Pharm exam 2

Skeletal Relaxants: What labs are important to evaluate when utilizing these medications? (p. 243; key search term: "damage obtain LFTS")

Centrally acting skeletal muscle relaxants: for patients taking metaxalone and tizanidine, obtain baseline liver function tests (LFTS), as these medications can cause liver damage. Chlorzonazone can cause hepatitis and potentially fatal hepatic necrosis. Baclofen: assess baseline data, including spasm, rigidity, pain, range of motion, and dexterity. Obtain baseline LFTS as well. Dantrolene: dantrolene is hepatotoxic. To reduce the risk of liver damage, liver function tests (LFTS) should be performed at baseline and periodically thereafter. If signs of liver dysfunction develop, withdraw dantrolene. Inform patients about signs of liver dysfunction (e.g., jaundice, abdominal pain, malaise) and instruct them to seck medical attention if these develop. Benzodiazepines (diazepam): contraindicated during breast feeding, pregnancy and may injure the developing fetus, especially during first trimester,

Benzodiazepines: Good agent to use for conscious sedation.

Conscious sedation can be produced by combining midazolam (Versed) with an opioid analgesic (morphine/fentanyl). This state is characterized by sedation, analgesia, amnesia, and lack of anxiety. The patient can still respond to commands like "open your eyes." Conscious sedation persists for an hour or so and is good for minor surgeries and endoscopic procedures. The risk of adverse effects related to midazolam use can be minimized by administering over two or more minutes and by waiting another two or more minutes for full effects before dosing again. This drug should only be used in a setting that permits constant monitoring of cardiac and respiratory status, and facilities for resuscitation must be immediately available.

Dantrolene

Dantrolene [Dantrium) acts directly on skeletal muscle (does not act within CNS). Relieves spasm by suppressing release of Ca from the sarcoplasmic reticulum, and hence the muscle is less able to contract. Dantrolene can relieve spasticity associated with multiple sclerosis, cerebral palsy, and spinal cord injury Malignant hyperthermia is a rare, life-threatening syndrome that can be triggered by any general anesthetic (except nitrous oxide) and by succinylcholine, a neuromuscular blocking agent. Prominent symptoms are muscle rigidity and profound clevation of temperature. Dantrolene relieves symptoms by acting on the SR to block calcium release. Dose-related liver damage is the most serious adverse effect. Hepatotonicity is most common in women over age 35 years.

Diazepam Diazepam [Valium]

Diazepam [Valium] is a member of the benzodiazepine family, and is the enly benzodiazepine labeled for treating spasticity. Like baclofen, diazepam acts in the CNS to suppress spasticity. Diazepam does not affect skeletal muscle directly. Benzodiazepines potentiate the actions of GABA, an inhibitory transmitter found throughout the CNS. They do not act as GABA agonists - they simply intensify the effects of GABA. Since benzodiazepines simply potentiate the inhibitory effects of endogenous GABA, and the amount of GABA in the CNS is finite, there is a built-in limit to the depth of CNS depression that benzodiarepines can produce. Effects on muscle tone are secondary to the actions in the CNS (it cannot relieve spasm without causing sedation)

Brief Overview of antipyschotics

FGAS' most disturbing adverse effect is extrapyramidal symptoms (EPS) - movement that include: acute dystonia, Parkinsonism, akathisia, and one that occurs late in therapy: tardive dyskinesia (TD). Other adverse effects: neuroleptic malignant syndrome (NMS) - "lead pipe" rigidity, sudden high fever, etc.; anti-cholinergic effects (FGAS); orthostatic hypotension; sedation; neuroendocrine effects (includes gynecomastia, galactorrhea, and menstrual irregularities prolactin levels); seizures; sexual dysfunction (FGAS); agranulocytosis (high risk with chlorpromazine and clozapine); severe dysrhythmias (due to prolonged QT interval and increased risk of torsades de pointes). Dysrhythmia risk factors: long QT syndrome, hypokalemia or hyperkalemia, history of dysrhythmias, heart attack, severe heart failure.

First generation antipsychotics (FGAS), blockade of dopamine the CNS, which

First generation antipsychotics (FGAS), aka "conventional antipsychotics." All FGAS produce strong blockade of dopamine in the CNS, which can result in extrapyramidal symptoms (EPS).

Headaches: Indications for Ca" channel blockers, tricyclics (Amitriptyline), triptans. (pp. 307, 313: key search term: "2013 mechanism")

Calcium Channel Blockers (p. 313) • (Verapamil and nimodipine) - indicated for migraine prevention but the role for prophylaxis remains unclear, there is little evidence that supports their use in migraine prevention. Tricyclies (p. 313) • (Amitriptyline, prevents migraine pts; may involve inhibiting reuptake of serotonin, making more of the transmitter available for action; Elavil dosage of 25-150 mg once at bedtime; adverse effects - hypotension and anticholinergic effects, excessive dosages Triptans (p. 307) • Serotonin receptor agonists. First line drugs to terminate migraines. Pain is relieved by constricting intraeranial blood vessels and suppressing release of inflammatory neuropeptides. Examples: sumatriptan (Imitrex. Sumavel DosePro).

DRUGS FOR MUSCLE SPASM:

Centrally Acting Muscle Relaxants Spasm is defined as involuntary contraction of a muscle or muscle group. Muscle spasm is often painful and reduces the ability to function. Pharmacokinetics For must centrally acting muscle relaxants, the mechanism of spasm relief is uncicar. Many investigators believe that relaxation of spasm results primarily from the sedative properties of these drugs, and not from specific actions exerted on CNS pathways that control muscle tone. Two drugs - dianepam and tiranidine - are thought to relieve spasm by enhancing presynaptic inhibition of motor neurons in the CNS. Diazepam promoted presynaptic inhibition by enhancing the effects of GABA, an inhibitory neurotransmitter. Tizanidine promotes inhibition by acting as an agonist at presynaptic alpha, receptors.

