Exam 2 - ENT, pulm, cardio Flashcards
What are the main bacteria that cause AOM?
S pneum, H inf, M cat
What is the mainstay of AOM?
High dose Amoxicillin; need higher doses because its hard to reach adequate concentrations to overcome strep pneumo.
If someone has a severe AOM and was given Amoxicillin, but failed therapy or its gotten worse, what do you do?
Step up to amoxicillin-clavulanate; helps expand coverage.
Also good for recurrent AOM.
If amoxicillin is intolerable for whatever reason, what else could you prescribe for AOM?
3rd gen CS = Cefdinir
OR Arithromycin
If kids can’t keep oral meds down for AOM, what do you prescribe?
Ceftriaxone; patient can come into the office for 3 IM doses.
What bacteria causes acute rhinosinusitis?
S aureus, gram negs, and those that cause AOM
How do you determine if acute bacterial rhinosinusitis is bacterial or viral?
Must have symptoms for over ten days.
If its bacterial, symptoms will worsen around 5-6 days.
What treats Acute Bacterial Rhinusitis?
Augmentin (Augmentin for those nose)
Why? Its important to increase your coverage. (B-lactamase influenza, etc).
If a patient has a PCN allergy and Acute Bacterial Rhinusitis; how do you treat it?
Clindamycin has good gram positive coverage, also levofloxacin
What is important when treating acute pharyngitis?
Worried about secondary infection – acute rheumatic fever, endocarditis, heart failure
How do we prevent overprescribing abx for acute pharyngitis?
Rapid strep test
If pos result; do a culture to see if you have to change coverage.
How is acute pharyngitis normally treated?
Amoxicillin
What med can you use to treat acute pharyngitis in children who are nauseous and vomitting?
Benzathine; given IM because its a suspension. One time dose.
What if the kids can’t tolerate PCN? (acute pharyngitis).
Cephalexin
Clindamycin
Azithromycin
What do otic antibiotics have in them?
Anti-infectives: inhibit bacterial growth
Glucocorticoids: decrease production of inflammatory cytokines.
Why don’t otic antibiotics get resistance as easily?
High concentrations are used to eradicate locally.
What are available otic agents?
phoncc
cipro cipro/dex neomycin polymixin b hydrocoritsone ofloxacin
What are main uses of otic antibiotics?
OM and OE
Risks of Neomycin?
Change for hypersensitivity
Contact dermatitis
If a patient has tubes or ruptured TM, what med can’t you use? Why?
Polymixin B (ototoxicity) Leads to cochlear damage and hearing loss
Why is it bad to prescribe cipro/dex?
Its expensive
Alternative: ofloxacin otic and dex opthalmic
EYE can go in EAR.
MOA Ketoconazole
Inhibit fungal cell wall permeability by inhibiting CYP450 from propagating cell wall
Happens in other AZOLES
ADR Ketoconazole
QT prolongation
Inhibit CYP450 in fungus and people! It’s not very selective; if used systemically, can have CYP3A4 interactions.
- statins
- hyperlipidemia meds
CHECK DRUG INTERACTIONS BEFORE PRESCRIBING.
What is a benefit of using nystatin?
Its a nonabsorbable antifungal, no systemic toxicity
When is nystatin used?
Used topically as powder for oral thrush.
Good for I/C pts
Prevent fungus growth
Treat infection
MOA Nystatin?
Binds to sterols in fungal membrane to increase cell wall permeability; opens up for contents to spill out.
What virus is responsible for infection in I/C patients, AIDs, and cancer pts?
CMV - Leads to esophagitis, retinitis, colitis.
What are the antiviral prodrugs?
Famicyclovir
Valacyclovir
Valgancyclovir
What are prodrugs?
Not active in current form, but when metabolized by liver are confirmed to “active compound”
Why are prodrugs prescribed?
A larger portion of drug goes through first pass; increase the bioavailability!
How do antivirals work?
Inhibit viral DNA replication; guanine analogs are incorporated, but they’re missing the sugar backbone so elongation can’t occur.
Triggers cell death.
What are uses for acyclovir and valacyclovir?
Herpes simplex, Shingles, Herpes stomatitis
Which drug has more bioavilability - acyclovir and valacyclovir?
Valacyclovir, because its a prodrug. Has better efficacy.
ADR of cyclovir meds?
