Definitions

Pharmacology Study of drugs

Pharmacology for Physical Therapists

Linda Lawless, Pharm.D. Paul LaStayo, Ph.D.,PT

Pharmacokinetics
Absorption, distribution, metabolism, and excretion of drugs

Pharmacodynamics
Biochemical and physical effects of drugs on the body

Pharmacotherapeutics
Use of drugs to treat diseases

Pharmacoeconomics Pharmacogenomics

Definitions
Pharmacophysicaltherapy Physicalpharmacotherapy Physiotherapeuticpharmacology Rehabilitativepharmacotherapeutics

Terminology
Chemical name Generic name Brand (Trade) name Drug class Over-the-Counter (OTC) vs Rx

How a chemical becomes a drug

Pre-clinical work
Lab Animal model

How a chemical becomes a drug

Phase III
Larger patient population
Efficacy and safety

Food and Drug Administration (FDA)

Investigational new drug (IND)

Phase IV
Post marketing analysis, safety

Phase 1
Healthy volunteers with exceptions
Kinetics and safety

Expedited or fast-track
Oncology, HIV

Phase II
Patients with disease being treated
Dose and safety

Methods of Administration
Oral (po)
Buccal, sublingual, gastric

Methods of Administration
Topical
Patch, cream, ointment, lotion, gel, ophthalmic, otic, nasal

Injection
Intradermal, subcutaneous (SC, SQ) Intravenous (IV) Intramuscular (IM) Intrathecal (IT) / epidural Intraosseaus (IO) Intrarticular (IA) Intraperitoneal

Respiratory
Metered dose inhaler (MDI), SVN, ET tube

Rectal / Vaginal

P-Kinetics
Absorption factors
Drug formulation Method of administration Blood supply First pass effect Food Patient specific physical factors

P-Kinetics
Distribution factors
Blood supply Solubility Protein binding

Metabolism factors
Liver disease and heart failure Genetics Age and stress

P-Kinetics
Excretion factors
Kidneys / urine, age, heart disease

P-Dynamics
Agonist Antagonist
Competitive / Noncompetitive

Onset, peak, duration Half life (t )

4-5 t s = steady state

Selective / Nonselective Potency Therapeutic index

Pharmacotherapeutics
Acute therapy Empiric therapy Maintenance therapy Supportive therapy Palliative therapy

Drug Interactions
Drug-drug interactions
Enzyme induction in liver Protein binding competition P-kinetic changes Potentiation Antagonistic effects

Adverse Drug Reactions (ADRs)

May be useful Difficult to predict
Individual differences

Drug allergy
Hypersensitivity not always anaphylaxis Symptoms vary: rash, itching, wheezing, swelling, gi, anaphylaxis

Food-drug interactions
P-kinetics changes

Classifications & Compliance

Antacids 17% Estrogens 42% Antihypertensives 61% Diabetic 78% Cardiac 89%

PAIN

Pain Definition
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
Merskey 1986

Pain Definitions
Acute pain Chronic pain
Nociceptive Neuropathic Idiopathic Mixed

Or Whatever the patient feels it is

Barriers to Adequate Pain Control

No access to services for pain control
Geographic, cultural, language, financial barriers Communication barriers Inadequate education of health care providers Inadequate numbers of facilities such as pain clinics

Barriers to Adequate Pain Control

Lack of knowledge about appropriate use of pain meds
Inadequate dose PRN rather than RTC Poor dose titration Failure to use adjuncts or non-pharmacologic methods

Barriers to Adequate Pain Control

Misconceptions
Minimizing patients reports of pain Belief that chronic pain is untreatable Fear of tolerance Fear of adverse effects

Tolerance, Dependence, Addiction

Tolerance
Disease progression is a factor Stable disease = less tolerance

Physical dependence
Tapering important

Addiction
Rare when treating pain

Pseudoaddiction
Solution = adequate pain control

Pain Assessment
At regular intervals At each new report of pain At suitable interval after Rx Initial Assessment
History Physical exam Psychosocial assessment Diagnostic evaluation

Pain Assessment
Patient Self-Report
Pain quality Location Intensity or severity Aggravating or relieving factors Cognitive response to pain Goals Palliation, Quality, Response, Severity, Time

Pain Assessment
Adults and children > 7 years old
0 10 scale Categorical scale Visual analog scale

Children < 7 and adults with cognitive impairment

Smiley face scale

Reassessment
Compliance, adverse effects, use Effectiveness at appropriate interval Positive and negative effects of nonpharmacologic treatments

Pharmacologic Agents
General Principles
Drug therapy most effective when combined with non-pharmacologic strategies Combinations of smaller doses of different drug classes may reduce risk of side effects

World Health Organization ThreeStep Analgesic Ladder

AHRQ Guidelines
Pain Score 14 56 >7 Recommended Treatment NSAID or APAP Weaker opioids MS, oxycodone, hydromorphone, fentanyl

Non-opioid analgesics
Ceiling effect for analgesia NO tolerance, physical or psychological dependence Antipyretic Should be part of an analgesic regimen unless contraindicated

Aspirin
Mild pain GI upset and bleeding preclude use Never use in children < 12 years old with viral illness Salicylate salts (choline magnesium trisalicylate, salsalate)
Possibly less affect on bleeding time and platelet aggregation No data in patients with severe clotting abnormalities

Acetaminophen
Mild pain Superior adverse effects profile Low cost Hepatotoxicity
Maximum 4gm/day Caution in alcoholics, liver disease, fasting

NSAIDs
Diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, sulindac

Mild to moderate pain Bone pain Variable response to different NSAIDs Reversible inhibition of platelet aggregation
Relative contraindication in anticoagulation, coagulopathy, thrombocytopenia

NSAIDs
GI effects
Most susceptible: steroids, previous ulcers, extremely ill, advanced age

NSAIDs
Nephrotoxicity: Increased risk
CHF CRF Cirrhosis with ascites SLE Dec. intravascular volume Diuretics Elderly Multiple Myeloma

Ibuprofen <1600mg/day & diclofenac possibly lower risk Tolmetin, ketoprofen, piroxicam possibly highest risk Prevention
Avoid ETOH H2 blocker, misoprostol, PPI, COX-2 inhibitor

NSAIDs
All NSAIDs can cause ARF
More likely with high dose

Opioids
Moderate to severe pain Underutilized in chronic non-cancer pain Psychological dependence and addiction extremely rare if using opioid for pain Challenge: efficacy versus side effects Chronic pain often requires around the clock (RTC) dosing plus short-acting for breakthrough pain