Propofol (IV)

• Most widely used IV anesthetic • Induction and maintenance • Promotes the release of GABA • No analgesic properties • Can cause respiratory depression and hypotension • Use cautiously in elderly patients, hypovolemic patients and patients with cardiac problems • Poses a medium high risk for bacterial infection due to its lipid base • Propofel infusion syndrome: metabolic acidosis, cardiac failure, renal failure, rhabdomyolysis • Monitor CPK daily to avoid complications listed. If> 5,000 units, discontinue drug

Desflurane (VL)

• Nearly identical to isoflurane • Used for maintenance anesthesia in adults and children • Only approved for induction anesthesia in adults due to risk of laryngospasm, apnea, and decreased secretions in children

Isoflurane (VL)

• Potent with a MAC I.15% • Properties just like halothane, except it is a better muscle relaxant • Does not cause myocardial depression; not associated with Q-T prolongation

Ketamine (IV)

• Produces a state known as dissociative anesthesia • Produces sedation, immobility, analgesia, and amnesia • Premedication with diazepam or midazolam reduces risk of hallucinations and disturbing dreams • Used primarily in children and babies 3-12 months; can also be used for adults Avoid use if patient has a psychiatric history • Schedule III

Thiopental (IV)

• Short acting barbiturate • Rapid anesthesia, low analgesia, and muscle relaxation • Preferred for geriatric, CV, neurosurgical, and cesarcan patients due to small drop in BP • One of the three drugs used for capital punishment (followed by pancuronium and potassium chloride)

Fospropofol (IV)

• Similar effects to propofol • Slower onset Water soluble, so less likely to cause bacterial infection • Schedule IV drug Supplemental 0, must be delivered

Sevoflurane (VL)

• Similar to desflurane • Approved for maintenance and induction in adults and children Pleasant odor • Occasionally has produced severe heat and fire in the administration apparatus

. Tricyclic Antidepressants • Headaches

• Tricyclic antidepressants can prevent migraine and tension-type headaches in some patients. Underlying mechanism has not been established but may involve inhibiting reuptake of serotonin, making more of the transmitter available for action. Agent used most often is amitriptyline (Elavil). Because amitriptyline is effective in patients who are not depressed, it would seem that benefits do not depend on elevation of mood. Like other tricyclic antidepressants, amitriptyline can cause hypotension and anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision, tachycardia). Excessive doses can cause dysrhythmias

Two types of inhalation anestheties:

• Two types of inhalation anestheties: gases and volatile (converted to vapor) liquids (VL) • Gases: nitrous oxide • Volatile liquids: halothane, enflurane, isoflurane, desflurane, sevoflurane

Enflurane (VL)

• Very similar to halothane • Used very rarely due to better available drugs

Halothane (VL)

Prototype developed in 1956 • Recently withdrawn due to concems of liver toxicity • High anesthesia low MAC • Weak analgesia • Adverse reactions bypotension, respiratory depression, dysrhythmias (prolonged Q-T), malignant hyperthermia, hepatotoxicity

Traditional Antiepileptic Drugs (AEDS)

Traditional major traditional AEDS include phenyton. fosphenytoin, carbamazepine, valproic acid ethosuximate, phenobarbital, and primidone.

Menstrual Headaches

An important trigger is the decline of estrogen levels that precedes menstruation; therefore, this can be prevented by taking estrogen supplements. -Topical preparations: estrogen gel and estrogen patches (Climara, Estraderm) -Premenstrual triptans (frovatriptan, naratriptan, zolmitriptan) can reduce frequency, intensity, and duration of menstrually-associated migraine. Dosing is done for 6 days each month, beginning 2 days before menses. -Naproxen sodium at a dosage of 550 mg twice daily, given 6 days before to 7 days after menses, has demonstrated effectiveness in migraine prevention.

What are prophylactic drugs for headaches?

Antiheadache drugs may be used in 2 ways: 1) to abort an ongoing attack or 2) to prevent an attack from occurring blockers (e.g., propranolol), tricyclic antidepressants (eg, amitriptyline). CGRP receptor antagonists, and antiepileptic drugs (e.g, divalproex). https://www.stubhub.com/my/listingsProphylactic therapy can reduce the frequency, intensity, and duration of migraine attacks and can improve responses to abortive drugs. Indicated for patients who have frequent attacks (3 or more a month), attacks that are especially severe, or attacks that do not respond adequately to abortive agents. Prophylaxis for migraine. Make take weeks to work

• Median (or minimum) alveolar concentration (MAC)

is an index of inhalation anesthetic potency. and is defined as the minimum concentration of drug in the alveolar air that will produce immobility in 50% of patients exposed to painful stimuli. • Low MAC indicates HIGH anesthesia potency. • MAC tells us how much anesthesia the inspired air must contain to produce anesthesia. • In all patients, the inspired anesthetic concentration must be 1.2-15 times the MAC.

10. Local Anesthetics: Think about ages of patients when prescribing these medications. (please see question #9 for additional information; pp. 250; key search term: "result warn)

Avoid topical bezocaine in children under the age of 2 years. Topical benzocaine can cause methemoglobinemia. Death can result. Warm parents to avoid topical benzocaine in children younger than 2 years, unless approved by a healthcare professional. For older children and adults, exercise caution when topical benzocaine is applied to the mucous membranes of the mouth. Use of local anesthetics during delivery can cause bradycardia and CNS depression in the newborm - make sure to monitor cardiac status and avoid concentrated (0.75%) bupivacaine.

What are Beta Blockers first line drug for ?

B blockers are first-line drugs for migraine prevention. Of the available B blockers, propranolol is used most often, although metoprolol is now deemed to be just as effective. Treatment can reduce the number and intensity of attacks in 70% of patients. Benefits take a few weeks to develop. In addition to propranolol and metoprolol, three other B blockers-timolol, atenolol, and nadolol-can help prevent migraine attacks. In contrast B blockers that possess intrinsic sympathomimetic activity (eg. acebutolol. pindolol) are not effective

20. Benzodiazepines: Insomnia

Benzodiazepines are preferred drugs for short-term treatment of insomnia. Only five benzodiazepines are marketed specifically for use as hypnoties (triazolam, flurazepam, quazepam, estazolam, temazepam). However, any benzodiazepine with a short to intermediate onset could be employed. Benzodiazepines are indicated for 2 to 3-weck course of treatment. If insomnia lasts longer, then benzodiazepine-like drugs Edluar, Edluar, are preferred, Zolpimist), Zolpimisti such and and as P Ramelteon Eszopiclone (Lunesta), Zolpidem (Ambien, 1. Tovalt Tovalt ODT, ODT, (Rozerem).

