Muscarinics AtropineMuscarinic Antagonist: AtropinePrototype: atropine (Sal-Tropine)

– MOA / TE: Competitive blocking of Ach at muscarinic receptors to treat the following:– Atropine is dose related

– Pre-anesthetic medication– Disorders of the eye (surgery)– Bradycardia, raises hrt rate– Intestinal hypertonicity and hypermotility – Muscarinic agonist poisoning (WMDs)– Peptic ulcer disease (Not DOC)– Asthmas (Not DOC)– Biliary colic bugers bugers bugers

– Adverse Effects– Xerostomia (dry mouth)– Blurred vision, photophobia– intraocular pressure (glaucoma)– Urinary retention– Constipation– Anhidrosis (no sweating)– Tachycardia– Thick bronchial secretions

– DDD– Antihistamines, makes drier– Phenothiazine antipsychotics, associated with; seretonin reuptace inhibitors, which increase bld pressure. Atropin

does same– Tricyclic antidepressants

– Adverse Effects– Xerostomia (dry mouth)– Blurred vision, photophobia– intraocular pressure (glaucoma)– Urinary retention– Constipation– Anhidrosis (no sweating)– Tachycardia– Thick bronchial secretions

– Atropine is dose related

SympathomimeticsEpinephrine Therapeutic Effects of Beta Blockade - the “olols and lols”

• Major effects: – ¯ heart rate & ¯force of contraction– ¯ velocity of impulses through AV node

• Therapeutic management of – *Angina pectoris & Myocardial infarction– *Hypertension – *cardiac dysrhythmias – Heart failure– Hyperthyroidism, migraine, stage fright– Pheochromocytoma – Glaucoma

Prototype: propranolol (Inderal)• MOA / TE: as above and as listed previously• Adverse effects

– Bradycardia, cause they slow production HR– AV heart block– *Precipitation of heart failure– Reduced cardiac output– Rebound cardiac excitation w abrupt cessation (ST and VT)– Bronchoconstriction (Beta2)– Blockade of glycogenolysis (Beta2)– A ymptom of hypoglicemia is incresed HR, but with a beta blocker you don’t get an increased HR… need to look at

glucose level• Precautions / contraindications:

– Severe allergic conditions• If occurs beta blockade interferes w EPI

– Diabetes• Compensatory glycogenolyis is impaired• Can mask sxms of hypoglycemia (ST)• Heart failure, AV block, bradycardia, asthma, bronchospasm and depression (crosses easily into CNS)

• Drug interactions– Calcium channel blockers – esp. verapamil – Insulin – sxms of hypoglycemia

• Nsg Implications– Taper off gradually– Masking of hypoglycemia reactions– Heart rates: Brady or Rebound tachy

Indirect-Acting Antiadrenergic AgentsCentrally Acting Alpha2 AgonistsClonidine 2Prototype: clonidine (Catapres)MOA / TE: decreases release of norEpi (flight or fight) , limiting vasoconstriction, therefore lowering blood pressure and heart rate. Also used in severe pain of cancer.

• ADME– Effects start in 30’ and can last for 24 hrs– Brain stem or brain– You don’t stop sudenly

• Adverse Effects – Rebound HTN fr. sudden withdrawal– Drowsiness, Xerostomia (DRY MOUTH), embryotoxic, constipation, impotence, gynecomastia

Administration: PO and patchesAnitseizuresphenytoin (Dilantin)

• MOA / Uses– Selective inhibition of sodium channels to suppress cerebral irritability to treat partial and tonic-clonic seizures &

selected cardiac dysrhythmias • ADME:

– Varied oral absorption– Half-life 8 to 60 hours– Metabolism variance– Blood levels (10 mcg/mL)

• Adverse effects– Nystagmus, diplopia – Sedation– Ataxia - gait– Cognitive impairment– Gingival hyperplasia – floss / gum massage

– Skin rash – stop therapy (Stevens-Johnson)– Effects in pregnancy - teratogen – Cardiovascular effects – IV use in SE, heart blocks

• DDD– Phenytoin decreases effects of

• oral contraceptives, warfarin (Coumadin), and glucocorticoids – Drugs that increases phenytoin levels:\

• diazepam (Valium), isoniazid, cimetidine (Tagamet), alcohol (acute), valproic acid (Depakote)– Drugs that decrease phenytoin levels

• Carbamazepine, phenobarbital, chronic ETOH • ADME

– Administration: po with food– IV – slowly! – compatibility issues

• Additional Nsg considerations– Driving– Hazardous work

Opiod AgonistStrong: morphine [Duramorph] CIIModerate to strong: codeine [Paveral] CIII

– Usual dose of 30 mg = about same relief as 325 mg of ASA or Tylenol– Combo meds more effective– Extremely effective cough suppressant at 10 mg dose range

• MOA / TE– Mimics action of endogenous opioid receptors (mu) to produce analgesia and thereby relieve pain– Other effects include drowsiness, mental clouding, anxiety reduction, sense of well-being

• Dosage – Highly individualized – Table 28-6

• Adverse Effects – Resp. depression

• Diminished by “tolerance” • Most common cause of OD death

– Others • Constipation, orthostatic hypotension, urinary retention / urgency, cough suppression, biliary colic,

emesis, elevated ICP, dysphoria, sedation, miosis, neurotixicity, immune and hormone suppression with prolonged use

– Toxicity • Classic triad (coma, resp. depression, pinpoint pupils)

• ADME (Pharmacokinetics) Nursing implications?– Given by several routes– Slowest to fastest– Time-frame for TE varies by mode of administration – Denatured in liver– Hard to cross blood-brain barrier

• Precautions / Contraindications– Decreased resp reserve, pregnancy, head injury, infants / elderly, hypotension, liver disease

• Interactions– CNS depressants, antihistamines, antihypertensives, MOAIs*, antiemetics, amphetamines, agonist-antagonist,

antagonists• ADME (Pharmacokinetics) Nursing implications?

