2. MODULE 10 Pharmacology II

3. 2 Lifespan Considerations  Pregnant Women If possible, drug therapy should be delayed until after the first trimester, especially when there is danger of drug-induced developmental defects. Potential fetal risks must be compared to maternal benefits when drug therapy is required. Minimum therapeutic dose should be used for as short a time period as possible.

4. 3 Lifespan Considerations (cont’d)  Pregnant Women FDA Pregnancy Categories:  Drugs in categories A and B most likely carry little or no risk to the fetus.  Drugs in categories C and D most likely carry some risk to the fetus.  Drugs in category X are contraindicated during pregnancy.

5. 4 Lifespan Considerations (cont’d)  Pregnant Women  There are certain situations that require judicious use of drugs during pregnancy: Hypertension Epilepsy Diabetes Infections that could seriously endanger the mother and fetus

6. 5 Lifespan Considerations (cont’d)  Breast-feeding Women Many drugs cross from the mother’s circulation into breast milk and subsequently to the infant, although in small amounts because this is not the primary excretion route. Again, the risk to benefit ratio must be evaluated.

7. 6 Lifespan Considerations (cont’d)  Children Parent is important source of:  Information about the child  Source of comfort for the child  Partner with the health care team during drug therapy. Should not be used to refer to a patient under 1 year of age.

8. 7 Lifespan Considerations (cont’d)  Children Differences in Physiology and Pharmacokinetics  Immaturity of organs most responsible  Anatomic structures and physiologic systems and functions are still in the process of developing

9. 8 Lifespan Considerations (cont’d)  Children Pharmacodynamics (Drug Actions)  Some drugs may be more toxic in children and some less.  More toxic – Phenobarbital, morphine, ASA  Same – Atropine, codeine, digoxin  Contraindicated – tetracycline (discolor teeth), corticosteroids (may suppress growth) Fluoroquinolone antibiotics (may damage cartilage leading to gait deformities)  Some tissues may be more sensitive – smaller doses

10. 9 Lifespan Considerations (cont’d)  Children - Kid Facts Safe, appropriate drug therapy must reflect the differences between adults and children. The child’s stage of growth and development must be considered when assessing core patient variables and the interaction of core drug knowledge and core patient variables. Pediatric drug dosages must be accurate to reduce risk of adverse effects and prevent over dosage.

11. 10 Lifespan Considerations (cont’d)  Children - Drug Administration Choice of appropriate route and/or site of drug administration will vary by the child’s age and size and the drug. Special techniques may be needed to minimize traumatic effects to the child:  EMLA cream can be used to numb an area prior to an injection.  A popsicle or ice chips can be used to numb taste buds before unpleasant-tasting oral drugs.  Do not mix drug therapy into infant formula.

12. 11 Lifespan Considerations (cont’d)  Children – Nursing Responsiblities Education about medications should be provided for the patient, at an appropriate developmental level, and to the family. Implement the “6 Rights.” It may often be necessary for 2 nurses to check the medication(s). Check agency policy.

13. 12 Lifespan Considerations (cont’d)  Older adults/Geriatric Considerations Share common age-related changes and risk factors that alter drug administration, dosage and expected response to drug therapy. All pharmacokinetic processes are altered, placing older adults at higher risk for adverse drug effects.

14. 13 Lifespan Considerations (cont’d)  Geriatric Considerations Pharmacokinetics: Alterations in absorption are more likely caused by disease processes. Distribution is altered because of:  Decreased body mass  Reduced levels of plasma albumin  Less effective blood-brain barrier Hepatic metabolism is slowed. Renal efficiency is decreased:  Serum creatinine levels will remain normal even though kidney function is impaired.

15. 14 Lifespan Considerations (cont’d)  Geriatric Considerations- Pharmacodynamic Changes Receptor site changes. Blood-brain barrier allows more drug to enter the brain. Normal aging-related decline in organ or system function occurs.

16. 15 Lifespan Considerations (cont’d) Geriatric Considerations o Polypharmacy  May see multiple MDs for various illnesses and all may prescribe meds.  Consume approx 32% of all R x drugs and 40% over the counter (OTC) drugs  Most common Prescriptions – antihypertensives, insulin, beta blockers, digitalis, diuretics, potassium (K) supplements  Most common OTC’s – analgesics, laxatives, nonsteroidal anti-inflammatory drugs (NSAIDS)

17. 16 Lifespan Considerations (cont’d) Geriatric Considerations  Nonadherence – Lack of knowledge or incomplete knowledge leads to misunderstanding about medication regime.  Lifestyle – Choices may have to be made between food, rent and purchase of medications.

18. 17 Lifespan Considerations (cont’d)  Geriatric Considerations: Simplify the therapeutic regimen. Give memory aids (if necessary). Give written instructions. Determine financial access to drug therapies. Assess cultural barriers. Titrate the dose upward slowly to minimize adverse effects.

19. 18 Cultural Considerations in Drug Therapy  The Law of Cultural Diversity Each patient needs to be considered an individual, regardless of cultural, ethnic or religious beliefs. Although members of a culture share certain beliefs and practices, individual variation will still occur. Many cultural groups in the U. S. have beliefs that reflect both their original ethnic culture and the dominant culture of the United States.

20. 19 Ethnic Considerations in Drug Therapy  Drug polymorphism Critical in understanding a patient’s response to drug therapy May explain many adverse and idiosyncratic reactions Refers to how individuals metabolize differently Looks at genetics that often have a common basis in ethnic background Opens up a new field of study in pharmacology that has been lacking for years due to societal factors  Examples: Why does the African-American respond differently to antihypertensives, the Chinese patient require lower doses of benzodiazepines, the Caucasian respond differently to some pain medications?

21. 20 Ethics and Drug Therapy Nurse’s responsibility is to always be a patient advocate and remain nonjudgmental.  ANA Code of Ethics  Canadian Nurses Association Code of Ethics  Various Nurse Practice Acts All share the framework for the professional practice of nursing. All believe that, professionally, the nurse provides safe nursing care to patients regardless of the group, community, ethnicity or culture. Nursing does not impose values or standards on the patient. Nurses assist the patient and family in facing decisions regarding health care.

22. 21 Botanical Dietary Supplements  For a complete list of botanical dietary supplements fact sheets, (National Institutes of Health), see : http://www.ods.od.nih.gov/Health_I nformation/Botanical_Supplements. aspx http://www.ods.od.nih.gov/Health_I nformation/Botanical_Supplements. aspx

23. Opioid & Non-Opioid Analgesics Aspirin NSAIDs COX-2 inhibitor Acetaminophen Narcotics The 5 th Vital Sign Pain

24. 23 Analgesics Definition of an analgesic: “Medications that relieve pain without causing loss of consciousness” Pain is a subjective experience. The nurse must believe the patient. PET scans now can visualize brain’s responses to many kinds of pain.

25. 24 Proposed Pain Pathway Nociceptors (free nerve endings) Afferent stimulation of sensory “A” or “C”fibers Dorsal horn spinal cord – the location of the “gate” 3 major brain pathways: Spinothalamic, spinoreticular, spinomesencephalic Release of peptide substance P from unmylinated “C” fibers in dorsal horn (Multiple neurotransmitters released)

26. 25 Pathophysiological  Nociceptive pain  Neuropathic pain  Psychogenic pain The type of pain determines the analgesic. Neuropathic pain is often treated with anticonvulsants, tricyclic antidepressants added onto narcotics Many theories of pain transmission are not completely understood.

27. 26 Pain Transmission These techniques also allow some non- pharmacological relief from pain:, Massage, Deep pressure, Distraction, Relaxation, Vibration Can be used as independent nursing intervention after assessment The above activate the large “A” fibers.

28. 27 Factors Influencing Pain Perception  Type of pain Acute vs. chronic Visceral vs. cutaneous Nociceptive, neuropathic, psychogenic  Intensity of pain & type of injury  Inflammatory process  Degree of Anxiety

29. 28 Factors Influencing Pain Perception  Sensory input  Social support  Fatigue  Age, sex & culture  Memory & information processing  Level of consciousness  Type, amount, route of analgesic

30. 29 Drugs Influencing Pain Perception  Narcotics (opioids) modify pain perception via Central Nervous System (CNS) & dorsal horn via binding to Mu, kappa & delta opioid receptors & inhibiting substance “P” and glutamate (an excitorary neurotransmitter). Alter perception of pain via opiate receptors, and alter psychological responses via brain.  Other mechanisms to alter pain involve effects on the Autonomic Nervous System (ANS), skeletal muscle response & diagnosis.

31. 30 Drugs Influencing Pain Perception  Nonopiate analgesics (salicylates, NSAIDS, etc.)  Control pain impulses in the periphery  Often involving the Arachidonic acid pathway responsible for inflammation and an immune response

32. 31 Some Pain Mysteries  Phantom pain  Referred pain  Pain experienced after cordectomy  Placebo response

33. 32 Prostaglandins  Associated with inflammation  Involved in the temperature set point of the hypothalamus  Sensitize pain receptors to mechanical and chemical stimulation  Found in many cells and body processes

34. 33 Leukotrines  Arachidonic acid metabolites  Mediators in inflammation  Synthesized when tissue injury occurs  May be involved in rheumatoid arthritis, asthma and system wide anaphylaxis  Bronchoconstrictor and vasodilator

35. 34 Synthesis of Prostaglandins Arachidonic acid Lipoxygenase Cyclooxygenase Leukotrines Prostaglandins enzymes

36. 35 TWO Enzyme FORMS CYCLOOXYGENASE-1 & CYLOOXYGENASE- 2 COX-1 COX-2 Prostaglandins Protects stomach lining Inflammation Pain

37. 36 Peripheral control of pain Release of prostaglandin inflammation & pain Prostaglandins mediate pain and swelling by triggering vasodilatation. Prostaglandins are synthesized by the enzyme cyclooxygenase which breaks down arachidonic acid to synthesize prostaglandin. This is the basic method of action of aspirin and NSAIDs.