Trifluoperazine

High potency/ 1st generation ACTIONS Treatment: schizophrenia and psychotic disorders. ADVERSE EFFECTS Early EPS. Occasional: sedation, orthostatic hypotension, anticholinergic effects, gymecomastia, galactorrhea, menstrual iregularities, and TD. Rare: NMS, convulsions, agranulocytosis.

Pimozide (Orap)

High potency/ first generation : ACTIONS Treatment: Tourettes syndrome only ADVERSE EFEFCTS Early EPS, sedation, postural hypotension. Can prolong QT interval risk for fatal cardiac dysrhythmias. CONTRAINDICATIONS Zoloft, Citalopram (Celexa), and Escitalopram (Lexapro) combined with Pimozide increases the risk of prolonged QT interval.

Dilantin when not to prescribe

, Do not give with liver dx, pregnancy, cardiac dysrhythmias, hypotension, rickets, osteomalacia, osteoporosis, warfarin, or blood clots.

and Cluster Headaches therapy is prophylaxis

-Glucocorticoids (prednisone and deramethasone) act rapidly, producing results within 48 hours, long-term use causes serious risks; therefore, treatment should stop in 1-2 months. -V'erapamil is 1" line agent for preventing chronic cluster headaches. -Lithium is 2" line drug for prophylaxis, dosing difficult and te multiple adverse effects, blood level needs to be monitored. If an attack occurs despite prophylaxis therapy, then these treatments would be used: -Sumatriptan, treatment of choice. -Oxygen, inhaling 100% oxygen for 15-20 minutes is highly effective. -Ergot preparations (intravenous dihydroergotamine, sublingual ergotamine) were commonly used. However, their use today is limited because lack of evidence that they are effective.

Preferred drugs for headache prophylaxis include

1) propranolol 2) Divalproex 3) amitriptyline.

Fluphenzaine formerly Prolixin)

High potency: first generation/ACTIONS Treatment: schizophrenia and other psychotic disorders ADVERSE EFFECTS Most common: early EPS symptoms and TD. Occasionally: sedation, orthostatic hypotension, anticholinergic effects, gynecomastia, galactorrhea, menstrual irregularities. Rare: NMS, covulsions, agranulocytosis.

Risperidone (Risperidal- rapid acting

2nd gen // INDICATIONS Treatment: schizophrenia, acute bipolar mania, children with autism. Used in children with autism schizeehrenia to to iritability symptoms like tantrums, aggression, mood swings, and self-injury. Used with improve positive and negative symptoms and cognitive function. Off label: elderly with dementia-related psychosis. Binds to several receptors; powerful antagonist at SHT2. Less powerful at D2 ACTIONS A powerful antagonist at 5-HT2 receptors and less powerful at D2 receptors. Does not block cholinergic receptors; does block HI receptors and alpha-adrenergic receptors. ADVERSE EFFECTS (Infrequent and mild) Low: EPS, increases prolactin levels (cause gynecomastia and galactorrhea but rare), metabolic effects (weight gain, DM, dyslipidemia), agitation, dizziness, somnolence and fatigue. Excessive dose: sedation, difficulty concentrating, disruption of sleep. Triples risk of stroke and doubles risk of death (from cardiac events and pneumonia).

Paliperidone (lavega, invega Siestenna)

2nd gen// ACTIONS Treatment: schizoaffective disorder, acute and maintenance therapy for schizophrenia ADVERSE EFFECTS Same as risperidone (paliperidone is the active metabolite of risperidonek prolongs QT interval (do not combine with QT-prolonging drugs).

Clozapine (Clozaril, FazaClo, Versacloz)-

2nd gen// INDICATIONS Schizophrenia (use safer alternatives first since clozapine agranulocytosisk reduces general symptoms and reduces suicidal behavior in patients with causes schizophrenia or schizoaffective disorder who are at chronic suicide risk. Highly eflective drug when others have failed. ACTIONS Blockade of receptors for dopamine and serotonin (5-HT). Blocks D2 dopamine receptors (affinity for these receptors is low, which may explain fewer EPS side effects). In contrast, strong blockade of S-HT2 serotonin receptors. Also blocks receptors for norepinephrinelepinephrine (alpha 1), histamine, and acetylcholine. Well-suited for patients who have experienced severe EPS with an FGA THERAPEUTIC USE Levodopa-induced psychosis: psychosis is a common side effect of levodopa (a drug used for PD) and clozapine is preferred treatment. PD results from insufficient dopamine in striatum and clozapine causes little-to-no blockade of dopamine receptors can alleviate levodopa-induced psychosis without making symptoms of PD worse. ADVERSE EFFECTS Common: sedation and weight gain (from blocking HI histamine receptors); orthostatic hypotension (from blocking alpha adrenergic receptors); dry mouth, blurred vision, urinary retention, constipation, and tachycardia (from blocking muscarinic cholinergic receptors). Minimal: neuroendocrine effects, interference with sexual function. Low: EPS and TD. • Agranulocytosis (1%-2%): Death (1 in 5,000) due to gram-negative septicemia and occurs in first six months. Mandatory monitoring of WBC count and absolute neutrophil count (ANC) prior to initiating treatment, and during treatment (weekly). Discontinue with WBC <2,000 or ANC<1,000. Will not be dispensed without labs. • Metabolic effects (weight gain, new onset diabetes, dyslipidemia): increases risk of cardiovascular events. Risk is highest with clozapine and olanzapine. Measure and monitor BMI, waist circumference, fasting blood sugar, and fasting lipid profile. Rare: seizures (generalized tonic-clonic in about 3% patients, dose relatedi, EPS effects, myocarditis can be fatal (fatigue, dyspneca, tachypnea, chest pain, palpitations) - hold until ruled out and if positive, discontinue use; orthostatic CONTRAINDICATIONS hypotension (and fainting). Older adult patients with dementia (doubled rate of mortality when used to treat dementia-related psychosis); patients taking other drugs for that can suppress bone marrow function (including many anti- cancer drugs) since it causes agranulocytosis. Use with caution: drugs that induce P450 enzymes (phenytoin, rifampin) lower clozapine levels and drugs that inhibit P450 isoenzymes (ketonazole, erythromycin) raise clozapine levels.