Nephrotoxicity - worry about drug crystallizing in renal tubule causing interstitial nephritis.
Bone marrow suppression.
CNS affects - might increase risk of seizures or altered mental status in the elderly.
What do you tell a patient on an antiviral?
Drink a lot of water to prevent crystallization in the kidneys.
What’re uses of pencyclovir and famcyclovir?
Herpes and Shingles
Toxicity is worse so they’re used less frequently than others; used mostly to step up therapy for resistant strains.
Which one is a prodrug - pencyclovir and famcyclovir?
Famicyclovir
Ganciclovir and Valgancyclovir uses? ADR?
CMV for transplant patients and cancer patients.
Can cause thrombocytopenis and CNS toxicity. Patients stop therapy due to side effects.
Monitor CBC
Which one is a prodrug - Ganciclovir and Valgancyclovir?
Valgancyclovir
What’s Foscarnet used for?
Is it a prodrug?
How is it administered and excreted?
Resistant viral strains; there is no pro drug for it.
» CMV retinitis, acyclovir resistant HSV, shingles, ganciclovir resistant CMV
Administered IV only and renally eliminated. Needs dose adjustment.
MOA Foscarnet?
Inhibits DNA polymerase, directly.
ADR Foscarnet?
Chelates cations - can lead to hypocalcemia, hypomagnesaemia, and hypokalemia
What is acetylsalycilic acid?
Aspirin (ASA)
What is aspirin used for?
Has anti-clotting effects and analgesic at higher levels.
Old drug, good absoprtion, hepatically conjugated, and excreted in kidneys.
MOA Aspirin?
Irreversible inhibitor of COX 1, 2, 3 - no selectivity. Used to protect the heart against MI.
Why wouldn’t you use Aspirin?
Inhibits PLT, causes bruising and bleeding.
Do not use in bleeding disorder or pregnancy.
Why is aspirin bad for kids under the age of 16?
In children with fever (esp. viral), there is an increased risk of Reye’s syndrome!
What is Reye’s Syndrome?
Fatty liver encephalopathy that affects children.
Symptoms are similar to viral illness - fever, vomitting, lethargy etc., but can cause CNS damage – can go unnoticed for a long period of time.
Stages of Reye’s syndrome?
1 - rash on hands and feet, vomiting, high fever, lethargy
2 - encephalitis, hyperventilation, fatty liver
3 - coma, cerebral edema
4 - deeper coma
5 - siezures, organ failure, death
What else causes Reye’s syndrome?
Peptobismol (Bismuth salicylate) - Has salicylate and can cause Reye’s Syndrome.
Motrin (ibuprofen)
Inhibits COX 1 and 2, nonselective
Reversible inhibitor! - not as high risk as ASA.
What is motrin used for?
Pain relief
If you have a sprain or inflammation, better drug to use bc it works on the inducable COX.
What is the risk of using motrin?
RISK - COX1 helps prevent erosion with stomach acids, so use can lead to ulcers (since this is the target); can have acute kidney injury, can worsen hypertension
Motrin interactions with other meds?
Decreases antihypertensives (ACEI)
Leads to accumulation of Lithium
Decrease secretion of methotrexate, which can lead to bone marrow suppression.
Don’t give Motrin tooooo…. ???
ASTHMATICS
Patients may have allergy to it that induces their asthma.
MOA Tylenol (acetaminophen)? Indications for Tylenol?
Inhibits COX3, which is located in CNS. Good for fevers!
Not good for a sprain, because it doesn’t target the periphery.
Tylenol puts you at risk for?
Liver toxicity; don’t exceed 4000mg a day!
Good for pain in pregnancy.
Why is histamine important?
Mediates immune reactions.
“Triple Response” -
- redness - vasodilation
- wheal - edema
- flare - redness
Where are H1 receptor antagonists located?
Located on the heart and bronchial smooth muscle.
When activated, will see vasodilation.
H1 receptor FXC?
H1 receptors increase post capillary permeability and vasodilation.
This leads to increased mucus secretion, bronchus constriction, and smooth muscle tone.
H2 receptors FXC?
Stimulate gastric acid secretion.
Used in long-term complications of allergies, i.e. anaphylaxis.
H3 receptors FXC?
Promote sleep and wakefulness.
H1 receptor antagonist - what do you see from their actions?