38. 37 Inhibition of Cox-1 & Cox-2  Inhibition of both Cox-1 & Cox-2 will be effective as an:  ANALGESIC  ANTIPYRETIC  ANTI-INFLAMMATORY AGENT  AGENT TO DECREASE PLATLET AGGREGATION  Also associated with stomach damage due to COX-1 inhibition

39. 38 Aspirin  Inhibits both Cox-1 and Cox-2  Is used as a analgesic  Is used as a anti-inflammatory agent  Is used as a antipyretic  But can cause stomach damage  Is used to prevent coronary heart disease (CHD) via platelet aggregation  In what other cases should aspirin NOT be used?

40. 39 Aspirin adverse effects & interactions  Tinnitus – sign of toxicity  Dyspepsia  Highly protein bound so it displaces other medications: oral anticoagulants, oral hypoglycemics, some anticonvulsives.  G.I. Bleeding increased with glucocorticoids, alcohol  High doses may cause excessive bruising  Highly lethal if taken in overdose - No known antidote  Caution with asthmatic patients (may have aspirin allergy also)

41. 40 Hold giving Aspirin

42. 41 Children under 15 with viral infection Reye’s syndrome is associated with aspirin use.

43. 42 NSAIDS Non-Steroidal Anti-Inflammatory Drug  First line treatment for inflammation  Both COX-1 & COX-2 inhibitors  Mild to moderate pain of various types  Good for dysmenorrhea  Antipyretic  Reversibly inhibit platelet aggregation (less than aspirin because aspirin has irreversible inhibition)  INHIBIT THE PRODUCTION OF PROSTAGLANDINS THAT MEDIATE PAIN AND INFLAMMATION

44. 43 Side effects & Interactions of NSAIDs  G.I. Bleeding, dyspepsia  Liver toxicity or renal damage with large doses, prolonged use  Highly bound to plasma protein so displace other medications, leading to exacerbation of their side effects These adverse effects can occur with oral or parenteral routes and even if enteric coated.

45. 44 Don’t give aspirin or NSAIDs Patients with ulcers Patients going to surgery Patients with an allergy to aspirin Alcoholic patients When patient is nauseated or vomiting Patients on glucocorticoids (without M.D. order) Patients taking ACEIs (Angiotensin Converting Enzyme Inhibitors) Caution with NSAIDs in patients with CHF

46. 45 COX-2 INHIBITOR  Celecoxib (Celebrex) Approved for osteoarthritis and rheumatoid arthritis  Acute pain & dysmenorrhea  Do not give if sulfa allergy Has anti-inflammatory properties Only COX-2 inhibitor currently available

47. 46 Acetaminophen (Tylenol)  Is a very weak inhibitor of both Cox-1 and Cox-2  Is used as an antipyretic  Is used as an analgesic  Can not be used as an anti-inflammatory agent  Does not stop platelet aggregation  May work by inhibiting prostaglandin synthesis in the CNS

48. 47 Acetaminophen  Is the drug of choice for mild to moderate pain  Is often combined with opioids to treat moderate to severe pain  Will cause liver failure in LARGE doses or prolonged use (2.4 to 4 grams/day)  Liver failure with alcohol due to metabolic pathways  Ceiling effect  Overdose is difficult to treat - use acetylcysteine

49. 48 Acetaminophen  Young children, older adults, daily drinkers of 3 or more alcoholic beverages and those with kidney or liver disease are at risk for accidental acetaminophen poisoning  Acetaminophen found in many pharmaceuticals Vicodin ES (5 tabs Q. D. = 4 gm) Tylenol extra-strength (8 tabs = 4 gm) What other OTC medications might contain acetaminophen?

50. 49 Neuropathic Pain  Difficult to treat  Use of opioids does not completely control pain  Usually add on another medication from a different class (co-analgesic agents) immipramine (Tofranil) Tricyclic antidepressant -TCA gabapentin (Neurontin) Anticonvulsant Duloxetine (Cymbalta) newest SNRI (serotonin norephinephrine reuptake inhibitor) - also used for depression  Effexor is another medication in this class New pregabalin (Lyrica) anticonvulsant - alpha2 - delta ligand + other medication classes

51. 50 Natural, synthetic and semisynthetic ALL COMPARED TO MORPHINE

52. 51 Opiates Narcotics: Very strong pain relievers Opiates: Pain relievers that contain opium, derived from opium, or are chemically related to opium

53. 52 Pain Transmission o Body has endogenous neurotransmitters o Endogenous neurotransmitters are: enkephalins & endorphins (morphine-like peptides) produced by body to fight pain o Opiates bind to these natural endogenous opioid receptors o Inhibit substance P in dorsal horn of spinal cord

54. 53 Chemical Classification of Opioids CHEMICAL CATEGORY & examples Natural: codeine, morphine Semi-synthetic: hydrocodone (Vicodin) oxycodone + salicylate Synthetic: meperdine (Demerol) can be neurotoxic and cause confusion/seizure - NEVER give to patients with Parkinson’s Disease butalbital (Fiorinal) (Percodan)

55. 54 Opiates u Three classifications based on their actions: agonist agonist-antagonist partial agonist

56. 55 CNS Opiate effects/uses  Analgesia  Cough suppression  Euphoria  Reduces fear/anxiety  Raises pain threshold (decreased awareness)  Sleep induction  Respiratory depression  Pupil constriction (miosis)  Nausea and vomiting

57. 56 Peripheral Nervous System OPIATE Effects  Constipation  Urinary retention  Diaphoresis & flushing  Hypotension due to vasodilatation

58. 57 Narcotic analgesic routes  PCA example Morphine (acute pain)  Transdermal example Duragesic patch (fentanyl) (chronic pain)  Epidural example fentanyl or morphine  Oral example MS Contin (morphine)(chronic pain)  I.M injections example meperidine (acute pain) (Demerol). Do not give for more than a day – neurotoxic, lowers seizure threshold, not first line agent. Metabolite normeperidine neurotoxic and may cause psychosis in the elderly patient.

59. 58 Gold Standard is Morphine No ceiling effect ADVANTAGES  Decreased awareness  Decreased anxiety  Increased sleep  Decreased pain perception DISADVANTAGES  Hypotension  Constipation  Nausea  Respiratory depression  Itching Secondary effects of cough suppression and constipation are used therapeutically

60. 59 Oral Morphine examples  Oxycontin (oxycodone)  MS Contin (morphine)  Kadian (morphine)  Oramorph SR (morphine)  Avinza (morphine) New Q day dosing (Do not crush, chew or dissolve the caps or could deliver fatal dose) If can not swallow, O.K. to open & sprinkle the beads on applesauce

61. 60 Mixed agonist-antagonists  Pentazocine (Talwin)  Buprenorphine (Bupreneax)  Butorphanol (Stadol)  Ultram (Tramadol) - mechanism of action not clearly understood, weak bond to opioid receptors & inhibits reuptake of norepinephrine (NE) & serotonin (5-HT) may cause chemical dependency  These medications are rarely used DO NOT GIVE THESE MEDICATIONS TO PATIENTS WHO ARE DEPENDENT ON NARCOTICS.

62. 61 Opiate Antagonists/blockers  Naloxone (narcan) opiate antagonist [competitive]  Naltrexone (ReVia) now used to help alcoholics stay abstinent

63. 62 Opiates Opioid Tolerance: a common physiologic result of chronic opioid treatment means larger doses of opioids are required to maintain the same level of analgesia

64. 63 Opiates Physical Dependence F The physiologic adaptation of the body to the presence of an opioid Opioid tolerance and physical dependence are expected with long-term opioid treatment and should not be confused with psychological dependence [addiction].

65. 64 Opiates Psychological Dependence [addiction] A pattern of compulsive drug use characterized by a continued craving for an opioid and the need to use the opioid for effects other than pain relief

66. 65 Opiates Misunderstanding these terms leads to ineffective pain management and contributes to the problem of under treatment.

67. 66 Opiates Physical dependence on opioids is known when the opioid is abruptly discontinued or when a opioid antagonist is administered.  narcotic withdrawal  opioid abstinence syndrome

68. 67 Opiates  Narcotic withdrawal  Opioid abstinence syndrome Manifested as: (flu-like symptoms) Anxiety, irritability, chills and hot flashes, joint pain, lacrimation, rhinorrhea, diaphoresis, nausea, vomiting, abdominal cramps and diarrhea

69. 68 Drugs Affecting the Autonomic Nervous System

70. 69 Photo Source: National Institutes of Health, Public Domain, http://catalog.niddk.nih.gov/ImageL ibrary/searchresults.cfm http://catalog.niddk.nih.gov/ImageL ibrary/searchresults.cfm

71. 70 Sympathetic NS FIGHTFLIGHT&

72. 71 Parasympathetic N.S. BREED&FEED

73. 72 Adrenergic Drugs  Mechanism of action Mimic Sympathetic Nervous System (N.S.) Have sympathomimetic properties Have sympatholytic action also since they oppose the parasympathic N.S. Catecholimines are neurotransmitters involved in adrenergic system  DA (dopamine) NE (norepinephrine) E (epinephrine)  Energizing neurotransmitters Direct-acting, indirect acting and mixed adrenergics

74. 73 Adrenergic Drugs (cont’d)  Indications Bronchodilation (albuterol) Cardiac stimulation, alpha1, beta 1, beta 2, increase blood pressure (dopamine, isoproterenol) Mental alertness & wakefulness (monafnil) Appetite suppression (adipex) Decongestion (pseudoephedrine) Open angle glaucoma (dipivefrin) produces mydriasis = pupil dilation ADHD (methylphenidate)  Adverse effects Tachycardia, hypertension, anxiety, insomnia, psychological dependency

75. 74 Alpha -Adrenergic Blocking Drugs  Drug examples: ergotamine tartrate (Egostat), Phenoxybenzamine, phentolamine (Regitine)  Indications: Raynaud’s disase, hypertension secondary to pheochromocytoma, extravasation of vasopressors, vascular headaches  Adverse effects: nasal congestion, orthostatic hypotension, tachycardia, dizziness, (Gastrointestinal) GI irritation, and miosis. Ergotamine may cause chronic poisoning.

