaminergic, and alpha-adrenergic junctions Activates serotonin receptors Suppresses inflammation by blocking calcitonin generelated peptide (CGRP) Promotes constriction Uses Migraine and cluster headaches Adverse Effects Nausea and vomiting Weakness in the legs, myalgias, tingling in the fingers and toes Angina-like pain Tachycardia or bradycardia

ERGOT ALKALOIDS Prototype: Ergotamine (Ergomar) Other Ergot Alkaloids

Dihydroergotamine (D.H.E. 45, Migranal) Ergotamine 1 caffeine (Cafergot, Ercaf)

Overdose can cause ergotism (ischemia due to constriction of vessels) Fetal harm

SEROTONIN1B/1DRECEPTOR AGONISTS (TRIPTANS) Prototype: Sumatriptan (Imitrex)

Mechanism of Action Binds to 5-HT1B/1D (serotonin) receptors to cause vasoconstriction Uses Migraine headache Adverse Effects Chest symptoms (heavy arms and chest pressure) Coronary vasospasm Teratogenesis Vertigo, malaise, fatigue, tingling sensation

SEROTONIN1B/1DRECEPTOR AGONISTS (TRIPTANS) Prototype: Sumatriptan (Imitrex) Other Triptans

Naratriptan (Amerge) Rizatriptan (Maxalt) Zolmitriptan (Zomig) Almotriptan (Axert) Frovatriptan (Frova) Eletriptan (Replax) Sumatriptan 1 naproxen (Treximet)

Prototype: Imipramine (Tofranil)

TRICYCLIC ANTIDEPRESSANTS (TCAs)

Mechanism of Action Inhibits reuptake of norepinephrine (NE) and serotonin (more serotonin and NE are available at the synapse). Uses First choice drug for major depression Depression, bipolar disorder, neuropathic pain Chronic insomnia Attention deficit/hyperactivity disorder Panic disorder, obsessive-compulsive disorder (OCD) Adverse Effects Orthostatic hypotension, anticholinergic effectsmost common blurry vision (no driving), dry mouth, constipation. Diaphoresis, sedation Cardiotoxicitymost dangerous A/Ehave a baseline EKG seizures, hypomania,yawngasm. Increased risk of suicide, especially in younger individuals/early in the treatment Many drug interactionswith MOIsincr. stim. of the heart.

Prototype: Imipramine (Tofranil) Other TCAs

TRICYCLIC ANTIDEPRESSANTS (TCAs)

They end on line or mine. Full effect1-2m, initial response 1-3 wks. Amitriptyline (Elavil) Clomipramine (Anafranil) Desipramine (Norpramin) Doxepin (Sinequan) Maprotiline Nortriptyline (Aventyl, Pamelor) Protriptyline (Vivactil) Trimipramine (Surmontil) Toxicity: Dysrhithmias Lethaal dose only 8xs the Average Daily Dose > dangerous than other meds. Gastric lavage, ingestion of activated charcoal (will bind with the med) and pysostigmine to counteract the anticholenergic action.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) Prototype: Fluoxetine

SELECTIVE SEROTONIN REUPTAKE INHIBITORS

(Prozac, Sarafem)
Mechanism of Action Inhibits serotonin reuptake (more serotonin is available at the synapse) Uses Primary- Major depression Other- bipolar disorder, Obsessivecompulsive disorder, Panic disorder, bulimia nervosa Premenstrual dysphoric disorder Adverse Effects Serotonin syndrome-within 2-72 hrs of tx. Excessive sweating, altered LOC, fever, tremor. Withdrawal syndrome-can begin 1-3 wks after last does. Taper! Sexual dysfunctiondrug holiday, Insomnia Weight gain, Neonatal abstinence syndrome Teratogenesis, Increased risk of suicide, Extrapyramidal side effects Bruxism (clenching and grinding of the teeth) Decrease in platelet aggregation!, leading to bleedingWatch Warfarin, NSAIDs Hyponatremia
Ch 32 Antidepressants Ch 32 Antidepressants

(SSRIs) Prototype: Fluoxetine (Prozac, Sarafem) Other SSRIs

Paroxetine (Paxil, Paxil CR, Pexeva)-Anxiety Fluvoxamine (Luvox)for OCD & anxiety Sertraline (Zoloft)less effect on seizure threshold, trouble sleeping. Citalopram (Celexa)similar S/E Escitalopram (Lexapro)similar S/E Most commonly prescribed antidepressants. As effective as TCAs without the side effects. Serotonin syndrome2-72 hr, death can occur. Sxaltered mental status, incoordination, excessive sweating, fever, tremor. Resolves spontaneously after discontinuation of drug. Stop the drug!

SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) Prototype: Venlafaxine (Effexor)

Mechanism of Action
Blocks NE and serotonin uptake; weak blockade of dopamine uptake (more transmitter available at synapse)

SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)

Prototype: Venlafaxine (Effexor) Other SNRIs Duloxetine (Cymbalta)for NE+serotonin (indicated for physical pain and diabetic neuropathy; can cause liver toxicity) Desvenlafaxine (Pristiq)

Uses

Major depression, generalized anxiety disorder Social anxiety disorder (social phobia)

Adverse Effects
Serious reactions if combined with MAOIs Nausea, headache, anorexia, nervousness, sweating, somnolence, and insomnia Weight loss, Diastolic hypertension!a medical crisis. Sexual dysfunction, Hyponatremia(elderly)Monitor electrolytes! Increased risk of suicide. Intense withdrawal syndrome with abrupt discontinuation (anxiety, agitation, tremors, headache,

vertigo, nausea, tachycardia, tinnitus) Neonatal withdrawal syndrome Serotonin syndrome Fetal harm

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Prototype: Isocarboxazid (Marplan)

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Prototype: Isocarboxazid (Marplan) Other MAOIs TransdermalSelegiline (Emsam) no dieatary restrictions, lower risk for hypertensive crisis. Phenelzine (Nardil) Tranylcypromine (Parnate) Transdermal selegiline (Emsam)

Mechanism of Action Increases NE and serotonin by blocking the enzyme that inactivates them. Irrevirsable inhibition. Uses-for those not responding to SSRIs & TCAs. Atypical depression, bulimia nervosa, OCD, and panic attacks. Not as 1st line. >dangerous. Adverse Effects CNS stimulation (anxiety, insomnia, agitation, hypomania, and mania) Orthostatic hypotension due to vasodilation Hypertensive crisis from high levels of dietary tyramine Many drug interactions & side effects so not 1st choice. SSRIs preferred for treatment of depression

No to yogurt, salame, liver, aged meats, cheese, beer, red wine, foods with yeast, chinese foods, chocolate, caffeinated beverages.

ATYPICAL ANTIDEPRESSANTS
Prototype: Bupropion (Wellbutrin, Zyban)

ATYPICAL ANTIDEPRESSANTS
Prototype: Bupropion (Wellbutrin, Zyban)

Mechanism of Action Unclear; may be related to blockade of dopamine uptake Uses Major depressive disorder Prevention of seasonal affective disorder (SAD) Smoking cessation Relief of neuropathic pain (unlabeled use) Attention deficit/hyperactivity disorder

Other Atypical Antidepressants

Nefazodone (can cause liver failure) Mirtazapine (Remeron)helps sleeping. Amoxapine Reboxetine Trazodone (Desyrel) has sedative effects No weight gain. Incr. sexual desire/pleasure.

(unlabeled use)

Adverse Effects Risk of seizure May increase the risk of suicide Agitation, headache, dry mouth, constipation, weight loss, GI upset, dizziness, tremor, insomnia, blurred vision, and tachycardia

MOOD-STABILIZING DRUGS
Prototype: Lithium (Lithobid, Lithonate, Lithotabs)

MOOD-STABILIZING DRUGS
Prototype: Lithium (Lithobid, Lithonate, Lithotabs) Other Mood-Stabilizing Drugs

Mechanism of Action Mechanism unclear; may alter ions and neurotransmitters May protect against neuronal atrophy and/or promote neuronal growth Uses Stabilizes both manic and depressive episodes in patients with bipolar disorder Reduces euphoria, hyperactivity, and other symptoms Preferred for patients with classic (euphoric) mania Adverse Effects Accumulates to toxic levels in the presence of a low sodium level. Lithium levels must be kept below 1.5 mEq/L0.8-1.4 mEq/L For maintenance therapy0.4-1.0 mEq/L Blood levels are drawn 12 hours after evening dose Signs of toxicity includefine hand tremor, GI upset, thirst, polyuria, and muscle weakness Chronic use can lead to renal toxicity and hypothyroidism Pregnancy Category D Reversible leukocytosis, dermatologic reactions Drug interactions occur with diuretics, NSAIDs, and anticholinergics!

Antiepileptic Drugs Valproic acid Carbamazepine Lamotrigine (Lamictal) Atypical Antipsychotics Olanzapine (Zyprexa) Aripiprazole (Abilify) Ziprasidone (Geodon)
Teach: If sickrisk for toxicity. Drink, eat salt, call doctor. Never give full dose all at once. At 2.5 mEq/Lhyponatremia, so-- muscle twitching, slurred speech, ataxia. Normal Sodium levels135 to 145 mEq/L

MOOD-STABILIZING ANTIEPILEPTIC DRUGS

Prototype: Valproic Acid (Depakote)

MOOD-STABILIZING ANTIEPILEPTIC DRUGS

Prototype: Valproic Acid (Depakote) Other AEDs used for BPD Carbamazepine (Equetro, Tegretol) monitor CBCget a baseline, can cause blood dyscrasias. Sunburn! Lamotrigine (Lamictal)Steven-Johnson.