Block smooth muscle and GI tract vasodilation, lowers edema (less itching).
What is doxylamine?
OTC Sleep Aid
H1 receptor antagonist
H1 receptors antagonists are commonly abused because?
euphoria, hallucinations at high doses
Second generation of H1 anatagonists - benefit?
Why?
Don’t cause sedation
Can’t cross blood-brain barrier
What is used to treat motion sickness, nausea, and vomitting?
Phenergan
Why are H1 receptor antagonists used?
allergic reactions, motion sickness, nausea, OTC sleep remedies.
ADR of H1 receptor antagonists?
Sedation, GI disturbance
Antimuscarinic, so dry mouth and blurred vision
blind as a bat dry as a bone red as a beat mad as a hatter hot as a match
ADR H1
What’s the difference between H1 first generation agents and second generation agents?
Second generation - Not antimuscarinic or antiemetic bc can’t get into CNS
What is azelastine?
Intranasal spray; H1 receptor antagonist.
Used for allergic and vasomotor rhinitis.
ADR Azelastine?
Nose bleeds, bitter taste
No systemic side effects or activity. i.e. Doesn’t help itching and rashes.
Beclomethasone Budesonide Fluticasone Mometasone Triamcinolone
Nasal Corticosteroids
ONES AND IDES
Benefit of nasal corticosteroids?
Can be used over longer period of time, chronically, to decrease nasal allergic reactions.
Do not use for acute allergies.
Why shouldn’t nasal corticosteroids be used for acute allergies?
Decrease transcription from site of nucleus (gene transcription and protein production).
Meds need to be taken consistently. Takes a week or so before effects are seen.
Why is it good to use brand names for corticosteroids?
Don’t want the pharmacist to fill inhaler version (for asthmatics only).
ADR Nasal Corticosteroids?
Epistaxis Septum perf (rare)
Dexamethosone (Decadron)
What is it used for?
Synthetic adrenocortical steroid
Used for drug hypersensitivity, severe rhinitis, asthma exacerbations.
Why are corticosteroids bad when given systemically?
They have glucocorticoid actions and mineralcorticoid actions
GC is anti-inflammatory, while mineralcorticoid does fluid retention, salt retention, etc. to maintain good volume for cardiac status.
MC effects cause worsening of CHF, HTN, fluid retention and weight gain. Can see glucose intolerance, because it can decrease insulin release. Bad for diabetics Can also see cataracts and increased IOP.
Short course use only!
Immunosupressive!
Dexamethosone and other systemic CS are bad, so why do we use them?
They’re very potent anti-inflammatories. Good for asthma exacerbations, anaphylaxis, etc.
Dexamethosone Drug Interactions
Decreased antidiabetic medications. Diabetics don’t mess with dex.
Electrolyte shift to hypokalemia = potassium deficiency.
When is dexamethosone not used?
Fungal infections, because it’ll further depress immune system.
MAJOR RED FLAG OF DEXAMETHOSONE
Adrenal gland insufficiency
Exogenous corticosteroids causes the adrenal glands to secrete less. If on for over a week and stopped, the adrenal glands would be insufficient.
Need to taper over a weeks time to prevent insufficiency.
Prednisone/Prednisolone (active liquid)
key points
ADR: Same as Dex.
Don’t use for fungal infections.
Taper off of it or you’ll have rebound symptoms.
Afrin MOA
Used intranasally
MOA constricts alpha receptor in nose to decrease edema and leaky capillaries.
What is afrin used for?
Local decongestant! Treats nasal congestion, but causes rebound hyperemia.
Receptors are down regulated; none to be activated to reconstrict when off medication.
Whats the name for rebound hyperemia?
Rhinitis medicamentosa
Risks of Afrin?
Worsen HTN
Pseudoephedrine MOA
Systemic decongestant; alpha agonist that constricts blood vessels in mucosa to decrease stuffiness.
Sudafed can make erections go down, because it constricts blood vessels.
Pseudoephedrine warnings
Can have some rebound congestion, but not like that in Afrin
Guaifenesin (Mucinex)
Mucolytic - loosens mucus secretions in airway and decreases viscosity of them.
Needs to be taken with water to decrease viscosity. Increase in drainage.
Pregnancy Category A
Shown in studies to have no fetal harm or harm in animals; totally safe.
Ex: folic acid, water-soluble vitamins.
