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Chapter 21: Parkinsons Disease Treatment

Background Information* *Parkinsons Disease (PD) A neurodegenerative disorder of the extrapyramidal system associated with disruption of neurotransmission in the striatum. Characterized by dyskinesias (disorders of movement) and akinesia (absence of movement) Affects over 1 million Americans Second only to Alzheimers disease as the most common degenerative disease of neurons Symptoms generally appear in middle age and progress No cure for motor symptoms Drug therapy can maintain functional mobility for years (prolongs/improves quality of life) *Cardinal Symptoms Dyskinesias: o Tremor at rest o Rigidity o Postural instability o Bradykinesia (slowed movement) o Tremor Also o Depression o Psychosis and dementia *Therapeutic Goals Ideal treatment (reverse neuronal degeneration or prevent further degeneration) o Does not exist Goal is to improve patients ability to carry out activities of daily life Drug selection and dosages are determined by extent to which the disease interferes with work, dressing, eating, bathing, etc.

LEVODOPA

Highly effective o Most effective in first 2 years Dopaminergic: activates dopamine receptors directly or indirectly o Promotes dopamine synthesis Benefits diminish over time (acute loss effect) o By the end of 5 years, symptoms may return to pretreatment level On-off phenomenon (can occur at any time during the dosing interval; abrupt loss of effect) Orally administered Treat more severe symptoms Rapid absorption from the small intestine o Food delays absorption Therapeutic Uses:

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To improve Parkinsons patients ability to carry out activities of daily living Adverse Effects: Nausea & Vomiting Dyskinesias (disorder of movement) Cardiovascular Effects o Orthostatic Hypotension (aka Postural Hypotension) o Dysrhythmias Psychosis o Hallucinations o Vivid dreams o Paranoia, etc. Darkened sweat and urine Activate malignant melanoma (should be avoided by patients with skin lesions) Drug Holidays: Defined as a brief interruption of treatment (usually 10 days) Successful if beneficial effects are achieved with lower doses Do not eliminate off times Dangerous because withdrawal will immobilize the patient Must take place in a hospital Immobilization presents risks for: o Severe psychological distress o Deep vein thrombosis (leg blood clots) o Aspiration pneumonitis (gastric content in lungs cause infection) o Decubitus ulcers (pressure ulcers) Drug Interactions: Anticholinergic Drugs: o Can enhance responses to Levodopa o Also increases risks of adverse psychiatric effects Second-generation Anti-psychotic Drugs: o Clozapine & Quetiapine o Do not block dopamine receptors in the striatum o Can be used safely with Levodopaz First-generation Anti-psychotic Drugs: (2 are safe clozapine & quetiapine) o Block receptors for dopamine in the striatum o Decrease therapeutic effects o Avoid these drugs Monoamine Oxidase Inhibitors: o Can cause hypertensive crisis if the MAOI is nonselective Pyridoxine (Vitamin B6): o Reduces therapeutic effects Food Interactions: High protein o Reduce therapeutic responses

ANTICHOLINERGIC DRUG USAGE:

Oldest medicines for treatment of PD Alleviate symptoms by blocking muscarinic receptors in the striatum thereby improving the functional imbalance between dopamine and Ach.

Pharmacology: Unit Three Study Guide Can reduce tremor and possibly rigidity but not bradykinesia Less effective than Levodopa or dopamine agonist but better tolerated Used as second-line therapy for tremor Most appropriate for younger patients with mild symptoms Generally avoided in the elderly, who are intolerant of CNS side effects (sedation, confusion, delusions, and hallucinations) They can also block cholinergic receptors in the periphery As a result: (decrease SLUD) o Dry mouth o Blurred vision o Photophobia o Urinary retention o Constipation o Tachycardia

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Chapter 22: Alzheimers Disease Treatment

Background Information* *Alzheimers Disease: Devastating illness Progressive memory loss Impaired thinking

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Inability to perform routine tasks of daily living Affects 4.5 million Americans Fourth leading cause of death: 100,000 deaths per year *Pathophysiology Degeneration of neurons Early stages o Emerge in hippocampus (region of brain) o Involves memory Later stages o In cerebral cortex o Involves speech, perception, reasoning, and higher functions Reduced cholinergic transmission o Level of ACh is 90% below normal ACh is critical in forming memory *Symptoms Symptoms may intensify during the evening, a phenomenon known as sundowning Memory loss Confusion Feeling disoriented Impaired judgment Personality changes Difficulty with self-care Behavior problems such as: o Wandering o Pacing o Agitation o Screaming Inability to recognize family members Inability to communicate Progressive symptoms: o Typically begin after age 65 o May appear as early as age 40 o Life expectancy from symptom onset 20 years or longer Usually 4-8 years *Therapeutic Goals To improve symptoms and reverse cognitive decline Available drugs cannot do this Drugs are not very effective *Drug Therapy Statistically significant improvement but clinically marginal improvement Treatment is not recommended to all patients because of the modest benefits Cholinesterase inhibitors may delay or slow progression of disease