Abrupt onset of oliguria with sodium and water retention DC NSAID

Opioids
Watch APAP dose when using combo products Avoid agonist/ antagonist Avoid meperidine Doses for non-cancer pain often smaller and more constant

Opioids
Mild-Moderate Pain (po)
codeine oxycodone/APAP meperidine propoxyphene hydrocodone/APAP tramadol

Severe Pain (po, IM, IV, SQ, transdermal)

morphine hydromorphone oxycodone methadone levorphanol fentanyl oxymorphone meperidine

Opioids
short-acting (PRN): codeine (converted to morphine by CYP2D6) meperidine morphine hydromorphone Oxycodone (combination products) hydrocodone fentanyl long-acting (RTC): morphine SR (MS Contin, Oramorph, Kadian) oxycodone SR (Oxycontin) methadone fentanyl transdermal patch (Duragesic)

Opioids Route of Administration

Oral
Generally preferred Some liquids available SL concentrates Transmucosal (fentanyl oralet)
Must have tolerance (60mg/day MS or more)

Rectal IM
Generally not recommended for chronic pain

SC or SQ
Bolus: Slower than IV Continuous Infusion: Alternative to IV

Opioids Route of Administration

IV
Bolus: Most rapid onset Continuous Infusion: Steady blood levels PCA: Patient Controlled Analgesia
Intermittent bolus Continuous infusion + bolus

Opioid Kinetics
Opioid t 1/2 Peak Usual Interval

Transdermal (fentanyl)
Not for acute pain Can accumulate

Intraspinal (epidural or intrathecal)

MS (preserv-free) or fentanyl

Codeine Hydromorphone Levorphanol Meperidine Methadone Morphine Oxycodone

3 hr 2-3 h 11-16 hr 2-3 hr 17-128 hr 2-3 hr 2-3 hr

0.5 - 1hr 0.5 - 1hr 0.5 - 1.5hr 0.5 - 1hr 0.5 - 1hr 0.5 - 1hr 1 hr

q4-6h q4-6h* q6-8h q3-4h* q4-8h q3-4h* ** q3-4h**

*IV more frequent dosing **SR formulations less frequent dosing

Opioid Equianalgesic Dosages

Opioid Codeine Fentanyl Hydromorphone Levorphanol Meperidine Methadone Morphine Oxycodone Oxymorphone IM(mg)* 130 0.1 2 2 75 10 acute 4 chronic 10 1 Oral(mg) 200 6 4 300 20 acute 4 chronic 30 20 -

Opioids
Transdermal Fentanyl (Duragesic)
Useful for chronic stable moderate to severe pain Useful if difficulty swallowing Increased compliance and reduced constipation Onset = 12 hours Steady state = 48 hours

*for IV boluses, use 1/2 IM dosage

Opioids
Transdermal Fentanyl (Duragesic)
Each patch lasts 72 hours Continued effects up to 17 hours after removal Requires breakthrough med 25 mcg/hr patch replaces approx 45mg/day MS Contin (package insert says 90mg/day) DO NOT APPLY HEAT TO PATCH

Patient Controlled Analgesia

sedation and anxiety patient satisfaction Patient selection important Drugs: Morphine, meperidine, hydromorphone, fentanyl Schedule: Continuous infusion, intermittent bolus, or both Route: IV, SC, epidural, intraspinal

Opioid Adverse Effects

Nausea, vomiting Mood alterations Drowsiness Respiratory depression Constipation Urinary retention Biliary colic Miosis Muscle rigidity Hypotension
histamine release, tachycardia (morphine) bradycardia (fentanyl)

Management of Adverse Effects to Opioids Nausea

Tolerance usually develops Antiemetics Switch drugs Convert to long-acting (smaller peaks)

Pruritus Seizures (meperidine)

Sedation
Tolerance usually develops Decrease dose or extend interval Can use stimulants (cautiously)
Methylphenidate 5-10mg po in am and noon Caffeine

Management of Adverse Effects to Opioids

Confusion/Hallucinations
Tolerance sometimes develops Antipsychotics
Haloperidol 0.5-1mg po bid-tid

Respiratory depression

Management of Adverse Effects to Opioids

Tolerance develops If naloxone necessary, dilute 0.4mg in 10ml NS and give in 0.5ml (0.02mg) increments q 2 min. until respiratory rate increases

Myoclonus
Mild myoclonus worse for observer More common with high dose Clonazepam 0.25-0.5mg po tid, lorazepam, diazepam, baclofen

Constipation
Tolerance DOES NOT develop Usually oral route Patient on chronic opioids usually needs laxative plus stool softener
Pericolace, Docusate + senna

Non-opioids (Adjuvants)
Neuropathic pain
Tri-cyclic antidepressants
Amitriptyline, desipramine, doxepin

Non-opioids (Adjuvants)
Bone pain
Pamidronate (and others)
90mg IV over 90 minutes q 4 weeks

Anticonvulsants
Carbamazepine, gabapentin, valproic acid, phenytoin, pregabalin

Calcitonin Radiopharmaceuticals

Corticosteroids
Short tapering doses useful for acute pain Avoid long term use Useful for CNS metastases

Non-Pharmacologic Treatment of Pain

Education Cognitive-behavioral therapy Exercise Acupuncture Transcutaneous nerve stimulation Chiropractic Heat, cold, massage Relaxation and distraction techniques

Osteoarthritis

Epidemiology
Degenerative process which begins by age 20 years Most prevalent form of arthritis in the US:
30 years - 40% population affected 75 years - >85% have disease evidence

OA Treatment Goals
Maintain ability to function Relieve joint inflammation and pain Prevent joint destruction Preserve quality and style of life

Most common cause of chronic disability

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Non-Drug Therapy
Physical therapy (ROM, water aerobics, strengthening exercises) Diet, weight loss Education (Self management programs) Appliances (OT, ADLs, joint protection) Surgery

Pharmacologic Therapy
Non-opioid analgesics
Acetaminophen 4gm/day

NSAIDs
Ibuprofen 3200mg/day

Opioid analgesics
Codeine, oxycodone

Actions of NSAIDs
Analgesia - Pg synthesis the sensitizing effect of Pgs on pain receptors Anti-inflammatory - Pg synthesis, inhibits other inflammatory mediators (bradykinin, histamine) Antipyretic - Pg synthesis sensitizing effect of Pgs in the posterior pituitary which controls temperature