Pregnancy Category B
Animal studies may show some harm, but shows no harm to human fetus in any trimester.
Ex: Amoxicillin
Pregnancy Category C
“Shrugging your shoulders” - not enough data to determine effect on humans. Majority of drugs!
Ex: Albuterol
Pregnancy Category D
Evidence of risk to the fetus, but benefits of treating mom outweight the protection of fetus. Need to do risk-benefit analysis.
Ex: Lithium
Pregnancy Category X
Definite harm and there’s no case where its beneficial to give it to the mother.
Ex: Teratogens
START OF PULMONOLOGY CARDS
START OF PULMONOLOGY CARDS
How can you stop cough?
Can target brain stem or the stretch receptors of the throat.
Need to reduce number and severity of coughing episodes and prevent complications
What meds can make you cough frequently?
Ace inhibitors
Tessalon pearls MOA?
Uses?
Patient Education ?
Hardest drug to dispense!
Anesthetize stretch receptor in the lungs to prevent cough.
Do NOT chew! Can numb mouth. Maybe not good for kids, might chew and can cause CNS depression.
Dextromethorphan (Robitussin, Delsym) - MOA? Use?
Related to codeine; helps to supress cough center in the brain.
RED FLAGS for Dextromethorpan (Robitussin) use?
Proserotinergic effects - If you’re taking other drugs that block reuptake of serotonin or decrease metabolism you may see tachycardia, altered mental status, hyperthermia.
Too much serotonin in the synapse.
What are viral causes of acute bronchitis?
rhinovirus, coronavirus, influenza, adenovirus
What do you want to avoid in treating bronchitis?
AVOID ANTIHISTAMINES because it’ll dehydrate the bronchial secretions and worsen symptoms.
How do you treat a viral bronchitis?
Usually self-limited, give NSAIDs.
If you suspect a bacterial bronchitis, how do you normally treat?
Bacterial - Those sick 3-5 days with a worsening of symptoms are bacterial: want to focus on atypicals.
Use doxycycline or azithromycin
If you suspect mycoplasma is resistant to macrolides in bronchitis, what medication would be most apropriate?
Doxycycline (teeth stain under 8yo) - treats mycoplasma resistant to macrolides!!
When is it okay to use a resp FQ to treat bronchitis?
Don’t want to use unless you had recent abx exposure; helps to cover for resistant strep pneumo (since they are more at risk for it).
- levofloxacin
- ciprofloxacin
- moxifloxacin
How do you manage CAP patient?
Curb 65
PSI
Guide if patient goes inpatient, outpatient, ICU
What factors increase risk of PCN-resistant Staph pneum?
Over 65yo, had a beta lactam within last three months, alcoholism, immunosupressed, and medical comorbidities.
What factors increase risk of enteric gram negatives?
nursing homes, cardiopulmonary disease, medical comorbidities, recent abx therapy.
What factors increase risk of pseudomonas aeruginosa?
lung disease, corticosteroid use, broad spectrum abx therapy, malnutrition
What is treatment for CAP outpatient when there’s no risk for strep pneum?
1st line is a macrolide like Azithromycin or Clarithromycin
Macrolides inhibit CYP3A4.
What is treatment for CAP outpatient when there is a risk for strep pneum?
Treat with Beta Lactam AND Macrolide
- augmentin, cefuroxim
- -azithromycin or clarithromycin
If can’t have beta-lactam, use resp FQ.
How do you treat CAP in non-ICU inpatient?
IV beta-lactam, ORAL macrolide
Cefotaxime, ampicillin, and macrolide
How do you treat CAP in ICU?
IV treatment only and MRSA coverage (Vanco).
CAP MRSA Pneumonia
Cavity infiltrates and GPC clusters.
Needs vancomycin (or linezolid, if CI to vanco).
Nosocomial Pneumonia
Occurs from nursing homes, hospitals, or other healthcare settings. Infection not present at time of admission.
HCAP is more likely to occur when?
Hospitalized in acute care facility for more than two days in past 90 days.
Nursing home IV antibiotics recently Chemotherapy wound care dialysis patients
What are un-modifiable risk factors of nosocomial pneumonia?
age, lung disease, depressed consciousness, large volume aspiration, hospitalization during winter months
What are modifiable risks of nosocomial pneumonia?
mechanical ventilation, placement of NG tube, or ICP monitor.
