N329 final new

rheumatoid arthritis

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1. Autoimmune inflammatory disorder
2. Symmetric joint stiffness and pain
3. Swollen, tender, and warm
4. Periods of spontaneous remission
5. Systemic manifestations
6. Overview


1. Inflammation begins in the synovium
2. Membrane thickens, starts to surround cartilage
3. Overgrowth is referred to as pannus
4. Cartilage undergoes destruction
7. Goals


1. Relieve symptoms
2. Maintain joint function
3. Minimize systemic involvement
4. Delay progression

antiarthritic drugs

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1. Provides symptomatic relief
2. Chronic drug therapy
3. Three major classes


1. NSAIDs
2. Glucocorticoids
3. Disease-modifying antirheumatic drugs (DMARDs)

NSAIDs in RA use

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1. Provide rapid relief, but do not prevent joint damage and do not slow down disease progression
2. Safest of all suggested drug therapies

glucocorticoids in RA use

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1. Provide rapid relief
2. CAN slow down disease progression
3. Long term use, serious TOXICITY


1. Relieve symptoms of RA


1. Can help delay disease progression
2. Generalized symptoms – PO administration
3. One-two joints affected, intra-articular injections
2. Long term adverse effects


1. Osteoporosis
2. Gastric ulceration
3. Adrenal suppression
3. Most common administered drugs are prednisone and prednisolone

DMARDs

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1. Reduce joint destruction and slow disease progression
2. Toxic with long-term use

drug selection for RA

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1. More aggressive compared to earlier times


1. Give a DMARD early, within 3 months of a diagnosis
2. Give NSAID until DMARD kicks in
3. Can stop NSAID once the effects of the DMARD are at their peak
4. Glucocorticoids, reserved for flare-ups

non-biologic (traditional) DMARDs

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1. Slow disease progression
2. More harmful than NSAIDs
3. Clinical responses develop slower
4. Cheaper than biological DMARDs

methotrexate (Trexall)

a non-biological DMARD


1. Therapeutic effects develop within 3-6 weeks
2. 80% of patients improve with this drug
3. \*\*Immunosuppression
4. Drug of choice
5. Toxicities


1. Bone marrow suppression
2. GI ulcers
3. Pneumonitis
4. Tetragenic
5. Hepatic/liver disorder
6. Administered PO or injection once a week

hydroxychloroquine (Plaquenil)

a non-biological DMARD

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1. Antimalarial actions
2. Generally combined with Methotrexate
3. Early use can improve long term outcomes
4. 3-6 months onset
5. Toxicities 


1. Retinal damage- related to dosage
6. Eye exams
7. Report any visual disturbances

Sulfasalazine (Azulfidine)

a non-biological DMARD


1. Traditional use: Inflammatory bowel disease
2. Slows progression of joint deterioration
3. Onset within one month
4. Adverse effects 


1. GI upset (Use enteric coated formula)
2. rash, urticaria

biologic DMARDs

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1. Target specific components of the inflammatory process
2. Usually combined with methotrexate
3. \*\*interfere with tumor necrosis factor (TNF), aka TNF antagonist

TNF

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1. Binds with receptors on cells in the synovium
2. It promotes infiltration of neutrophils and macrophages, causing inflammation and joint destruction

TNF antagonists

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1. Drugs work by neutralizing the TNF, an immune mediator
2. Due to this, pose serious risk for infections


1. Fungal infections
2. Hep B
3. TB
4. Bacterial sepsis

ETANERCEPT (Enbrel)

a biological DMARD


1. Prototype 
2. Reduces RA symptoms and disease progression 
3. MOA 


1. Suppresses inflammation by neutralizing TNF
4. Used for moderate to severe RA 
5. Adverse effects 


1. Injection site reactions 
2. TB, HBV
3. SJS, Heart failure, Cancer 
6. Drug interactions- use cautiously with immunocompromised individuals or immunocompromised medications


1. Avoid with live vaccines

gout

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1. Overview


1. **Disease of altered purine metabolism**
2. **Associated with hyperuricemia, although may occur in patients with normal uric acid levels**
3. **Acute vs chronic**
2. Goals of therapy


1. **Block the inflammatory process**
2. **Increase excretion of uric acid**
3. **Decrease production of uric acid**

gout drug therapy

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1. Short-term to relieve acute gouty attack


1. NSAIDS
2. Glucocorticoids
3. Colchicine
2. Long term to lower blood levels of uric acid

acute gouty arthritis - NSAIDs

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1. Start ASAP
2. Relief within 24 hours, swelling subsides within a few days
3. Commonly used NSAIDs


1. Naproxen
2. Indocin
3. Voltaren

acute gouty arthritis - glucocorticoids

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1. Ex: prednisone


1. Given to those sensitive to NSAIDs
2. Avoid in patients with hyperglycemia
3. PO or IM

acute gouty arthritis - colchicine

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1. Does not relieve pain other than gout
2. GI toxicity is the most adverse effect
3. Anti-inflammatory agent
4. MOA unknown

urate lowering therapy (ULT)

drugs for hyperuricemia

* for those with frequent gouty attacks

allopurinol

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1. By reducing uric acid, prevents tophus formation, and improving joint function
2. Decreases the risk of neuropathy fur to excretion of urate crystals
3. MOA: inhibits xanthine oxidase (XO), and enzyme needed for uric acid formation
4. Drug interactions


1. can inhibit hepatic drug-metabolizing enzymes, delaying the inactivation of other drugs 
2. \*\*watch out with warfarin, whose dosage should be reduced

probenecid

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1. Acts on renal tubules to inhibit reabsorption of uric acid. As a result, excretion of uric acid is increased and hyperuricemia is reduced
2. Adverse effects


1. GI effects 
2. Hypersensitivity reactions 
3. Renal injury
3. Drug interactions


1. ASA and other salicylates interfere with absorption

glucocorticoids

1. Physiological effects


1. Low doses needed (physiologic)
2. Low dose effects


1. Metabolic Effects


1. Glucocorticoids reduce the peripheral reuptake of blood glucose, reducing its utilization, therefore increasing blood glucose levels
2. Cardiovascular effects 


1. When needed, they increase the number of circulating red blood cells and decrease the number of leukocytes 
3. Water and Electrolyte Effects


1. Act like aldosterone (to some extent)
2. Can act on the kidney to promote retention of sodium and water, while increasing urinary excretion of potassium
3. Causing hypernatremia, hypokalemia, edema
3. Used to treat adrenocortical insufficiencies 
4. Naturally, the adrenal cortex produces corticosteroids (includes glucocorticoids)
2. Pharmacological effects