COX -1 vs COX - 2
COX - 1 produced continuously for housekeeping functions of the organs/cells (GI cytoprotection, vascular homeostasis, renal function,etc..) COX 2 produced by macrophages and synoviocytes during an inflammatory process - inducible

NSAID efficacy
Every NSAID has some anti-inflammatory efficacy greater than placebo No NSAID has been shown to be more effective than aspirin No NSAID has been shown to be less effective than aspirin

March 23, 2007

Suffering Boomers want to fill Vioxx void Celebrex sales surge despite possible heart risks; firms seek OK on new pain drugs

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RA Treatment Goals Rheumatoid Arthritis

Pain control to improve function Disease management to prevent further degeneration

RA
Aspirin / NSAID initial therapy for pain
No effect on disease progression

Chronic Corticosteroid Adverse Effects

Adrenocortical suppression Cushing syndrome Hypertension Hyperglycemia Worsening of glaucoma and cataracts Catabolic effect on muscle tendon and bone osteoporosis, muscle wasting and weakness

Glucocorticoids (prednisone) pain

No effect on disease progression Often used short term for flare

Disease-Modifying Antirheumatic Drugs (DMARDS)

Help prevent disease progression

DMARDS
Chloroquine, azathioprine, cyclophosphamide, cyclosporine, etanercept, infliximab, adalamab, gold, leflunomide, methotrexate, penicillamine, sulfasalazine

TNF inhibitors
Etanercept (Enbrel), inflixumab (Remicade), adalamab (Humira)

Risk vs benefit is of concern Most have significant adverse effect profiles Earlier use appears more beneficial

Binds TNF and thus limits its ability to do joint damage Must be given parenterally
Etanercept - Usually 2 SC injections weekly (2 different sites) Inflixumab Usually loading dose IV then q 8 weeks Adalamab SC q 2 weeks

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TNF Inhibitors Adverse Effects

Hypersensitivity reaction to infusion of inflixumab risk of opportunistic infections Not to be used with anakinra

Anakinra (Kineret)
IL-1 receptor antagonist Daily SC injection infection risk if used with TNF inhibitor Most common ADR injection site reactions

Leflunomide (Arava)
Used for those who cant tolerate MTX Similar in efficacy to MTX MOA uncertain but may be TKI inhibitor Daily oral dose Adverse Effects: diarrhea, gi upset, alopecia, teratogenic

Abatacept (Orencia)
Costimulation modulator
Inhibits T cell activation

IV monthly Used if inadequate response to TNF inhibitor Cannot be used in combination with anakinra or TNF inhibitor Increased risk of infections Adverse Effects: HA, infections

Parkinsons Disease Pathophysiology

Parkinsons Disease
Disorder of the extrapyramidal system of the brain involving the basal ganglia Loss of melanin containing cells in the substantia nigra (dopaminergic activity) Progressive loss of the inhibitory transmitter dopamine in the nigrostriatal tracts and a relative increase in excitatory neurotransmitter acetylcholine Decreases in serotonin and norepinephrine are also present

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Parkinsons Disease Treatment

Initial treatment for early disease
Exercise Education Nutrition Speech Therapy Group Support

Anticholinergics
Block excitatory neurotransmitter acetylcholine in the substantia nigra Most effective in early disease when dopamine depletion is not substantial Improve tremor and rigidity, little effect on bradykinesia, postural imbalance or gait disturbances

Anticholinergics
All agents are equally efficacious benztropine (Cogentin) trihexyphenidyl (Artane) diphenhydramine (Benadryl) procyclidine (Kemadrin) biperiden (Akineton) orphenadrine (Disipal)

Anticholinergic Adverse Effects

dry mouth blurred vision constipation urinary retention increased intraocular pressure confusion memory impairment hallucinations

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Amantadine (Symmetrel)
Antiviral with unclear mechanism of action in treating Parkinsons All symptoms are improved within days of initiating drug in 50% of patients. Tachyphylaxis develops in 1 to 3 months; use drug holidays Especially effective against tremor

Amantadine Adverse Effects

Sedation, vivid dreams ( with time) Depression, hallucinations, anxiety, dizziness, psychosis, confusion Dry mouth, nausea, vomiting Livedo Reticularis in up to 80% of patients Eliminated renally so must dose adjust for poor renal function

Livedo Reticularis

Levodopa (Larodopa)
Crosses the blood-brain barrier where it is converted to dopamine by enzyme L-amino acid decarboxylase Peripheral conversion also occurs so doses need to be large to overcome this 80% of patients have improvement in symptoms, but may take up to 4 months to see full effect (due to dose titration)

L-dopa Adverse Effects

Most are caused by the peripherally circulating dopamine Nausea, vomiting, anorexia Postural hypotension, cardiac arrhythmias Confusion, depression, psychosis, vivid dreams
These occur in long-term therapy or in patients with underlying psychiatric disorders. Aggravated by anticholinergics and amantadine

Carbidopa
Dopa decarboxylase inhibitor that does not cross the blood-brain barrier Decreases peripheral conversion to dopamine ( levodopa dose by 80%) Response time increased (dont need slow titration to decrease side effects) Peripheral side effects decreased; mental side effects the same. Dyskinesias may develop more quickly

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Sinemet
Sinemet 10/100 = 10mg carbidopa + 100mg levodopa Short-acting and long-acting formulations

Honeymoon Period
Early phase of levodopa therapy where patients have good response May last for 3 to 5 years Many practitioners delay initiation of levodopa until patients are clearly bothered by the disease

On-Off Effects
Random fluctuations from mobility to the parkinsonian state suddenly as if a switch had been turned off Fluctuations can last for minutes to hours with increasing severity Occurs with long-term levodopa use No relationship between timing of doses or levodopa serum levels

Wearing Off Effect

End of dose deterioration More predictable effect Occurs at the end of a dosing interval following period of relief Can be improved by shortening the dosing interval or adding a dopamine agonist

Drug Holidays
Brief period of drug withdrawal Attempted to improve response and lessen side effects for patients on long-term levodopa therapy Allows striatal dopamine receptors to be resensitized Controversial and risky- many complications associated with immobility

Dopamine Agonists
Directly stimulate postsynaptic dopamine receptors in the corpus striatum All agents produce essentially the same clinical effects Improve efficacy of levodopa in patients experiencing response fluctuations May also be used as monotherapy in early stages of Parkinsons