Pharmacology: Unit Three Study Guide NMDA receptor antagonist for moderate to severe: o Memantine (Namenda) Better tolerated than cholinesterase inhibitors Adverse effects: Dizziness Headache Confusion Constipation

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CHOLINESTERASE INHIBITORS:

May delay or slow progression of disease but will not stop it Prevent breakdown of ACh therefore, increases amount of ACh at cholinergic synapses ACh is needed for memories Only three recommended for use (with equivalent benefits) o Donepezil (Aricept) o Galantamine (Razadyne) o Rivastigmine (Exelon) Not recommended because of liver damage: Tacrine Therapeutic Uses: Indicated for mild to moderate Alzheimers Adverse Effects: Cholinergic side effects ( SLUD) Gastrointestinal: o Nausea & Vomiting o Diarrhea Dizziness Headache Bronchoconstriction Liver injury (with use of Tacrine) Drug Interactions: Avoid the following (reduce therapeutic effects): o First-generation antihistamines o Tricyclic antidepressants o Conventional antipsychotics

RISK FACTORS FOR ALZHEIMERS:

Major: o Aging o Family history Possible: o Female o Head injury o Low educational level o Nicotine in cigarette smoke

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Chapter 23: Multiple Sclerosis Treatment

Background Information* *Multiple Sclerosis A chronic, inflammatory, autoimmune disorder that damages the myelin sheath of neurons in the CNS Exact cause is unknown Causes a wide variety of sensory and motor deficits Most patients experience periods of acute clinical exacerbations (relapses) alternating with periods of complete or partial recovery (remissions) Over time, symptoms grow progressively worse

Pharmacology: Unit Three Study Guide *Signs & Symptoms Vary depending on where the region of demyelination is Paresthesias (pins & needles) Muscle or motor problems Visual impairment Bladder or bowel symptoms (hypo or hyperactive) Sexual dysfunction Disabling fatigue Emotional lability Depression *Drug Therapy Immunomodulators (immune system modifiers) Immunosuppressants (suppress immune system) Symptoms that MS drugs help: o Bladder dysfunction o Bowel dysfunction o Fatigue o Depression o Spasticity o Sexual dysfunction o Neuropathic pain o Ataxia and tremor o Cognitive dysfunction o Dizziness and vertigo

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INTERFERON BETA PREPARATIONS

Naturally occurring glycoprotein Type of Immunomodulators (immune system modifiers): Recommended for all patients with relapsing remitting MS and those with secondary progressive MS who are experiencing acute exacerbations Decrease relapse rate by about 30% Self-injected (in single use syringes and viles)----IM & SubQ One year of treatment costs between $12,000 and $24,000 Three types: o Interferon Beta-1a (Avonex) o Interferon Beta-1a (Rebif) o Interferon Beta-1b (Betaseron) Therapeutic Uses: Used to decrease the frequency and severity of relapses and slow disease progression in pts with relapsing forms of MS; Betaseron is used to treat secondary progressive MS Treating secondary progressive MS Reduction of the frequency and severity of attacks Delay of progression of disability Adverse Effects:

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Flu-like reactions o Headache o Fever o Chills Hepatotoxicity o Liver function tests should be performed at: Baseline 1 month later Every 3 months for 1 year Every 6 months thereafter Myelosuppression o Can suppress bone marrow function o Thereby, decreasing production of all blood cell types o Complete Blood Count tests should be performed as liver function tests Injection-site reactions o Pain o Redness o Itching Depression Neutralizing antibodies o Can stimulate production of antibodies against itself o Can decrease clinical benefits Drug Interactions Use with caution when combining with other drugs that suppress bone marrow or cause liver injury

Chapter 24: Epilepsy Treatment

Background Information* *Epilepsy (Seizures) Group of disorders characterized by excessive excitability of neurons in the CNS Can produce a variety of symptoms ranging from brief periods of unconsciousness to violent convulsions Types of Seizures: o Partial (focal) seizures: Simple partial No loss of consciousness Persist for 20-60 seconds Complex partial

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Impaired consciousness Lack of responsiveness Last 45-90 seconds Secondarily generalized Consciousness is lost Last 1-2 minutes o Generalized seizures Tonic-clonic (grand mal) Impairment of consciousness Followed by a period of CNS depression Lasts 90 seconds or less Absence (petit mal) Loss of consciousness for 10 to 30 seconds Atonic head drop or suddenly collapse Occur mainly in children Myoclonic Sudden muscle contraction for 1 second Status epilepticus (SE) Persists for 30 minutes or longer Hospitalization Febrile Common in children 6 months to 5 years Short duration *Drug Therapy Treated with antiepileptic drugs (AEDs) that: o Suppress propagation of seizure activity from the focus to other areas of the brain o Suppress discharge of neurons within a seizure focus Mechanisms of action: o Suppress sodium influx Prolong channel inactivation Decrease the ability of neurons to fire at high frequency o Suppress calcium influx Suppress transmission o Antagonism of glutamate Glutamate is the primary excitatory transmitter in the CNS Block glutamate= suppress neuronal excitation o Potentiation of GABA GABA is the inhibitory neurotransmitter that is widely distributed throughout the brain Increase in GABA availability = decrease neuronal excitability Two major types of Drugs: o Traditional antiepileptic drugs