– Given by several routes– Slowest to fastest– Time-frame for TE varies by mode of administration – Denatured in liver– Hard to cross blood-brain barrier

• Dosage – Highly individualized – Table 28-6

• Administration– po, IM, IV, SQ, topical

– Oral associated with chronic– Preferably fixed schedule– Site specific – hazards- epidural- effects delayed

Special Clinical Concepts r/t Use of Opioids• Pain assessment – including evaluation!• Dosing amt and schedule• Fear of addiction in clinical setting• Avoiding withdrawal – 20 days or more• Patient controlled anesthesia (PCA)• Morphine: DOC - heart attack (MI)• Meperidine [Demerol]: DOC OB• Avoid opioids in Head Injury…

Meperidine [Demerol]– Interacts with several drugs– Toxic metabolite

• Avoid use past 48 hrs and not to exceed 600mg/24hr. Opioid Antagonists naloxone [Narcan]

• MOA – TE / Use– competes for opiate site and blocks effects of opioid agonists / agonist-antagonists – no significant effect given

alone – resulting in REVERSAL of narcotic– Used to reverse the affects of morphine

• ADME– Rebound effect

• Adverse effects: acute withdrawal• Dosage/Admin: 04. mg IM, IV, SubQ • Others: naltrexone [ReVia] ETOH/Opioid abuse

AntidepressantsGeneral Points

• Most common psychiatric disorder• Major treatment method - medications

– Five major groups• Goal? • Sxms

– Depressed mood, loss of pleasure / interest in all or nearly all of one’s usual activities• Under-treated • More prevalent in women• Suicidal thoughts may increase w Rx

Nursing ImplicationsATI p. 203 (220)

Tricyclic Antidepressants (TCAs)• Prototype: imipramine [Tofranil]• MOA – TE / Use

– Blocks reuptake of the MAO transmitters NE (norepinephrine) and serotonin. Elevates mood, thereby treating depression.

– Other uses: bipolar disorder, neuropathic pain, insomnia, fibromyalgia, OCD• Adverse effects

– Orthostatic hypotension, sedation, anticholinergic effects, sedation, diaphoresis, cardiotoxicity, seizures, hypomania, “yawngasm”

• Precautions / Interactions – TCAs w MAOI can lead to severe HTN– Potentiates drugs like NE (norepinephrine)– Potentiate CNS depressants

• Antidote: activated charcoal after gavage • Dosing

– Based on clinical response – don’t give more than a week supply– Dose at bedtime once levels achieved – EXCEPT in elderly (cardiac reasons)

SSRI Antidepressants• Prototype: fluoxetine [Prozac]• MOA / TE / Use

– Selective serotonin re-uptake inhibitor resulting in elevated serotonin levels – elevating mood and relieving depression.

– Helps in bulimia nervosa• Adverse effects

– Impotence, weight gain, Serotonin syndrome, withdrawal syndrome, EPS, bruxism, bleeding, hyponatremia.• Interactions: MAOIs, Warfarin, & TCAs

MAOI Antidepressants• Prototype: phenelzine [Nardil]• MAO / TE / Use

– Enzyme – deactivates NE, serotonin, dopamine, and tyramine (NE stimulator) from foods– NOT 1st CHOICE

• Relevant P-kinetics– Tyramine

• Adverse effects: – CNS stimulation – agitation – hypomania – mania – hypotension – HTN crisis – meperidine (hyperpyrexia)

Atypical Antidepressants• Bupropion [Wellbutrin]

– Action unclear– Effect

• Stimulant ergo no wt gain• No sexual dysfunction – may augment

• Adverse effects: – agitation, HA, dry mouth, constipation, wt loss, insomnia, tachycardia, seizure

• Note: St. John’s Wort Box 32-2

Classification:Sedative-Hypnotics• Major Effects

– CNS depression• Therapeutic Uses

– Relieve anxiety, facilitate sleep, manage muscle spasms, seizure and panic disorders, augment anesthesia, and manage ETOH withdrawal

Barbiturates Prototype: secobarbital [Seconal]

• MAO / TE / Use– Mimics GABA and depresses CNS directly causing relaxation and anxiety reduction. Other uses: seizure

management, anesthesia, sleep disorders, mania• ADME

– NO CEILING TO LIMITS OF CNS depression • Adverse effects:

– Resp. depression, hypotension in toxic doses, can readily cause death • Precautions

– Highly addictive - physical dependence – withdrawal can be severe – Caution in elderly– Caution with other CNS agents– Caution with IM injection

BenzodiazepinesBenzodiazepines (CIV)Category DPrototype: diazepam [Valium]

– Others: clonazepam, lorazepam, clorazepate • MOA

– Depress neuronal function at multiple CNS sites by potentiating endogenous GABA (gamma-aminobutyric acid) and is limited because GABA is finite®safer

– Cardiac • PO effect - heart & blood vessels • IV effect – potentially ? Can be vary bad

– Respiratory• Minimal alone, serious if combo or IV

• Pharmacokinetics: – Readily absorbed – Differ in respect to time of course of action

• (main indicator for which one chosen for which job)• Adverse effects

– CNS – daytime vs nighttime impacts– Amnesia– Paradoxical.. Opposite effect of what you thought you would get – Abuse– Malnutrition, liver disease and blood levels..

• DDD w other CNS depressants Dosage: varies by agent Nursing Implications

• ATI pp. 218Benzodiazapine-likes Prototype: Zolpidem [Ambien] CIV

• MOA – TE / Use– Agonists at benzodiazepine receptor site on GABA channel prolonging sleep duration and helps relieve insomnia– Low potential for tolerance or abuse

• Adverse effects– Similar to benzodiazepines (daytime drowsiness / dizziness)– Can intensify CNS depressants

• Dosage / Administration – Before bedtime?

DiureticsReview of renal anatomy and physiology

• Introduction to diuretics • High-ceiling (loop) diuretics • Thiazides and related diuretics

Physiology• Three basic functions

– Cleanse ECF and maintain volume and composition– Maintain acid-base balance– Excrete metabolic wastes and foreign substances – e.g. ?