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Dopamine Agonists
Mirapex - pramipexole Requip - ropinirole Permax - pergolide Parlodel - bromocriptine Neupro patch - rotigotine

Dopamine Agonists Adverse Effects

Nausea, vomiting Orthostatic hypotension, arrhythmias Peripheral vascular effects - Raynauds, angina, digital vasospasm Dyskinesias Confusion, hallucinations

Tolcapone (Tasmar)
Catechol-O-methyltransferase inhibitor that will increase response to levodopa Side effects
Nausea, vomiting, diarrhea, confusion, dyskinesias, orthostasis, HA Fatal liver disease

Entacapone (Comtan)
Catechol-O-methyltransferase inhibitor Adjunct to levodopa/carbidopa in patients with end-of-dose wearing-off Adverse Effects
hypotension, syncope, diarrhea, hallucinations, dyskinesias, rhabdomyolysis, hyperpyrexia, confusion

Contraindicated in patients with underlying liver disease (Black Box Warning)

Use caution in liver disease

Selegiline (Eldepryl)
MAO-B inhibitor (blocks dopamine metabolism) Blocks breakdown of dopamine so may extend levodopa effects; usually can decrease dose of levodopa Adverse Effects
insomnia, hallucinations, dyskinesias

Adjunctive Treatments
-adrenergic blockers
Useful to treat parkinsonian tremor in 50% of patients. Propranolol (Inderal) and nadolol (Corgard) have been used most often. Nadolol can be dosed QD and has fewer CNS side effects

Not effective as monotherapy

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Skeletal Muscle Relaxants Centrally-Acting Muscle Relaxants and Treatment of Spasticity

Baclofen, diazepam, tizanidine, carisoprodol, chlorphenesin, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, orphenadrine, tizanidine MOA: Unknown but may be related to CNS depression / sedation Use: Painful muscle spasms associated with inflammation or trauma

Skeletal Muscle Relaxants Centrally-Acting

Adverse Effects
Dizziness, drowsiness, gi distress, heartburn, diarrhea, ataxia, constipation, nausea, vomiting, arrhythmias, bradycardia, withdrawal if stopped abruptly

Skeletal Muscle Relaxants Direct-Acting

Dantrolene MOA: Interference with calcium ion release from sarcoplasmic reticulum and weakens muscle contraction force Use: Management of spasticity
Cerebral palsy, MS, spinal cord injury, stroke

Drug Interactions
Many Watch for additive drowsy and anticholinergic effects

Skeletal Muscle Relaxants Direct-Acting

Adverse Effects:
Drowsiness, dizziness, malaise, fatigue, and weakness, seizures, hepatitis

Drugs for Spasticity

Diazepam and baclofen both work by promoting the inhibitory effects of GABA on muscle contractions Diazepam causes more sedation and tolerance than baclofen Dantrolene causes more weakness than baclofen Baclofen is drug of choice

Drug Interactions:
Watch for additive effects from other CNS depressants

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Baclofen
Use: Primarily for paraplegic or quadriplegic patients with spinal cord lesions caused by MS or trauma Reduces number and severity of painful flexor spasms Does not improve gait stiffness, manual dexterity, or residual muscle function May be given intrathecally

Diabetes Mellitus

CAMP LEO!!!!

Diabetes Incidence and Prevalence

15.7 million people with diabetes in the US
5.9% of the population

10.3 million diagnosed 5.4 million undiagnosed (34%) 798,000 new cases diagnosed each year

Diabetes Incidence and Prevalence

Prevalence for people over 20 years old
7.8% in non-Hispanic white Americans 10.8% in non-Hispanic African Americans 10.6% in Hispanic Americans 5 50% in Native Americans

Metabolism and Utilization of Carbohydrate, Protein, and Fat

Insulin functions
uptake of glucose by muscle and fat liver glycogen stores glycogen breakdown (glycogenolysis) by liver synthesis of fatty acids breakdown of fatty acids into ketone bodies Promote incorporation of amino acids into protein

Leading cause of blindness in ages 20-74 Leading cause of ESRD Account for 67,000 lower extremity amputations annually

Pancreas secretes 0.5 1 unit / hr of insulin

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Metabolism and Utilization of Carbohydrate, Protein, and Fat

Total daily insulin release from normal pancreas = 25 50 units Normal plasma glucose concentrations = 60 160mg/dl Minimum glucose concentration for brain function = 40mg/dl Glucose can diffuse into CNS without insulin Muscle and fat require presence of insulin to receive glucose

Typical Characteristics
Characteristic Age at diagnosis Onset Etiology Antibodies and immunity Body weight Insulin Type 1 Childhood or adolescence Rapid Unknown Yes Thin Secretion diminished initially then absent, insulin therapy required Common Polyuria, polydipsia, polyphagia Type 2 Over 40 Gradual Unknown No Obese Levels may be low, normal, or high Uncommon Asymptomatic, polyuria and/or polydipsia may be present

Ketosis Symptoms

Complications
Macrovascular
Coronary heart disease, stroke, peripheral vascular disease

Goals of Therapy
A1C(%) 6 7 8 9 10 11 12 MeanPlasmaGlucose 135mg/dl 170mg/dl 205mg/dl 240mg/dl 275mg/dl 310mg/dl 345mg/dl

Microvascular
Nephropathy, retinopathy, neuropathy

Goals of Therapy
Whole blood
Fasting 80-120mg/dl Bedtime 100-140mg/dl 2 hour post-prandial < 180mg/dl

Insulin
Fast: Lispro (Humalog), aspart (Novolog),Regular Med: NPH, Lente Slow: Ultralente, glargine (Lantus)

Plasma
Fasting = 90-130mg/dl Bedtime = 110-150mg/dl 2 hour post-prandial < 190mg/dl

Chemically identical to human insulin by recombinant DNA technology Insulin analogs Humalog/Novolog (lispro/ aspart) developed by modifying amino acid sequence of insulin molecule Lantus (glargine)
No peak Once daily at bedtime Clear

HbA1c = <7%

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Insulin Dosing
Basal insulin = 40 60% of total daily dose Conventional
1-2 doses mixed intermed/rapid-acting Inflexible and simple

Insulin Complicating Factors

Honeymoon phase
Remission phase (weeks to months) Continue low dose insulin

Dawn Phenomenon
5am 8am elevations in growth hormone and cortisol induce insulin resistance Reduced clearance of glucose by fat and muscle
May need increase in pm basal (NPH or U)