1. High doses needed 
2. Used to treat inflammatory disorders (asthma, RA, certain cancers, etc)
3. Used to suppress immune responses in organ transplant recipients 
4. At high doses, an array of adverse effects
5. When administered in high doses, used to treat non-endocrine related disorders. They have anti-inflammatory and immunosuppressive effects (not seen at the physiologic doses). 
6. HOWEVER, can see the physiologic effects with pharmacologic doses
7. Effects on metabolism and electrolytes


1. More intense when compared to physiologic.
2. Elevated blood glucose levels
8. ANTI-INFLAMMATORY AND IMMUNOSUPPRESSANT EFFECTS


1. Inhibit synthesis of prostaglandins, histamine, leukotriene (reducing a part of the inflammatory system that is responsible for swelling, warmth, redness, and pain
2. Suppress proliferation of lymphocytes, reducing the immune response
3. Produce greater anti-inflammatory effects when compared to NSAIDs 

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2. Pharmacokinetics


1. PO, IM, Topically
2. Can cross the placental barrier


1. If used in large doses, fetus should be screened for adrenal insufficiencies
3. Lactation


1. Enter breast milk
2. At physiologic doses, too low to reach infant 
3. Pharmacological doses, women should avoid breast feeding 
3. Adverse effects (pharmacological)


1. Intensity of effects are related to dosage size and treatment duration
2. Adrenal insufficiency


1. Prolonged administration can suppress adrenal production of glucocorticoids
3. Osteoporosis


1. Fractures, ribs and vertebrae are impacted the most 
2. HOW? (Glucocorticoids accelerate bone reabsorption, decrease intestinal absorption of calcium, causing hypocalcemia
4. Infection


1. By suppressing immune responses
2. Avoid close contact with people who are sick
5. Glucose intolerance


1. Hyperglycemia
2. Those diabetic may need to increase their insulin requirements
6. Minimal fluid/electrolyte effects
7. Growth delay


1. Can cause growth delay in children by inhibiting DNA synthesis
8. Cataracts
9. PUD


1. By inhibiting prostaglandins, it can increase section of gastric acid and reduce gastric mucosal barriers

types of glucocorticoids

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1. Dexamethasone (Decadron)
2. Cortisone
3. Betamethasone
4. Methylprednisoloine (Solumedrol)
5. Prednisone

Cyclooxygenase (COX) inhibitors

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1. Consists of ASA and related drugs
2. Only ASA can reduce the chance of a CVA and MI
3. Inhibition of COX → enzymes responsible for synthesis of prostaglandins

cyclooxygenase (COX)

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1. An enzyme responsible for:


1. Pain and inflammation
2. Protection of gastric mucosa
3. Stimulation of platelet aggregation
4. Renal vasodilation...promotes renal blood flow
5. Promotes contractions in the uterus
2. At sites of tissue injury, COX catalyzes the synthesis of prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2, aka prostacyclin), which promotes INFLAMMATION & sensitize receptors to painful stimuli
3. In the stomach, COX helps protect the gastric mucosa


1. Reduced secretion of gastric acid
2. 2) Increased secretion of bicarbonate  & cryoprotective mucous
3. 3) Maintenance of submucosal blood flow
4. How COX works


1. In platelets, stimulates aggregation 
2. In blood vessels, causes vasodilation


1. Helps maintain renal bloodfloow 
3. In the brain, helps mediate fever and perception of pain
4. In the uterus, promotes contraction at term

COX-1 vs. COX-2

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1. COX-1


1. Mediates beneficial process
2. AKA “The housekeeper”
3. Aka Good Cox 
2. COX-2


1. PRODUCED AT SITES OF TISSUE INJURY
2. AKA “BAD COX”

COX-1

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1. Naturally occurring


1. MEDIATES BENEFICIAL PROCESS AKA “THE HOUSEKEEPER”  
2. PROTECTS GASTRIC MUCOSA, SUPPORTS RENAL FUNCTION, PROMOTES PLATELET AGGREGATION
2. When we inhibit


1. Beneficial Effects


1. Protection against MI and stroke secondary to decreased platelet aggregation *(only 1 beneficial effect)*
2. Harmful effects


1. Gastric erosion and bleeding
2. Bleeding tendencies
3. Renal impairment

COX-2

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1. Naturally occurring


1. MEDIATES/STIMULATES:


1. INFLAMMATION
2. SENSITIZES RECEPTORS TO PAINFUL STIMULI
3. VASODILATION
4. FEVER 
5. SUPPORTS RENAL FUNCTION
2. When we inhibit


1. Beneficial effects


1. Suppression of inflammation
2. Alleviation of pain
3. Reduction of fever
4. Protects against colon cancer
2. Harmful effects


1. Renal Impairment
2. Promotes MI and Stroke (secondary to suppressing vasodilation

COX inhibitors

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1. Two classifications:


1. Drugs with anti-inflammatory properties


1. Aka Nonsteroidal anti-inflammatory drugs (NSAID)


1. ASA, ibuprofen, advil, motrin, naproxen (alieve), celebrex
2.  Drugs without anti-inflammatory properties


1. Tylenol

first generation NSAIDs

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1. **Conventional NSAIDS (aspirin, ibuprofen)**
2. Inhibits both COX-1 and COX-2
3. Uses: RA, OA, fever, alleviate mild to moderate pain
4. Drugs


1. ASA, ibuprofen, Toradol, Naproxen
5. MOA


1. Nonselective inhibitor of COX
2. Inhibiting COX-2, reductions in inflammation, pain and fever. 
3. Benefits, protect against MI and ischemic stroke from inhibiting COX-1
4. IRREVERSIBLE inhibitor 
6. Pharmacokinetics


1. PO or suppository
2. Excreted by kidneys

aspirin

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1. Effectiveness underappreciated
2. Most widely used member of the NSAIDs group
3. Drug of choice for arthritis RA, OA, JRA
4. Reduction of fever, pain, inflammation
5. Chemistry → belongs to the chemical family called salicylates, acetylsalicylic acid (ASA)
6. Distribution


1. Distributed to all body tissues and fluids, including breast milk, fetal tissue
2. Excreted by the kidneys
7. Therapeutic uses


1. Suppress inflammation
2. Analgesia
3. Fever reducer
4. Suppress platelet aggregation
5. Dysmenorrhea
8. Adverse effects


1. GI bleeding, heartburn, nausea
2. Renal impairment
3. Salicylism
4. REYES Syndrome (risk for those < 18)
5. Hypersensitivity
6. Pregnancy category D


1. Post partum hemorrhage, prolonged labor, crosses placenta
9. Drug interactions


1. Anticoagulants → warfarin, heparin
2. Glucocorticoids → promote gastric ulceration
3. Alcohol → combining ASA with ETOH increases the risk for GI bleeding
4. Nonaspirin NSAIDs (ibuprofen, naproxen, etc.) → Patients taking low dose ASA to prevent MI/stroke non ASA-NSAIDS reduce the antiplatelet effects