Relevant Concepts • Filtration - non-selective• Re-absorption – highly selective

– Diuretics interfere• Active pumps for organic acids/bases in proximal tubule• Sodium-Potassium Exchange

– Aldosterone Purpose of Diuretics

• Increase urinary output • Major applications

– Treatment of hypertension– Mobilization of edematous fluid– Maintain urine flow, thereby aids prevention of renal failure

High-Ceiling (Loop) DiureticsPrototype: furosemide (Lasix)

• MOA: • Acts on the ascending loop of Henle to block re-absorption

• ADME– Rapid onset w IV in minutes– PO - starts in 1°

• Therapeutic Uses– Pulmonary edema of CHF (IV indicated) – Edematous states (liver, heart, kidney)– Hypertension– Hypercalcemia

• Adverse effects– Hyponatremia, hypochloremia, and dehydration– Hypotension from decreased afterload

• Loss of volume• Relaxation of venous smooth muscle

– Hypokalemia – esp. with digitalis Symptoms; Nausea, vomiting, general weakness

– Ototoxicity – esp. with rapid infusion– Hyperglycemia– Hyperuricemia – Use in pregnancy– LDL – cholesterol - triglycerides, ¯HDL– ¯Calcium• ¯Magnesium

• Drug interactions– Digoxin – Ototoxic drugs– Potassium-sparing diuretics– Lithium – Antihypertensive agents– Nonsteroidal anti-inflammatory drugs

Decreases renal blood flow

Ace InhibitorsDrugs Acting on the Renin-Angiotensin-Aldosterone System

• Physiology of the renin-angiotensin-aldosterone system (RAAS)• Angiotensin-converting enzyme inhibitors• Angiotensin II receptor blockers• Aldosterone antagonists

Physiology of the Renin-Angiotensin-Aldosterone System• Angiotensins I, II, & III• Actions of angiotensin II

– Vasoconstriction– Release aldosterone – Alter structure of heart & vessels

• Actions of aldosterone – Sodium and water– Fibrosis (hardening) of vessels

Formation of Angiotensin II• Renin

– Released in response to BP, Na+, volume, and renal perfusion – Converts angiotensinogen to angiotensin I

• Angiotensin-converting enzyme (ACE)– Catalyzes conversion of angiotensin I (inactive) into angiotensin II (highly active)

Regulation of BP by RAAS

• Effect modest in normal hemodynamics & Na+• Effect MAJOR in hemorrhage, dehydration, or sodium depletion• Acts in two ways

– Constricts renal blood vessels– Stimulates release of aldosterone fr. Adrenals thereby ….

Tissue (local) angiotensin II productionAngiotensin-Converting Enzyme (ACE) Inhibitors – the “Prils”Prototypes: ramipril (Altace)

• MOA / TE– Reduces angiotensin II & increases bradykinin to dilate vessels, excrete Na+ & H20, conserve K+ & help prevent

vessel and heart tissue changes• Uses

– HTN, – heart failure ( slowing down the production of myocytes) – diabetic nephropathy( a key indicator fotr the use of this drug, help keep BP down)( is protective to use this drug),– prevention of MI, stroke and death

• Special benefits of ACE Inhibitors– Do NOT interfere with heart reflexes – ok with exercise– Safe in asthma– Do NOT cause hypokalemia(like diurestoics, hyperuricemia, or hyperglycemia– Do NOT induce lethargy, weakness or sexual dysfunction– DO reduce risk of cardiovascular mortality fr. HTN, MI, & stroke (22%)– Reduce mortality following MI– Reduce chance of developing heart failure– Slow progression of renal disease

– ADME– Nearly all are PO– Captopril and moexipril NOT with food– Renal excretion (monitor who?)anybody with reduced kidney function

– Adverse effects– 1st Dose hypotension– Cough, dry hacking– Hyperkalemia, does not excrete potassium. – RF in renal artery stenosis (hardening) can drop GFR to low..– Angioedema – Neutropenia (rare) prevalent among people w collagen disease or lupis – Dysgeusia (taste) and rash

– Drug D Drug– Diuretics – withdraw 1 wk prior to starting ace’s– Antihypertensive agents– Drugs that raise potassium levels (salt sub)– Lithium – raised– NSAIDs (counter effect)– Nonsteroidal anti-inflammatory drugs

ARBsValsartan Angiotensin II Receptor Blockers(ARBs) – the “Sartans”Prototypes: iosartan (Cozaar), valsartan (Diovan)

• MOA / TE– Blocks action of angiotensin II – Protects fr. cardiovascular structural changes– Reduces excretion of K+ and ¯ aldosterone – Increases renal excretion of Na++ & H2O– Useful in migraine– Does the same stuff as the ace

• MOA cont’d

– Does not inhibit kinase II or increase bradykinin – MAIN difference between ACEs & ARBs – no cough or hyperkalemia with ARBs

• ADME: All po, All ok with or without food• Adverse effects

– Same as ACEs, but less angioedema • DrugDDrug

– Antihypertensives

Calcium Channel Blockers• Normal physiology:

– Calcium in = contraction / force of• Effects of Blocking

– Dilation of Vascular Smooth Muscles (VSM) = dilated peripheral arterioles / arteries & arteries of heart• Heart Ca++ Blocking Effects

– ¯ Inotropic effect ( wrd used to express the contraction or force of the heart– Slows conduction thru SA & AV nodes– Same effect as Beta1 blockers

Prototypes: Verapamil [Calan, Isoptin, Verelan]Diltiazem [Cardizem, Diltia XT]

• MOA / TE– Peripheral arterial dilation, ¯ arterial pressure, coronary perfusion, blockade at SA & AV nodes ¯ HR, ¯ force of

contraction aiding in the relief of:• Angina pectoris• Essential hypertension –1st line for chronic• Cardiac dysrhythmias – A-flutter / fib / SVT• Migraine

Adverse Effects of verapamil / diltiazem – Constipation – can be severe in elderly

• Diltiazem not as constipating– Dizziness, Facial flushing– Headache– Edema of ankles and feet– Gingival hyperplasia– Bradycardia – Heart block & ¯ stroke volume

• Contraindications? Some one who has a heart block already

AnticoagulantsPrototype: warfarin (Coumadin)

• MOA / TE / Uses: Antagonist of vitamin K, blocks biosynthesis of factors VII, IX, X, and prothrombin used in– Long-term prophylaxis of thrombosis– Prevention of VTE and associated PE– Prevention of thromboembolism (in patients with prosthetic heart valves)– Prevention of thrombosis during AF, thickens bld

• ADME– Longer onset sec. to circulating clotting factors – may be days on & off– So Some of these different therapies will over lap..– Implications for surgery, ok for DDS

• Adverse effects– Hemorrhage, teratogenesis (Cat X)– Red-orange urine (not blood)– Alopecia

• DDD & DDF (Table 51-4)– Drugs that ¯or anticoagulant effects– Drugs that promote bleeding: NSAIDs – including acetominphen, Heparin– Foods: broccoli, spinach, dark greens, and grape fruit

• Nursing considerations

– Monitoring INR, PT (Table 51-3)– Vit K (the antidote) for OD (po, diluted IV - NO subcut)

B12Prototype: Vitamin B12 (Cyanocobalamin)Stored in liver

• MOA / Uses: provide B12 for synthesis of DNA to alleviate macrocytic anemia, neuro damage, and GI disturbances from deficiency