76. 75 Beta-Adrenergic Blocking Drugs  Drug examples: selective for beta 1 receptors - atenolol, metoprolol Non-selective for beta 1 & 2 receptors - propranolol (contraindicated in pt. with COPD, asthma, depression)  Indications: treat hypertension, angina, tachyarrhythmias, CHF, Post MI because they are cardio- cardio-protective  Contraindications: bradyarrhythmias, bronchospasm, heart blocks  Adverse effects: arrhythmias, bradycardia, bronchospasm, nausea, vomiting, diarrhea, increased sensitivity to cold, rebound HTN if stopped abruptly

77. 76 Cholinergic Drugs  cholinergics  cholinergic agonists  parasympathomimetics  Sympatholytics  All are terms that refer to drugs that stimulate the Parasympathic Nervous System  MIMIC ACETYLCHOLINE  Cholinergic drugs

78. 77 Cholinergic Drugs  Cholinergic receptors [two types]  Based on location & their action  Nicotinic {N} &  Muscarinic {M}

79. 78 Drug & Side Effects of Cholinergics Salivation Lacrimation Urinary incontinence Diarrhea Gastrointestinal cramps Emesis (Also bronchospasm, decreased intra ocular pressure (IOP), decreased heart rate, increased bronchial secretions, miotic, sweating)

80. 79 Cholinergic Drugs  Indications  Direct- acting Cholinergic agonists – used to treat open angle glaucoma and dry eyes and to stimulate bladder  Indirect-acting Cholinesterase inhibitors (reversible) – for Alzheimer’s & to treat myasthenia gravis (MG) and open angle glaucoma not responsive to other agents – prevents postoperative paralytic ileus  Drug examples – bethanechol, pilocarpine Bethanechol – treat nonobstructive urine retention, neurogenic bladder, adynamic ileus Pilocarpine – treat glaucoma  Contraindications Possible urinary or GI obstruction and pregnancy

81. 80 Cholinergic-blocking drugs  Class of drugs that block or inhibit the actions of Acetylcholine in the Parasympathetic Nervous System  anticholinergics  parasympatholytics  antimuscarinic agents

82. 81 Cholinergic-blocking drugs (also called anti-cholinergic drugs)  Inhibit nicotinic {N} or muscarinic {M} receptors  Anticholinergic effects are the result of muscarinic blockage, primarily on the post synaptic receptor of the Parasympathetic Nervous System.  There are medications that are designed for their anticholinergic effect.  Many medications have anticholinergic side effects that are NOT wanted.

83. 82 Cholinergic-blocking drugs  Atropine Preop for secretion control, therapeutic anticholinergic effect, Bradycardia, anticholinesterase effect for insecticide poisioning CNS excitation  Dicyclomine (Bentyl) Irritable bowel syndrome (IBS)  Propantheline bromide (Pro-Banthine) Adjunct in Treatment of peptic ulcer, IBS, pancreatitis

84. 83 Cholinergic-blocking drugs  Glycopyrrolate (Robinul) Control of secretions intraoperative, preop control of secretions, preop for electro convulsive therapy (ECT)  Scopolamine (Transderm-Scop) Prevents motion sickness  Orphendrine (Norflex) A central acting anticholinergic muscle relaxant

85. 84 Therapeutic effects of Anticholinergics  Tolterodine (Detrol) & Trospium Chloride (Sanctura) new Overactive bladder  Benztropine (Cogentin) Parkinson’s DZ and EPS (neurological side effects) from antipsychotics  Ipratropium Bromide (Atrovent) Inhaled drug used to treat COPD, asthma, little systemic effect because inhaled

86. 85 Drug Interactions ADDITIVE EFFECTS WITH: antihistamines, anticholinergics, phenothiazines,tricyclic antidepressants, MAOI’s (monoamine oxidase inhibitor) Antihistamines have anticholinergic effects This could cause confusion & or psychosis in the ELDERLY PATIENT. Contraindicated in: glaucoma, benign prostatic hypertrophy (BPH), Cardiac disease and obstructive bowl & asthma unless inhaled

87. 86 Secondary effects/Side effects (anticholinergic)  Xerotomia (dry mouth)  Blurred vision  Urinary retention  Decreased perspiration  Constipation  Tachycardia  These are common in many of the psychoactive drugs

88. 87 Neuromuscular Blocking Agents Prevent nerve transmission in certain muscles, leading to paralysis of the muscle at neuromuscular junction by binding to Ach receptor Indications – Maintains controlled ventilation during mechanical ventilation or during endotracheal intubation Contraindications – Drug allergy, previous history of malignant hypertension, penetrating eye injuries and narrow-angle glaucoma Side/Adverse Effects – Hypokalemia, dysrhythmias, fasciculations, muscle pain, increased intraocular and intracranial pressure and apnea

89. 88 CNS Depressants Hypnotics and Sedatives  Classified into barbiturates, benzodiazepines and miscellaneous agents  Act primarily on the brainstem; sedative and hypnotic effects are dose related.

90. 89 Barbiturates  Habit forming and have narrow therapeutic index  Contraindications –pregnancy, significant respiratory difficulties and severe liver disease  Side Effects – Drowsiness, lethargy, dizziness, hangover, and paradoxical restlessness or excitement  Adverse Effects – Vasodilatation, hypotension blood dyscrasias, hypersensitivity reactions  Interactions – synergistic with other Central Nervous System (CNS) depressants  Can be lethal in overdose  Can have lethal consequences of uncontrolled withdrawal

91. 90  Short-term treatment of insomnia (rare)  Sedation in lower doses  Ultra-short acting for anesthesia induction  Pre-op medication  Epilepsy, mainly status, but the long-acting Phenobarbital can be used as anticonvulsant - at small doses does not produce sedation, but seizure activity  Not used as often today because of newer agents for sleep, seizure and anxiety Barbiturates Uses

92. 91 Action and General Characteristics of Benzodiazepines  Specific for cerebral cortex and limbic system  Also called anxiolytics  Increase action of GABA + other inhibitory neurotransmitters  Highly lipid soluble to facilitate crossing into CNS  Highly bound to plasma protein  Metabolized by the liver, some with long duration of action due to active metabolites

93. 92 Benzodiazepine Uses  Anxiolytics – examples: alprazolam (Xanax)  Anticonvulsants – examples: clonazepam (Klonopin) and diazepam (Valium)  Anesthesia induction – examples: midazolam (Versed), diazepam (Valium)  Muscle Relaxant – example: diazepam (Valium)  Withdrawal from alcohol – example: chlordiazepoxide (Librium), diazepam (Valium)  Hypnotics – examples: flurazepam (Dalmane), and temazepam (Restoril) do not depress REM sleep; but prevent deep sleep (not natural)

94. 93 Secondary/side effects of Benzodiazipines  Daytime sedation  Ataxia  Dizziness  Anterograde amnesia  Idiosyncratic paradoxical excitement  SELDOM FATAL IF TAKEN ALONE  Can be dangerous for the elderly because of fall potential

95. 94 Centrally Acting Muscle Relaxants  Primarily used for the relief of painful musculoskeletal conditions–muscle spasms and spasticity.  Side Effects – Euphoria, lightheadedness, dizziness, drowsiness, fatigue and muscle weakness - usually short-lived  Adverse Effects – GI upset, headache, slurred speech, constipation, sexual difficulties in men, hypotension, tachycardia and weight gain

96. 95 Anticonvulsant Medication  Congenital abnormalities  Metabolic disorders – hypocalcemia  Trauma – accidents  Tumors – brain plus status post craniotomy  Vascular diseases – stroke  Degenerative disorders- Alzheimer’s  Infectious diseases – meningitis, AIDS  Fever & toxins  Medications – example = antipsychotics  Alcohol withdrawal + hypomagnesemia Causes of Seizure

97. 96 Types of Seizure according to International League Against Epilepsy Partial Seizures: focal area of brain initiates seizure Simple partial: focal symptoms, aura, conscious Complex partial: simple then impairment in consciousness Generalized partial: spread to both hemispheres

98. 97 Types of Seizure  Generalized Seizures: both hemispheres usually effected, unconscious  Absence seizures: impairment of consciousness, autonomic components, usually in children/adolescence  Tonic-clonic: (grand mal) tonic is muscle stiffing, clonic is jerking  Monoclonic: single or multiple jerks

99. 98 Status Epilepticus  Single seizure lasting for 20 minutes or longer  Or recurrent generalized seizures without regaining of consciousness in between each seizure episode  Considered a medical emergency

100. 99 Possible Action of Anticonvulsants  Pharmacologically distinct action for each group of anticonvulsants is PROPOSED Many mediate actions by limiting discharge from a focal point – surrounding it Others elevate seizure threshold through neurotransmitters or ions

101. 100 Possible General Mode of Action Increase concentration of GABA by Blocking reuptake into glia & nerve endings Inhibiting enzymes that catabolize GABA Facilitating GABA & other inhibitory receptors

102. 101 Mode of Action other than potentiation of GABA Suppression of calcium influx Inhibition of voltage-sensitive sodium channels Binding to the amino acid glycine (neurotransmitter & inhibitory A.A.) at receptor site Decreasing metabolism of glutamate EXACT MODE OF ACTION NOT KNOWN Agent chosen depends on type of seizure, age, sex, pharmacologic properties, side effects and cost

103. 102 Anticonvulsants FIRST LINE AGENTS - USED AS MONOTHERAPY for Tonic Clonic Seizures  Phenytoin ( Dilantin)  Carbamazepine (Tegretol)  Valproic acid (Depakene or Depakote)  Primidone (Mysoline)  Phenobarbital

104. 103 Anticonvulsants  FIRST LINE AGENTS USED AS MONOTHERAPY for Partial Seizure  Carbamazepine (Tegretol)  Valproic Acid (Depakene or Depakote)  Lamotrigine (Lamictal)  Topiramate (Topamax)*  Gabapentin (Neurontin)* * Not FDA approved for monotherapy, but studies support

105. 104 Anti-convulsant Drugs(Antiepilieptics)  Indications: Prevention and control of seizures  Main adverse effects of most anticonvulsants are mental confusion and drowsiness  Interactions of many older meds: Potentiate CNS depressants and alcohol Concurrent use with tricyclic antidepressants or phenothaizines lowers the seizure threshold and decreases the effectiveness of anticonvulsants Many drugs alter hepatic metabolism of anticonvulsants leading to decreased serum levels and loss of seizure control and toxicity Phenytoin’s cytochrome P-450 enymatic reaction inhibits atazanavir’s action (depakote becomes the drug of choice in this example).