Preventing these lowers your risk for resistant bugs!
What bugs are in nosocomial pneumonia?
SPACE bugs
Psuedomonas E coli Klebsiella Acinetobacter Enterobacter
MRSA
strep pneum
If you put a patient with nosocomial infection on apropriate empiric coverage and they aren’t getting better, what do you consider?
Fungal infection
When you suspect nosocomial pneumonia, what do you do?
What should you cover for?
Start therapy as soon as possible; don’t wait for definitive culture!
Initiate broad spectrum abx
- Consider MDR, esp if at risk
- Must cover MRSA and pseudomomas
When cultures come back, you can streamline therapy to target the bug.
A patient was on previous abx 3 months ago. He is now in the hospital for two weeks, undergoing chemotherapy for cancer – what types of drugs does he need to be on for recently contracted nosocomial pneumonia?
He has multiple risk factors for MDR pathogens. – Need to go with 3 drug coverage. 2 for gram negative psuedomonas so on its hit, plus aminoglycoside, and MRSA coverage.
Cefepime - antipseud CS
Imipenem/Meri - antipseud carbapenem
PLUS
Gentamycin - aminoglycoside
or antipseud FQ - levofloxacin.
PLUS vanco (or linezolid).
If your patient has low risk factors for MDR pathogens, what do you prescribe for nosocomial pneumonia?
3rd gen CS = Ceftriaxone
OR levofloxacin
OR ampicillin/sublactam
OR ertapenem
What are antipseud CS?
Ceftazidime and Cefepime!
What are 2 antipseud carbapenems work? Any red flags?
Imipenem - use with caution for patients with seizure history
Meropenem
What are antipseud PCNs?
Piperacillin/tazobactam
Ticarcillin/clavulanate
What are antipseud FQs? Why?
ciprofloxacin
levofloxacin
Have good penetration to the lungs!
What is ADR of FQ?
QT prolongation
Tendon rupture in young patients
- ciprofloxacin
- levofloxacin
Aminoglycosides
- Gentamycin
- Tobramycin
- Amikacin
Nosocomial Uses?
What needs to be monitored?
Once daily dosing, because they’re conc-dependent killer. Also, need higher doses because they have poor lung penetration.
Need TDM; nephrotoxicity and ototoxicity
Vancomycin is used in nosocomial pneumonia for MRSA coverage.
Why do yo uneed higher trough levels for lungs, brain, and bones?
Lungs, brain, and bones are hard to penetrate, so they require higher trough levels.
When is trough drawn?
3-4th dose to make sure you’re at a steady state
What is monitored on vanco?
ototoxicity and nephrotoxicity
What is linezolid used for?
MRSA, VRE
Can penetrate lungs
Used when vanco isn’t tolerated.
NO DOSE ADJUSTMENT FOR RENAL FUNCTION.
What drug isn’t good for pneumonias, bc its inactivated by surfactant?
Daptomycin
Reasons for nosocomial pneumonia failure of tx?
Could be a resistant pathogen and wrong therapy. May have been misdiagnosed. Complications, such as empyema or lung abscess.
How long is nosocomial treatment normally for?
7-8 days, but 10-14 for more resistant bugs
Anaphylaxis Symptoms
Laryngeal and lower airway edema, stridor, wheezing, rhinitis, GI symptoms
What is the first thing you do in anaphylaxis?
Worried about “leaky cappillaries” and intravascular depletion of fluid causing edema.
Start with epinephrine and volume expansion!
What are crystalloids used for?
Crystalloids are salt-based, ex: lactate ringers, NaCl.
Good for intravascular volume replacement in anaphylaxis.
What are choloids used for?
Albumen and starch.
Why is 0.9% NaCl used?
Its a crystalloid isotonic solution - osmolarity is 308, which is isotonic to blood osmolarity (300).
It will stay in intravascular space!
If you’re giving a fluid bolus, what dose is it?
20ml/kg! (20kg patient gets 400ml bolus).
Top off at 1-2 L and reassess. volume status.
What do you do for a fluid bolus with a renal patient?
Might need to give less than regular fluid bolus; also applies to peds patient.
What is the rule when doing maintenance fluids after a fluid bolus?
4:2:1 rule
4ml/kg for first 10kg
2ml/kg for second 10kg
1ml/kg for every kg after 20.