• ADME• Not given IV= anaphilaxis

– A: requires intrinsic factor (IF)– E: very slow – stored ______________– Routes: PO, IM, deep SubQ, Intranasal

• Adverse effects– Secondary hypokalemia

• Dietary sources• Treatment regimen

– Lifelong if Ø IF (intrinsic factor)

IronIron Deficiency: Oral TreatmentPrototype: Ferrous sulfate (Feosol)

• MOA / TE: DOC -restores iron for production of hemoglobin to prevent or relieve symptoms of microcytic hypochromic anemia

• ADME– Absorbed from Fe rich foods, uptake in GI tract, stored by liver – Lose 1 g / d - requirements r/t rate of RBC production - pregnancy / menses

• Adverse effects– GI: N, heartburn, bloating, constipation, & diarrhea– Aggravation of: PUD ( irritates stomach lining), regional enteritis, ulcerative & colitis – shouldn’t take p.o.– Dark green / black stools– Liquid form – stains teeth, drink through strw

• Toxicity– Leading cause of poison death in kids– Tx: Lavage if tabs in gut / deferoxamine

• DDD– Antacids – reduce (2 hr B4, 4 hr after– Tetracycline - reduce– Ascorbic acid – increases & potentiates adverse effects– Avoid time- release in elderly - erratic

• DDF– Absorbs best w/o food– Foods protect against bad effects- milk, cereals, dietary fiber, tea, coffee and eggs,may decrease absoption

Iron Deficiency: Parenteral TxPrototype: Iron dextran (INFeD)

• MOA / Use: Indicated when orals don’t work – can’t be absorbed – blood loss is excessive – and GI problems• Adverse effects

– Anaphylaxis fr. Dextran (test dose of0.5 ml) observe for an1hr, have epi, available – Hypotension– Pain / tumors at IM sites – intervention? Z trach – Can develop tumors at site

– Extreme caustion in serious liver inparement – Nursing Implications

– Monitor serum Fe for rise of 2 g /dL – goal is 15 g / dL – If unresponsive – monitor for adherence– Therapy possibly for months, if your iron deficient.. May not know in 120 days

– IV – test dose

– 25 mg– Monitor 15 min

– Avoid IM site if possible– Tumors– Greatest risk of anaphylaxis– Prolonged pain / discoloration at site

INSULINS – SHORT, INTERMEDIATE, LONG-ACTING

In Short: When mixing – draw short-acting first, refrigerated, do not freeze (breaks down cell wall), pre-filled syringes –

needle up, agitate before injection In Detail: Insulins

• Human Recombinant DNA and analogs• Beef and pork (’98 & ’05 respectively)• Types: natural and modified• Prolonging effect• Attach to protein or alter molecule

MOST are manufactured as clear / colorless suspensions Discard if abnormal

When mixing – draw short-acting first (fast- acting)SubQ, IM, PO, Off label IV

Only form also available as U-500

SHORT DURATION – RAPID ACTING, not for IV use

• Insulin lispro (Humalog)• Can mix with NPH – right before meal or after meal

• Insulin aspart (NovoLog)• Can mix with NPH – 5 to 10 minutes before meal

SHORT DURATION – SLOWER ACTING

Regular insulin (Humulin R, Novolin R)

• 30-60 mins before a meal, can be given all routes: subq, IM, PO, off label IV (only one for IV use), only form also available as U-500 (has it’s own syringe), added to TPN to help pt metabolize sugar

INTERMEDIATE DURATION

Neutral Protamine Hagedorn (NPH) insulin

• Not intended for postprandial hyperglycemic control, only one that is cloudy – all others are clear• Can mix with other drugs or insulins

Insulin determir (Levemir)

Cannot mix with other insulins

LONG DURATION

Insulin glargine (Lantus)

• Cannot mix with any others, 24 hr duration• AE –– hypoglycemia (too much insulin): tachycardia, sweating, nervousness. Lipodystrophies (atrophic-hypertrophic),

rotation of sites prevents lipodystrophies– Treatment of hypoglycemia – must be rapid! – if conscious: OJ, sugar cubes, honey, corn syrup, non-diet soda,

glucose tabs. If unconscious: IV glucose (D50W) or glucagon

Administration Subcutaneous injection

Syringe and needle• Pen injectors• Jet injectors

Inhalation Exubera – off market Oct ‘07

Subcutaneous infusion Portable insulin pumps

Implantable insulin pumps Intravenous infusion

• D/D – – hypoglycemic agents, alcohol, hyperglycemic agents (thiazide diuretics, glucocorticosteroids, sympathomimetics-

stimulates adrenalin which produces sugar for ForF), beta blockers (slows HR and drops BP-masks sx of hypoglycemia)

Antidote – Glucagon: exact opposite of insulin, may see response in 20 mins in unconsious pt, no effect on hypoglycemia of starvation (no sugar to call out), relaxes GI smooth muscle

Insulin Storage Refrigerated• DO NOT FREEZE• Current use vial – room temp ok for 1 mo.• Pre-filled syringes

Refrigerate• Needle up• Agitate before injection

Therapy Regimens Tight control- produces better management – people who are checking their sugar many times a

day??• Conventional Therapy (look up) – none at lunch or bedtime

Adverse Effects Hypoglycemia (less than 50 mg/dL)

Acute -tachy, palpitations, sweating, nervous, Slow – HA, drowsiness, fatigue, confusion• Overdose (of insulin)

Food, GI, ETOH, Exercise, and childbirth Treatment – must be rapid!

If conscious: OJ, sugar cubes, honey, non-diet soda, glucose tabs, corn syrup• If unconscious: IV glucose (D50W) or glucagon

Lipodystrophies (atrophic – hypertrophic) D/D

Hypoglycemic agents Oral hypoglycemics

ETOH Hyperglycemic agents

Thiazide diuretics Glucocorticosteroids (“sweet poison”) Sympathomimetics Beta blockers

Delay awareness of hypoglycemia and impairs glycogenesis

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Glucagon Exact opposite effect of insulin

In unconscious – may see response in 20 min. No effect on hypoglycemia of starvation Relaxes GI smooth muscle

Use in endoscopyAntihistamines: 1 st Generation dyphenhydramine [Benadryl] H1 Antagonists (classic antihistamines)

• MOA– Blockers (1st Gen)

• Selectively bind to histaminic receptors• Can also bind to nonhistaminic receptor (muscarinic)