Headaches: Review the indications for Topamax (topiramate). (pp. 231, 312: key search term: "2004 benefits")

Actions/uses: 1. Adjunctive treatment adults and children 2 years and older with partial seizures, primarily generalized tonic-clonic seizures, and seizures associated with Lennon- Gastaut syndrome. 2. Monotherapy of adults and children 10 years and older with partial seinures or primary generalized tonic-clonic seirures.

Local Anesthetics: What are some SEs of these medications? "administration local effects")

Adverse effects can occur locally or distant from the site of administration; local effects are common CNS: when absorbed in sufficient amounts, local anesthetics cause CNS excitation, followed by depression. -During excitation phase, seizures may occur. -Depressant effects range from drowsiness to unconsciousness to coma; death can occur secondary to respiratory depression; mechanical ventilator with O, may be indicated if respiratory depression is prominent. Cardiovascular system: when absorbed in sufficient amounts, can affect heart and blood vessels. -In the heart, these drugs suppress excitability in the myocandium and condacting system causing bradycardia, heart block, reduced contractile force, and even cardiac arrest. -In blood vessels, vascular smooth muscle is relaxed, resulting in vasodilation and hypotension. Allergic Reactions: range from allergic dermatitis to anaphylaxis. -These reactions are relatively uncommon are much more likely with the ester-type anesthetics (e.g procaine), than with the amides. -Patients allergic to one type of ester are likely allergic to all ester agents. -Amide-type anesthetics have largely replaced ester-type agents when administration by injection is required because less likely to cause hypersensitivity reaction. Labor and Delivery: locals can depress uterine contractility and matemal effort, prolonging labor. -Can cross the placenta, causing bradycardia and CNS depression in the neonate. Methemoglobinemia: caused by topical benzocaine; a blood disorder in which Hgb is modified such that it cannot release O, to tissues; if enough Hgb is converted to methemoglobin, can result in death. -Methemoglobinemia associated with benzocaine liquids, sprays, and gels (most cases in children <2 years old treated with benzocaine gel for teething pain). -Do not use topical benzocaine kids <2 years old without advice of healthcare professional. Use with caution in older children and adults when applied to mucous membranes of mouth

Baclofen Baclofen (Lioresal,

Baclofen (Lioresal, Gablofen] acts within the spinal cord (CNS) to suppress hyperactive reflexes involved in regulation of muscle movement, though the precise mechanism of reflex attenuation is unknown. It is a structural analog of GABA, so it may act by mimicking the actions of GABA on nerves. No direct effects on skeletal muscle. Therapeutic Use Baclofen can reduce spasticity associated with multiple sclerosis, spinal cord injury, and cercbral palsy but not with stroke. Adverse Effects CNS effects: baclofen is a CNS depressant and hence frequently causes drowsiness, dizziness, weakness, and fatigue. Overdose can produce coma and respiratory depression. Since there is no antidote to baclofen overdose, treatment is supportive. Withdrawal: abrupt withdrawal of oral baclofen can cause visual hallucinations, paranoid ideation, and seizures. Withdrawal should be done slowly (over 1 to 2 weeks). Preparations, Dosage, and Administration Recommended initial starting dose for oral preparations is 5 mg 3 times a day and then gradually increased by 5 mg every 3 days up to a maximum dose of 80 mg day. Intrathecal administration is ve to or intolerant of oral baclofen.

Schizophrenia has three groups of symptoms:

Schizophrenia has three groups of symptoms: 1) positive symptoms, which are eaggerations or distortions of normal function (hallucinations, delusions, disordered thinking, disorganized speech, combativeness, agitation, paranoia), 2) negative symptoms, which include loss or diminution of nomal function (lack of motivation, poverty of speech, poor self-care, social withdrawal, etc.), and 3) cognitive symptoms, which include disordered thinking, reduced ability to focus attention, learning and memory difficulties.

When not to prescribe Carbamazepine [Tegretol]

Do not give with liver dx, low WBC count, pregnancy, migraine, or kidney dx.

Valproic acid when not to prescribe

Do not give with liver dx, pancreatitis, or pregnancy.

Contraindications for benzos

Do not take with other CNS depressants (eg, alcohol, barbituates, opioids). Drug must be tapered off after use.

Local Anesthetics: Esters versus amides.

Esters vs. Amides: - Differ in 2 important ways: I) method of inactivation, and 2) promotion of allergic responses. Amide-type agents represented by lidocaine [Xylocaine) Ester-type agents: represented by procaine Novocaine].

Seizures: Actions, side effects, contraindications, monitoring and assessment (e.g. phenytoin, valproic acid, carnamazapine, phenobarbital with dosing, when can it cause CNS depression, target levels). (p. 218;

Five hasic mechanisms of action 1) Suppression of Na- influx: phenytoin, carbamazepine, valproic acid, and lamotrigine reversibly bind to Na' channels while they are in the inactivated state, prolonging channel inactivation. By delaying return to the active state, these drugs decrease the ability of neurons to fire at high frequency, as a result, seizures that depend on high frequency discharge are suppressed. 2) Suppression of Ca- influx: in axon terminals, influx of Ca through voltage-gated Ca channels promotes transmitter release. Hence, drugs that block these Ca" channels can suppress transmission. Includes valproic acid and ethosuximide. 3) Promotion of K- eflux: during an action potential, influx of Na causes neurons to depolarize, and then efflux of K causes neurons to repolarize. Ezogabine acts on voltage gated K channels to facilitate K' efflux. This action is believed to underlie the drug's ability to slow repetitive neuronal firing and thereby provide seizure control. 4) Antagonism of glutamate glutamate is the primary excitatory transmitter in the CNS. The compound works through two receptors known as NMDA and AMPA. Two drugs, felbamate and topiramate, block the actions of glutamate at NMDA and AMPA receptors and thereby suppress neuronal excitation. 5) Potentiation of GABA: GABA is an inhibitory neurotransmitter that is widely distributed throughout the brain. By augmenting the inhibitory influence of GABA, these drugs decrease neuronal excitability and thereby suppress seizure activity.