1. GIVE 2 HOURS APART
10. Acute poisoning


1. Rarely fatal in adults
2. Lethal in children
3. S/S *-*  initially compensated respiratory alkalosis with progression respiratory depression, acidosis, hyperthermia, sweating and dehydration
4. Treat symptoms


1. Fluids, gastric lavage, activated charcoal 
11. Formulations


1. Plain
2. Enteric coated
3. Buffered
4. Timed released
5. Rectal suppositories (poor absorption)
12. Dosage and administration


1. Give food or full glass of water to reduce GI upset

non-ASA first generation NSAIDs

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1. The difference between 1st generation ASA NSAID and 1st generation non ASA NSAID


1. Nonaspirin first generation NSAIDs cause reversible inhibition
2. All have the following effects:


1. Nonselective COX inhibitors 
2. Antiinflammatory, Analgesic, Antipyretic
3. Can cause GI and renal issues (although the intensity and likelihood is decreased)
4. Hypersensitivity to ASA will likely have cross sensitivity
3. Biggest use for OA, RA
4. Do not protect against MI and stroke
5. Increase the risk for thrombotic events

ibuprofen (Motrin)

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1. Fever (> 102)
2. Mild to moderate pain, dysmenorrhea
3. Less gastric bleeding, less inhibition of platelet aggregation
4. Don’t give in infants < 6 months old

ketorolac (Toradol)

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1. Powerful analgesic with minimal anti-inflammatory properties
2. Pain relief equivalent to morphine & opioids
3. Acute pain moderate to severe
4. Post-operative pain, *great in orthopedics*


1. Kidney Stone Pain
2. Short term use (2 days! IV)

Naproxen (Aleve, Naprosyn)

Prolonged half-life therefore can be administered less frequently

second generation NSAIDs

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1. Selective COX-2 inhibitors, inhibits COX-2 only 
2. Can suppress pain and inflammation, IN THEORY, without posing a risk of serious adverse effects (decreasing risk)
3. HOWEVER, IN REALITY, appear even less safe compared to 1st generation  because of increased risk for stroke and MI
4. **Celebrex**


1. Does not inhibit COX-1
2. Therapeutic use


1. OA, RA, dysmenorrhea, acute pain
3. Adverse effects


1. Similar to ibuprofen 
2. Avoid in those with sulfa allergy or sulfonamide allergy 
3. Contraindicated in pregnancy
4. \*\*Remember does not protect against MI/Stroke d/t not inhibiting COX-1, which suppresses platelet aggregation

acetaminophen (Tylenol)

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1. Therapeutic Uses


1. Anti-pyretic, analgesic
2. NO ANTI-INFLAMMATORY EFFECTS
2. Mechanism is unknown
3. Excreted in urine but metabolized by the liver


1. Contraindications – ETOH abuse, hepatic disease, & viral hepatitis
4. Does not have anti-inflammatory properties
5. Does not suppress platelet aggregation
6. Does not cause gastric ulcers
7. Does not impair renal blood flow
8. Adverse effects/interactions


1. Adverse effects


1. Minimal compared to NSAIDs
2. Those who take Tylenol daily (500 mg/day or more) may develop HTN, asthma
2. Drug interactions


1. Alcohol
2. Warfarin
9. Tylenol acute toxicity: liver damage


1. Risk of liver injury is increased by fasting, chronic ETOH abuse and taking more than 4000mg/day
2. Leading cause of acute liver failure by about 50% of all cases
3. Signs and symptoms


1. Hepatic necrosis


1. N/V/D, sweating, abdominal discomfort
4. Treatment


1. Mucomyst

erectile dysfunction (ED)

1. 30 million men in the US
2. Increased risk with advancing age
3. Associated with


1. Drug use
2. Diabetes
3. SSRIs

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2. First line of treatment


1. Lifestyle measures


1. Increased exercise
2. Smoking cessation 
3. Changing drug regimens 
4. Drug management with Viagra 
5. Surgical management like penile prosthesis 
3. Physiology


1. When sexually aroused


1. Arterial dilation increases local blood flow and blood pressure 
2. Causing expansion 
3. The expansion then causes venous occlusion and reduces venous outflow
4. The engorgement is the result of the arterial inflow with the stasis of venous outflow
5. Erection subsides when an enzyme, phosphodiesterase type 5 (PDE5) carries out cGMP (an enzyme which initiates this process)

Sildenafil (Viagra)

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1. Reliable, easy to use
2. Does not directly cause an erection
3. Dangerous in men taking vasodilators and nitrates
4. Therapeutic use:


1. Pulmonary arterial hypertension
5. MOA


1. Inhibition of PDE5, therefore reserving cGMP levels in the penis
2. \*\*Important to know that it only enhances the normal erectile response to sexual stimuli
3. In the absence of sexual stimuli, nothing will happen 
6. Pharmacokinetics


1. PO
2. High fat meals slow absorption 
3. About 1 hour to peak
4. Half life is 4 hours
7. Adverse effects


1. Hypotension
2. Priapism


1. Painful, long erection
3. Nonarteritic ischemic optic neuropathy
4. Sudden hearing loss
8. Drug interactions


1. Nitrates


1. At least 24 hours to elapse between viagra and nitrate dose
2. Alpha blockers
3. Other


1. Grapefruit juice, erythromycin, cimetidine can increase drug levels by interfering with metabolism

cialis

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1. Very similar to viagra
2. Half life is the big difference! (17.5 hrs)

benign prostate hyperplasia (BPH)

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1. Prostate heart shaped gland that surrounds the urethra
2. BPH is a nonmalignant prostate enlargement caused by excessive epithelial growth and smooth muscle cells


1. Epithelial cells → mechanical obstruction
2. Smooth muscle → dynamic 
3. Signs and symptoms


1. Greater effort to try and start a urine stream
2. Dribbling (not a stable stream)
3. Feeling of not emptying
4. drug therapy


1. 5-alpha-reductase inhibitors

Finastide (Proscar)

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1. Acts in reproduction tissue to inhibit 5-alpha-reductase


1. An enzyme that converts testosterone to dihydrotestosterone (DHT)
2. Treatment reduces levels of DHT by 70% without decreasing testosterone 
3. By doing this, proscar promotes the regression of the prostate epithelial tissue. 
4. So, what do you think? Mechanical obstruction or smooth muscle obstruction? 