• Therapeutic Effects (TE)– Vessels (If blocks histamine, then ?)– Capillaries (If blocks, then ?) shrink,, not ngorged- edema goes down– Sensory nerves (If, then) – itching relief– Mucous membranes (If, then) dryness– CNS

• Therapeutic doses (If, then) - sedation• Overdose – stimulation, seizures – esp. in young

– Other: relieve N & V, motion sickness– Clinical uses

– Mild allergies, seasonal rhinitis, acute urticaria, allergic conjunctivitis, mild transfusion reactions– Some block muscarinic & H1 receptor sites – useful for motion sickness

• promethazine [Phenergan] and dimenhydrinate [Dramamine]– Insomnia (diphenhydramine [Benadryl])

• Adverse Effects– CNS

• Sedation = to excess ETOH (If this, then?)• Dizziness, lack of coordination, confusion; take at bed time, don’t drive, elderly and children need to be

cautious. • Paradoxical: insomnia, excitation, tremors, convulsions

– GI• N, V, Diarrhea / constipation, loss of appetite

Dry mouth, throat nasal passages, thickened secretion, urinary hesitancy, constipation, palpation– Anticholinergic effects – Cardiac Dysrhythmias w some 2nd Gen.

• Torsades de pointes, V-fib • terfenadine [Seldane] & astemizole [Hismanal]

• Contraindications – third trimester• Precautions: asthma ( bronchio constrictions, antihistamines thicken secretion..), children/elderly, urinary

retention, HTN, OA(open angal) glaucoma, prostatic hypertrophy • D D D

• ETOH, barbs/benzos/ opioids • Toxicity

• Sxms similar to atropine poisoning (anticholinergic), hyperpyrexia• Can lead to death in children via excitation, hallucinations, convulsion, coma, CV collapse, death.• Tx: remove and support – may use charcoal to bind with it followed with cathartics to remove it

Cox InhibitorsCox 1 vs Cox 2 (sometimes referred to as prostaglandin) Cox 1 Enzyme Only

• helps prevent gastric ulcers(protects stomach)• causes platelet aggregation (bad for heart disease)

Cox 1 & 2 • Both maintain renal Function, dilation and perfusion

Cox 2 enzyme only• Causes inflammation (bad for RA • Causes fever• Causes pain • Causes fever

COX InhibitorsAnti-inflammatory properties NSAIDs – Non steroid anti-inflammatory drug

1 generation drugs (Asprin)• inhibits both cox 1 and cox 2 enzyme

2nd generation (celebrex)• Is selective to only inhibiting the effects of COX 2 enzyme

Non- anti-inflammatory propertieso Acetaminophen (Tylenol) is a cox inhibitor, but does not have anti-inflammatory properties

Tylenol (2nd generation properties but Anti-inflamtory• MOA - Inhibits prostaglandin synthesis in CNS• Uses – pain, fever – not anti-inflammatory• Benefits – Ø GI (maintain protection in stomach( no ulcer development) ,on bleeding(doesn’t effect platelets),

renal impairment• Adverse effects– Hepatotoxicity Tylenol has its main affect in the liver…(4g/d)– ETOH connection (¯g/d) lower Tylenol intake

• Acute Toxicity – Sxms 24-72 h post OD– N,V, D, sweating, abd. pain, liver failure, coma– Mucomyst the antidote for Tylenol overdose if given within 24h

Aspirin acetylsalicylic acid (ASA NSAIDs – Non steroid anti-inflammatory drug 1 generation drugs Non-selective(COX Inhibitor of both COX 1&2) MOA / TE / Uses

– Analgesic, antipyretic, anti-inflammatory– Suppression of platelet aggregation(irreversible for * days, life of platelet

• Treat / prevent Ischemic stroke (makes blood flow smoothly) not hemorrhagic stroke, TIA, MIs (acute & old), anginas, addition to angioplasty & revascularization

• Dysmenorrhea (cramps) • Cancer prevention• Prevention of Alzheimer’s disease, not in treatment• An initial DOC for RA and juvenile arthritis• Dose related to use!

• ADME– Rapidly absorbed orally, slower rectally– Half-life (2 h to 20 h)– Distributes to all body tissues – pregnant? Contraindicated in pregnancy– Excretion pH dependent (increase pH increase excretion 4x)

• Side effects– Gastric distress, heartburn, nausea

• Adverse effects– Gastrointestinal – (occult (hidden) and overt)– Bleeding– Renal impairment – Signs?

• acute/reversible – Na+/H2O• Pre-existing condition dependent• Cox1 is a broud specrum and 1st generation Imparest the benefit of the cox 2 side, whch means can

damage the kidneys– Salicylism (over dose of aspirin)– acid/base – tinnitis (symptom of ringing in the ears) often irreversible– Reye’s syndrome( liver failure) in children, so contraindicated in use of children.– Hypersensitivity – asthma –ranges from rhinorrhe to shock

• Contraindications– PUD & Bleeding disorders– Hypersensitivity– Extreme caution in pregnancy

• DDD– Anticoagulants & other NSAIDs– Glucocorticoids supress the effects of prostoglandin.. (gastric ulcertion)– Ibuprofen – impairs cardioprotective properties

• Acute Poisoning– LD (lethal dose) adult = 20-25 g - LD children = 4 your body becomes acidic– Sxms

• Resp excitation ® depression ® • Hyperthermia, stupor, coma, death

– Treatment• Supportive, charcoal, alkalinization of urine to help ecrcretion , and dialysis

2 nd Gen Selective Cox Inhibitors Prototype: celecoxib (Celebrex)

• Benefits –lower GI bleeding risk• Uses

– OA, RA, Acute pain, dysmenorrhea – Familial adenomatous polyposis – NOT cardioprotective

• Adverse effects– Dyspepsia, Abdominal pain– Renal toxicity– GI ulceration / bleeding– Sulfonamide allergy

Acetaminophen (Tylenol) is a cox inhibitor, but does not have anti-inflammatory properties• MOA - Inhibits prostaglandin synthesis in CNS• Uses – pain, fever – not anti-inflammatory• Benefits – Ø GI, bleeding, renal impairment• Adverse effects

– Hepatotoxicity (4g/d)– ETOH connection (¯g/d) lower Tylenol intake

• Acute Toxicity – Sxms 24-72 h post OD– N,V, D, sweating, abd. pain, liver failure, coma– Mucomyst the antidote for Tylenol overdose if given with in 24 h –