General anesthetics // two types

General anesthetics are drugs that produce unconsciousness and a lack of responsiveness to all painful stimuli. • Two types: inhalation and intravenous. • Analgesia refers to decreased sensitivity to pain; anesthesia refers to decreased or complete loss of pain as well as other sensations (e.g., temperature, consciousness, sensation).

Haloperidol (Haldol)

HIGH POTENCY AGENTS/ 1st generation Haloperidol (Haldol) ACTIONS Treatment: schizophrenia and acute psychosis. Preferred treatment for Tourettes syndrome. Other Use: to control behavioral problems in children (combative, explosive hyperexcitability unrelated to any immediate provocation), but used as last resort. ADVERSE EFFECTS Common: early EPS symptoms and TD. Occasionally: neuroendocrine effects. Rare: NMS, photosensitivity, convulsions, and impotence. Can prolong QT interval with IV or high doses serious dysrhythmias. Use with caution in dysrhythmia risk factors. CONTRAINDICATIONS Do not use with other QT-prolonging drugs (e.g., amiodarone, erthryrommycin, quinidine)

SECOND GENERATION (ATYPICAL) ANTIPSYCHOTICS

Less likely to cause EPS and TD; more serious risk of metabolic effects (weight gain, DM, dyslipidemia) that lead to cardiovascular events and premature death. Also cause sedation and orthostatic hypotension like all FGAS. No advantage over FGAS. All approved for schizophrenia and bipolar disorder.

Thioridazine (formerly Mellaril)

Low potency/ 1st gen / ACTIONS Treatment: schizophrenia for patients that do not respond to safer agents because thioridazine prolongs QT and can cause fatal dysrhythmias. ADVERSE EFFECTS Common: sedation, orthostatic hypotension, anticholinergic effects, weight gain, inhibition of ejaculation. Occasional: EPS effects, TD, neuroendocrine effects, photosensitivity. Rare: NMS, convulsions, agranulocytosis, pigmentary retinopathy.

Chlorpromazine (formerly Thorazine):

Low potency/ 1st gen// superior at relieving SS of psychotic illnesses. ACTIONS Treatment: schizophrenia and psychotic disorders, schizoaffective disorder, manic phase of bipolar disorder, suppression of emesis, relief of intractable hiccups, control of severe behavioral problems in children. ADVERSE EFFECTS Common: sedation, orthostatic hypotension, anticholinergic effects (dry mouth, etc.), TD. Occasional: neuroendocrine effects, photosensitivity reactions. Rare: early EPS reactions. Lowers seizure threshold (must take anti-seizure meds), prolongs QT interval (risk of fatal dysrhythmias, caution with dyszhythmia risk factor patients). Rare: agranulocytosis and NMS. DRUG INTERACTIONS Can intensify responses s to to CNS depressants (antihistamines, benzodiazepines, barbituates) and anticholinergic drugs (antihistamines, tricyclic antidepressants, atropine-like drugs).

Topamax (topiramate). Pharmokinetics/side effects/ dose

Pharmacokineties: oral administration is rapid and not affected by food. Plasma levels peak 2 hours after dosing. Most of the drug is eliminated unchanged in the urine. Side effects: paresthesias, fatigue, cognitive dysfunction, metabolic acidosis, and weight loss. Adverse effects: somnolence, dizziness, ataxia, nervousness, diplopia, nausea, anorexia, and weight loss. It may also cause metabolic acidosis. Drug interactions: phenytoin and carbamazepine can decrease levels of sopiramate by about 45%, and topiramate can increase levels of phenytoin. Dose: 25 mg in the evening the first week, 25 mg in the morning and evening the second week, 25 mg in the morning and 50 mg in the evening the third week, and 50 mg in the morning and evening thereafter.

Seizures: Understand which drug is appropriate for the type of seizure. term: "seizures in partial")

Making a diagnosis requires physical, neurologie, and laboratory evaluations along with a thorough history. The history should determine the age at which seinures began the frequency and duration of seizure events, precipitating factors, and times when seizures occur. Very often, patients must try several AEDS before a regimen that is both effective and well tolerated can be established. Initial treatment should be done with just one AED. If this drug fails, it should be discontinued and a different AED should be tried. If this second drug fails, two options are open: (1) treatment with a third AED alone, or (2) treatment with a combination of AEDS.

Loxapine (Loxitane, Adasve)

Medium potency/ 1st gen /Treatment: schizophrenia only. ADVERSE EFFECTS Same as fluphenazine.

Perphenazine (formmerly Trilafon)

Medium potency/ first gen / ACTIONS Treatment: schizophrenia and other psychotic disorders. ADVERSE EFFECTS Same as fluphenazine.

Antidotes: Benzos

O Gastric lavage followed by activated charcoal and a saline cathartic for oral benzodiazepines. o Dialysis may be helpful if symptoms are especially severe. • Support of blood pressure with IV fluids and norepinephrine may be required. o Flumazenil (Romazicon): competitive benzodiazepine receptor antagonist administered IV; can reverse sedative effects, but not respiratory depression. Principle adverse reaction of its administration is precipitation of seizures.

Headaches: Actions/role of opioids in headaches. (p. 306; key search term: "analgesies are reserved")

Opioid analgesics are reserved for severe migraine that has not responded te first-line medications. The agents used most often are meperidine [Demerol) and butorphanol nasal spray [Stadol NSJ. Of the two, butorphanol is preferred because meperidine can cause all of the adverse effects associated with other pure opioid agonists (e.g., respiratory depression, sedation, constipation), and also has significant abuse potential. These drawbacks are less pronounced with butorphanol.