Mechanism of Action Suppresses mania and stabilizes mood Uses Mood stabilizer for patients with bipolar disorder

Adverse Effects GI disturbances, Marked weight gain 60-70lbs. Thrombocytopenia, pancreatitis, liver failureDraw blood levels closely! Target trough level is 50 to 120 mg/mL Fetal harm

Valproic Acidworks faster and has a higher therapeutic index than Lithium as well as a better side effect profile.

BENZODIAZEPINES (BZDs)
Prototype: Alprazolam (Xanax)

BENZODIAZEPINES (BZDs)
Prototype: Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Estazolam (ProSom) Flurazepam (Dalmane)reversal agent Lorazepam (Ativan) Midazolam (Versed) Oxazepam (Serax) Quazepam (Doral) Temazepam (Restoril) Triazolam (Halcion)- antegrade amnesia Lipid Solublegive with milk For overdoseemetic+gastric lagavage Limited CNS depression effect compared to barbs.

Mechanism of Action Depresses central nervous system function Reduces anxiety, promotes sleep Potentiates the actions of GABA (an inhibitory neurotransmitter) Uses Anxiety, insomnia, seizure disorder, induction of anesthesia Muscle spasm, panic disorder, and withdrawal from alcohol Adverse Effects CNS depression, anterograde amnesia Sleep driving and other complex sleeprelated behaviors Paradoxic effectsinsomnia, excitation, euphoria. Weak respiratory depression if given orally IV administration can cause severe respiratory depression Abuse and addiction, teratogenic Do not mix with other CNS depressants or alcohol!! Reversal agent is flumazenil (Romazicon)

BENZODIAZEPINE-LIKE DRUGS
Prototype: Zolpidem (Ambien)

BENZODIAZEPINE-LIKE DRUGS
Prototype: Zolpidem (Ambien) Other BZD-like drugs Zaleplon (Sonata) Eszopiclone (Lunesta)

Mechanism of Action Potentiate the actions of GABA (an inhibitory neurotransmitter) Uses Short-term management of insomnia! Does not reduce anxiety Adverse Effects Daytime drowsiness, dizziness Sleep driving and other complex sleeprelated behaviors Do not use with alcohol or other CNS depressants

Melatonin Agonist Ramelteon (Rozerem)

BARBITURATES
CNS Depressants

BARBITURATES
CNS Depressants Thiopental Secobarbital Phenobarbitalhigh potential for abuse, a selective CNS depressant

Mechanism of Action Potentiate the actions of GABA (an inhibitory neurotransmitter) Uses Insomnia Suppression of seizures, induction of general anesthesia Treatment of manic states Adverse Effects No in pts with suicidal tendencies! Respiratory depression, decreased blood pressure and heart rate Paradozical excitement in elderly Induction of hepatic drug-metabolizing enzymes (increases the metabolism of other drugs rendering them less effective) May lead to tolerance and dependence Frequently used as vehicles for suicide Tolerance but not to Resp. depressant effects/Dependence

Miscellaneous SedativeHypnotics
Chloral hydrate (Aquachloral Supprettes, Somnote) Meprobamate (Miltown) Paraldehyde (Paral) Trazodone (Desyrel) antidepressant Diphenhydramine (Sominex) Doxylamine (Unisom)

DISULFIRAM (ANTABUSE)
Aversion Therapy for Alcoholism

DISULFIRAM (ANTABUSE)
Aversion Therapy for Alcoholism ReViadecreases cravings for alcohol. BenzodiazepinesLibriumfor acute withdrawal. Give- Vit. B, thiamine, folic acid, cyanocobalamin. Fluid replacement Teach: Avoid all forms of alcohol!

Mechanism of Action Disrupts alcohol metabolism by blocking enzyme Acetaldehyde accumulates and produces unpleasant effects Uses Alcohol abuse to maintain withdrawal. Adverse Effects Nausea, vomiting, flushing, palpitations, headache Sweating, blurry vision, hypotension, chest pain Shock occurs with ingestion of 7 mL of alcohol

CNS STIMULANTS Prototype: Methylphenidate (Ritalin, Metadate, Concerta, Daytrana)

Mechanism of Action Promotes norepinephrine (NE) and dopamine (DA) release. Essentially like amphetamines but different structure and name. Inhibits NE and DA reuptake Uses Attention deficit/hyperactivity disorder (ADHD) Narcolepsy Adverse Effects Insomnia, reduced appetite, weight loss Palpitations, hypertension, angina, dysrhythmias, psychosis Abrupt discontinuation can lead to withdrawal reactions Potential for abuse (Schedule II) Sudden death

Take in am During or after meals Dont crush and chew!