Glucocorticosteroids (immunosuppressant) in Non-endocrine Diseases Physiology

• Artificial nearly identical to natural, if you use you lose• Metabolic effects

– Breakdown of fats, proteins, carbs - glucose– Robs proteins for glucose production– Fats redistributed long-term to “moon” face

• Cardiovascular– Low levels – cause permeable vessels, dilated vessels, with hypotension– Increase RBCs and PMN (polymorhonucular) Leukocytes– Decrease Lymphs, Eosins, basophils, and monocyts– Effects during stress - define Glucocorticosteroids are produce increasing amount during stress– Large qty glucocorts / epi secreted– If inadequate sreroids – circulatory failure® – Effects on water and electrolytes– Aldosterone effect – increased Na+,? H2O, decreases K+; hypokalemia – High doses – impair intestinal calcium absorption (hypocalcemia)– Respiratory system in neonates – RSD– Inhibits prostaglandins, leucotriens, and histamines – hinder phagocytes and lymphocytes in the inflammatory response

• TE / Uses– Anti-inflammatory and immunosuppressant effects (high doses)– Rheumatoid arthritis (Autoimmune disorders)– Systemic lupus erythematosus – Inflammatory bowel disease– Miscellaneous inflammatory disorders– Allergic conditions– Asthma

– Dermatologic disorders– Neoplasms – toxic to malignant lymphocytes– Stimulates appetite– Suppression of allograft rejection– Prevention of respiratory distress syndrome

• Adverse effects– Adrenal insufficiency– Osteoporosis (resorption, rebuilding & calcium)– monitor for bone loss, use calcium and Vit D supplement– common can cause hyperglycemia– Infection – esp. Pneumocystis Carinii Pneumonia (PCP)– Glucose intolerance, can cause Diabetic– Myopathy – Fluid and electrolyte disturbance, monitor for fluid excess(crackes, weight gain edema – Growth retardation– Psychologic disturbances– Cataracts and glaucoma– Peptic ulcer disease, Do take wth asprin, choose tylenol– Iatrogenic Cushing’s syndrome– Use in pregnancy and lactation

• DDD– Interactions related to potassium loss, whatever Na increases, K decreases– Non-steroidal anti-inflammatory drugs– Insulin and oral hypoglycemic – Vaccines. Won’t get the inflammation response, or the immune response you looking for

• Adrenal suppression– Atrophy– Stress & “flat” response (Alt. day Tx)

• Glucocorticoid withdrawal– Don’t stop taking immunosupreants abruptly– Taper over 7 days– Switch from multiple doses to single doses– Taper the dosage to 50% of physiologic values– Monitor for signs of insufficiency, remember if you use the drud the adrenal gland normal exretion of this is

limited.. natural soiu• HypoTN, hyoglycemia, myalgia, arthralgia & fatigue

Drugs Affecting Calcium Levels and Bone MineralizationCalcium Physiology

• Critical to skeletal, nervous, muscular, and cardiovascular systems• Body stores – review, bones store 99% of calium• Absorption – occurs in the gut

– with PTH & vitD – Glucocorticoids – effect? Impair absorbtion in the gut

• Excretion in kidneys– Calcitonin augment (Boost) calcium eliminationVitamin D, calcitonin, and parathyroid hormone are essential in the metabolism of calcium.

Hypercalcemia: Drug Therapy • Usually asymptomatic (don’t know)• Causes: PTH, Vit D toxicity, thiazides (diuretic)• Drug Therapy

– Promote urinary excretion – furosemide & IV saline – Decrease mobilization from bone

• calcitonin, bisphosphonates, inorganic phosphates, gallium nitrate– Decrease intestinal absorption

• glucocorticoids

Hypocalcemia: Drug Therapy• Increases neuromuscular excitability• Causes: ¯PTH, ¯Vit D & Ca++

• Clinical presentation– Tetany, convulsions, and spasm of the pharynx Treatment

• Treatment– IV Calcium (calcium gluconate)– Vitamin D

Drugs for Ca++ Disorders: (IV bisphosphanates)Prototype: Alendronate (Fosamax)

• MOA – TE – Uses– Structural analogs of pyrophosphate of bone incorporated into bone and inhibit resorption by decreasing osteoclast activity and – used to treat osteoporosis, glucocorticoid induced osteopororis, Paget’s, and hypercalcemia of malignancy.

• ADME - CRITICAL! • Bioavailability drops if taken with food (0.7%) or drinks other than water (60%)! • Remains for decades once incorporated• Never to be taken with cofee or tea, food • only with water

• Adverse effects– Esophagitis – implications usually with IV admin– Ocular inflammation– Osteonecrosis of the jaw (ONJ) – mostly IV

ExpectorantsPrototype - guaifenesin (Mucinex)

• MOA / Use – increases flow of respiratory tract secretions• Makes cough more productive

Sympathomimetics (Decongestants ) mimics the sympathetic (sympatheic sytem) fight or flightPrototype: phenylephrine (Neo-Synephrine)

• Action / Uses - Reduce nasal congestion via ?– Topical - rapid and intense– Oral - prolonged, moderate, systemic effects– Also used in sinusitis and colds

• Adverse effects– Rebound congestion depends if allergin is still around– CNS stimulation– Cardiovascular caution HTN– Hemorrhagic stroke w phenylporpanolamine – Abuse (pseudoephedrine and ephedrine)

– Nasal sprays– 2 – 3 sprays every 4 hours needed – not to exceed 5 consecutive days

Pseudoephedrine

Proton Pump Inhibitors Prototype - omeprazole (Prilosec)

Action / Uses – suppress secretion of gastric acid – Irreversible - days - up to weeks after cessation; Superior to H2RAs

Adverse effects– HA, diarrhea, N & V; Long term may increase risk of CA

ADME – give 30 min before meal – once daily

D/D, D/F– Reduced absorption of atazanavir, ketocanazole and itracanazole – NOT recommended concurrently with atazanavir

Famotadine (Pepcid) For heartburn, acid indigestion, sour stomach Cut dose in renal compromise/ failure

No antiandrogenic effects No effect on hepatic metabolism of other drugs

Histamine2-Receptor AntagonistsPrototype: cemetadine (Tagamet)

First choice for gastric / duodenal ulcers Action / Uses:

– Promote healing through acid reduction– GERD, Aspiration Pneumonitis in obese & gyne prior to anesthesia

Adverse effects– Low incidence of gynecomastia, reduced libido, impotence, CNS depression / excitement, pneumonia

D/ D– Inhibits hepatic drug metabolism – therefore? Major Drugs of concern – warfarin, phenytoin, theophylline,

lidocaineBulk-formingPrototype(s): methylcellulose, psyllium (Metamucil)

• Action / Use– Behave like dietary fiber – nonabsorbable – swell to form viscous solution / gel and softening fecal mass and

increasing transit.– Temp relief of constipation, diarrhea, irritable bowel, ostomies

• Adverse effects– Esophageal & intestinal obstruction if not enough fluid ® ?