Intensive
Basal/prandial/correction Flexible and complex

Insulin Complicating Factors

Somogyi Effect
Morning hyperglycemia from response to 3am hypoglycemia
Check 3am glucose Switch NPH to bedtime

Insulin Complicating Factors

Site absorption variable
Fastest abdomen then arms then buttocks then thigh

Exercise
Hypoglycemia for 12-24 hours after Avoid exercise if BS > 250mg/dl with ketonuria or > 300mg/dl Extra carbs prior of BS < 100mg/dl

Continuous Subcutaneous Insulin Infusion (CSII)

Great flexibility Must be motivated and capable Basal rate plus bolus doses prior to each meal and snack Site changes every 48-72 hours Usually contains lispro
Undetected interruptions = rapid DKA

Insulin Adverse Effects

HYPOGLYCEMIA
Symptoms Quick sugar source (10-20gm glucose) followed by complex carb/protein snack if next meal not within 2 hours Glucagon 1mg SC/IM/IV if unconscious followed by carb when awake Glucose 25gm IV (D50W 50ml) Determine cause and correct

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Insulin Adverse Effects

Lipoatrophy
Due to impure insulin Uncommon now

Sick Day Guidelines

Use usual insulin BS more frequently ketones in urine if BS>240mg/dl Drink lots of non caloric fluids Maintain caloric intake with easily digested food like jello Give supplemental insulin doses

Lipohypertrophy
Insulin injected repeatedly in same site Solution = site rotation

Oral Antidiabetic Drugs

Classes: Sulfonylureas, thiazolidnediones, biguanide, meglitinide, amino acid derivative, combinations Uses: Type II diabetes

Oral Antidiabetic Drugs

MOA
Increase pancreatic insulin release (sulfonylureas, repaglinide, nateglinide) Decrease insulin resistance at the tissue level (pioglitzone, rosiglitzone) Decrease liver glucose production (metformin) Delay gastric absorption of glucose (acarbose, miglitol)

Oral Antidiabetic Drugs

Adverse Reactions:
Sulfonylureas: Hypoglycemia, nausea, rash, water retention, photosensitivity Metformin: Nausea and vomiting, abdominal discomfort, metallic taste Acarbose: Abdominal pain, diarrhea, flatulence Thiazolidinediones: Weight gain, swelling

Oral Antidiabetic Agents

Drug Interactions:
Watch for other drugs known to alter blood sugar Metformin must be held when renal function compromised (IV contrast dye)

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Hypertension treatment
Lifestyle Modifications

Hypertension

Weight reduction Moderation of alcohol intake Physical activity Moderation of dietary sodium Potassium, calcium, magnesium intake Dietary fats, caffeine Relaxation and biofeedback Smoking cessation

Pharmacologic Treatment
Start with lowest dose of initial drug choice Provide 24-hour efficacy with once-daily dose, with at least 50% of the peak effect remaining at 24 hours
Increase compliance Decrease cost Better management with persistent smooth control of once-daily dosing (especially if miss one or more doses/week

Diuretics
Sensitive African-American Elderly Obese Diabetic Renal Insufficiency Non-Sensitive Caucasian Younger Non-obese

Classification of Diuretics
Filtration Diuretics
Theophylline, Caffeine

Classification of Diuretics
Distal Tubular Diuretics (K+ losing)
Thiazides Chlorthalidone(Hygroton) Metolazone(Zaroxolyn)

Proximal Tubular Diuretics

Mannitol Acetazolamide(Diamox)

Collecting Duct Diuretics (K+ retaining)

Amiloride(Midamor) Triamterene(Dyrenium) Spironolactone(Aldactone) Indapamide(Lozol) K+ Neutral

Loop of Henle Diuretics

Bumetanide(Bumex), Ethacrynic Acid(Edecrin) Torsemide(Demadex), Furosemide(Lasix)

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DIURETICS
Effective as monotherapy for primary HTN Thiazides are DOC for HTN - can be dosed once daily Loop diuretics more potent, but must be dosed 2-3x/day and no arterial vasodilation Potassium-sparing diuretics should be reserved for patients with hypokalemia from previous diuretic use

Diuretics Adverse Effects

Hypokalemia - dose related Hyperuricemia - dose related Hyperglycemia - dose related (K+ loss) Hypomagnesemia - dose related Hyponatremia - dose related Lipid abnormalities not dose related Sexual dysfunction (thiazides)

-ADRENERGIC BLOCKERS
Atenolol, carvedilol, metoprolol, nadolol, propranolol

First-line therapy Decrease vascular resistance Reduce morbidity and mortality Intrinsic sympathomimetic activity (ISA)
Avoid in asthma & CHF

Cardioselectivity
Can be used in asthma

Beta Blocker Adverse Effects

Diarrhea or constipation Bradycardia Hypotension Drowsiness, lethargy, depression Bronchospasm Weakness

ACE INHIBITORS
Benazepril, captopril, enalapril, enalaprilat, fosinopril, lisinopril, moexipril, quinapril, ramipril, trandolapril

BP by renin-angiotensin-aldosterone mechanism Slow the decline in renal function and delay or prevent the onset of ESRN in hypertensive and diabetic patients DOC for patients with diabetes and CHF

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ACE Inhibitors Adverse Effects

1st dose hypotension if volume depleted; hold diuretic for 1-2 days before starting Rash Angioedema Cough Taste disturbance Hyperkalemia

Angioedema

ANGIOTENSIN RECEPTOR ANTAGONISTS (ARBs)

Candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, (aliskiren renin inhibitor)

Angiotensin II Receptor Blocker Adverse Effects

Angioedema Hypotension Headache Fatigue Dyspepsia Diarrhea Musculoskeletal pain Hyperkalemia

Mechanism similar to ACEIs; block angiotensin receptor Similar indications as ACEIs Less cough

CALCIUM CHANNEL BLOCKERS

Amlodipine, diltiazem, nicardipine, nifedipine, verapamil

Calcium Channel Blockers Adverse Effects

Orthostatic hypotension Hypotension Edema Worsening of heart failure Arrhythmias

All agents are indicated for hypertension Vasodilatory effects decrease blood pressure Controversy over risk/benefit Nifedipine may increase risk of MI Avoid use if concomitant CHF

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CENTRAL 2-AGONISTS
CLONIDINE central 2-agonist Decreases blood pressure by vasodilation Third line agent due to many side effects Advantage is availability as a once-weekly patch