106. 105 Anti-convulsant Drugs  Hydantoins  Drug examples: Mephenytoin, phenytoin (Dilantin) Indications: treat tonic-clonic (grand mal) seizures and complex partial seizures, arrhythmias, and painful condition such as trigeminal neuralgia Adverse effects: (long term) gingival hyperplasia, liver function abnormalities, blood dyscrasias, (toxicity) as evidenced by diplopia, nystagmus, ataxia, and drowsiness Caution driving or operating equipment because of mental confusion

107. 106 Anti-convulsant Drugs  Tell patient to use alternate birth control if on the pill  Supplement with Vitamin D, Calcium and folic acid  Interactions with Calcium Channel Blockers, Antipsychotics and steroids  P-450 = many interactions

108. 107 Anti-convulsant Drugs  Interactions… Oral tube feedings with osmolite or isocal may interfere with absorption of oral dilantin diminishing drug’s effectiveness IV dilantin precipitates with D5W.  Characteristics of fosphenytoin (Cerebyx) – preferred over IV Dilantin  Prodrug of phenytoin  Rapidly converted by blood and liver enzymes to phenytoin (Dilantin)  Given I.V. only

109. 108 Anti-convulsant Drugs Barbiturates and deoxybarbiturates Examples: Mephobarbital, phenobarbital, primidone Indications:  Treat tonic-clonic seizures, partial seizures and insomnia  Used as adjuncts to anesthesia Adverse effects: Dizziness, drowsiness, hypotension, respiratory depression with high doses Interactions: Drugs decreases serum dilantin level when used concurrently Primidone plus phenobarbital may cause phenobarbital toxicity

110. 109 Anti-convulsant Drugs Benzodiazepines Examples: clonazepam (Klonopin) Diazepam (Valium) Indications: treat absence seizures, status epilepticus, anxiety and skeletal muscle spasms. Adverse effects: ataxia, drug dependence, respiratory and cardiovascular depression

111. 110 Valproic acid (Depakene) Divalproex (Depakote)  Low side effect profile, well tolerated  May cause liver failure (rare) in first 6 months of therapy  Lethargy, muscle weakness, sedation  Leukopenia  Ataxia  Depakene causes nausea/vomiting  Interacts with many other anticonvulsants

112. 111 Nursing Considerations  Good for generalized and partial seizure  Monitor blood levels  Monitor CBC and liver function tests  Highly protein bound, do not take with NSAIDs, aspirin & other drugs that alter coagulation  Potentiates CNS depressants  Reassure patient of alopecia, hair will re- grow  Used as mood stabilizer for bipolar disorder and has FDA approval for this

113. 112 Carbamazepine (Tegretol)  Blood dyscrasias * Notify health care provider  Liver toxicity  Rash  Drowsiness  Low side effect profile – well tolerated * Immediately discontinue & switch to another agent

114. 113 Nursing Considerations  Low behavioral and toxicologic profile  Good for both generalized and partial seizures  Autoinduction – dosage needs monitoring via blood levels, decreases after initial doses  Advise alternate birth control if on pill  Monitor CBC for bone marrow depression  Used “off label” as mood stabilizer for bipolar disorder

115. 114 Lamotrigine (Lamictal)  Monotherapy in partial seizures  Well tolerated  No weight gain, no sedation  Rare, but can be associated with life threatening rash (Stevens-Johnson syndrome)  Nausea, vomiting, weight loss (rare)  Dizziness, ataxia

116. 115 Nursing Considerations  Discontinue at once if rash/inform health care provider  Nurse asks patient every visit  Taper on very slowly to avoid rash – 25 mg Q 2 weeks until 200 mg  No blood levels required  Note many anticonvulsants raise or lower plasma levels  Monitor for adverse reactions if not monotherapy  May reduce effectiveness of estrogen  Used for mood disorder in bipolar, good for depressive side, and has FDA approval for this

117. 116 Topiramate (Topamax)  Adjunctive therapy in partial and generalized seizures (studies support monotherapy)  Well tolerated  Fatigue  Confusion  Difficulty concentrating, speech problems (unable to recall words)  Nausea  Weight loss  No blood levels required

118. 117 Gabapentin (Neurontin)  Adjunct therapy for partial seizures (studies demonstrate monotherapy)  Excellent side effect profile  Main problem is initial sedation, ataxia  Not metabolized by liver so no interactions with other anticonvulsants  Used extensively for neurogenic pain  Excellent for elderly and those on poly drugs  No blood levels required  Used “off label” as mood stabilizer for bipolar disorder but no FDA approval for this

119. 118 Other uses for Anticonvulsants  Mood stabilizers  Migraine headache  Neurological pain  Chronic pain syndrome  Anxiolytics

120. 119 Anti-Parkinsonian Drugs Groups of Drugs Used  Antidyskinetic Drugs or anticholinergics  Antihistamines (have anticholinergic effects)  Dopaminergics Dopaminergic agonists MAOI-B (monoamine oxidase inhibitor) COMT Inhibitors (catechol-0-methyl-transferase)

121. 120 Anti-Parkinsonian Drugs  Dopaminergic agonists are mainstay Contraindications and precautions:  Used with caution in patients with residual arrhythmias after MI, history of peptic ulcer, psychosis or seizure disorders  Contraindicated with narrow angle glaucoma  Used with caution for patients with bronchial asthma, emphysema, or severe cardiovascular, pulmonary, renal, hepatic or endocrine disease Adverse Effects:  Dizziness, confusion, mood changes, orthostatic hypotension, nausea, vomiting, hallucinations

122. 121 Anti-Parkinsonian Drugs  General Information Mechanism of of action: Restore the natural balance of the neurotransmitters in CNS to decrease S/S of Parkinson’s Disease. Imbalance between Achetylcholine (ACH) and Dopamine. Too much ACH and too little dopamine. Meds correct this.  Dopaminergic agonists Mechanism of Action is to increase the amount of DA available in the CNS or enhance the neurotransmission of Dopamine Medication examples:  Levodopa restores dopamine levels  Amantadine increases the amount of dopamine in the brain  Pramipexole (Mirapex) – newer DA receptor agonist  Ropinirole (Requip) – newer DA receptor agonist

123. 122 Anti-Parkinsonian Drugs anticholinergics  Drug examples : Benztropine (Cogentin) Trihexyphenidyl (Artane) Procyclidine (Kemadrin)  Indications: Bradyarrhythmias, dyskinesia, parkinsonism, peptic ulcer and bowel spasms Nausea, vomiting, induce mydriasis, decrease salivation and bronchial secretions before surgery  Contraindications: Narrow-angle glaucoma, severe hemorrhage, uncontrolled tachycardia, urinary tract/GI obstruction, BPH  Adverse effects: Blurred vision, conjunctivitis, and photophobia, tachycardia, constipation, dry mouth and urinary hesitancy CAN CAUSE PSYCHOTIC CONFUSION IN THE ELDERLY when drugs with anticholinergic effects are combined.

124. 123 Two Newer class to treat Parkinsons  Selegiline (Eldepryl) MAOIB (monoamine oxidase inhibitor – B)  May have neuroprotective effects slowing the progression of the Disease  Tolcapone (Tasmar) & entacapone (Comtan) Catechol O-methyltransferase (COMT) inhibitors = newest class  Not used as monotherapy, but as add on to levadopa to increase its efficacy.  Tasmar has been associated with liver dysfunction.

125. 124 Two classes that reduce dosage of Levadopa  MAOI-B DA in brain by inhibiting its metabolism by MAO. Form “B” metabolizes DA. At oral doses < 10mg Q.D. like MAOI- A so acts more on tyramine NE, E, DA & 5H-T. No food restrictions with low doses. COMT inhibitors work by inhibiting the enzyme catechol- O-methyltransferase the 2nd enzyme involved in the metabolism of levodopa - so increased amount of levodopa available.

126. 125 Wearing off syndrome Doses need to be adjusted upward and downward as adverse mental changes occur or Parkinson’s symptoms worsen. Changing doses is done slowly.

127. 126 Advanced Parkinson’s A new DA agonist Apomorphine (Apokyn) given S.Q. is available for advanced Parkinson’s as a rescue drug for acute rigidity. This is temporary add on, not replacement. N/V. Rx for antiemetic. Not 5-HT3 antagonists like ondansetron (Zofran) because of hypotension. Use trimethobenzamide (Tigan). Why do you NOT want to use prochlorperazine (Compazine)??