(If this, then?)StimulantsPrototype(s): bisacodyl (Dulcolax), senna (Senekot)

• Action / Legitimate Uses– Directly stimulate gut motility, increase secretion of water and ions into intestine, and reduce water and

electrolyte absorption.– Uses: Treatment of (1) opioid-induced constipation and (2) slow transit constipation

• Dosage: related to formulation administered– Take bisacodyl no sooner than 1 hour after ingesting milk or antacids – do not crush

• Adverse reactions– Bowel rupture can occur

CephalosporinsPROTOTYPE: Cefalexin (Keflex)

• MOA/Use– Cephs are most widely used of antibiotics (22)– Beta-lactam antibiotics– Similar to penicillin – bactericidal

• ADME– Usually given parenterally – Renal excretion (Probenacid)

• Adverse effects– Hypersensitivity & anaphylaxis– Thrombophlebitis – AAPMC fr. C-Diff (Antibiotic-Associated Pseudomembraneous Colitis– Three agents (cefmetazole, cefoperazine, cefotetan)

• ¯PTT, Bleeding, Pain at injection site• ETOH intolerance

• DDD– Probenacid

• keeps drug in system longer b/c it impairs excretion from the kidneys– ETOH intolerance

• Induce a state of alcohol intoleranceIngestion of alcohol- disulfiram-like reaction could occur Must not consume alcohol in any form

– Disulfiram/antabuse First generation

Cefazolin [Ancef]

– Highly active against gram + bacteria– Most active of all cephalosporins against staphylococci and nonenterococcal streptococci– Be given only to patients with a history of mild PCN allergy– Employed widely for prophylaxis against infection in surgical patients– Have only modest activity against gram – bacteria and don’t reach effective concentrations in CSF– As effective as the newer drugs, less expensive, have more narrow spectrum

Second generation Cefaclor [Ceclor]

– Enhanced activity against gram – bacteria– Increase is due to a combo of factors:

• Increased affinity for PBPs of gram – bacteria• Increased ability to penetrate the gram – cell envelope• Increased resistance to beta-lactamases produced by gram - organisms

– None is active against Pseudomonas aeruginose• Don’t reach effective concentrations in CSF• Used against pneumonia caused by H. influenzae, Klebsiella, pneumococci, staphylococci• Oral is useful for otitis, sinusitis, RTI

Third generation Cefoperazone [Cefobid]

– Increased resistance to beta-lactamases, considerabley more active against gram – aerobes than 1st & 2nd generation

– Some have important activity against P. aeruginosa, other lack activity– Reach clinically effective concentrations in CSF– Drug of choice for meningitis caused by enteric, gram negative bacilli

Fourth generation – β-lactamase resistant Cefepime [Maxipime]

– Highly resistant to beta-lactamases– Activity against P. aeruginosa equals that of ceftazidime– Penetration to CSF is good

CSF Distribution Curve, & Spectrum of Cephs Spectrum, CSF, and Betalatamase susceptibility– Half lives of cephs range from 30 min to 9 hrs – Only 3rd and 4th agents achieve CSF concentrations– Most eliminated by kidneys– Many must be absorbed by IM or IV, only 12 can be given orally

Monobactam PROTOTYPE: Vancomycin [Vancocin]

**Always try another drug before you use Vanco (used to be this way, but now MRSA is becoming more widespread) Used to fight MRSA (very hard to fight if the infection is in the bones)

• MOA / Uses– Disrupts cell wall– Used in severe infections and DOC MR s. aureus or s. epidermis– Used to treat C. Diff

• ADME– Poor oral absorption– Poor CSF

• Adverse effects– Ototoxicity (ear) – esp. when taken w/ others

– If a patient is on Vanco, you need to check patient’s hearing (signs: tingling, ringing in ears, hearing loss) – sometimes reversible, but not always

– Thrombophlebitis – dilute– can cause painful infection & possibly a clot (check IV site regularly – ask patient if it hurts, look for swelling,

palpate area)– Allergy– Red Man Syndrome w rapid infusion

Tetracyclines PROTOTYPE: tetracycline (Sumycin)

• MOA / Uses– Inhibits protein synthesis – broad spect. used in rickettsial disease, Chlamydia trachomatis, lyme disease, acne,

PUD, and peridontal disease• ADME

– ¯ absorption w Ca+, Fe-, Mg++, laxatives, antacids, milk• Adverse effects

– Gastrointestinal - esophageal• Prevention? Dosing? Meals?

– Effect on bone and teeth, will become weak and brittle – Superinfection - AAPMC – Hepatotoxicity – Renal toxicity – prevention/contraindication Bone & teeth will become weak and brittle – Contraindicated in patients who are renal impaired (patients need to take drug with lots of water) Be careful:

congested heart failure patients sensitive to lots of water– Photosensitivity – prevention

• Sunscreen & limit sun exposure while on drug– Pregnancy & children under 8

• Preparations, Dosage, Administration Systemic infection- admin. Intermittent infusion over 60+ min– Usual adult dosage: 2 mg/day in divided doses at 12 or 24 hr intervals– Children dosage: 22 mg/kg/day in divided doses at 6 or 12 hr intervals– Renal impairment- dosages reduced

• Peak blood levels should be drawn at 1.5 hr to 2.5 hr after completing IV infusion- normal = 30 to 40 mcg/mL Oral- treatment of antibiotic associated pseudomembranous colitis

– Adult dosage = 125 to 500 mg every 6 hr– Child dosage = 11 mg/kg every 6 hours– Renal impairment- dose not need to be decreased b/c it is not absorbed in GI track

Chloramphenicol [Chloromycetin]• Broad spectrum antibiotic• Inhibits protein synthesis• Uses

– Only for life-threatening infections for which safer drugs are ineffective or contraindicated • Adverse effects

– Reversible bone marrow depression• your body won’t make as many RBCs, WBCs, and platelets – turns into aplastic anemia (without)

– Aplastic anemia – potentially fatalSpecial Concepts r/t Anitmicrobials

Selective toxicity– Ability to target without harming host

Susceptibility (1+2+3+4+)– Sensitive<1

Prophylaxis– Neutropenia, Surgery, Endocarditis (valvular heart disease or artificial valve have to have prophylactic antibiotic)