Clonidine Side Effects

Drowsiness, dry mouth , lethargy Orthostatic hypotension Rebound hypertension (exacerbated with -blockers Do not abruptly DC. Must taper off slowly. DC -blockers first

PERIPHERAL 1ANTAGONISTS
Doxazosin (Cardura), phentolamine, prazosin (Minipress), terazosin (Hytrin)

Alpha-adrenergic Blockers Adverse Effects

Significant 1st dose hypotension take at bedtime Dizziness, HA Drowsiness Tachycardia Fluid retention Tachyphylaxis

Blocks post synaptic alpha receptors resulting in decreased arterial and venous vasoconstriction 2nd or 3rd line agent for HTN BPH Alternative in diabetics

,-BLOCKER
Carvedilol (Coreg) No benefit over other cheaper betablockers for hypertension May provide more benefit in heart failure Intrinsic sympathomimetic activity

Heart Failure Definition

A syndrome characterized by left ventricular dysfunction, reduced exercise tolerance, impaired quality of life and reduced life expectancy NYHA Classification of Heart Failure

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CHF Signs and Symptoms

RIGHT VENTRICULAR FAILURE Symptoms Abdominal pain, anorexia, bloating, constipation, nausea Signs Peripheral edema, JVD, hepatojugular reflux, hepatomegaly, ascites

CHF Signs and Symptoms

LEFT VENTRICULAR FAILURE Symptoms
DOE, orthopnea, paroxysmal nocturnal dyspnea, tachypnea, hemoptysis, cough

CHF Signs and Symptoms

NONSPECIFIC FINDINGS Symptoms Exercise intolerance, fatigue, weakness, nocturia, CNS symptoms Signs Tachycardia, pallor, cyanosis of digits, cardiomegaly

Signs
Bibasilar rales, S3 gallop, pulmonary edema, pleural effusion, cheyne-stokes respirations

CHF Compensatory Mechanisms

Diuretics
Should be prescribed for all patients with symptoms of heart failure who have evidence of fluid retention Should be combined with an ACE inhibitor and a -blocker Monitor efficacy and toxicity by having patients do daily weights Overdosing can lead to renal insufficiency and hypotension if used with ACEIs, ARBs and vasodilators

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Diuretic Resistance
Accompanies the progression of heart failure Intravenous diuretics Two diuretics in combination (add metolazone or indapamide) Short-term use of drugs that increase renal blood flow (dopamine, dobutamine) Caused by concomitant use of NSAIDs

Clinical Trials
No long term studies on effect of diuretics on morbidity and mortality Many trials have shown efficacy of diuretics in increasing urinary sodium excretion and reducing physical signs of fluid retention

ACE Inhibitors
Drugs of choice for all patients with LV dysfunction No absolute minimum BP (e.g. 100 mm Hg) A rise in serum creatinine is acceptable Titrate up to recommended doses All agents decrease mortality and risk of hospitalization

Angiotensin II Receptor Blockers

Indications similar to ACE inhibitors High cost and lack of clinical trials limit these to patients who are ACEI intolerant

Aldosterone Antagonist
Spironolactone Aldosterone antagonist that counteracts the retention of sodium, loss of magnesium and potassium, myocardial and vascular fibrosis, vascular damage, baroreceptor damage. Decreased risk of mortality and hospitalization

Spironolactone Adverse Hyperkalemia Effects

Gynecomastia Use caution with concomitant ACEI due to hyperkalemia

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Digoxin
Positive inotrope force of contraction Negative chronotrope - heart rate Indicated for systolic heart failure No effect on mortality, but relieves symptoms Use in patients with HF who have rapid AF Monitoring of levels not indicated except for compliance or toxicity

Digoxin Adverse Effects

Visual disturbances Nausea, vomiting Ventricular arrhythmias Sinus bradycardia Fatigue, weakness

Mortality in the Digoxin and Placebo Groups

The Digitalis Investigation Group. N Engl J Med 1997;336:525-533

Incidence of death or admission to hospital due to worsening heart failure in two groups of patients: those receiving digoxin and those receiving placebo Digitalis Investigation Group's study

BMJ. 2000 February 19; 320(7233): 495498.

-Adrenergic Blockers
All patients with stable NYHA class II or III HF due to LV systolic dysfunction should receive a -blocker unless contraindicated or intolerant (dec mortality in clinical trials) Use in combo with ACEIs and diuretics SE occur early & with time Need 2-3 months for complete response May decrease disease progression

Vasodilators
Nitrates, hydralazine Most useful in ischemic cardiomyopathy Shown to decrease mortality and improve symptoms Need 10-12 hour nitrate free period Hydralazine dosed 2-3x/day Can improve cardiac output and relieve pulmonary congestion

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Vasodilator Adverse Effects

Dizziness Hypotension Headache Nitrate tolerance

Calcium Channel Blockers

No effect on mortality or risk of hospitalization overall Amlodipine may be of some benefit in diastolic dysfunction

Antiarrhythmic Agents
Class I agents (e.g. quinidine, procainamide) should not be used in HF, except in treatment of refractory life-threatening ventricular arrhythmias Amiodarone (class III) does not appear to increase risk of death when used to treat atrial arrhythmias in chronic HF Monitor & correct K+ and Mg+ to prevent arrhythmias

Amiodarone Adverse Effects

Electrolyte depletion Neurohormonal activation Hypotension and azotemia Rash, hearing difficulties Pulmonary toxicity (pneumonitis) Liver toxicity Arrhythmias

Coronary Artery Disease Coronary Artery Disease

Chronic Stable Exertional Angina Variant Angina (Coronary Artery Spasm) Silent Myocardial Ischemia Unstable Angina Microvascular Ischemia

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Pathophysiology
Atherosclerotic plaques obstruct coronary blood flow, therefore oxygen delivery
Fixed obstruction - hardening of the arteries Dynamic obstruction - degree of stenosis varies with changes in smooth muscle tone (spasms) Platelet aggregation (thrombus) - arterial vessel wall damage results in platelet aggregation

Nitrates
Decrease myocardial oxygen demand by venous and arterial dilation (workload) Can be used alone in mild angina Use in conjunction with beta blocker or calcium channel blocker in moderate or severe angina (nitrate free interval)

Nitrate Tolerance
Mechanism unclear All nitrates can induce tolerance Incidence is highest with long-acting and continuous IV infusion Need 10-12 hours/day nitrate free