128. 127 Drugs used to Treat Alzheimer’s Cholinesterase inhibitors  Increase Acetylcholine (Ach) in key areas of brain (cerebral cortex)  Reversible cholinesterase inhibitors  Used to Treat mild to moderate disease  Do not reverse symptoms; slow progression  Check P450 for drug interactions Examples  Donepezil (Aricept)  Tacrine (Cognex) (1 st, most adverse effects, not used today)  Rivastigmine (Exelon) – newer {may have greater efficiacy}

129. 128 New class to Treat Alzheimer’s  Memantine (Nameda)  Released Jan. 2004 for Treatment of moderate to severe Alzheimer’s Disease  May have more favorable side effect profile than Ach inhibitors  May be possible to combine with ACh inhibitors for better result

130. 129 Drugs Affecting the Cardiovascular and Renal Systems Drugs to Treat: Congestive heart failure Hypertension Angina

131. 130 Inotropic (increase force of contraction) Drugs and Cardiac Glycosides  Indications Used to treat CHF in combination with other medications. Control ventricular rate in atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia  Contraindications and precautions Uncontrolled ventricular arrhythmias, constrictive pericarditis, complete heart block Increased risk of toxicity with hypercalcemia, hypokalemia, hypomagnesemia, hypothyroidism, or renal failure Very narrow therapeutic index Elderly patients more sensitive to toxic drug effects  Adverse effects – bradycardia, fatigue, weakness, nausea, vomiting, diarrhea, visual disturbances Monitor pulse – hold if less than 60/min. apical Do not increase longevity in CHF

132. 131 Inotropic Drugs and Cardiac Glycosides  Interactions K-wasting diuretics and other drugs causing K loss increase risk of toxicity Amiodarone, diflunisal, diltiazem, nifedipine, quinidine, verapamil increase the serum drug level and may cause toxicity Concurrent use of beta adrenergic blocking drugs causes additive bradycardia Antacids, cholestyramine, and colestipol decrease the absorption of cardiac glycosides  Digitalis preparations Examples: Digitoxin (long ½ life –not used often), digoxin Nursing responsibilities  Digoxin excreted unchanged by the kidneys, dosage must be reduce with renal impairment  Monitor serum digoxin levels to prevent toxicity  Digoxin Immune Fab IV to reverse toxicity

133. 132 Antihypertensive Drugs  Antihypertensive drugs Indications  HTN not controlled by life style modifications Classes  Beta-adrenergic blocking drugs, angiotensin- converting enzymes (ACE) Inhibitors, angiotensin- receptor blockers,(ARB’s), calcium channel blockers, alpha 1 blockers, centrally acting alpha 2 agonists, diuretics, peripheral acting vasodilators Contraindications and precautions  Each class has own action, side effects, specific recommendations and adverse reactions

134. 133 Antihypertensive Drugs 2 nd line agent  Peripheral vasodilating drugs Drug examples: hydralazine Mechanism of action: exert direct action on both arteries and veins to decrease peripheral vascular resistance (with beta blockers) Indications: treatment for hypertension and hypertensive crisis Adverse effects: fluid retention, tachycardia, orthostatic hypotension, severe hypotension and nausea Nursing responsibilities  Closely monitor for fluid volume excess  Rarely used

135. 134 Antihypertensive Drugs  ACE Inhibitors (1 st line agent) Drug examples: benazepril, catopril, enalapril, fosinopril, lisinopril Mechanism of action: block conversion of angiotensin I to angiotensin II  Mode of Action Vasodilation due to inhibition of Renin Angiotension Aldosterone system, decreased blood volume due to decreased (Sodium) Na+  Adverse effects: dizziness, light-headedness, fainting, tachycardia, palpitations, rash, proteinuria  Nursing responsibilities Not effective with African Americans Do not give with Na+ sparing diuretics Monitor for dry cough Contraindicated in pregnancy and renal stenosis Not to be given with lithium and caution with NSAIDs  Indications: HTN, CHF, diabetes, Angina

136. 135 Antihypertensive Drugs  Calcium channel blockers (1 st line agent) Drug examples:  Amlodipine, diltiazem, felodipine, verapamil, nifedipine Mechanism of action:  Dilate vessels by blocking the slow channel, preventing calcium from entering the cell Adverse effects:  Grapefruit juice can cause toxic overdose  Dizziness, AV blocks, headache, edema, flushing, nausea, constipation, bradycardia  P-450 interaction with other meds  Do not give with grapefruit juice- can cause toxic overdose Nursing responsibilities  Watch for weight gain if CHF Indications: Angina, arrhythmias, HTN

137. 136 Antihypertensive Drugs  Diuretics – thiazide (1 st line agent) Drug examples: chlorothiazide, hydrochlorothiazide Mechanism of action: inhibit sodium and chloride reabsorption, distal tubule, reduce blood volume Adverse effects:  Fatigue, dizziness, orthostatic hypotension, rash, hypokalemia, hyperglycemia  Indications: 1 st line for HTN, take in the morning  Diuretics – loop Mechanism of action: Loop of Henley, reduce blood volume example: furosemide (Lasix) Adverse effects: electrolytes Indications: CHF

138. 137 Antihypertensive Drugs Selective Beta Blockers – 1 st line agent  Drug examples: Atenolol  Mechanism of action: Selectively block beta 1 receptors in the heart so slows heart rate – chronotropic effect and – inotropic effect  Adverse effects: Bradycardia, rebound HTN if abruptly stopped, fatigue, dizziness, dyspnea  Indications: HTN, Prophylaxis for angina, CHF, post M.I. for cardioprotective effects  Nursing responsibilities: Monitor pulse, watch for drug interactions (CCBs), potentiated by alcohol and other CNS depressants, give cautiously with asthma patients

139. 138 Antihypertensive Drugs  Angiotensin-receptor blockers  Alpha 1 blockers  Centrally acting alpha 2 agonists All 2 nd line agents

140. 139 Antianginal Drugs Mechanism of action:  Reduce myocardial oxygen demand or increase coronary blood supply Indication:  Angina pectoris Contraindications:  Hypotension, uncorrected hypovolemia Adverse effects:  Flushing, headache, orthostatic hypotension Interactions:  Produce additive hypotension when used with alcohol, antihypertensives, beta-adrenergic blocking drugs or calcium channel blocker drugs for erectile dysfunction.

141. 140 Antianginal Drugs  Nitrates Drug examples:  Erythrityl tetranitrate, isosorbide dinitrate (Isordil) Nitroglycerin, Nitro-BID Mechanism of action:  Produce vasodilation. Decrease preload and afterload, and reduce myocardial oxygen consumption Indications:  Management of angina, and chronic anginal attacks Beta Blockers and Calcium Channel Blockers also for long term management

142. 141 Diuretic Drugs  Thiazide and thiazide like diuretics Drug examples: Clorothiazide, hydrochlorothiazide Mechanism of action: Increase sodium and water excretion by inhibiting sodium reabsorption in the distal tubule of the kidney Contraindications: Sensitivity to sulfonamides Adverse effects: Hypokalemia, hyperglycemia, arrhythmias, orthostatic hypotension, weakness, muscle cramps, photosensitivity reactions Interactions:  Decrease excretion of lithium causing toxicity  Concurrent use with other K-depleting drugs and cardiac glycosides may cause low K and risk of digitalis toxicity  NSAID may reduce response to thiazide diuretics  Do not take if allergic to sulfa drugs

143. 142 Diuretic Drugs  Loop diuretics Drug examples:  Bumetanide (bumex) ethacrynic acid, lasix, torsemide Mechanism of action:  Inhibit sodium and chloride reabsorption from the loop of Henle and the distal tubule Adverse effects:  Metabolic alkalosis, hypovolemia, dehydration. Hyponatremia, hypokalemia, hypochloremia, hypomagnesemia, photosensitivity, orthostatic hypotension

144. 143 Diuretic Drugs  K-sparing diuretics Drug examples:  Amiloride, spironolactone, triamterene Mechanism of action:  Act at the distal tubule to cause excretion of sodium, bicarbonate, and calcium and conservation of K Adverse effects:  Hyperkalemia, nausea, vomiting, diarrhea Interactions:  Decrease excretion of lithium  Concurrent use with ACE inhibitors or K increases risk of hyperkalemia  NSAIDs may reduce the effects of K sparing diuretics.  Give cautiously with renal insufficiency patients

145. 144 Diuretic Drugs  Osmotic diuretics Drug examples:  Mannitol, Urea Mechanism of action:  Increase osmotic pressure of the glomerular filtrate inhibiting reabsorption of water and electrolytes  Osmotic diuretics create an osmotic gradient in the glomerular filtrate and the blood Adverse Effects:  Hyponatremia, dehydration, circulatory overload, rebound IICP

146. Antilipemics DRUGS TO LOWER CHOLESTEROL: VDRL, LDL and TGs WE EAT TOO MUCH FAT in the typical American diet.

147. 146 Syndrome X metabolic syndrome Glucose intolerance Insulin resistance Hypertension Dyslipidemia Hypertriglyceridemia Male-shaped obesity Female hip-to-waist ratio Associated with Cardiac Disease

148. 147 Classes that lower lipids  HMG-CoA Reductase Inhibitors or Statins  Nicotinic Acid  Fibric Acid Derivatives  Cholesterol Absorption Inhibitors Bile Acid Sequestrants

149. 148 Anticoagulant, antiplatelet and thrombolytic drugs Anticoagulant drugs prevent extension and formation of clots by inhibiting factors in the clotting cascade Thrombolytic drugs activate plasminogen, leading to its conversion to plasmin Antiplatelet drugs interfere with platelet aggregation, preventing thromboembolic events

150. 149 Common Pathway Prothrombin (factor II) Thrombin Fibrinogen Fibrin clot Factor X Heparin + antithrombin = Activated Heparin Low molecular weight heparin Vit. K + warfarin Clot dissolves plasminogenplasmin Thrombolytics Photo Source: Used courtesy of E. McCabe, RN, Santa Barbara City College