How much fluid should a 60kg patient get for fluid maintenance after bolus?
100ml per hour.
What is the first drug given for anaphylaxis?
Epinephrine
Epinephrine MOA
MOA: activates alpha and beta receptors
Alpha - increases vasoconstriction to prevent the leak
Beta - helps cause smooth muscle relaxation to release airway contraction and improve oxygenation.
Know to relieve pruritus, urticaria, and angioedema.
What do you do if they’re allergic to epinephrine?
Use preservative free product, because of allergy.
If not possible, you treat allergy during tx.
How is epi given?
IM or subQ
Can be given IV for SEVERE reactions, when patient isn’t perfusing.
If a patient is coding, how do you give epi?
IV
They’re not perfusing so it won’t be circulated if IM or subQ. without blood flow to these areas, it wont work well.
1:1000 epi dose
1mg in 1mL
1:10,000 epi dose
1mg in 10mL
If you give too much epinephrine, what happens?
intercranial hemorrhage
MI, pulmonary edema, etc.
What is slammed into a patient when they’re coding?
1 in 10 via IV.
What is adminsitered after epi in anaphylaxis?
Histamine blockers! B/c there’s a huge amount of histamine being released in reaction and these help alleviate itching, etc.
What are H1 blockers?
diphenhydramine and hydroxyzine
Most commonly used!
What are H2 blockers?
Rantidine
Mainly GI drugs; optional add on drugs.
H2 blockers prevent gastric acid in GI tract. They end up increasing pH of stomach so more things can grow and ulcers can occur.
After epi, fluid, histamine – what is administered?
bronchodilators, such as albuterol, which relax bronchial smooth muscle.
What happens in albuterol overdose?
anxiousness, tremors, tachycardia
H1 antagonists - first generation
benadryl
dephenhydramine
H1 antagonists - second generation
zyrtec
allegra
claritin
What are some Inhaled Corticosteroids?
Beclomethasone Budesonide Fluticasone Mometasone Triamcinolone
What’s the benefit of using inhaled corticosteroids rather than systemic ones?
There are less systemic side effects; they work locally in the lungs.
MOA Inhaled Corticosteroids
Inhibiting the anti-inflammatory cascade by working at site of nucleus to decrease transcription of genes that makes inflammatory cytokines.
How long do ICS take before they have an effect?
Inhaled corticosteroids take longer to work. Tell patient to take drug consistently, as prescribed, every single day.
Takes 8 weeks for maximal effects.
What are adverse reactions to ICS? What do you tell patients?
Well tolerated compared to systemic CS.
May develop oral candidasis, because the drug goes to the back of the throat and causes immunosuppression there. Must swish out mouth with water and spit afterward.
Exceedingly high doses may suppress normal growth.
Why do we see combination drugs with ICS?
LABA like formoteral and salmeterol can be combined with ICS.
LABA will provide some control throughout the day while the ICS start to kick in.
What are examples of combination drugs for Asthma with ICS?
Symbicort (Formoterol/budesonide)
Dulera (Formoterol/momentasone)
Advair (Salmeterol/fluticasone)
Frequently, if patients are having mild, persistent symptoms, what can you get away with?
Using ICS by itself. Combination products can be very expensive for patients.
If its severe, do combination initially.
Why are Leukotriene Modifiers used?
Leukotrienes are responsible for the bronchial constriction .
If we get something to block at receptor site, it prevents them from bronchoconstriction in the first place and stops asthmatic symptoms.
What are the Leukotriene modifiers?
Zafirlukast (Accolate)
Montelukast (Singulair)
Montelukast (Singulair)
Primary leukotriene modifier used clinically
Zafirlukast (Accolate)
CYP2C9 and CYP3A4 inhibition, which is hard to use clinically without causing drug interactions.
MOA of leukotriene modifiers
What can it treat?
Block LTD4 receptors to prevent mucus secretion, edema, and inflammation.
Considered a controller medication for asthma. Also works for aspirin induced asthma (non-atopic asthma).
Zileuton MOA?
Directly inhibits lipoxygenase to prevent leukotrienes from being formed in the first place.
Zileuton ADR?
Rarely used, inhibits CYP1A2 and CYP3A4.
Can cause flu, drowsiness, hepatic elevation
COX is inhibited by?
NSAIDs
Lipoxygenase forms leukotrienes.