1. Mechanical obstruction!
2. Contraindicated for pregnant women or may become pregnant
3. Men should not donate blood while taking
4. Adverse effects


1. Decrease ejaculation volume 
2. Decrease libido 
3. Teratogenic to the male fetus

alpha 1-adrenergic antagonists

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1. Five approved:


1. Alfuzosin 
2. Terazosin 
3. Doxazosin 
4. Silodasin (rapaflo) \*
5. Tamsulosin (Flomax)\* 
6. MOA


1. Blockade of alpha1- adrenergic receptors relaxes the smooth muscle in the bladder, prostate capsule, and prostatic urethra
2. Unlike 5-alpha, does not reduce size of the prostate, but does help with increased urinary flow

HIV

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1. Human immunodeficiency virus


1. Kills CD4 lymphocytes
2. It is a retrovirus that must transcribe their RNA into DNA to replicate
3. At risk for opportunistic infections
4. Not synonymous with AIDs
2. Retroviruses must transcribe their RNA into DNA to replicate, cannot self replicate
3. There are three viral enzymes needed for HIV replications


1. Reverse transcriptase


1. Transcribing RNA into DNA
2. Integrase


1. Integrate DNA into the cytoplasm of the HIV cell
3. Protease


1. Procreate; divide and grow the CD4 cells
4. Drugs have been developed to inhibit all three of these enzymes

role of CD4 cells in immune function

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1. CD4 cells are essential for effective immune response


1. Virus invades
2. Ingested by a macrophage
3. T-helper cell sounds the alarm to activate the immune system


1. B cell responds to produce antibodies
2. CD4 count


1. Normal 700-1200 cells/mm3
2. Initiate treatment 351-500 cells/mm3
3. AIDS: < 200 cells/mm3

types of HIV

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1. HIV-1


1. Found worldwide
2. HIV-2


1. Found in West Africa
2. Different genetic make-up
3. Cause similar disease syndromes
4. Not all drugs work on both types of HIV

pathophysiology of HIV

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1. Replication rate


1. Massive replication during the initial phase of infection


1. Very high viral load (10 million virions/mL)
2. Patients experience flu like acute retroviral syndrome
3. Replication rate slows as the immune system mounts its attack


1. Steady state levels 1000 – 100,000 virions/mL
4. Can be asymptomatic up to 10 years
2. Mutation and drug resistance


1. Mutates rapidly
2. Easily mutates to drug resistant forms
3. Probability of developing resistance is directly related to viral load

transmission of HIV

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1. HIV is present in all body fluids of infected individuals


1. Not in saliva
2. Transmission can be via intimate contact with semen, vaginal secretions, and blood
3. Sexual contact, transfusion, sharing IV needles, accidental needle sticks
4. Also transmitted to the fetus by an infected mother

laboratory monitoring of HIV

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1. Viral load (HIV-RNA count)


1. Indicate magnitude of HIV replication & predict rate of CD4 T-cell destruction
2. Disease progression
3. Measurement for effective therapy – less than 50 copies/mL
2. Monitor CD4 counts


1. When to start therapy
2. When to change drugs
3. Degree of immunodeficiency
4. Damage to immune system
3. Monitor plasma HIV viral load


1. Predictor of patient prognosis
2. Goal is to decrease viral load to undetectable numbers (

HIV/AIDS treatment

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1. ALWAYS give 3 drugs:


1. 2 must be NRTI’s (Nucleoside/nucleotide reverse transcriptase inhibitors)
2. 1 must be: 


1. Protease Inhibitor
2. NNRTI
3. Integrase Inhibitor
4. Fusion Inhibitor  or CCR5 Antagonist

classification of antiretroviral drugs

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1. Inhibit enzymes required for HIV replication


1. Reverse transcriptase inhibitors (two types)


1. Nucleoside/nucleotide reverse transcriptase inhibitor (NRTIs)
2. Non-nucleoside reverse transcriptase inhibitor (NNRTIs)
2. Integrase strand transfer inhibitor (INSTIs)
3. Protease inhibitors (PIs)
2. Block viral entry into cells


1. Fusion inhibitors
2. Chemokine receptor 5 (CCR5)

Nucleoside/nucleotide reverse transcriptase inhibitor (NRTIs)

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1. Suppress the synthesis of viral DNA by reverse transcriptase


1. **Zidovudine (Retrovir) (AZT)** is the prototype for NRTIs


1. Decreases viral load 
2. Increases CD4 count 
3. Delays the onset of disease symptoms
4. Therapeutic Uses 


1. HIV 1 
2. Prevents mother-to-infant transmission of HIV during labor and delivery 
3. Used in combination with other antiretroviral drugs 
5. Administration 


1. PO or IV
6. Adverse Effects


1. Anemia and neutropenia
2. Monitor Hgb and neutrophil counts at least q4 weeks
3. Hold for Hgb below 5gm/dL or 25% drop from baseline
4. Hold for neutrophil count below 750 cells/mL


1. In some cases can transfuse and or use granulocyte colony stimulating factors (GCSF) in order to continue therapy
5. GI effects
6. Lactic acidosis/hepatic steatosis (rare)


1. Liver enlargement with fatty degeneration of the liver
2. N,V, abd pain, fatigue, malaise, hyperventilation (related to lactic acidosis)
7. Drug interactions


1. Any myelopsuppressive drugs, nephrotoxic drugs, or drugs toxic to circulating blood cells


1. Ganciclovir
2. Bactrim
3. Ampho B
4. Flucytosine

tenofovir

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1. emtricitabine/tenofovir (Truvada)


1. Combination NRTI
2. Pre-exposure prophylaxis “PrEP”
3. Recommended for:


1. MSM who have multiple sex partners
2. HIV-neg individuals in relationship with HIV-positive partner
3. Heterosexual women who have multiple partners with unknown HIV status (clinically speaking, often sex workers fall in this group receiving PreP)
4. IV drug users
4. MOA


1. Blocks reverse transcriptase
2. Prevents HIV from making more copies of itself in the body
5. Side effects


1. Mostly mild
2. GI effects
6. They need to periodically get tested for HIV while on treatment.  The **regimen is approved for HIV-neg people only.**  So must remain HIV neg before and while on therapy.  __If convert to positive__, then of course treatment plan changes
2. Controversy


1. Concerns for resistance
2. Concerns about whether or not people will stick to daily dosing
3. Concerns about people selling these drugs on black market to inappropriate populations - again resistance and safety concerns
4. Some suggest that PreP will provide false reassurance and increase the frequency of high risk behaviors. Studies to date are not finding this

Non-nucleoside reverse transcriptase inhibitor (NNRTI)

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1. MOA


1. Constrain HIV replication by binding non competitively to reverse transcriptase; blocks HIV replication by preventing RNA to DNA 
2. Think about it, it is called a non-nucleoside because it stops the RNA from changing, RNA doesn’t have a nucleus!! 
2. Drug interactions


1. Decreases effectiveness of oral contraceptives 
2. Avoid taking with St. John’s wort (may reduce levels of Sustiva by accelerating metabolism of the p450 enzyme
3. **Efavirenz (Sustiva)**


1. Used in treating HIV infection in combination with NRTIs
2. Only NNRTI deemed a preferred agent
3. Adverse effects


1. Rash
2. Altered mood and sleep, increased anxiety
3. Teratogenic

protease inhibitors (PI)