151. 150 Anticoagulants  Examples: Dalteparin, enoxaparin, heparin, warfarin  Indications: prevent and treat thromboembolic disorders such as DVT, PE, and atrial fibrillation with embolization  Adverse effects: thrombocytopenia (with heparin) Androgens, chloral hydrate, chloramphenical, metronidazone, quinidine, sulfonamides, thrombolytic drugs, and valproic acid increase the risk of bleeding and enhance the effects of coumadin Alcohol, barbiturates, estrogen-containing oral contraceptives and foods high in Vitamin K increase risk of clotting and may decrease effect of heparin

152. 151 Heparin  Accidentally discovered by medical student in 1916, used medically first time in 1935 on humans  High molecular weight – called unfractionated  Does not cross the blood brain barrier – can be used during pregnancy  Half life IV = 45 to 90 minutes  Half life SQ = 60 to 120 minutes  Bioavailabity is about 20 to 30 %

153. 152 Heparin  Destroyed by enzymes in the GI tract  Administered IV or SQ – IM = muscular hematomas  Varying bioavailability  Monitor with - aPTT (activated partial thromboplastin time) =  Preferred because more sensitive to intrinsic pathway

154. 153 Heparin  Most serious side effect is hemorrhage  Administer protamine sulfate by slow IV infusion to neutralize heparin  Drug-drug interactions: antiplatelet drugs, NSAIDs oral anticoagulants, nitroglycerin, cephalosporins, penicillins, salicylates all may affect of heparin  Uses: Hemodialysis, open-heart surgery, prevention of thromboembolism, post MI, inhibits platelets from binding, DVT, PE, atrial fib, stroke prevention a.k.a. acute brain attack or CVA Highly protein bound = variable anticoagulation b/c the ill have reactive proteins that also bind to heparin.

155. 154 Anticoagulants  Nursing Responsibilities Heparin given initially because of its rapid action, then switch to coumadin over several days until therapeutic level is reached Heparin affects PTT and coumadin PT Inject SQ in abdomen and do not aspirate or rub at injection site Protamine sulfate antidote for heparin Vitamin K antidote for coumadin Soft toothbrush and electric razor

156. 155 Anticoagulants  Monitoring heparin therapy Obtain baseline PTT Administer a bolus dose of heparin IV, as ordered Follow with continuous infusion as ordered Obtain follow up PTT at specified  Values> 1 ½ time the control Continue to monitor Assess for S/S of bleeding  Values < 1 ½ time the control Contact MD Anticipate dosage increase Increase dosage as ordered

157. 156 Low molecular wt. Heparin example enoxaparin (Lovenox)  Given by SQ injection  Mainly Acts on factor X to begin the coagulation cascade to inhibit the conversion of prothrombin to thrombin. Produces greater prothrombin effect than binding to factor II as Heparin does.  Also called fractionated heparin

158. 157 Low Molecular wt. Heparin  T.I.A.s  Ischemic symptoms  Unstable angina  Atherosclerosis  Non ST elevation M.I. a.k.a, Q wave M.I. (without elevated enzymes - homocystine)  ST elevations a.k.a. acute M.I. (with elevated enzymes- homocystine)

159. 158 Low molecular wt. Heparin  High bioavailability and so more predictable than heparin because binds to factor X  No routine testing required  Can be administered at home  Bleeding is main adverse effect  Usually weaned off and when stable onto warfarin (Coumadin)

160. 159 Oral anticoagulant Warfarin (Coumadin)  AKA “rat poison”  May also be given IV, but rarely is  Bound tightly to plasma protein – other drugs can displace + other proteins may be present during tissue breakdown (example C- reactive protein)  Very difficult to monitor PT (prothrombin time) and dosed by INR (international normalized ratio)  Long half- life 1 to 3 days

161. 160 Warfarin (Coumadin)  Variable dosing and unpredictable; MUST COME IN FOR FREQUENT MONITORING.  Used prophylaxis for deep vein thrombosis (DVT), Pulmonary Embolus (PE), atrial fibrillation, off label for recurrent Transient Ischemic Attack (TIA), recurrent Myocardial Infarction (MI)  Suppresses coagulation activity by interfering with the production of vitamin K-dependent clotting factors in the liver.  Reduced amount of available Vitamin K for clotting factors II, VII, IX and X

162. 161 Warfarin (Coumadin)  Humans can not synthesize Vitamin K, but bacteria in GI tract can  Treat excessive bleeding with Vitamin K  Watch for bruising  Careful in older adult because MANY drug interactions and fall can cause excessive bleeding  Used to prevent clot formation in conditions such as atrial fib, not acute situations  IV Heparin to PO warfarin administer the 2 drugs simultaneously for 2 to 3 days to ensure continuous therapeutic anticoagulation

163. 162 Antiplatelets Clopidogel (Plavix) & ticlopidine (Ticlid) bind to ADP (adenosine dephosphate) which inhibits its effect on platelets (60 – 70% ) Aspirin inhibits thromboxane (TX2) in Arachidonic Acid Pathway (30-40%) Abciximab (ReoPro) binds to the GP IIb/IIIa receptor and inhibits platelet aggregation (90%) Tirofiban (Aggrastat) {new}

164. 163 Antiplatelet Drugs  Drug examples: Aspirin, dipyridamole (persantine), Ticlopidine (Ticlid)  Indications for use: Prophylaxis for thrombo-embolic events Ticlid – second line drug use to prevent stroke in high risk individuals, decrease intermittent claudication, and decrease graft occlusion after coronary artery bypass  Contraindications: Active bleeding, thrombocytopenia, severe liver impairment  Adverse effects: Bleeding, tinnitus, dizziness, neutropenia (Ticlid)

165. 164 Thrombolytic Drugs  Drug examples: Alteplase (tissue plasminogen activator) (activase), streptokinase, urokinase  Indications for use: Drugs used to lysis coronary artery thrombi Alteplase, streptokinase, and urokinase used to treat PE Streptokinase and urokinase used to treat DVT and to clear arterial catheters and arteriovenous shunt MRI needed for CVA to determine cause

166. 165 Thrombolytic Drugs  Contraindications: Recent streptococcal infection, active internal bleeding  Adverse effects: urticaria, fever  Nursing responsibilities: Monitor V/S for bleeding or hypotension, check peripheral pulses to ensure circulation Keep typed and cross matched blood on hand to administer in case of hemorrhage Thrombolytic drugs should be administered only when the patient’s hematologic function and clinical response can be monitored Ensure that aminocaproic acid (Amicar), the antidote for thrombolytic overdose, is readily available

167. 166 Antiplatelet Drugs  Drug examples: Aspirin, dipyridamole (persantine), Ticlopidine (Ticlid)  Indications for use: Prophylaxis for thrombo-embolic events Ticlid – second line drug use to prevent stroke in high risk individuals, decrease intermittent claudication, and decrease graft occlusion after coronary artery bypass  Contraindications: Active bleeding, thrombocytopenia, severe liver impairment  Adverse effects: Bleeding, tinnitus, dizzines, neutropenia (ticlid)

168. 167 Drugs Affecting the Endocrine System

169. 168 Thyroid Hormones  Thyroid replacement increases metabolism, cardiac output, regulates cell growth and causes diuresis. Most commonly used: – thyroid and levothyroxine (Synthroid) Contraindications: – Recent MI, adrenal insufficiency, hyperthyroidism Side Effects: – Cardiac dysrhythmias Adverse Effects: – Tachycardia, angina, hypertension, insomnia, headache, anxiety, increased or decreased appetite, menstrual irregularities, weight loss, heat intolerance (“hot flashes”) and thyroid storm

170. 169 Antithyroid Drugs  Used to treat hyperthyroidism Most commonly used: – methimazole and propylthiouracil which inhibit formation of thyroid hormone Contraindication: – Drug allergy, avoid in pregnancy if at all possible Side Effects: – Drowsiness, smoky colored urine, aching Adverse Effects: – Increased BUN and creatinine, enlarged thyroid, liver and bone marrow toxicity Interactions:– Increase in activity of anticoagulants Propranolol (Inderal) (non-selective beta blocker) given to control symptoms before antithyroid drugs work 2-3 weeks

171. 170 Insulin  Replaces insulin not made or made defectively in the body. Indicated primarily for Type I diabetes but may be used with Type II Requires careful dosing regimen Contraindications: – Drug allergy to specific product. Adverse Effect: – Hypoglycemia from overdose, weight gain Interactions: – corticosteroids, epinephrine, furosemide, phenytoin, thiazides, thyroid hormones, alcohol, anabolic steroids, MAO inhibitors

172. 171 Action of Insulins PreparationOnset of ActionPeak ActionDuration of Action Humalog 10-15 minutes 30-60 minutes 5 hours or less Regular*30-60 min2-4 hrs6-10 hrs NPH/Lente1-2 hrs4-8 hrs10-18 hrs Ultralente2-4 hrs8-14 hrs18-24 hrs Insulin glargine (Lantus) - a basal insulin for tighter glycemic control. Do not mix with insulin. May be used also for type 2 glycemic control. Regular insulin can be given IV in emergency situations

173. 172 Sliding Scale (Rainbow Coverage)  Regular insulin is given according to blood glucose results. Used mostly with newly diagnosed diabetics when stress occurs, such as illnesses requiring hospitalization and surgery Used with blood glucose greater than 200 mg/dl Example:  4 units = 200 – 250  6 units = 251 – 300  8 units = Greater than 300 May need to call MD – Carefully check order.

174. 173 Classes of agents for Type 2  SULFONYLUREAS 1 ST generation 2 nd generation  ALPHA-GLUCOSIDASE INHIBITORS  BIGUANIDES  MEGLITINDES  THIAZOLIDINEDIONES  INCRETIN MIMETICS (injected, new for type 2)  SYNTHETIC ANALOGS OF AMYLIN (injected, new (1 & 2)  Insulin glargine for tighter control (1 & 2)  Inhaled insulin (1 & 2) “EXTRA, EXTRA! Two new classes!”