What blocks receptors?
Montelukast
Lipoxygenase forms leukotrienes.
What will specifically inhibit lipoxygenase from being made?
Zileuton
Works at source - Prevents leukotrienes from being made by inhibiting LOX.
Aspirin-induced asthma
Asthma attacks induced by NSAIDs and aspirin.
Occurs when you block COX from making prostaglandins, it shifts over to the other side forming leukotrienes. Pathway is ramped up and can induce an asthma attack.
If you have a patient with aspirin induced asthma, what do you prescribe?
You can put them on leukotriene receptor antagonists to prevent symptoms from occurring in the first place. - Montelukast
Pt who you wanted on aspirin, you can put on Montelukast as well to help aspirin induced asthma from occurring.
If you have a patient with aspirin-induced asthma, but needed them to take it for cardiac protection, what do you put them on to prevent the asthma attacks from production of leukotrienes?
Put them on montelukast, which will “shunt” the path over to COX production, rather than LOX.
Issues with Zileutin and Zaphrolukast?
Liver Function Decline!
Anorexia, abdominal pain, nausea, jaundice, pruritis
What are side effects of leukotriene modifiers?
Non specific headache or heartburn, but very well tolerated.
Montelukast is mainly used as an?
Adjuvant therapy if asthma symptoms aren’t controlled by corticosteroids.
How do you prevent asthma exacerbations in first place?
Remove trigger and stabilize the mast cells with MCS.
Why are MCS limited use?
They’re for prevention and only block one step of pathway.
They aren’t that effective, which is why they aren’t used as often.
Cromolyn and Nedocromil
Mast cell stabilizers; an inhalation product.
It has to be taken before the insult occurs to be effective against asthma.
MOA not known, but prevent Ca from activating mast cells.
Patient education for MCS?
The drug takes 4 weeks before you see total efficacy.
Tell patient it will take time so they won’t discontinue drug.
Side effects to Cromolyn and Nedocromil?
Bad taste in mouth; well tolerated.
Sore throat, stuffy nose, headache, cough… nothing important
When is Omalizumab (Xolair) used?
Gets used regularly for patients who have significant allergies that are difficult to control and are on other medications.
Used for kids with bad asthma at Nemours.
Suffix -mab
Monoclonal antibody - Used for AI conditions, rheumatology, Crohn’s, and colitis.
Ex: Omalizumab for asthma.
Benefits to use of a monoclonal antibody?
Targets a specific receptor, so these meds won’t have as many side effects since they have one particular target.
Less tissue damage, etc.
Risks when using a Mab?
It is a protein, so any time you inject it into the blood stream, you’re at risk for an immune reaction like anaphylaxis. Monitor patient during infusion.
Also expensive to produce; used when other treatments are failed.
Omalizumab administration
Subcutaneous injection.
Given every two to four weeks at the clinic.
Omalizumab MOA
Specifically targets against IgE.
Requirements of Omalizumab treatment
Requires a
Prior Authorixation, because insurance companies won’t cover unless you have evidence of documented treatment failures.
During administration, you have to monitor the patient for anaphylaxis until you know how they tolerate the treatment.
What’re risks for Omalizumab?
Secondary malignancy like leukemia may pop up, but is exceedingly rare.
Anti IgE Antibody Side Effects
Omalizumab
Urticaria
Anaphylaxis
Injection site pain
Bruising
They’re rare, but concerned about anaphylaxis.
Methylxanthines group
MOA and use?
Theophylline and Aminophyline
Nonspecific phosphodiesterase inhibitor.
Not used frequently, bc they’re less effective and less well tolerated. Controller meds LABA and ICS are better.
What is Aminophyline?
IV form of Theophylline
Whats a common methylxanthine abused by PA students?
Caffeine; same class as Theophyline
What can be given to neonates to stimulate respiratory drive?
Caffeine
Theophyline MOA?
Nonspecific phosphodiesterase inhibitor – Phosphodiesterase is an enzyme responsible for metabolizing cyclic GMP (secondary messenger), which is responsible for relaxation of smooth muscle.
In asthma attack, bronchial smooth muscle constricts. So giving this drug will relax that muscle.
By inhibiting phosphodiesterase, you see higher cyclic GMP. Which means?
More smooth muscle relaxation.
Viagra MOA?