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1. The PIs represent the __**most effective**__ anti-retroviral drugs known.
2. When used in combination with NRTI’s they can reduce viral load to a undetectable level
3. MOA- By blocking the protease enzyme, prevents the immature HIV cell from budding and becoming a mature virus
4. PIs have been associated with


1. Hyperglycemia
2. Deposition of fatty-like tissue at the base of the posterior neck and the abdominal area
3. Hyperlipidemia, & bone loss 
5. Currently there are 9 PI available


1. Lopinavir/Ritonavir (Kaletra)
2. Ritonavir (Norvir)
3. Indinavir (Crixivan)
4. Saquinavir (Invirase)
6. Interactions


1. Agents that inhibit P450 (grapefruit juice), can increase the levels of PIs
2. Agents that induce P450, will decrease the levels of PIs
3. St. John’s Wort decreases levels of PIs
4. Garlic decreases levels of PIs

Integrase strand transfer inhibitor (INSTI)

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1. Aka integrase inhibitor
2. MOA


1. Prevents insertion of HIV DNA, stops replication 
3. Pharmacokinetics


1. Administered PO
4. Adverse effects


1. Generally well tolerated
2. N, D, fatigue, HA, and itching
3. Pregnancy category C


1. No adequate well-controlled studies have been done
2. Not recommended in breastfeeding

Enfuvirtide (Fuzeon)

a fusion inhibitor

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1. MOA- Blocks entry of HIV into CD4 cells
2. Requires sub q injections twice a day
3. Expensive 
4. Use in combination
5. Therapeutic Uses


1. Adults and children 6 years of age and older who are treatment experienced and continue to HIV replication despite ongoing antiretroviral treatment
6. Adverse Effects


1. Injection site reactions
2. Bacterial pneumonia
3. Hypersensitivity reactions

postexposure prophylaxis

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1. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for post-exposure prophylaxis
2. This report updates US Public Health Service (2013)  recommendations for the management of healthcare personnel (HCP) who experience occupational exposure to blood and/or other body fluids that might contain human immunodeficiency virus (HIV)
3. The following is a summary of recommendations: 


1. PEP is recommended when occupational exposures to HIV occur
2. the HIV status of the exposure source patient should be determined, if possible, to guide need for HIV PEP
3. PEP medication regimens should be started as soon as possible after occupational exposure to HIV, and they should be continued for a 4-week duration 
4. new recommendation-PEP medication regimens should contain 3 (or more) antiretroviral drugs for all occupational exposures to HIV
5. expert consultation is recommended for any occupational exposures to HIV and at a minimum for situations described in Box 1 
6. close follow-up for exposed personnel should be provided that includes counseling, baseline and follow-up HIV testing, and monitoring for drug toxicity; follow-up appointments should begin within 72 hours of an HIV exposure
7. new recommendation-if a newer fourth-generation combination HIV p24 antigen-HIV antibody test is utilized for follow-up HIV testing of exposed HCP, HIV testing may be concluded 4 months after exposure; if a newer testing platform is not available, follow-up HIV testing is typically concluded 6 months after an HIV exposure

prophylaxis of opportunistic infections

\

1. PCP pneumonia
2. TB
3. Candidiasis
4. CMV retinitis
5. HSV

HIV vaccine

\

1. Obstacles to development
2. Wide global variation in HIV strains
3. Lack of info on natural immunity to HIV
4. Multiple modes of HIV transmission
5. Lack of ideal animal model to study effects
6. Had 34 now a few vaccines testing
7. AIDSVAX only one to go to Phase III trials
8. Ongoing

ADHD

\

1. Most common neuropsychiatric disorder of childhood
2. Higher in boys than girls
3. Most commonly treated with Ritalin
4. Signs and symptoms


1. Hyperactivity
2. Impulsivity
3. Inattention
5. How to diagnose


1. Symptoms must appear before the age of 7 and be present for at least 6 months
6. Stimulants are the primary treatment
7. No data supports one stimulant over another
8. Why a stimulant to suppress hyperactivity?


1. Stimulant gives child to focus in on positive behaviors that they are supposed to have
9. Drug holidays


1. Appetite suppression is an adverse effect


1. Give after meals
2. Or, give children the weekend or summer off from the medications

CNS stimulants

\

1. Increase activity of neurons by enhancing neuronal excitability and by suppressing neuronal inhibition
2. In high doses, CNS stimulants can cause:


1. More energy
2. Impact on HR and BP
3. Drug abuse

Amphetamines

\

1. Overview


1. CNS stimulant
2. CNS actions


1. Creates higher levels of productivity
2. Causes release of norepinephrine (NE) and dopamine and partly inhibiting both transmitters
3. These actions take place in both the CNS and peripheral nerves
3. High potential for abuse


1. IVs most common illicit drug use of amphetamines for abuse
2. Pharmacologic effects


1. CNS


1. Increase wakefulness, alertness, reduce fatigue, elevate mood, and augment self confidence and initiative
2. Euphoria, talkativeness and increased motor are likely 
3. Can decrease appetite, increase respirations
2. CV
3. Physical dependence


1. If abruptly withdrawn, abstinence syndrome will ensue 


1. Exhaustion, depression, prolonged sleep, excessive eating
2. Sleep patterns may take months to normalize 
4. Abuse


1. Due to the euphoria, high potential for abuse


1. Considered a controlled substance, schedule II
5. Adverse effects


1. Weight loss
2. CV


1. With significant heart history, can cause dysrhythmias, angina pain, HTN
3. Psychosis


1. Paranoid psychosis, characterized by hallucinations and paranoid delusions (looks like schizophrenia) (resulting from the release of some dopamine)
2. If occurs, administer dopamine blocker (haloperidol)
3. Withdrawal from treatment (psychosis usually goes away within a week)
6. Therapeutic uses


1. ADHD
2. Narcolepsy
7. Administration


1. PO
2. Not approved for IV
3. If IV, this is an illegal substance

Methylphenidate (i.e., Ritalin)

\

1. MOA is exactly the same as Amphetamines (promotion of NE and dopamine release and inhibition of reuptake)
2. Same side effects 
3. Structurally, dissimilar 
4. Three forms 


1. IR, SR, once-daily doses

Dexmethylphenidate (Focalin)

\

1. Drug for ADHD
2. Dissimilar compounds, exactly the same as amphetamines and Ritalin in all other aspects

Methylxanthines

\

1. Caffeine


1. Found in various forms
2. MOA


1. Reversible blockade of adenosine receptors 
2. Enhancement of calcium permeability 
3. Pharmacological effects


1. CNS 


1. Decreases drowsiness, fatigue 
2. Increases the capacity for intellectual exertion
3. Increased doses can cause tremors, insomnia, nervousness 
2. Heart 