Short-Acting Nitrates
Nitroglycerin SL tablets Nitroglycerin translingual spray Onset 1-3 minutes Duration of action 10-30 minutes Use for acute anginal episodes (infrequent) Counsel pts to sit down, may repeat dose q5 min x 2 doses; if no relief then call 911 Pay attention to shelf life

Long-Acting Nitrates
Indicated to control more frequent anginal episodes Nitroglycerin ointment and patches Isosorbide dinitrate(Isordil) Isosorbide mononitrate (Imdur, Ismo) Onset 30-60 minutes Duration 2-12 hours

Nitrates Adverse Effects

Headache Syncope Dizziness Hypotension Bradycardia Tolerance if dosed more then QD

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-Adrenergic Blockers
myocardial oxygen demand by catecholamine-mediated in heart rate, blood pressure and myocardial contractility Start with low doses and titrate up Should not be stopped abruptly! Patients must titrate off slowly to avoid acute MI or sudden cardiac death

-Adrenergic Blockers
Decrease mortality by 30-40% post-MI Questionable effectiveness in vasospastic angina -1 selectivity
COPD Asthma PVD DM will not mask signs of hypoglycemia

Calcium Channel Blockers

myocardial oxygen demand and myocardial blood flow by dilating blood vessels and resistance to blood flow Different actions and side effect profiles within the class All can be used in angina Start with low dose as may make angina worse (10%)

Antiplatelet Therapy
Aspirin Ticlopidine (Ticlid) Clopidogrel (Plavix)

Aspirin
Platelet activation produces coronary occlusion Aspirin inhibits cyclooxygenase which then blocks the formation of prostaglandin endoperoxides from arachadonic acid This results in decreased platelet aggregation

Aspirin
Antiplatelet drug of choice - cheap Contraindications Allergy PUD, GI bleed

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Ticlopidine (Ticlid) and Clopidogrel (Plavix)

Second-line antiplatelet agents for aspirin intolerant patients Inhibit ADP-induced platelet aggregation Ticlopidine rarely used due to neutropenia Side effects related to bleeding

Anticoagulants

Heparin
Unfractionated: Heparin Low Molecular Weight: dalteparin (Fragmin), enoxaparin (Lovenox), tinzaparin (Innohep) Not well absorbed via GI tract must be administered parenterally
Heparin=IV LMW=SC

Heparin
MOA: Prevents clot formation and extension of existing clots Partial thromboplastin time (PTT) must be monitored for unfractionated heparin Use: venous thrombus (DVT, PE), DIC, embolus prevention in atrial fibrillation, embolus prevention during MI, clot prevention for surgery

Heparin
Heparin-induced thrombocytopenia
Must switch to a direct thrombin inhibitor (argatroban, bivalirudin, or lepirudin)

Adverse Effects:
Bleeding (reversed with protamine sulfate) Bruising, hematoma formation

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Heparin
risk of bleeding with coumadin (except when used together before INR is therapeutic) bleeding risk with NSAID, iron dextran, clopidogrel, dilostazol, or drugs that affect platelets such as aspirin Many others

Oral Anticoagulants
Warfarin (Coumadin ) MOA: Alters the livers ability to make Vitamin K dependent clotting factors Clotting factors already circulating are unaffected Use: treatment of thromboembolism (DVT, PE), prevention of DVT, prevention of clots in pts with prosthetic heart valves or diseased mitral valve

Warfarin
In patients receiving heparin, warfarin must be started before stopping heparin Sometimes combined with antiplatelet drugs to prevent arterial clotting. Adverse Effects: Bleeding (reversed with Vit K) Drug Interactions:
MANY MANY MANY Also food/drug interactions

ASTHMA and COPD

ASTHMA
Lung disease with the following characteristics (NIH definition)
airway obstruction that is reversible (but not completely so in some patients) airway inflammation increased airway responsiveness to a variety of stimuli episodic symptoms: wheezing, chest tightness, cough and dyspnea

Pathophysiology
Hyperreactivity (exaggerated response of the bronchial smooth muscles to trigger stimuli) of the airways to physical, chemical, immunological and pharmacological stimuli.
Inhaled allergens, respiratory viral infections, cold air, dry air, smoke and pollutants, ASA, exercise, emotions, beta-blockers

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Pathophysiology
The release of chemical mediators (e.g., leukotrienes) of inflammation from mast cells thought to be the central mechanism. Mast cell mediator release plays a role in allergen induced asthma in atopic individuals, some occupationally-induced syndromes and exercise induced asthma

Treatment Goals
Achieve and maintain control of symptoms Prevent acute exacerbations Maintain PFTs as close to normal as able Maintain normal activity Avoid adverse effects of medication Prevent fixed, irreversible airway obstruction and damage Avoid mortality

Drug Therapy
Theophylline 2-Agonists Mast cell stabilizers Leukotriene modifiers Inhaled corticosteroids Inhaled anticholinergic Systemic corticosteroids

Theophylline
Relaxes smooth muscle of respiratory tract production of anti-inflammatory cytokine Structural analog of caffeine Useful as alternative to ICSs in patients with mild persistent asthma and as add-on agent to ICSs in patients with moderate to severe persistent asthma

Theophylline - Limitations
Caffeine like action can be troublesome Requires drug level monitoring - new recommendations are 5-15 mcg/ml Many drug interactions
Erythromycin, cimetidine & quinolone antibiotics inhibit theo metabolism so theo level Phenytoin, phenobarb, carbamazepine, rifampin, cigarette smoking induce theo metabolism so theo level

Theophylline - Side Effects

GI - nausea, vomiting, diarrhea CNS headache, irritability, insomnia, seizures Cardiac - arrhythmias Side effects may or may not be related to serum levels

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2-Agonists
Short-acting are often referred to as rescue inhalers and are indicated to relieve acute symptoms Long-acting are recommended only as adjunctive therapy to ICSs in patients diagnosed with moderate or severe asthma

2-Agonists Mechanism of Action

Sympathomimetic Induces bronchodilation by relaxing smooth muscles of bronchioles

Available Products
Albuterol (Ventolin, Proventil) Metaproterenol (Metaprel, Alupent) Isoetharine, (Bronkosol) Isoproterenol (Isuprel) Salmeterol (Serevent)

2-agonist - Contraindications
Angina Arrhythmias Hyperthyroidism Hypertension

Bitolterol (Tornalate) Epinephrine (Primatene) Pirbuterol, (Maxair) Terbutaline (Brethaire, Brethine)