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o Newer antiepileptic drugs *Management of Generalized Convulsive Status Epileptic Goals of treatment: o Maintain ventilation (oxygen to the brain) o Correct hypoglycemia o Terminate seizures IV benzodiazepines (lorazepam or diazepam) Valium can be given in addition to Dilantin for status epileptics

PHENYTOIN (Dilantin)

Traditional antiepileptic drug Therapeutic Uses: Partial and tonic-clonic seizures via oral administration Status epileptic treated via IV Adverse Effects Nystagmus (involuntary eye movement) Sedation Ataxia (lack of movement coordination) Diplopia (double vision) Cognitive impairment Gingival hyperplasia (bleeding gums) Skin rash Fetal hydantoin syndrome o abnormalities of the skull and facial features, growth deficiencies, underdeveloped nails of the fingers and toes, and/or mild developmental delays Cardiac dysrhythmias (IV) Hypotension (IV) Hirsutism (overgrowth of hair in unusual places) Drug Interactions Phenytoin decreases effects of: o Hepatic Drug-Metabolizing Enzymes: Oral contraceptives Warfarin (anticoagulant) Glucocorticoids (anti-inflammatory/immunosuppressive drugs) Drugs that elevate Phenytoin levels: o Diazepam (antianxiety agent) o Isoniazid (Tuberculosis drug) o Cimetidine (gastric ulcer drug) o Alcohol o Valproic acid Drugs that decrease plasma levels of Phenytoin: o Carbamazepine o Phenobarbital o Alcohol CNS Depressants: o Alcohol & Barbiturates

Pharmacology: Unit Three Study Guide o Will add with effects of Phenytoin

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CARBAMAZEPINE (Tegretol)

Oral Therapeutic Uses: Epilepsy Bipolar disorder Adverse Effects: Nystagmus Ataxia Leucopenia (low WBC) Anemia Thrombocytopenia (low platelets) Birth defects Rash Photosensitivity reactions Interactions: No grapefruit juice (lasts in system for 3 days)

VALPROIC ACID (Depakote)

Also known as: Depakene, Depacon

Oral & IV Therapeutic Uses: Seizure disorders Bipolar disorder Migraine Adverse Effects: Nausea & Vomiting Hepatotoxicity (liver failure) Pancreatitis Teratogenic effects

Chapter 25: Muscle Spasm & Spasticity Treatment

Background Information* *Muscle Spasm & Spasticity Muscle Spasm: involuntary contraction of muscle or muscle group o Caused by: Epilepsy Hypocalcemia (low calcium) Pain syndrome: adult and chronic Trauma: localized skeletal muscle injury Muscle Spasticity: movement disorders of CNS origin o Caused by: Multiple sclerosis Cerebral palsy o Characteristics include: Heightened muscle tone Spasm Loss of dexterity (skill performing tasks) Two groups of drugs that cause skeletal muscle relaxation o One for localized muscle spasms

Pharmacology: Unit Three Study Guide o One for spasticity *Drug Therapy For treatment of spasms: o physical measures immobilization of affected muscle cold compress whirlpool baths physical therapy o Drug Therapy Analgesic anti-inflammatory (Aspirin) Centrally acting muscle relaxants

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DANTROLENE (Dantrium)

Oral Acts directly on skeletal muscle CNS depressant Therapeutic Uses: Spasticity associated with: o Multiple sclerosis o Cerebral palsy o Spinal cord injury Malignant Hyperthermia Relieves spasm by suppressing release of calcium from the sarcoplasmic reticulum and hence the muscle is less able to contract Only has minimal effects on contraction of smooth muscle and cardiac muscle Adverse Effects: Hepatic toxicity Muscle weakness Drowsiness Diarrhea Acne-like rash Drug Interactions: Intensified depressant effects caused by: o Alcohol o Benzodiazepines (treat insomnia) o Opiods o Antihistamines o Other CNS depressants

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Chapter 26: Local Anesthetics

Background Information* *Local Anesthetics These medications decrease pain by blocking conduction of pain impulses in a circumscribed area. Loss of consciousness does not occur. (can be topical or injection) Classification: o Esters Tetracaine (Pontocaine) Procaine (Novocain) o Amides Contain mixture of Lidocaine & Prilocaine (EMLA cream) Suppress pain by blocking sodium channels, thereby blocking impulse conduction along axons Local anesthetics o Are nonselective o Will block action potentials in all neurons which they have access o Selectivity is achieved by delivering anesthetic to a limited area Time:

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Onset usually begins promptly and persist as long as needed Termination: impact of regional blood flow: High blood flow areas carries the anesthetic away quickly Low blood flow areas may prolong Use with vasoconstrictors (usually epinephrine) o Prolongs anesthesia by delaying absorption o Reduces the risk for toxicity by allowing for less to be used