Newer seizure meds examples

Oxcarbazepine (Trileptal), Lamotrigine (Lamictal), Gabapentin (Neurontin). Gabapentin Enacarbil (Horizant), Pregabalin (Lyrica), Levetiracetam (Keppra). Topiramate (Topamax), Tiagabien (Gabitril), Zonisamide (Zonogran), Felbamate (Felbatol), Lacosamide (Vimpat), Rufinamide (Bazel), Vigabatrin (Sabril), Ezogabine (Potiga)

Panic Attacks Diserder & benzos

Panic disorder: characterized by recurrent, intensely uncomfortable episodes known as panic attacks. Panic attacks have a sudden onset of intense fear or intense discomfort, which peak in a few minutes and dissipate within 30 minutes during which 4 or 5 of the following are prescnt: palpitations, sweating. trembling or shaking, sensation of being SOB, feeling of choking, chest pain, nausca or abdominal distress, dizzy or lightheaded, chills or heat sensations, paresthesias, dercalization or depersonalization, fear of losing control, fear of dying Between 70% to 90% of patients respond well to treatment. Treatments include two modalities: drug therapy and CBT (cognitive behavioral therapy). Combining the two modalities is more effective than either modality alone. Panic disorder responds well to all four classes of antidepressants medicines: SSRIs, SNRIS, tricyclic antidepressants (TCA), and monoamine oxidase inhibitors (MAOI) SSRIS are usually preferred. Full benefits take 6 to 12 weeks to develop and drug therapy should continue at least 6 to 9 months to avoid relapse. Take not- these are not benzodiazepines. Although benzodiazepines are effective in panic disorder, they are now considered second-line drugs because, unlike SSRIS, 20 benzodiazepines pose a risk of abuse, dependence, and rapid reemergence of symptoms after discontinuation. Of the available benzodiazepines, the agents used most often are alprazolam [Xanax, Niravam), clonazepam [Klonopin, Rivotril), and lorazepam [Ativan]. All three provided rapid and effective protection again panic attacks, these drugs also reduce anticipatory anxiety and phobic avoidance.

1. Headaches: Appropriate drugs for prophylaxis. (p. 312; key search term: "drugs preventive")

Preventative therapy: can reduce frequency, intensity, and duration of migraines Can improve response to abortive medications Preferred medications: propranolol, divalproex, and amitriptyline all take work • Beta blockers: I" line - propranolol, timolol O Antiepileptic drugs: divalproex, topriamate o Tricyclie antidepressants: amitriptyline o Estrogen and triptans: menstrual migraine - estrogen Gel, estrogen Patch o Calcium channel blockers: verapamil o Botulinum Toxin: Botox - chronic migraine O ACE inhibitors and ARBS: prophylaxis of migraine; 2" or 3 line drugs o Supplements: riboflavin; coenzyme Q-10, butterbur

DRUGS FOR SPASTICITY

Spasticity refers to a group of movement disorders of CNS origin. The most common causes are multiple sclerosis and cerebral palsy. Spasticity is managed with a combination of drugs and physical therapy. Pharmacokinetics Three drugs - baclofen, diazepam, and dantrolene - can relieve spasticity. Two of these - baclofen and diazepam - act in the CNS. In contrast, dantrolene acts directly on skeletal muscle. With the exception of baclofen and diazepam, the drugs employed to treat muscle spasms (ie, the centrally acting muscle relaxants) are not effective against spasticity.

Seizures: Make sure you understand how these drugs are impacted by the cytochrome P450 system. (p. 221; key search term: "owing to effects on drug")

The pharmacokinetics of traditional AEDS are often complex. Owing to effects on drug- metabolizing enzymes (either induction or inhibition), they have complex interactions with other drugs, including other AEDS.

prolonged Headaches: Which drugs have vasoconstrictive effects? (pp. 306-308; key search term:

The serotonin receptor agonists, also known as triptans, are first-line drugs for terminating a migraine attack. These agents relieve pain by constricting intracranial blood vessels and suppressing release of inflammatory neuropeptides. All are well tolerated Rarely, they cause symptomatic coronary vasospasm. These drugs should not be administered to patients with coronary artery disease, curent symptoms of angina, or uncontrolled HTN. And, triptans should not be combined with one another or with ergot derivatives because excessive vasoconstriction could occur Sumatriptan, other triptans, and ergot alkaloids (c.g, ergotamine, dihydroergotamin) all cause vasoconstriction.

DRUGS FOR MUSCLE SPASM: Centrally Acting Muscle Relaxants side effects / therapeutic use

Therapeutic Use The centrally acting muscle relaxants are used to relieve localized spasm resulting from musele injury. CNS depression: all of the centrally acting muscle relaxants can prodace generalized depression of the CNS. Patients should be warned not to participate in hazardous activities (eg driving) if CNS depression is significant. Hepatic toxicity: tizanidine [Zanaflex] and metaxalone (Skelaxin] can cause liver damage. Liver function should be assessed before starting treatment and periodically thereafter. If liver injury develops, these drugs should be discontinued. If the patient has preexisting liver discase, these drugs should be avoided. Chlorzasazone (Lorzone. Parafon Forte DSC) can cause hepatitis and potentially fatal hepatic necrosis. Because of this potential for harm, and because other drugs are more effective, the risk of harm generally the drug's benefits. Other adverse effects: cyclobenzaprine and orphenadrine have significant anticholinergie properties, and hence may cause dry mouth, blurred vision, photophobia, urinary retention, (atropine-like) and constipation. Dosage and Administration. Methocarbamol and diazepam can be administered by IM and IV injection.

2 groups of skeletal relaxants

There are two groups of drugs that cause skeletal muscle relaxation. One group is used for lecalized muscle spasm. The other is used for spasticity. The drugs used to treat spasticity do not relieve acute muscle spasm and vice versa.