175. 174 Complications of uncontrolled Type 2  Vascular disease especially hypertension  Urinary Tract Infections (UTIs)  Vaginitis  Prostatitis  Retinopathy  Nephropathy  Nonketotic coma (uncontrolled)

176. 175 Sulfonylureas (secretagogues)- means stimulates the secretion of insulin  First generation  EXAMPLE=Diabinese (chlorpropamide) Potentiated by NSAIDs Highly protein bound P450 system so drug interactions Hypoglycemia Stimulates pancreas May increase incidence of increased glucose intolerance Rarely used today  Second generation EXAMPLE= Diabeta (glyburide) Much the same as 1 st generation May increase insulin sensitivity Also potential hypoglycemia

177. 176 Biguanides  EXAMPLES Metformin (Glucophage XR) & Metformin (Fortamet XR)  Action Decrease hepatic glucose production Increases insulin sensitivity Decreases intestinal absorption of glucose  Improves lipid profile, decreases Triglycerides  DOES NOT produce hypoglycemia  Used as monotherapy or combination therapy

178. 177 Biguanides New use as prevention of Type II with FBS 125 mg/dL & History in family May lower vitamin B12 levels ? Best to supplement Side effects: Usually good side effect profile, GI symptoms, WEIGHT REDUCTION Do not give to patients who are being treated for CHF because of possibility of lactic-acidosis

179. 178 Alpha-Glucosidase Inhibitors  EXAMPLES Acarbose (Pecose) Miglitol (Glyset)  Action: Blocks intestinal amylase so delays breakdown of complex carbohydrates Decreases postprandial glucose  Monotherapy or combination therapy  Side effects: are minimal - flatulence, diarrhea, abdominal cramps

180. 179 Thiazolidinediones  EXAMPLES Pioglitazone (Actos) Rosiglitazone (Avandia)  Action: Reduce insulin resistance Monotherapy or combination with sulfonylureas, metformin Enhance insulin action in skeletal muscle, liver and fat tissue Reduce hepatic glucose output Glucose uptake into peripheral tissue

181. 180 Thiazolidinediones  Precautions: Do not use in patients with hepatic dysfunction Monitor liver function tests Caution with cardiac patients In combination with other antidiabetic agents, can cause fluid retention, may exacerbate CHF; caution with insulin use  Side effects: May cause edema and weight gain, headache, upper respiratory infection  Does not cause hypoglycemia when used as monotherapy

182. 181 Meglitinides (partial secretagogues)  EXAMPLES Repaglidine (Prandin) Taken ½ hour before meals Rapidly absorbed Needs presence of glucose to exert it’s action Stimulates release of insulin  Side effects: Potential for hypoglycemia, URI  Monotherapy or combination with metformin

183. 182 Amino Acid Derivative a secretagogue  EXAMPLE Naeglinide (Starlix)  Give adjunct with diet & exercise  Give to those who have not been treated chronically with other antidiabetic agents  Take 1 hr. to 30 min. before meals  Caution if patient is malnourished  Skip dose if meal skipped  Contraindicated in Type I and ketoacidosis  Not recommended in pregnancy  Monitor when concurrent highly protein-bound drug given

184. 183

185. 184 Parathyroid hormone (PTH)  Stimulated by low serum calcium  Inhibited by normal or high levels of calcium via negative feedback system  Phosphate also regulated by PTH via an inverse relationship with calcium  PTH activates Vitamin D which increases intestinal absorption  Less urinary excretion of calcium  Bone reabsorption of calcium from bone

186. 185 Calcitonin & decreased PTH  Hypercalcemia decreases secretion of PTH  Calcitonin is synthesized in the thyroid  Calcium is lost in urine  Decreased absorption of calcium from the intestine  Decreased reabsorption of calcium from bone

187. 186 Vitamin D  In activated form acts like hormone (intermediate metabolism in liver then to active form in kidney called calcitriol)  Obtained from foods and by sunlight on skin  Deficiency limits amount of calcium absorbed from diet  Causes release of calcium from the bone (reabsorption)  Causes G.I. absorption of calcium  Decreased levels caused by medications including tetracyclines and Dilantin

188. 187 Osteoporosis  Risk factors Current low bone mass (DXA) [dual energy x- ray absorptiometry] Thin, small frame female Advancing age Family history of osteoporosis Estrogen/testosterone deficiency Anorexia nervosa Low lifetime calcium intake History of fracture after age 50 Smoking, alcohol and sedentary life style Use of oral glucocorticoids for chronic disease

189. 188 Drugs used for Calcium/bone Disorders (osteoporosis & osteopenia)  Biphosphonates: alendronate (Fosamax), risedronate (Actonel) new once a month ibandronate (Boniva) used for osteopenia, osteoporosis, Paget’s disease Action: undergo incorporation into bone. Osteoclasts begin to reabsorb biphosphonate- containing bone so they ingest some of the drug, which then acts to inhibit their activity All poorly absorbed from GI tract. Take in a.m. with full glass of water, but without food for 30 minutes and remain in upright position to minimize risk of esophagitis.

190. 189 Drugs used for Calcium/bone Disorders ( osteoporosis & osteopenia)  Thyroid hormone: Calcitonin (Miacalcin) Produced by body when low levels of calcium Used to treat osteopenia Nasal spray Suppresses bone reabsorption Main side effect is runny nose and sneezing Hormone Replacement Therapy

191. 190 Mechanisms that raise serum calcium levels If decreased Serum Calcium Parathyroid hormone secretion renal excretion of calcium Intestinal absorption of calcium via activation of Vit D Bone resorption so calcium

192. 191 Mechanisms that lower serum calcium levels If increased Serum calcium Parathyroid hormone secretion Calcitonin secretion Renal excretion of calcium Intestinal absorption of calcium Bone resorption Serum calcium

193. 192 Arthritis OsteoarthritisRheummatoid arthritis (RA) Acute gouty arthritis Excessive wear & tear of wt. bearing joints Autoimmune disorder with autoantibodies (rheumatoid factors) Uric acid crystals accumulate in joints Often thought as normal part of aging process Systemic manifestations Sudden onset, triggered by diet, injury/stress; often big toe

194. 193 Corticosteroids  There are 2 types – Glucocorticoids and Mineralcorticoids Cortisol is primary glucocorticoid Aldosterone is primary mineralcorticoid  Some Indications: Replacement therapy for Addison’s Disease Inflammatory diseases  Arthritis  Ulcerative Colitis  Nephrotic syndrome  Liver disorders  Ocular inflammations

195. 194 Corticosteroids (cont’d) o Some indications: (cont’d) o Allergic conditions – status asthmaticus, asthma, allergic reactions o Neoplastic diseases o Brain-injuries (cerebral edema) o Skin conditions (psoriasis/dermatitis) o Collagen disease (Lupus) o Ophthalmic – conjunctivitis, corneal abrasions o Asthma

196. 195 Corticosteroids (cont’d)  Precautions: Therapy is tapered and not discontinued abruptly Vaccinations are contraindicated Use with caution during pregnancy, lactation, clients high risk for infections, peptic ulcer disease (PUD), cardiac or renal failure, diabetes, myasthenia gravis Do not use with fungal or viral eye infections  Interactions – Increased risk of: Hypokalemia with K-depleting diuretics Digitalis toxicity Gastric ulcers with NSAIDS Hyperglycemia

197. 196 Estrogen  Indications: Hormone replacement therapy Normal sexual development with estrogen deficiency Androgen suppression with prostate Ca Oral contraception by inhibiting ovulation  Side Effects: Headache Depression  Adverse Effects: Hypertension Thrombo-embolic disorders Abnormal uterine bleeding Unopposed may lead to endometrial cancer

198. 197 Estrogen (cont’d)  Contraindications: Pregnancy and lactation Previous or active thrombo-phlebitis or embolic disorders Estrogen-dependent Cancers History of CVA or Coronary Artery Disease (CAD), Breast Cancer, liver disorders  Precautions: Oral contraceptives by diabetics or smokers  Interactions: Some anti-convulsants decrease the effectives of oral contraceptives due to P450 system

199. 198 Progentins (not progesterone)  Indications - Oral contraception with estrogen, HRT, endometriosis, dysmenorrhea, uterine bleeding  Adverse Effects: Breakthrough bleeding Impaired glucose tolerance Depression Edema and weight gain  Contraindications: Pregnancy, undiagnosed vaginal bleeding, Thrombo- phlebitic or embolic disorders, Ca of reproductive organs

200. 199 Androgens  Most important is testosterone  Uses: Males – erectile dysfunction, delayed puberty, muscle wasting in AIDS Females – Endometriosis, fibrocystic breast changes, some menopausal symptoms, advanced breast cancer Females – increases libido  Adverse Effects: Virilization, hepatotoxicity, edema, gynecomastia in males

201. 200 Androgens (cont’d )  Precautions: Contraindicated in pregnancy and prostate enlargement Children must have bone growth evaluated q 6 months Anabolic Steroids – Schedule III controlled substance (not same as testosterone) Testosterone  Interactions: Enhance effects of oral anticoagulants, oral hypoglycemics and insulin Barbiturates and calcitonin interfere with the effects of androgens

202. 201 Drugs Affecting the Respiratory System Photo Source: National Cancer Society, Public Domain, http://visualsonline.cancer.gov/details.cfm?imageid=1775 http://visualsonline.cancer.gov/details.cfm?imageid=1775

203. 202 Antihistamines  Indications: Various allergic reactions Induce sleep Relieve nausea Prevent motion sickness  Side Effects: Drowsiness Dry mouth and blurred vision  Elderly are at high risk for dizziness, confusion, hypotension, unsteady gait & CNS stimulation - Lower doses due to anticholinergic effects