LIDOCAINE

Most widely used local anesthetic Topical and injectable applications Anesthesia is more rapid, more intense, and more prolonged that procaine Effects extended if given with epinephrine No longer used for cardiac dysrhythmias Duration: 15-45 minutes Peak effect: 2-5 minutes Preparations of Lidocaine: Cream Ointment Jelly Solution Aerosol Patch Therapeutic Uses: Reduction of discomfort associated with local disorders of the skin & mucous membranes Production of local anesthesia for surgical, dental, and obstetric procedures Adverse Effects: CNS effects: o seizures followed by respiratory depression leading to unconsciousness Cardiovascular o Hypotension o Bradycardia Allergic reaction o More common with ester Labor and delivery o Prolonged labor o Fetal bradycardia o Spinal headache

CLINICAL USE OF TOPICAL & INJECTED LOCAL ANESTHETICS

Topical used for: o Surface anesthesia Injected used for: o Infiltration anesthesia o Nerve block anesthesia

Pharmacology: Unit Three Study Guide o o o Intravenous regional anesthesia Epidural anesthesia Spinal anesthesia

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TOPICAL ANESTHESIA

Therapeutic Uses: Applied to the skin to relieve: o Pain, itching, and soreness of various causes including: Infection Thermal burns Sunburn Diaper rash Wounds Bruises Abrasions Plant poisoning Insect bites o Discomfort associated with: Hemorrhoids Anal fissures Pruritus ani (anal itching) Application may be made to o Mucous membranes of the: Nose Mouth Pharynx Larynx Trachea Bronchi Vagina Urethra Adverse Effects: CNS effects: o seizures followed by respiratory depression leading to unconsciousness Cardiovascular o Hypotension o Bradycardia Allergic reaction o More common with ester

INJECTED ANESTHESIA

Therapeutic Uses: Infiltration anesthesia Nerve block anesthesia Intravenous regional anesthesia Epidural anesthesia Spinal anesthesia Adverse Effects:

Pharmacology: Unit Three Study Guide CNS effects: o seizures followed by respiratory depression leading to unconsciousness Cardiovascular o Hypotension o Bradycardia Allergic reaction o More common with ester Labor and delivery o Prolonged labor o Fetal bradycardia o Spinal headache

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Chapter 28: Opioids (Narcotics)

Background Information* *Analgesics & Opioids Analgesics o Drugs that relieve pain without causing loss of consciousness Opioids o Any drug, natural or synthetic, that has actions similar to those of morphine o The most effective pain relievers for moderate to severe pain o Most reduce pain by attaching to a receptor in the CNS & alter perception & response to pain o Opioid dosage must be individualized o Administered on a fixed schedule o Evaluate your personal thoughts on abuse/addiction and give opiods based on patients need to relieve pain and suffering

MORPHINE

Pure Opioid Agonist Prototype o Activates mu & kappa receptors o Can produce analgesia, euphoria, sedation, respiratory depression, physical dependence, constipation o Strong Pure Opioid Agonist Source: seedpod of the poppy plant o Activates mu receptors producing analgesia, respiratory depression, euphoria, sedation o Acts on kappa receptors producing same effects as mu and decreased GI motility

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Oral, IM, IV, SubQ, epidural, and intrathecal Therapeutic Uses: More effective against constant dull pain rather than sharp intermittent pain Relief of moderate to severe pain such as: o Post-op pain o Chronic pain of cancer o Labor & delivery pain Given as a pre-op treatment of anxiety Adverse Effects: Respiratory depression (especially in infants and elderly) Constipation Orthostatic hypotension Urinary retention Cough suppression (accumulation of secretions in the airway) Biliary colic (can induce spasm of the common bile duct) Emesis (Nausea & Vomiting) Elevation of intracranial pressure Euphoria/dysphoria (sense of well-being/anxiety) Sedation Miosis (pupil constriction) Neurotoxicity (can cause): o Delirium o Agitation o Myoclonus (involuntary twitching) o Hyperalgesia (increased sensitivity to pain) From prolonged use: o Hormonal changes (decreased) o Alter immune function (suppressed) Tolerance: Increased doses needed to obtain same response Develop tolerance to: o Analgesia (pain relief) o Euphoria o Sedation o Respiratory depression Cross-tolerance to other Opioid agonists o If your pt is tolerate to one, the pt is tolerant to all Opioid agonists No tolerance to miosis or constipation develops (constipation & miosis remain chronic problems) Physical Dependence: Abstinence syndrome with abrupt discontinuation Intensity of withdrawal symptoms parallels the degree of physical dependence Infants exposed to opioids in utero may be born dependent About 10 hours after the last dose: o Initial reaction: Yawning Rhinorrhea- runny nose Sweating o Progresses to:

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Violent sneezing Weakness Nausea & vomiting Diarrhea and cramps Bone and muscle pain Muscle spasms Kicking movements Lasts 7-10 days if untreated Not lethal, just unpleasant Precautions: Decreased respiratory reserve Can compromise patients with impaired pulmonary function (because it causes respiratory depression): o Asthma o Emphysema o Kyohoscoliosis (abnormal curvature of the spine) o Chronic corpulmonale (enlargement of right ventricle of heart) o Bariatric (overweight) Pregnancy o Causes dependence in the fetus Labor & Delivery o Can suppress contractions Head injury o Elevation of intracranial pressure Infants & Elderly are especially sensitive to morphine-induced respiratory depression o Because their respiratory systems are compromised Inflammatory bowel disease o Because it can cause toxic megacolon or paralytic ileus Liver impaired patients o Intensifies & prolongs morphine Hypotension patients o Severe hypotension Prostatic hypertrophy o May cause acute urinary retention Drug Interactions: CNS Depressants o Intensify sedation and respiratory depression Anticholinergic Drugs o Intensifies constipation & urinary retention Hypotensive Drugs o Intensifies hypotension (decreases blood pressure) MAO Inhibitors o Cause: Excitation Delirium Hyperpyrexia (fever) Convulsions Severe respiratory depression Death

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o Combination should be avoided Agonist-Antagonist Opioids o Precipitates a withdrawal syndrome o Pt should be weaned from pure opioid agonists before beginning agonist-antagonist opioids Opioid Antagonist o Counteract o Antidote of opioid agonist Antiemetics o Reduce nausea & vomiting when combined with opioid agonists Amphetamines o Offset sedation o Enhance analgesia (pain relief) Clonidine (Alpha 2 Agonist) o Enhances analgesia (pain relief) Dextromethorphan (cough suppressant) o Enhances analgesia (pain relief) Toxicity Opioid overdose produces classic triad signs: o Coma o Respiratory depression o Pin-point pupils Treatment: o Ventilator support o Opioid antagonists (Narcan)

BUTORPHANOL (Stadol) & PENTAZOCINE (Talwin)

Agonist-Antagonist Opioid Prototype o When administered alone, produce analgesia o With pure opioid agonist, can antagonize analgesia (no pain relief) Maximal pain relief is generally lower than pure opioid agonists Cause little euphoria Increase cardiac work and should not be given to patients with acute

myocardial infarction Can precipitate an abstinence syndrome (withdrawal)

Analgesic effects are less than those of morphine Relieves moderate to severe pain There is a ceiling to respiratory depression o After a certain dose, no further respiratory depression occurs Agonist at kappa receptors Antagonist at mu receptors Low potential for abuse (Schedule IV) Toxicity can be reversed with Naloxone (Narcan)- opioid antagonist

NALOXONE (Narcan)

Opioid Antagonist Prototype o Block the effects of opioid agonist (reverses opioid overdose) o Reverses post-op opioid effects

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Reverse excessive respiratory and CNS depression caused by opioids given pre-op or intra-op Reverses neonatal respiratory depression Restores ventilation if respiratory depression is substantial

CLINICAL USE OF OPIOIDS

Balance the need to provide pain relief with the desire to minimize abuse Minimize fears about: o Physical dependence o Abuse o Addiction Conduct pain assessment o Essential component of pain management o Based on patients description Location Characteristics Duration Alleviating/Aggravating factors Status prior to drug 1 hour after The objective is to dispel excessive concerns about dependence, abuse, and addiction in the medical patient so these concerns do not result in undermedication and needless suffering. Concerning factors when using opioids to relieve pain: o Physical dependence A state in which an abstinence syndrome will occur if the dependence-producing drug is abruptly withdrawn ---not equated with addiction o Abuse Drug use that is inconsistent with medical or social norms o Addiction A behavior pattern characterized by continued use of a psychoactive substance despite physical, psychological, or social harm Patient-controlled analgesia (PCA) o Permits patient to self-administer opioids on an as-needed basis Specific Settings: o Postoperative pain o Obstetric analgesia o Myocardial infarction o Head injury o Cancer-related pain o Chronic non-cancer pain

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Chapter 30: Drugs for Headache

Background Information* *Treatment for Migraine Headache Objective: o To abort ongoing attack (eliminate head pain & suppress nausea & vomiting) o To prevent attacks (prophylaxis)

ERGOTAMINE (Ergomar)

Ergot Alkaloid type Well tolerated drug Prototype for abortive therapy o For headaches that have already begun Promotes constriction in cranial arteries and reduces amplitude of pulsations Alone: sublingual With caffeine: oral, rectal Therapeutic Uses: Stops ongoing migraine attacks Adverse Effects: Slight nausea and vomiting Weakness in legs Myalgia (muscle pain) Numbness and tingling Angina-like pain Tachycardia Bradycardia Overdose: Ergotism (serious toxicity) Ischemia of extremities: o Cold o Pale