Etomidate (IV)

Used for induction • Rapid onset and lasts about 5 minutes Cardiovascular effects less than with barbiturates, so it is preferred for cardiovascular patients

Second generation antipsychotics (SGAS),

aka "atypical antipsychotics" The SGAS produce moderate blockade of receptors for dopamine and much stronger blockade of receptors for serotonin. The risk for EPS is much lower with SGAS than with FGAS, since restriction for the dopamine receptors is lower. SGAS do carry significant risk for metabolic effects (weight gain, diabetes, dyslipidemia), which can cause cardiovascular events and carly death.

Antidepressants:

amitriptyline (Elavilj: benefits equal those of propranolol. Like other tricyclic antidepressants, amitriptyline can cause hypotension and anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision, tachycardia). Excessive doses can cause dysrhythmias.

Carbamazepine (Tegretol. Tegretol-XR, Tegretol-CR. Carbatrol. Epitol.

comerstone of epilepsy therapy. Active against partial seizures and tonic-clonic seizures but not absence seizures. Action: suppresses high-frequency neuronal discharge in and around seizure foci. The mechanism appears to be the same as that of phenytoin: delayed recovery of sodium channels from their inactivated state. Pharmacokinetiss: Absorption of carbamazepine is delayed and variable. Levels peak 4 tol2 hours after dosing. Overall bioavailability is about 80%. The drug distributes well to tissues. Elimination is by hepatic metabolism. • Half-life decreases as therapy progresses. Because it induces hepatic drug-metabolizing

Clozapine:

common adverse effects include sedation and weight (H1) receptors); orthostatic hypotension (from dry mouth, blurred vision, urinary retention, constipation, cholinergic receptors). Neuroendocrine effects (galactorrhea, interference with sexual function are minimal. Compared with of extrapyramidal effects, including TD. Clozapine produces patients. The overall risk of death is about I in 5000. The monitoring of the WBC count and absolute neutrophil count (ANC) clozapine, both the total WBC count and ANC must be in the normal. below 3000/mm3 or if the ANC falls below 1500 mm3, treatment should be and the other SGAS can cause a group of closely linked metabolic effects-obesity, dyslipidemia all of which increase the risk of cardiovascular events. and olanzapine, and lowest with aripiprazole, lurasidone, and ziprasidone. Weight metabolic effect of greatest concern because it seems to underlie development of diabetes and dyslipidemia. Generalized tonic-clonic seizures occur in 3% of patients. The risk of seizures is related. Although the risk of EPS with SGAS is relatively low, clozapine and other SGAS can cause parkinsonism, acute dystonia, akathisia, and clozapine has been associated with myocarditis (inflammation of the heart muscle), fatal. If a patient develops signs and symptoms (eg, unexplained fatigue, dyspnca, pain, palpitations), clozapine should be withheld until myocarditis has been ruled diagnosed, clozapine should not be used again. Clozapine can cause orthostatic sometimes with fainting. Rarely, collapse is severe, and accompanied by respiratory arrest. Hypotension is most likely during initial dosage titration, especially if dosage escalation is rapid. Like the FGAS, the SGAS about double the rate of mortality when used off-label to treat dementia-related psychosis in older adults. Accordingly, since SGAS are not approved for this use, and since they pose a risk to these patients, it is clear that SGAS should not be preseribed for this condition.

be used for cardiac dysrhythmias. Pharmacokinetics: Absorption varies substantially

contraceptives, warfarin, and glucocorticoids. Women should increase the contraceptive dosage, or switch to an alternative form. • Drugs that increase plasma levels of phenytoin: slight increase in phenytoin levels can cause toxicity. Drugs known to increase levels: diazepam (atianxiety and AED), isoniazid (tuberculosis), cimetidine (gastric ulcers), and alcohol. Increase phenytoin levels by reducing the rate at which phenytoin is metabolized. Valproic acid (an AED) elevates levels of free phenytoin by displacing phenytoin from binding sites on plasma proteins. Drugs that decrease plasma levels of phenytoin: carbamazepine, phenobarbital, and akohol used chronically) can accelerate the mctabolism of phenytoin, thereby decreasing its levels. Breakthrough seizures can result Acute use of alcobol Increases phenytoin levels! Chronic use of alcohol Decreases phenytoin levels! • CNS depressants: the depressant effects of alcohol, barbiturates, and other CNS depressants will add with those of phenytoin. Preparations, Dosage, and Administration: Available in solution for injection and three oral formations, Dosage: highly individualized. Initial doses are usually given twice daily. Once a maintenance dosage has been established, once-a-day dosing is often possible. * Plasma levels are often monitored as an aid to establish dosage. The dosage objective is to produce levels between 10 and 20 meg/ml. Levels below 10 are too low to control seizures, levels above 20 produce toxicity. Narrow therapeutic range and a non-linear relationship betwoen phenytoin dosage and phenytoin plasma levels, once a safe and effective dosage has been established, the patient should adhere to it rigidly. • When treatment is discontinued, dosage should be reduced gradually. Abrupt withdrawal may precipitate seizures. Administration: oral may cause gastric discomfort. Administer with or immediately after a meal. Shake well before dispensing, since failure to do so can result in uneven dosage. IV: used to treat generalized convulsive SE. Infuse slowly, because rapid infusion can cause cardiovascul (watch for hypotension and bradycardia). Mas IV de Drug venous irritation. Irritation can be reduced by flushi the infusion.