1. Stimulates the heart, dysrhythmias can occur
3. Blood vessels 


1. Vasoconstriction 
4. Bronchi 


1. Relaxation of bronchial smooth muscle, bronchodilation 
5. Kidney 


1. Diuretic 
6. Reproduction 


1. Crosses the placenta 
4. Pharmacokinetics


1. Readily absorbed in the GI tract
2. Peaks in 1 hour
5. Therapeutic uses


1. Neonatal apnea
6. Acute toxicity


1. Intensification of the low, expected response
7. Administration


1. Other than food, oral intake


1. PO – tablets, capsules, lozenges
2. IV

Modafinil (Provigil)

\

1. Nonamphetamine stimulant
2. Promoting wakefulness in patients with excessive sleepiness (narcolepsy, shift-work sleep disorder)
3. Off-label uses 


1. Fatigue 
2. Depression 
3. ADHD
4. MOA- unknown 
5. PO

non-CNS stimulants

\

1. Less effective than stimulants, considered a second-choice drug
2. Not regulated as a controlled substance
3. **Atomoxetine (Strattera)**


1. No potential for abuse 
2. Prescriptions can be refilled over the phone
3. MOA is unclear, a selective inhibitor of norepinephrine, causes NE to accumulate at the synapse
4. ADVERSE EFFECTS 


1. Generally well tolerated 
2. GI (n/v)
3. Sexual dysfunction and urinary retention 
4. Can cause suicidal thinking

parkinson’s disease

\

1. Progressive neurodegenerative disease


1. Afflicts 1 million Americans
2. 2nd to Alzheimer’s
2. Cardinal symptoms


1. Tremor
2. Rigidity
3. Postural instability
4. Slowed movements
5. Depression and flat effect
6. Dementia
7. Dyskinesias (movement disorders)


1. Tremor at rest
2. Rigidity
3. Postural instability
4. Bradykinesia
5. Akinesia
8. Other symptoms


1. Psychological disturbances
2. Sleep disturbances 
3. Early s/s (middle age)


1. Voice changes (decreased volume)
4. Excessive salivation 
5. Poor handwriting
6. Clumsiness with hands
7. Loss of smell
8. Tremors
9. Slow gait

neurotransmitter involvement - parkinson’s

\

1. Two neurotransmitters


1. **Dopamine**


1. ***Inhibit*** release of gamma-aminobutyric acid (GABA)
2. **Acetylcholine (Ach)**


1. ***Excite*** neurons that release GABA
2. With Parkinson’s disease, there is not enough striatal Dopamine and too much Acetylcholine

therapeutics - parkinson’s

\

1. Therapeutic Goals


1. Reverse neuronal degeneration
2. Control symptoms
3. Improve ability to perform ADLs
2. Most beneficial drug selection


1. Improve bradykinesias, gait disturbance & postural instability


1. work, walking, dressing, eating, and bathing
2. *(Tremor and rigidity less disabling)*
3. Drug Goal


1. Neurochemical basis of Parkinson’s


1. Too little striatal dopamine and too much ACH, approach…
2. Give drugs that restore function!


1. Dopaminergic agents


1. Multiple MOAs
2. Directly or indirectly cause activation of dopamine receptors
2. Anticholinergic agents


1. Block muscarinic receptors for ACH in the striatum

Levodopa, Levodopa/carbidopa

\

1. **Levodopa** or **a dopamine agonist** are considered treatment of choice for patients with more __*severe symptoms*__


1. Levodopa almost always given in combination with carbidopa
2. Then add dopamine antagonists, MOA-B inhibitor, or COMT inhibitor to help with off times & dyskinesias
2. Full therapeutic response may take a few months
3. Well controlled during first two years
4. Deterioration to pretreatment condition by end of fifth year related to disease progression


1. Decrease in effect may be gradual or abrupt
5. Gradual loss


1. Subtherapeutic drug levels near end of dosing interval
2. So what can be done?


1. Shorten dosing interval
2. Add a drug to prolong levodopa’s ½ life


1. Carbidopa or a COMT Inhibitor
3. Give a direct acting dopamine agonist
6. Abrupt loss with long-term treatment


1. ON/OFF phenomenon
2. Episodes of the ability to be mobile  (on) to an unpredictable period of immobility (off), loss of symptom relief


1. Occurs at anytime
2. OFF periods can be minutes to hours
3. Usually see increased intensity and frequency of OFF periods
7. Pharmacokinetics


1. Reduces symptoms by promoting synthesis of dopamine in the striatum
2. Administered orally
3. Rapid absorption from small intestine
4. Food delays absorption by delaying gastric emptying
5. High protein foods decrease therapeutic effects
8. Adverse effects


1. Dose dependent
2. Nausea and vomiting


1. Activates the CTZ *(chemoreceptor trigger zone)* in medulla
2. Administer low doses
3. Avoid with food if possible


1. Giving with food may help reduce N/V but does decrease absorption so __ideally given without food__
3. Cardiovascular


1. Postural hypotension


1. ↑ Na and H2O in diet
2. Dysrhythmias


1. Related to stimulation of B1 receptors
2. More common in patients with heart disease 
4. Dyskinesias (80% develop)


1. Within first year of treatment
2. Head bobbing, tics, grimacing, severe involuntary jerks or writhing movements
3. How can we treat these?


1. Reduce Levodopa dosage (*but then subtherapeutic*)
2. Add a dopamine releasing agent (Amantadine)
5. Extra Pyramidal Symptoms (EPS)
6. Psychosis (20% of patients)


1. Visual hallucinations, vivid dreams, nightmares, paranoid ideations
2. ↓ dosage can help psychosis 
3. Treatment with an antipsychotic can be a problem
4. Clozapine (atypical antipsychotic (2nd gen.), does not block dopamine receptors)
7. CNS effects
8. Dark sweat and urine
9. Activation of malignant melanoma


1. From levodopa or from Parkinson’s Disease?


1. Melanoma patients have increased risk of developing PD and vice versa
2. Cutaneous and ocular melanoma surveillance 
3. Need more research…replication studies
9. **COMBINATION WITH CARBIDOPA = SINEMET**

carbidopa

\

1. No therapeutic effects on its own
2. Inhibits decarboxylation of levodopa in the intestine and periphery
3. Increases amount of levodopa available in the brain from

other parkinson’s drugs

\

1. Dopamine agonists


1. Bromocriptine, pramipexole, ropinirole
2. Catecholamine-*O*-methyl transferase (COMT) Inhibitors


1. Entacapone, tolcapone
3. MAO-B inhibitor


1. Selegiline (Eldepryl, Zelapar)
2. Rasagiline (Azilect)
3. Recommended as initial therapy for mild symptoms

amantadine

dopamine releaser


1. Promote release of dopamine from dopaminergic receptors
2. Blocks dopamine reuptake
3. 2-3 day response time
4. Responses begin to diminish within 3-6 months
5. Not 1st line agent
6. **Best for managing dyskinesias secondary to levodopa**
7. Adverse effects