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Drug

o Numb o With muscle pain o Can lead to gangrene Significant risk of peripheral vascular disease Significant risk of renal or hepatic impairment Treatment of overdose o Discontinuing Ergotamine o Followed by measures to maintain circulation including: Anticoagulants Low-molecular-weight dextran IV nitroprusside Interactions/Contraindications: Physical dependence causes withdrawal-like migraine attack Triptans o Prolonged vasospastic reaction can occur SSRIs (antidepressants) o Dont take within 24 hours Contraindicated for patients with: o Hepatic or renal impairment o Sepsis (infection) can lead to gangrene o Coronary artery disease o Peripheral vascular disease (PVD) o Pregnancy (class X) will promote uterine contractions and cause spontaneous abortion

ABORTIVE THERAPY DRUGS

Analgesics Aspirin-like analgesics o NSAIDS o ASA o Acetaminophen Opioid analgesics o Demerol o Stadol o Morphine o Talwin o Narcan Ergot alkaloids o Ergotamine (Ergomar) Serotonin agonists o Sumatriptan (Imitrex)
(Not on study guide)

PREVENTIVE THERAPY DRUGS (Drugs for Prophylaxis)

Beta blockers o Propranolol (used most often) o Can reduce the number and intensity of attacks in 70% of patients (because it promotes constriction) Anticonvulsants (antiepileptic) o Divalproex [Depakote]

Pharmacology: Unit Three Study Guide Tricyclic Antidepressants o Amitriptyline Estrogens Calcium channel blockers o Verpamil Methysergide (Sansert) Vitamin B 12

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SUMATRIPTAN (Imitrex)

Serotonin Agonists or Triptans Prototype Causes vasoconstriction and decreased vascular inflammation Oral SubQ Intranasal Therapeutic Uses: Relief of headache and symptoms (nausea, photophobia, phonophobia) o Successful in 70-80% of patients o 40% recurrence in 24 hours Adverse Effects: Well tolerated Burning sensation in upper chest Neck warmth Pressure in neck and throat Coronary vasospasm (of greatest concern) will cause angina Teratogenic (should be avoided during pregnancy) Drug Interactions: Ergotamines/Triptans o Cause vasoconstriction o Excessive & prolonged vasospasms MAO inhibitors o Suppresses degradation of sumatriptan o Reach toxic levels because its plasma level rises (builds up in blood)

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Chapter 31: Schizophrenia Treatment

Background Information* *Schizophrenia Chronic illness Characterized by disordered thinking Reduced ability to comprehend reality Usually emerges in adolescence or early adulthood *Antipsychotic Agents Antipsychotic Agents have 2 major groups: o Conventional antipsychotics (aka Neuroleptics) Block dopamine, ACh, histamine, & NE receptors Low, medium, & high potency o Atypical antipsychotics Moderate blockade of dopamine receptors *Compliance Check swallowing Cheeking (held in mouth) Support systems Written & verbal instructions Side effect interventions Depot preparations (long acting injectable for long term maintenance)

DEPOT ANTIPSYCHOTIC PREPARATIONS

Long-acting, injectable formulations used for long-term maintenance therapy of schizophrenia Objective: o Prevent relapse Rate of relapse is lower with depot therapy than oral o Maintain the highest possible level of functioning The risk of Tardive Dyskinesia is reduced Three preparations are currently available: o Haloperidol decanoate (Haldol, Decanoate) o Fluphenazine decanoate (Prolixin, Decanoate) o Risperidone microspheres (Risperdal Contra)

EXTRAPYRAMIDAL SYMPTOMS (EPS)- Adverse Effects of Antipsychotic drugs

EPS are movement disorders resulting from the effects of antipsychotic drugs on the extrapyramidal motor system.

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Unknown cause; although blockade of D2 receptors is strongly suspected Four types occur: o Acute dystonia Spasm of muscles of tongue, face, neck, and back; opisthotonus (bridging) Occurs early in therapy (a few hours to 5 days) Managed with anticholinergic drugs o Parkinsonism Bradykinesia, mask-like facies, tremor, rigidity, shuffling gait, drooling, cogwheeling, stooped posture Occurs early in therapy (5-30 days) Managed with anticholinergics, amantadine, or both Severe symptoms: switch to a second generation antipsychotic o Akathisia Compulsive, restless movement; symptoms of anxiety or agitation Occurs early in therapy (5-60 days) Managed with reduced dosage or lower potency Also, treat with a benzodiazepine, beta blocker, or anticholinergic o Tardive dyskinesia Oral-facial dyskinesias, choreoathetoid movements Occurs late in therapy (months to years) No satisfactory treatment Best approach is prevention: discontinue all anticholinergic drugs Give benzodiazepines Reduce antipsychotic dosage For severe: switch to second-generation antipsychotic

CHLORPROMAZINE (Thorazine)

First generation (conventional antipsychotic) Low-potency Oral, IM, IV, SubQ, Rectal Therapeutic Use: Treatment of: o Schizophrenia o Schizoaffective disorders o Manic phase of bipolar disorder o Suppression of emesis (vomiting) o Relief of intractable hiccups Adverse Effects: Sedation Orthostatic hypotension Anticholinergic effects (dry mouth, blurred vision, urinary retention, photophobia, constipation, tachycardia) Risk of EPS is relatively low (with the exception of TD) Lowers seizure threshold Drug Interactions:

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Can intensify responses to: o CNS depressants (antihistamines, benzodiazepines, barbiturates) o Anticholinergic drugs (antihistamines, tricyclic antidepressants, atropine-like drugs)

HALOPERIDOL (Haldol)

First-generation conventional antipsychotic Oral, IM, IV, SubQ, Rectal High potency (cause more early EPS, less sedation, orthostatic hypotension, and anticholinergic effects) Because of the reduced side effects, high potency agents are generally preferred with initial therapy Therapeutic Use: Treatment for: o Schizophrenia o Acute psychosis o Tourettes syndrome (preferred) o Refractory migraine (not approved for use but is effective in treatment) Adverse Effects: Acute dystonia Parkinsonism Akathisia Tardive Dyskinesia (same incidence as low potency) Risk of serious dysrhythmias (prolong QT interval) Drug Interactions: Avoid combined use with other QT-prolonging drugs: o Amiodarone o Erythromycin o Quinidine

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Chapter 32: Antidepressants

Background Information* *Depression: Depressed mood Loss of pleasure Insomnia Anorexia or hyperphagia Mental slowing Loss of concentration Feelings of guilt Suicidal behavior 30% of the US population will experience some form of depression o Treated with o Drugs o Electroconvulsive therapy (ECT) o Psychotherapy

IMIPRAMINE (Tofrail)

Oral (usual); IM (occasional) Tricyclic antidepressant First choice for major depression Blocks monoamine reuptake Half life is long and variable Response occurs in 1-3 weeks Maximal response occurs within 1-2 months Therapeutic Uses: Depression o Elevate mood o Increase activity and alertness o Decrease morbid preoccupation o Improve appetite o Normalize sleep patterns Bipolar disorder (manic-depressive illness) o Can help during depressive episodes Adverse Effects: Orthostatic hypotension o Dizziness, lightheadedness o Most serious o Advise patients to move slowly when assuming an upright posture Anticholinergic effects o Block muscarinic cholinergic receptors

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o Decrease SLUD, tachycardia Diaphoresis o Sweating Sedation o Common Cardiac toxicity Seizures Hypomania Suicide risk Yawngasm o Rare; Spontaneous orgasm while yawning Drug Interactions: MAOIs o Can lead to severe hypertension Direct-Acting Sympathomimetic drugs o TCAs increase these drug responses Indirect-acting Sympathomimetic drugs o TCAs decrease these drug responses Anticholinergic agents o Intensify effects CNS depressants o Intensified depression of CNS Toxicity: Most life threatening of all antidepressants Lethal does is only 8 times the average dose Dysrhythmias, AV block, V-tach & V fib Confusion, agitation, hallucinations; seizure and coma follow Treatment: o Antidote: Gastric lavage (stomach pump) followed by ingestion of activated charcoal o Cholinesterase inhibitor Physostigmine o Propranolol, lidocaine, Phenytoin(antiepileptic): control dysrhythmias

FLUOXETINE (Prozac)

Oral SSRI Most widely prescribed antidepressant in the U.S. As effective as tricyclic but with fewer side effects & less dangerous when overdosed Half life of 2 days Steady state takes 4 weeks Therapeutic Uses: Primarily for major depression Also approved for: o Bipolar disorder o Obsessive compulsive disorder o Panic disorder o Bulimia nervosa o Premenstrual dysphoric disorder Adverse Effects:

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Safer and better tolerated than TCAs and MAOIs Death from overdose has not been reported Sexual dysfunction Weight gain Nausea Headache Insomnia (give in the morning) Suicide risk Serotonin syndrome (agitation, confusion, anxiety, hallucinations, incoordination, hyperreflexia, tremor, sweating, fever) Withdrawal syndrome (dizziness, headache, nausea, sensory disturbances, tremor, anxiety, dysphoria) Neonatal effects during pregnancy: o Small risk of neonatal abstinence syndrome o Persistent pulmonary hypertension Teratogenesis o May cause heart defects o Very low risk Interactions: MAOIs & other Serotonergic Drugs o Risk of serotonin syndrome o These drugs should be withdrawn at least 14 days before starting Prozac o Prozac should be discontinued for at least 5 weeks before giving an MAOI Warfarin (anticoagulant) o Prozac can displace highly bound drugs o Monitor closely Tricyclic Antidepressants & Lithium o Elevate plasma levels of TCAs and lithium o Exercise caution

ORAL MAOIs

Second or third choice Causes irreversible inhibition of MAO-A o Increases amount of NE available for release o lasts for 2 weeks after drug withdrawal Therapeutic Use: Depression Bulimia OCD Adverse Effects: CNS stimulation (anxiety, agitation, mania) Orthostatic hypotension (dizziness, lightheadedness) Hypertensive crisis from dietary tyramine (a substance that promotes the release of NE) o Characterized by headache, tachycardia, hypertension, nausea and vomiting Drug/Food Interactions: Foods high in tyramine