2-agonist Adverse Effects

Palpitations, tachycardia, arrhythmias, angina, hypertension Tremor, shakiness, dizziness, restlessness, headache, insomnia, anxiety Nausea, cough, throat dryness Sweating, flushing

Mast Cell Stabilizers

Prophylactic agents only not rescue inhalers Must be used regularly to be of benefit Do not discontinue therapy abruptly Most useful when allergic component is present or in pediatrics due to better safety profile than ICSs

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Mast Cell Stabilizer - MOA

Inhibits degranulation of sensitized mast cells after exposure to antigens No intrinsic antihistaminic, anticholinergic, anti-inflammatory, bronchodilator or vasoconstrictor activity Effective only if used prophylactically

Mast Cell Stabilizers Available Products

Cromolyn (Intal) Nedocromil (Tilade)

Mast Cell Stabilizers Contraindications/Side Effects

Hypersensitivity Cough, wheezing, dry irritated throat Lacrimation, swollen parotid glands Dizziness, headache Bad taste, substernal burning

Inhaled Corticosteroids
Most potent anti-inflammatory agents used to treat asthma Most effective control of persistent asthma Only long-term therapy that has been shown to prevent and reverse airway remodeling

ICSs Mechanism of Action

Precise mechanism of action in lung unknown Decrease number and activity of inflammatory cells

ICSs Available Products

Beclomethasone (Beclovent, Vanceril) Triamcinolone (Azmacort) Flunisolide (AeroBid) Dexamethasone (Decadron) Budesonide (Pulmicort) Fluticasone (Flovent) Ciclesonide (Alvesco)

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ICSs Contraindications/ Warnings

Acute episodes (effective only prophylactically) Systemic fungal infections, persistently positive sputum culture for C. albicans Caution during transfer from systemic corticosteroids to inhaled corticosteroids several months required for recovery of HPA axis function

ICSs Side Effects

Adrenal Insufficiency: During/after transfer from systemic steroids to inhaled steroids or at high doses (e.g., beclomethasone 40 puffs/day or triamcinolonne 20 puffs/day) Dysphonia, hoarseness, throat irritation Cough, wheezing Dry mouth, bad taste, fungal infections Bone loss

ICSs Patient Education

ICSs are not bronchodilators; not effective for rapid relief of acute bronchospasm Require 1-2 weeks of regular use for improvement May need supplemental systemic steroids during acute stress or severe attacks Use bronchodilator first Rinse mouth with water or mouthwash to minimize bad taste and prevent fungal infection

Leukotriene Modifiers
Inhibit the action cysteinyl leukotrienes. Block the pro-inflammatory action of leukotrienes thereby decreasing bronchoconstriction May be alternative to low-dose ICSs in mild persistent asthma or an adjunct to ICSs in severe asthma May decrease dose of ICSs needed to control more severe asthma

Leukotriene Modifiers Available Products

Zileuton (Zyflo) Montelukast (Singulair) Zafirlukast (Accolate)

Leukotriene Modifiers Contraindications

Hypersensitivity Pregnancy
Zileuton category C Zafirlukast, montelukast category B

Zileuton age >18yrs Zafirlukast age >12 years Montelukast age >6 years

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Leukotriene Modifiers Side Effects

Headache, pain, asthenia, dyspepsia, nausea, myalgia, fever Elevation in LFTs (except montelukast) Monitor LFTs at baseline, qmonth x3, q3months x3, then yearly

Leukotriene Modifiers Drug Interactions

Zafirlukast /Food take on empty stomach Zafirlukast/Warfarin increase pT/INR Zileuton/Warfarin incease pT/INR Zileuton/Theophyline increase theophylline levels

Inhaled Anticholinergic
Competitive inhibitors of muscarinic receptors produces bronchodilation Has no effect on bronchoconstriction caused by vagal pathway (e.g., allergens, histamine, exercise) Useful as an adjuct in acute severe asthma not completely responsive to 2agonists

Inhaled Anticholinergic
Ipatropium (Atrovent) Adverse Effects:
Dry mouth, cough, nervousness, gi upset, dizziness, headache

Systemic Corticosteroids
Potent anti-inflammatory action Useful in Acute severe asthma, status asthmaticus and impending episodes of severe asthma unresponsive to bronchodilators Oral agents - prednisone, methylprednisolone

Systemic Corticosteroids
Limit to short courses of 5-10 days Multiple daily dosing provides better asthma control Side effects of HPA axis apparent after 8 bursts/year in adults and 4 bursts/year in children

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Corticosteroid Side Effects

HPA axis suppression Osteoporosis Immunosuppression Growth retardation Cataracts, glaucoma Hypertension

Other Asthma Treatment

Exercise Induced Asthma
2-3 puffs of short-acting 2-agonist 15-30 minutes prior to exercise

Nocturnal Asthma
1-2 puffs of long-acting 2-agonist prior to bedtime

Controversies
MDIs vs nebulizers
Equivalent if proper technique or spacer used

COPD - Pathophysiology
Inflammation, fibrosis, and narrowing of small airways contribute to increased airway resistance and obstruction Bronchial changes of enlarged mucous glands with smooth muscle hyperplasia, inflammation and bronchial wall thickening Emphysematous changes of acinar enlargement occur after prolonged unchecked protease activity on lung tissue

2-agonists
When to initiate Can they increase mortality? Monitor number of refills

Emphysema
Anatomical defects of lung characterized by permanent enlargement of the air spaces and destruction of alveolar walls thus obstruction and airway collapse occur on expiration. Patients adapt and use accessory muscles to breathe prolonged expiratory phase Pink Puffers adequate oxygenation through increased work of breathing

Chronic Bronchitis
Chronic excessive mucous production and secretion resulting in airflow obstruction secondary to inflammation and edema Inflammation and edema of mucosa and mucous glands in airways of bronchial tree Result in copious tenacious sputum that is good medium for recurrent infections Blue bloaters- obese, hypoxic, cyanotic

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Goals of Therapy
Bronchodilation Reduced inflammation Mucous mobilization Pharmacotherapy may offer limited benefit since lung damage is irreversible (asthma is reversible) These patients often dont tolerate medications as well as patients with asthma

TREATMENT
Smoking Cessation Pulmonary Rehab
Physical conditioning, breathing exercises Adequate nutrition

Immunizations Proper coughing techniques, postural drainage and chest percussion

The Winstones

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