204. 203 Antihistamines (cont’d)  Adverse Reactions: Headache, hypertension, GI distress Drug allergy – anaphylaxis Excessive sedation with other CNS depressants  Contraindications: Narrow angle glaucoma, prostatic hypertrophy, pregnancy, bladder neck obstruction, PUD Not recommended in bronchitis or pneumonia because they dry secretions making it difficult for removal.  Interactions: Some antibiotics enhance effects MAOIs inhibit metabolism thus enhancing effects

205. 204 Mode of Action Antitussives narcotic antitussives directly suppress cough reflex in medulla of the brain (CNS) dextromethorphan same mode of action as narcotic benzonatate anesthetizes or numbs the cough reflex Photo Source: Wikimedia Commons, Creative Commons, http://commons.wikimedia.org/wiki/Image:Brain_bulbar_region.svg

206. 205 Antitussives  Used to relieve coughs: suppresses cough center in medulla if centrally acting Antitussives containing codeine are Schedule IV meds. Dextromethorphan, non-opioid  Side Effects for centrally acting: Drowsiness, sedation, dizziness, restlessness, agitation, euphoria  Adverse Effects : Respiratory depression – antidote opioid toxicity (Narcan) Hypotension, Tachy or bradycardia Drug allergy - Anaphylaxis

207. 206 Drugs Affecting the Respiratory System  Beta-Agonists inhaled - short acting + long acting  Beta-agonists – oral agents  Methylxanthines  Anticholinergics  Antiasthmatics [cromolyn & nedocromil]  Corticosteroids  Leukotriene modifiers

208. 207 Bronchodilators  Used to relax smooth muscles in bronchi and bronchioles for asthma, bronchitis, emphysema  3 Types of Drugs Adrenergics(beta -2) Xanthines Anticholinergics (given by inhalation)

209. 208  Follow step approach guidelines when doing health teaching.  See health care provider at least every 6 months for evaluation.  Identify and list triggers.  Keep asthma diary & record “personal best” from peakflow meter. Record three times a day.  Contact provider if peak flow drops and go to established plan.

210. 209 Step Approach Terms  Step one Mild Intermittent  Step Two Mild Persistent  Step Three Moderate Persistent  Step Four Severe Persistent

211. 210 Beta-Agonists Rescue drugs (short acting)  Used most often  During acute phase of asthmatic attack  For COPD acute attack of SOB  Quickly reduce airway constriction  Are Sympathomimetics  Stimulate beta-2 receptors

212. 211 Anticholinergics Corticosteroids Indirect-acting Agents

213. 212 Anticholinergics Controller drugs  Ipratropium bromide = Atrovent  New powder inhaler (not metered dose inhaler) 24 hr. duration & may be superior to atrovent = tiotropium bromide (Spiriva)  NOT for acute attacks!  For maintenance tx of bronchospasms  MAINSTAY FOR COPD (when combined with atrovent is called Combvient – brand name)

214. 213 Side Effects of Anticholinergics  Respiratory: Dry mouth or throat and coughing  Gastrointestinal: GI distress  CNS: Headache & anxiety Mild anticholinergic effects if inhaled – do not use if patient has glaucoma or BPH Atrovent or Combivent inhalers produce serious allergic reactions to those with peanut allergy

215. 214 Xanthine Bronchodilators Controller agent  Aminophylline *usually I.V. when patient in distress  Theophylline *[examples] aerolate, bronkodyl, elixophyllin, slo-bid, theobid, theo-dur, theolair, & uniphyl

216. 215 Theophylline  Wide variability as to plasma half-life  Narrow therapeutic index  Unpleasant side effects of anxiety, agitation, insomnia, tachycardia, palpitations  Need to draw blood samples to stabilize patient on correct dosage to minimize adverse effects  Older adults with liver disease and CHF with pulmonary edema have prolonged half-life  Smokers and children have shorter half-life

217. 216 Antibiotic classes: Sulfonamides, Penicillins, Cephalosporins, Macrolides, Quinolones, Aminoglycosides, Tetracyclines, Glycycyclines Carbapenems, Monobactams, Oxazolidinones Streptogramins, Ketolides & Glycylcyclines

218. 217 Drugs Used to Treat Infections  Drugs for treating infections are referred to as antibiotics (most common term) or anti-infectives, antimicrobial  Antibiotics are not effective against viruses  Resistance is the BIG PROBLEM

219. 218 Anti-infectives General Action Types of antibiotic action Damages the cell wall Modifies protein synthesis Modifies DNA synthesis Modifies energy metabolism via folic acid

220. 219 Antibiotics Actions Inhibit the growth of bacteria Inhibit cell wall synthesis Are bacteriostatitic and bacteriocidal  Adverse Reactions: Some are very nephrotoxic Hearing impairment- ototoxic Superinfections May potentiate decreased effectiveness of other medications (Be aware of specific interactions with specific drugs) “Sunburn” reaction – Avoid direct sunlight with tetracyclines  Contraindications: Known drug allergy Many should not be used during pregnancy  Many resistance patterns

221. 220 Penicillin resistance Penicillinases (enzymes) produced by bacteria that destroy penicillin by cleaving the beta-lactam ring of the drug Clavulanic acid enhances the activity of penicillins. Binds to the active sites of penicillinases rendering the enzyme inactive

222. 221 Some Commonly Used Antibiotics  Sulfonamides One of the first anti-infectives Often used today for Urinary Tract Infections Drink fluids to prevent urinary crystals  Septra  Bactrim Assess allergy to other sulfa medications (Sulfonylureas,Thiazide diuretics)  Penicillins Penicillin G, Ampicillin, Amoxicillin Observe for clostridium difficule Fruit juices can inactivate the drug Assess electrolytes

223. 222 Some Commonly Used Antibiotics (cont’d)  Tetracyclines (not with milk, CA products) Take one hour before or two hours after meal Causes brown teeth in children! Photosensitivity  Macrolides – Erythromycin and Biaxin can have many drug interactions, problems with G.I. distress Used to treat mycoplasma (penicillins & cephalosporins not effective!) Used when patient is allergic to penicillin Use cautiously with heart, renal, liver disease Not given with fruit juice

224. 223 Cephalosporins Similar to PCN but broader spectrum Differ as to generation for coverage. When anaphylaxic reaction to PCN, should not be given a cephalosporin A beta-Lactam antibiotic May be ineffective against bacteria that produce enzyme beta-lactamase Called cephalosporinase Avoid alcohol. Also, now may not be effective against MRSA

225. 224 Quinolones  Kill bacteria = bactericidal  Active on a wide variety of bacteria gm- & gm+ as well as a-typical infections  Excellent oral absorption  Antacids reduce their absorption  * gm- coverage & excellent [drug] for kidneys Great for treating UTI’s & prostatitis first oral class of antibiotic to kill gram- bugs Good for Salmonella typhi and Shigella Not used in children. May damage cartilage, leading to deformities in gait

226. 225 Quinolones  Used to treat: lower respiratory tract infections bone & joint infections infectious diarrhea urinary tract infections skin infections  Overuse! They should be reserved for serious infections and resistant strains. MRSA can be susceptible. Do not want to create resistance  Should not be used in children - may damage cartilage leading to deformities in gait

227. 226 Aminoglycosides Used to Treat: Pneumonias, resistant UTIs, septicemia, CNS infections – serious & life threatening Action: Bind to 30S & 50S ribosomal subunits Cause inhibition of protein synthesis Precautions: Nephrotoxicity & ototoxicity (8 th cranial nerve) Drug levels help prevent high peaks & troughs, many drug interactions; must monitor carefully.

228. 227 Miscellaneous antibiotics  Vancomycin Rapidly bactericidal so low resistance Glycopeptide antibiotic not related to PCNs Given by intermittent IV infusion Used in life-threatening staph or strep infections and MRSA Adverse reactions are nausea, flushing and itching  Red Man Syndrome Toxic reactions: tinnitus, hearing loss, nephrotoxicity Often given with piperacillin (Zosyn) IV a broad spectrum PCN + B-lactamace inhibitor for MRSA

229. 228  Ethambutol (Myambutol) RARE retrobulbar neuritis & blindness GI upset  INH isoniazid (Nydrazid) Peripheral neuritis & rarely hepatotoxicity Don’t give for prophylaxis after age 40 because of increase in side effects Peripheral neuropathy Selegiline (SEL)-like syndrome  Pyrazinamide Hepatotoxicity & hyperuricemia (reports of liver failure)  Rifampin Hepatitis, body fluids turn orange/red color  Streptomycin Antituberculars

230. 229 Latent TB  If skin test is positive  Follow up with chest x-ray  Use INH for 9 months or rifampin for 4 months for latent TB

231. 230 Antifungal Agents = drug interactions + liver toxicity  Itaconazole (Sporanox): inhibitor of cytochrome 3A4 = increased statins, Ca + channel blockers, some Benzodiazipines, etc.  Ketoconazole (Nizoral): inhibitor of cytochrome 2C19 = increased levels of phenytonin, some Tricyclic Antidepressants, some Benzodiazipines, etc.  Fluconazole (Diflucan): inhibitor of cytochrome 2C9 = increased level of celebrex, NSAIDs, Warfarin, phenytoin, etc. Examples of systemic antifungals

232. 231 Antivirals  Drugs used to kill viruses Inhibit their ability to replicate Difficult to kill because they live inside our cells  Utilize our cells to replicate Any drug that kills a virus may kill our cells Only work during viral replication Mutations & resistance common Antimicrobials not effective unless accompanying secondary bacterial infection

233. 232 Photo Acknowledgement: Unless noted otherwise, all photos and clip art contained in this module were obtained from the 2003 Microsoft Office Clip Art Gallery.