Antiepileptic Drugs - Several drugs for headache

duration of Indicated - Several drugs that were developed for epilepsy can reduce migraine attacks. Proof of efficacy is strongest for divalproex (Depakote ER) and topiramate (Topamax). Gabapentin (Neurontin) and tiagabine (Gabitril) appear promising. . Divalproex • form of valproic acid (see Chapter 21). Divalproex reduces the incidence of attacks by 50% or more in 30% to 50% of patients. However, when attacks do occur, their intensity and duration are not diminished. In patients with migraine, the most common side effect is nausea. Other side effects include fatigue, weight gain, tremor, bone loss, and reversible hair loss. • Black Bax Warning • Potentially fatal pancreatitis and hepatitis can occur.Can cause neural tube defects in the developing fetus. Contraindicated during pregnancy.

constipation, Triptans: most 50% of patients

most side effects are transient and mild. Coronary vasospasm is the biggest concem. About 50% of patients experience unpleasant chest symptoms, usually described as ischemic heavy arms" or "chest pressure" rather than pain. These symptoms are transient and not related to heart disease. Possible causes are pulmonary vasoconstriction, esophageal spasm, intercostal muscle spasm, and bronchoconstriction. Patients should be forewarned of these symptoms and reassured they are not dangerous. Very rarely, sumatriptan and other triptans can cause angina secondary to coronary vasospasm. Electrocardiographic changes have been observed in patients with coronary artery discase (CAD) or Prinzmetal's (vasospastic) angina. To reduce the risk of angina, avoid sumatriptan in patients with risk factors for CAD until CAD has been ruled out. Owing to the risk of coronary vasospasm, sumatriptan is contraindicated for patients with a history of ischemic heart discase, myocardial infarction (MI), uncontrolled hypertension, or other heart disease. Sumatriptan should be avoided during pregnancy. If one triptan is combined with another or with an ergot alkaloid, excessive and prolonged vasospasm could result. Accordingly, sumatriptan should not be used within 24 hours of an ergot derivative or another triptan typical dose. Mild reactions include vertigo, malaise, fatigue, and tingling sensations. Transient pain and redness may occur at sites of subcutaneous injection. The intranasal formulation tastes bad and may imitate the nose and throat.

Newer seizure meds-what are advantages? "members although most")

o Better tolerated than traditional AEDS o May pose smaller risk to developing fetus • Only one (oxcarbazepine) induces drug-metabolizing enzymes to a significant degree, and hence interactions with other drugs, including other AEDS, are relatively minor. • Both old and new AEDS appear equally effective. Newer AEDS are prescribed less often than the traditional AEDS, because clinical experience with newer drugs is still limited. Oxcarbazepine and lamotrigine are the primary exceptions to this rule. When the newer AEDS were introduced, FDA-approved indications were limited to adjunctive therapy of certain seizure disorders. None of these drugs was approved for monotherapy, because clinical trials were limited to patients who were refractory to traditional AEDS. When the trials were completed, the experimental AEDS were only added to the patient's existing regimen, and so all that was known was that the new AED was effective when used together with an older AED. The FDA had no option but to approve the new drug for adjunctive therapy. Since being released, several of the newer AEDS have received FDA approval for monotherapy. o Oxcarbazepine is approved for adjunctive therapy of partial seirures im adults and children. Anti-seizure effects result from blockade of voltage-sensitive sodium channels in neuronal membranes, an action that stabilizes hyperexcitable neurons and thereby suppresses seizure spread. The drug does not affect neuronal GABA receptors. o Lamotrigine (Lamictal) has a broad spectrum of anti-seizure activity. Benefits derive mainly from blocking sodium channels and partly from blocking calcium channels. Both actions decrease release of glutamate, an excitatory neurotransmitter.

Seizures: Review phenytoin - understand action of drugs, SEs of texicity, etc. (please see Table 24-2 on p. 219 for dosing of all AEDS: p. 221; key search term: "most widely used AED)

prolonging channel inactivation. By delaying return to the active state, the drugs decrease the ability of neurons to fire at high frequency. As a result, seizures that depend on high-frequency discharge are suppressed. Phenytoin is used to treat epilepsy, while leaving most CNS functions undiminished. It causes selective inhibition of sodium channels. Slows recovery of sodium channels from the inactive state back to the active state. As a result, entry of sodium into neurons is inhibited, and hence action potentials are suppressed. Blockade of sodium entry is limited to neurons that are hyperactive. As a result, the drug suppresses activity of seizure generating neurons while leaving healthy neurons unaffected. It may also be used for cardiac dysrhythmias.

Beta blockers:

propranolol is used most often. The most common side effects are extreme tiredness and fatigue, which occur in about 10% of patients. In addition, the drug can exacerbate symptoms of asthma, and might promote depression. If rizatriptan is used for abortive therapy., its dosage must be reduced. Beta blockers that possess intrinsic sympathomimetic activity (eg, acebutolol, pindolol) are not effective.

Antipsychotic drugs used for:

schizophrenia, delusional disorders, bipolar, depressive psychoses, and drug induced psychoses. Two major groups of antipsychotic drugs, and both are equally effective. First and Second

Nitrous Oxide (gas)

• "Laughing gas" Low anesthetic potency • Used to supplement general anesthesia • Is used for analgesia • Primary side effect n'v

Miazolam (IV)

• Benzodiazepine • Can be used for induction anesthesia or conscious sedation • Must be constantly monitored and resuscitation equipment must be immediately available

Diazepam (IV)

• Benzodiazepine • Usually takes about I minute • Low analgesia and muscle relaxant

Benzodiazepines: Side effects,

• CNS depression: drowsiness, lighthcadedness, incoordination, and difficulty concentrating, also important Sleep-related - confusion and anterograde amnesia o behaviors: may carry out complex behaviors in their sleep with no memory of their actions (e.g, sleep driging, preparing and cating meals, making phone calls). Paradoxical effects: may cause insomnia, excitation, cuphoria, heightened anxiety, and rage. o Cardiovascular system: when taken orally, almost effect on heart or blood vessels; conversely. when given IV, can produce profound hypotension and cardiac arrest. o Respiratory depression: weak respiratory depressants; moderate at most with toxic doses. Significant depression usually only occurs when combined with other CNS depressants, or when administered IV. • Abuse: Schedule IV ("addiction" not common with those that take benzos for therapeutic Purposes). O Most are in pregnancy risk category D. Five (estazolam, flurazepam, quazepam, temazepam, and triazolam) are in category X. Should be avoided in breast-feeding mothers.

Intravenous Anesthetics

• Can supplement inhalation drugs • Can be used alone to produce greater effect than inhalation. Three drug families discussed: opioids, barbiturates, and benuzodiazepines.

Neuroleptic-Opioid Combination (IV)

• Droperidol and fentanyl • Produces neuroleptanesthesia (quiescence, indifference to surroundings, and insensitivity to pain) • Usually for diagnostic procedures • Contraindicated in patients with Q-T prolongation