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o Avocados o Fermented bean curd o Fermented soybean o Soybean paste o Figs o Bananas (in large amounts) o Fermented, smoked or aged meat or fish o Spoiled meats o Liver (unless very fresh) o Bologna o Pepperoni o Salami o All cheeses (except cottage & cream) o Yeast extract o Some imported beers o Chianti wine o Protein dietary supplements o Soups (with protein extract) o Shrimp paste o Soy sauce Other foods that can precipitate hypertension: o Chocolate o Fava beans o Ginseng o Caffeinated beverages Multiple drug-drug interactions: o Indirect-acting sympathomimetic agents May be present in cold remedies, nasal decongestants, and asthma medications Can produce hypertensive crisis o Tricyclic antidepressants Can produce hypertensive episodes or hypertensive crisis However, combination can benefit certain patients Exercise caution o Serotonergic drugs Risk of serotonin syndrome o Antihypertensive drugs Excessive lowering of blood pressure o Meperidine (Demerol) Can cause hyperpyrexia (fever) If a strong analgesic is required, Meperidine should not be chosen

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Chapter 33: Bipolar Disorder Treatment

Background Information* *Bipolar Disorder Fluctuations of mania & depression Goal is to stay in the middle of manic and depressed states Treated with drugs and psychotherapy

LITHIUM

Oral Used in the initial phase and depressive phase Low therapeutic index (less safe) Simple inorganic ion Drug of choice for treatment of mania Decreases risk of suicide Short half life (due to rapid renal excretion) Lithium levels must be between 0.4 to 1.4 mEq/L Therapeutic Uses: Bipolar Disorder Adverse Effects: Early: o Nausea, Vomiting, Diarrhea, Abdominal bloating, Anorexia, Transient fatigue, Muscle weakness, Headache, Confusion, Memory impairment, Polyuria, Thirst Polyuria (50-70% of patients) o Output may exceed 3L/day o Can be reduced with amiloride (Midamor)= potassium sparing diuretic Renal Toxicity Goiter and Hypothyroidism Teratogenesis o Pregnancy Risk Category D (should be avoided within first trimester) When lithium levels are within a therapeutic range: o Below 1.5 mEq/L Nausea, vomiting Diarrhea Thirst Polyuria (excessive urination) Lethargy Slurred speech Muscle weakness Fine hand tremor When lithium levels are excessive: o 1.5-2 mEq/L Persistent gastrointestinal upset Coarse hand tremor Confusion Hyperirritability of muscles ECG changes

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Drug

Sedation Incoordination o 2-2.5 mEq/L Ataxia Giddiness High output of dilute urine Serious ECG changes Fasciculations (muscle twitch) Tinnitus (ringing of ears) Blurred vision Clonic movements Seizures Stupor Severe hypotension Coma Death (usually secondary to pulmonary complications) o Above 2.5 mEq/L Symptoms progress rapidly to generalized convulsions, oliguria (low urine output), and death Interactions: Diuretics (promote sodium loss) o Increase risk of lithium toxicity NSAIDS o Can increase lithium levels by as much as 60% o If needed, aspirin would be the best choice Anticholinergic Drugs (cause urinary retention) o Can result in considerable discomfort (urine retention from one & polyuria from another)

VALPROIC ACID (Depakote)

Anticonvulsant/Antiepileptic Works faster and has a higher therapeutic index Because of its rapid onset, efficacy, and safety, Valproic acid has become a first-line treatment Increases risk of suicide Target plasma levels 50-120 ug/mL Therapeutic Use: Can control symptoms in acute manic episodes Can proved prophylaxis against recurrent episodes of mania and depression Adverse Effects: Sedation Nausea, vomiting, diarrhea, indigestion are common Weight gain Tremor Hepatotoxicity Hair loss Teratogen o Should not be used in pregnancy Can cause serious toxicity o Greatest concern:

Pharmacology: Unit Three Study Guide Rare cases of thrombocytopenia Pancreatitis Liver failure All require immediate withdrawal

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Chapter 34: Anxiety & Insomnia Treatment

FLUMAZENIL (Romazicon) Competitive benzodiazepine receptor antagonist Can reverse sedative effects of benzodiazepines but may not reverse respiratory depression o Benzodiazepines (sedatives)---example, Xanax Treat: Anxiety Insomnia

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Seizure disorders Muscle spasms Panic disorder Alcohol withdrawal Adverse: CNS depression Respiratory depression Toxicity (Overdose): Rarely serious Drowsiness, lethargy & confusion Seriousness increases when used with other drugs Oral: rare; drowsiness, lethargy, and confusion IV: profound hypotension, respiratory arrest cardiac arrest Therapeutic Uses: Benzodiazepine overdose Reversing effects of benzodiazepines following general anesthesia Adverse Effects: Precipitation of convulsions o Likely in patients taking benzodiazepines to treat epilepsy o & likely in patients who are physically dependent on benzodiazepines Contraindications: Do not give with certain benzodiazepines such as: o Life threatening disorder treated with benzodiazepines: Status Epilepticus patients Increased cranial pressure