1. CNS effects - Confusion, lightheadedness, and anxiety
2. Peripheral effects – blurred vision, urinary retention, dry mouth and constipation
3. Livedo reticularis –  taking amantadine  one month or longer 


1. benign mottled discoloration of the skin 
2. subsides when Amantadine is stopped

epilepsy

\

1. A group of chronic neurological disorders characterized by recurrent seizures, due to excessive excitability of neurons in the brain.
2. Symptoms can range from periods of unconsciousness to violent convulsions
3. 2.3 million Americans affected
4. Seizure: general term for all types of epileptic events
5. Convulsion: abnormal motor activity, i.e., jerking movement seen with tonic-clonic attack
6. Antiepileptic drugs (AED): classification of medications used to treat epilepsy

seizure activity

\

1. Seizure generation - think focus and spread


1. Elicited from a focus: abnormal hyperexcitable discharge from neurons 
2. Spreads to other brain areas
3. Causes normal neurons to fire abnormally
4. Type of seizure determined by area of brain involved
2. Causes


1. Head trauma, congenital defects, hypoxia at birth, cancer

AEDs

\

1. Suppress discharge of neurons within a seizure focus
2. Suppress spread of seizure activity from focus to other areas
3. Five basic functions


1. Suppression of sodium influx


1. Na influx propagates action potential of the cell/certain drugs delay the action potential
2. Suppression of calcium influx


1. Ca influx promotes transmitter release/drugs that block Ca channel suppress transmission
3. Promotion of potassium efflux
4. Antagonism of glutamate
5. Potentiation of GABA


1. GABA an inhibitory neurotransmitter decreases neuronal excitability, suppress seizure activity

therapeutic goals and drug selection - epilepsy

\

1. Reduce


1. Reduce seizures to an extent that enables the patient to live a normal to near-normal life


1. May not be possible to totally eliminate seizure activity 
2. Balance


1. Balance between side effects and seizure control
3. Drug selection


1. Depends on the type of seizure
2. Need physical, neurological, and lab findings, patient history
3. Many times patients may have to try multiple drug therapies to find the best regimen

phenytoin (Dilantin)

\

1. Most widely used AED 
2. Used for partial or tonic-clonic 
3. First drug to suppress seizures without totally suppressing the CNS
4. MOA


1. Selective inhibition of sodium channels 
2. Action potentials suppressed
3. Blockade of sodium entry is limited to neurons that are hyperactive
4. *As a result, this drug only suppresses activity of seizure generating neurons while leaving the healthy ones unaffected*
5. Adverse effects


1. CNS 


1. *When above therapeutic levels, nystagmus, sedation, ataxia, diplopia* 
2. Hirsutism
3. Gingival hyperplasia 


1. *Excessive growth of gum tissue* 
4. Morbilliform Rash 


1. *(looks like measles; ? d/t HLA-B genetic mutation)*
5. Pregnancy


1. *Can cause cleft palate, heart murmurs, motor or mental deficiency* 
2. *Decrease vitamin K absorption, bleeding risk*
6. Dysrhythmias/CV effects with IV admin


1. *Administer slowly in IV solution to prevent*
6. Drug interactions - Hepatic enzyme inhibitor


1. Can decrease the effect of birth control, warfarin, glucocorticoids 


1. *Women should increase the contraception dose, especially since pregnancy should be avoided when on this medication* 
2. Drugs that increase plasma levels of Dilantin 


1. Valium, isoniazid, cimetidine, ETOH (*acutely* used)
3. Drugs that decrease plasma levels of Dilantin 


1. ETOH (*chronically* used)
2. Phenobarbital 
4. CNS depressants: additive effect

carbamezapine (Tegretol)

\

1. Works against partial and tonic-clonic 
2. MOA 


1. Suppresses high-frequency neuron activity by delayed recovery of sodium channels
3. PO only
4. Absorption varies widely
5. Hepatic metabolism -- *inducer*
6. Therapeutic uses


1. *Epilepsy* 
2. *Bipolar disorder* 
3. *Trigeminal nerve pain*
7. Adverse effects


1. Minimal CNS effects
2. Neurologic effects 
3. Hematological effects 


1. Can induce bone marrow suppression (anemia, leukopenia, thrombocytopenia)
2. CBC performed periodically and before treatment
4. **Teratogenic** 
5. Water retention
8. Drug interactions


1. Inactivation of oral contraceptives and Warfarin  
2. Phenobarbital and Phenytoin can decrease the effects of carbamazepine
3. Valproic acid inhibits metabolism of carbamazepine
9. Food interactions


1. Grapefruit juice


1. Can increase peak and trough levels

Valproic acid (Depakote)

\

1. Used widely to treat **all seizure types** 
2. Available in three forms 


1. valproic acid 
2. the sodium salt of valproic acid (valproate) 
3. divalproex sodium (the combo of the first two)
3. May be administered PO, IV (also rectal)
4. MOA


1. Suppresses high-frequency neuronal activity  through blocking sodium channels 
2. Suppresses calcium influx 
5. Therapeutic uses


1. Seizure disorder 
2. Bipolar disorder
3. Migraines 
6. Adverse effects


1. Common: GI


1. *Minimized with food, enteric form*
2. **Hepatotoxicity** 


1. Avoid with other drugs in children under 2 
2. Avoid with preexisting liver issues 
3. Check LFTs
3. **Pancreatitis**
4. **Highly Teratogenic**
7. Drug interactions


1. Decreases the rate of phenobarbital metabolism


1. If used together, monitor plasma blood levels, may have to decrease the phenobarbital dose 
2. Phenytoin (Dilantin)


1. Displaces phenytoin from binding sites on albumin leading to toxicity, monitor drug levels 
3. Carbapenem antibiotic 


1. Meropenem and imipenem/cilastin can reduce plasma drug levels of valproic acid
2. Break through seizures have occurred 
4. Caffeine, ASA


1. Inhibit clearance

Oxcarbazepine (Trileptal)

newer anti-epileptic

\

1. Approved for adjunct therapy of *partial seizures* in adults, children
2. MOA


1. Blockade of voltage-sensitive sodium channels, stabilizing the hyper-excitability of neurons, suppressing seizure spread
3. Adverse effects


1. Dizziness, drowsiness, double vision, nystagmus, headache, N/V, ataxia *(many times have to avoid driving because drowsiness is so profound)*
2. SJS
3. Hyponatremia (rare but significant in whom it occurs)
4. Pregnancy risk C
4. Drug interactions


1. Decrease effect of oral contraception and Warfarin
2. Can raise Phenytoin levels 
3. Avoid ETOH, potentiates CNS effects
5. Preparation


1. Can be given PO, oral suspension

gabapentin (Neurontin)

newer anti-epileptic


1. *Neurontin is only form of gabapentin indicated for epilepsy* 
2. Can only be used as adjunct therapy 
3. Therapeutic uses 