Combination Therapy– Use 2 drugs to achieve a purpose

Misuse – non-specific fevers, viruses (antibiotic not indicated but if immunocompromised might use prophylactically)

Aminoglycosides: Background Resistance is beginning to limit use

Gentamicin – cheaper but commonly used Used to treat local bugs

20 diff aminoglycoside-inactivating enzymes Inactivated by 20 enzymes

Reserve amikacin (Big Guy) Bactericidal

concentration dependent More you get the more it kills

Post-antibiotic effect – several hours NOT effective against anaerobes (not used in gut)

Gentamicin (Garamycin) MOA / Use: narrow spectrum for gram- bacilli – esp. pseud. aerugenosa, E. coli, Klebs., Serratia ADME:

Poor CSF Not absorbed orally (so? Typically IV)

– High levels in gut so will kill gut bugs Toxicity w/ wound irrigation

– Has to have peak & trough– Absorbed into system when used to irrigate wound

Binds tightly to renal tissue– Monitor closely and reduce dose for renal compromised

Excretion primarily renal Dosage varies widely (0.5 mg/kg to 25 mg/kg)

Adverse Effects Ototoxic – r/t excess trough levels – sensory hairs

Want trough to go below the trough line between doses to keep from being ototoxic HA, N, vertigo then high-pitched tinnitis (Action? Stop the dose first then call Dr) Nephrotoxic – r/t Total cumulative dose– ATN (acute tubular necrosis) (proteinuria, casts (slough), BUN, Creatinine – Elderly & young

Neuromuscular blockade Hypersensitivity & blood dyscrasias (rare but can happen)

DDD p998 – PCNs, Cephs, Vanco used in combo– PCNs inactivate – schedule issue?– Ethacrynic Acid – potenciate the ototoxicity – Other nephrotoxics – Skeletal Muscle relaxants

Resp arrest Special Concerns

Neomycin most nephrotoxic – Not used IM, IV– PO = sterilize gut– Topically used

Scheduling once daily – Safer?– Post-antibiotic effect– Washout – esp. in vestibule and kidneys– Typically only measure trough – up to 1hr prior to next dose – level should be ?

Antifungals Systemic mycotic (fungal) infections

Opportunistic – host is immunocompromised/debilitated pts o Candidiasis

– Colonized on you already– Warm moist areas

– Thrush in mouth– Combination therapies (antifungal, antibiotic, antifungal)

aspergillosis, cryptococcosis, Non-opportunistic

blastomycosis, histoplasmosis, coccidioidomycosis Superficial mycotic infections

Candidiasis Dermatophytes

Amphotericin B [Fungizone] MOA / TE

Broad spectrum antifungal agent binds to ergosterol component of fungal cell wall and increases permeability. DOC for most progressive, potentially fatal systemic mycoses – Use when bug is going to kill the person– Highly TOXIC to people

ADME Highly toxic (sterols)

– Breaks down bugs sterols along with persons Poor GI absorption - SLOW IV USE ONLY Poor CSF Watch pt carefully

Adverse effects – almost 100% - varying Phlebitis so give slow Fever, chills, nausea (all common)– pre-treat w benadryl / acetaminophen to reduce effects of side effects Nephrotoxicity – residual if 4 g/day, 1 L NS, Monitor q 3-4 days

– Treat c NaCl – Monitor urine for protein & serum creatnine – Hydration status will change BUN

Hypokalemia – Monitor K

Bone marrow suppression– Decreased CBC

DDD: nephrotoxics – flucytosine

Drugs for Superficial Mycoses Dermatophytic infections (e.g., ringworm)

Tinea pedis, tinea corporis, t. cruris, & t. capitis

Griseofulvin (Grifulvin V) MOA / TE

Superficial mycoses only – inhibits fungal mitosis – incorporates into keratin Adverse effects

Transient headache, rash, GI Contraindicated in hepatocellular disease

– Liver intensive– Closely monitor if have liver disease

DDD Decreases warfarin

Antivirals Dilemma

Mutate readily c resistence Live inside the cell nucleus Harder to treat because harder to target

Types HSV (Herpes-simplex) more sensitive to anti virals

Genitalia, mouth, face (HSV-2) VZV (Varicella Zoster) moderately sensitive

Chicken pox – Shingles

CMV (Cytomegalovirus) less sensitive = more resistance Prototype: Acyclovir [Zovirax]

MOA / TE: Suppress synthesis of viral DNA and is useful in treating HSV1,2 & VZV – no cure Adverse Effects

• Intravenous: reversible nephrotoxicity, phlebitis– Infuse slowly – hydration – during & 2 hr after

• Oral: GI, vertigo• Topical: stinging

Nursing Implications• Resistance – type of clients

– All pt on drugs long term HIV – trying to develop new drugs to decrease resistance– Goal to get viral load low (SVR/VL)

• If severely immunocompromised then IV therapy is indicated– IV indicated for oral lesions in

• STI control– Not mean that you are safe if you take the drug– Herpes can colonate in other areas besides genitals (can be legs too)

Condom not always keeping you safe No sexual contact during an outbreak

• Treatment for VZV in elderly and children (w/in 24 hr)• ONLY give po (low availability), can be used topically or IV (double check)

– NO IV bolus, NO IM, or NO SubQ injections• Valacyclovir [Valtrex] – prodrug that increases oral bioavailability (alone not available to use) by 55%

– Without regard to mealsInterferon alfa (Peg-Intron)immune modulatory, antineoplastic, antiviral

MOA / TE Blocks entry of virus, synthesis of viral m-RNA and proteins, and viral assembly. Tx of chronic Hep B & C

Hep B - vaccinate ADME

Pegylated - makes drug longer acting Only parenterally (subQ)

Adverse Effects Flu-like (fever, myalgia, HA, fatigue) & significant depression Long/High dose – thyroid dysfunction, heart damage, bone marrow suppression Alopecia (lose hair), GI, injection site pain, bruising

Ribavirin (Rebetol) MOA unclear

Used with Interferon A - together are DOC for Hep C (HCV). Therapy 24 to 48 weeks. Goal is SVR – sustained virologic response (loss of detectable viral RNA)

Lower the viral load = is goal Adverse effects

Hemolytic anemia Broken RBCs= increased Fe levels Trash can clot vessel

Teratogenic (Category X) – two forms of BC Dosage based on weight