1. Neuropathic pain, migraines
4. MOA- unknown 
5. Drug interactions limited 
6. Adverse effects 


1. Generally well tolerated 
2. Somnolence, dizziness, fatigue, nystagmus, peripheral edema

Levetiracetam (Keppra)

newer anti-epileptic


1. Used for partial and tonic-clonic seizures
2. Unknown action
3. Does not interact with other drugs


1. Minimal hepatic metabolism; no use of P450 enzyme system
4. *Drug of choice for seizure prophylaxis in patients with traumatic head injury*

promoting patient adherence - epilepsy

\

1. 50% of all treatment failures are a result of non-adherence
2. PRIORITY to promote


1. Educate patients and family, importance of taking medication
2. Monitoring plasma drug levels 
3. Deeping involvement through keeping the seizure activity chart

withdrawing AEDs

\

1. For an unknown reason, some forms of epilepsy undergo spontaneous remission
2. No steadfast way to withdraw meds, HOWEVER, agreement is that it should be withdrawn slowly


1. *Some say over 6 weeks to several months*
2. *If taking two or more, withdrawn sequentially, not simultaneously*

suicide risk related to AEDs

\

1. AEDs can increase suicidal thoughts and behaviors
2. Screening must take place
3. All patients should be monitored for increased anxiety, agitation, mania, and hostility
4. Alert patients and families to look out for these s/s

Antiviral medications

\

1. Limited in number
2. Viruses use host cell biochemical processes to reproduce
3. Hard to suppress viral replication without harming host

Acyclovir (Zovirax)

1. 1st choice agent
2. MOA


1. Inhibits viral replication by suppressing synthesis of viral DNA
3. Pharmacokinetics


1. Topically, IV, PO
4. Adverse effects


1. Phlebitis (infuse over an hour)
2. Reversible nephrotoxicity 
5. For HSV-2


1. **Initial infection**


1. topical acyclovir reduces duration of viral shedding, does NOT accelerate healing
2. **Recurrent genital infections**


1. topical acyclovir, not effective. Oral treatment best for both initial & recurrent infection
3. **Severe initial infection** 


1. IV Acyclovir
4. Acyclovir eliminates symptoms, does not eliminate the virus or cure it
5. Teaching…always wear a condom!

valacyclovir (Valtrex)

\

1. Prodrug of Acyclovir
2. Oral Valacyclovir converts to Acyclovir in the body.


1. Acyclovir given   bioavailability is 15-30%
2. Valacyclovir given bioavailability is 55%
3. Used to treat:


1. Herpes Zoster 
2. Herpes simplex genitalis (HSV-2)
3. Herpes labialis (cold sores) 
4. Varicella (shingles or chickenpox) 
4. Adverse effects


1. In immunocompromised, Valtrex can cause TTP/HUS 


1. Thrombotic thromboycteopenic purpura 
2. Hemolytic uremic syndrome

Care of: varicella zoster precautions

\

1. Isolation precautions 


1. If lesions covered, standard precautions 
2. NO pregnant women
3. Airborne if open
2. Drug therapy 


1. High doses of oral acyclovir 
2. IV for immunocompromised 
3. Vaccine available

cytomegalovirus (CMV)

\

1. Member of the Herpes group
2. Transmission person to person via direct contact with saliva, blood, urine, tears, breast milk, semen, & other body fluids. Organ transplantation.
3. Very common 50%-85% of Americans age 40 and up harbor the virus


1. Most individuals are __asymptomatic__!
4. Symptoms similar to mononucleosis in immunocompromised individuals
5. Drug therapy


1. **Ganciclovir (Cytovene, Vitrasert)**


1. Active against herpes viruses and CMV
2. Requires maintenance therapy indefinitely
3. Adverse effects


1. Essential to avoid pregnancy for 90 days after treatment


1. Possibility of infertility/sterility (both genders)
2. Thrombocytopenia → Monitor PLT count (stop below 25,000/mm3)
3. Granulocytopenia → Stop if ANC below 500/mm3

hepatitis

\

1. 6 types: A, B, C, D, E, G
2. All can cause acute hepatitis


1. 6 months or less
3. Liver inflammation, jaundice, elevated ALT
4. Most resolves spontaneously (acute)
5. B, C, D cause chronic hepatitis


1. Leads to cirrhosis, liver CA, & life-threatening liver failure

Hepatitis C virus (HCV)

\

1. 3.9 million Americans have chronic Hepatitis C
2. Not all HCV are the same! 6 genotypes & 50 subtypes


1. 75% of HCV are genotype 1
3. No vaccine
4. Slow progression, can lead to liver failure, cancer, death
5. From blood, drugs, HIV, dialysis, organ transplant, born with from mom

CV Treatment recommendations

\

1. Individualized treatment based on the age, genotype, healthy, co-infection, & PMH of patient!
2. Individualized treatment based on the age, genotype, healthy, co-infection, & PMH of patient!


1. Interferon Alfa (usually Peginterferon alfa) - older
2. Ribavirin (nucleoside analog) 
3. Direct acting antivirals (DDAs)


1. Protease Inhibitors 
2. NS5A Inhibitors
3. NS5B nucleoside polymerase inhibitors 
4. NS5B non-nucleoside polymerase inhibitors
4. New drugs being developed/marketed!

interferon preparations

\

1. MOA: blocks viral DNA from entering the host. Binds with host cell and blocks entry.
2. 3 major classes


1. -alpha
2. -beta
3. -gamma
4. All interferons used for hepatitis belong to the __alpha class__
3. Conventional vs Long-acting InterferonsWhat’s the difference?


1. Conventional short acting  half lives (administer a few times a week)
2. Long-acting administered once a week & blood levels remain high between the doses, hence a better clinical response

interferon alfa

hepatitis C drug


1. Preparations


1. Parenteral (IM) or subcutaneous (used SQ primarily for Hep C)
2. Mechanism of action


1. Effects the viral replication cycle
3. Long acting interferon (once a week)


1. Peginterferon alpha-2a or Peginterferon alpha-2b
4. Adverse effects


1. Flu like syndrome (fever, headache, chills, fever)
2. Neuropsychiatric effects – depression suicidal thoughts 
3. GI disturbances
4. Alopecia
5. Injection site reactions
6. Bone marrow suppression

Ribavirin (Rebetol, Copegus)

\

1. Nucleoside analog with Broad spectrum antiviral activity
2. Unknown mechanism of action
3. Must be combined with peginterferon alpha for traditional tx of HCV, not effective alone!
4. Aerosol form treats RSV in children
5. Adverse effects


1. Flu like syndrome
2. Neuropsychiatric effects – depression 
3. Hemolytic anemia
4. Birth defects or death
5. Do not use during Pregnancy