Phosphodiesterase inhibitor.
If a child has pulmonary hypertension, what can you prescribe?
Viagra. Used bc same enzyme is seen in lungs.
Why are Theophyline and other methylxanthines less frequently used?
Narrow therapeutic index - therapeutic and toxic blood levels are close together.
Need to draw troughs!
ADR Theophyline
Arrhythmia, convulsions, nausea and GI issues.
Its an older drug - will see in old women who physician never changed the drug.
If there’s a child in the PICU with status asthmaticus (prolonged asthma attack) that isn’t responding to anything - What can you use to bronchodilate?
IV Theophyline formulation to have extra bronchodilation.
When is Theophyline commonly used?
COPD patients
What are mechanisms of Theophyline? There’s 3.
Inhibit phosphodiesterase to have higher cGMP/cAMP to help bronchodilate.
Adenosine receptor antagonist
Anti-inflammatory reactions
If you have a patient with supraventricular tachcardia, HR is 180, and ventricles trying to keep up. What can you give?
Adenosine - Give to stop heart and reset the rhythm.
If you block affects of adenosine, you have the tachy arrythmias.
Theophyline can cause this, bc it blocks adenosine.
If you block adenosine in CNS, what happens?
Seizures occur
Theophyline can cause this, bc it blocks adenosine.
ADR Theophyline
GI issues, smooth muscle relax in bronchioles, but also vascular smooth muscle = results in hypotension.
Whats important about Theophyline dosing??
Renally eliminated drug; needs to be adjusted so levels don’t get too high or drug can accumulate and get into CNS causing convulsions and sizures.
Levels over 20mcg/mL are BAD!!!
Theophyline Plasma levels
5-20
15-20
30-40
5-20 is therapeutic
Toxic effects start at 15 - nausea, vomitting, and cardiac effects.
30-40 TOXIC - siezures and arrythmias.
84yo nursing home patient was on theophylline and had decrease in renal function. Why is this bad?
Drug accumulated in the CNS and caused a siezure.
Levels over 20mcg/mL become toxic.
How would you treat this old lady with high CNS levels of Theophyline?
Dialyze drug off.
CNS levels were so high, she ended up in non-convulsive epilepsy and died.
Scary drug, not used frequently
Anticholinergics MOA
Short acting rescue medications; block effects of muscarinic receptors which cause bronchodilation.
Methylcolene
Used in provocative tests that induces an asthma attack.
Ipratropium (Atrovent)
short acting anticholinergic that lasts for eight hours
Tiotropium (Spireva)
Long acting; only used for COPD and lasts 24 hours or more.
When prescribing rescue meds, what do you give?
What about in ER?
Albuterol inhaler
Albuterol and ipratropium can be used synergistically to have more oomph into bronchodilation to see how reversible airflow obstruction is. Tells if you need another therapy.
MDI
Meter dose inhaler
DPI
Dry powder inhaler; comes in a discus where you turn it open and hit a trigger to puncture packet so patient can inhale drug itself. Relies on patient to inhale drug.
May not be good for older or younger patients who dont have faculty to inhale.
Spireva Administration
Comes as a capsule. Capsule goes into inhaler and is punctured for inhalation.
If you accidentally swallow spireva, what happens?
Its not absorbed systemically.
TEll patients not to store with normal medications.
What is HFA?
CFC based propellent which damaged ozone layers, so they switched to HFA which is a new repellent.
Side effects to anticholinergics?
Ipatropium (Atrovent) and Tiotropium (Spiriva)
By giving these drugs in lungs, you’re less likely to see systemic effects.
Midriasis, blurry vision, hallucinations, delirium, memory loss, psychosis, flushing, fever, hyperthermia, dry mouth/eyes, urinary retention, constipation, tachycardia, and hypertension.
Side effects to anticholinergics.
Midriasis, blurry vision, hallucinations, delirium, memory loss, psychosis, flushing, fever, hyperthermia, dry mouth/eyes, urinary retention, constipation, tachycardia, and hypertension.
Anticholinergic
What receptors do they act on?
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system.
Nicotinic receptors - skeletal muscle and nerve conduction through CNS.
Muscarinic receptors - tissues.
Patient is on controller meds, but has attacks and uses SABA often. What do you do?
Use short courses of systemic corticosteroids to decrease the inflammation occurring.
Helps suppress and reverse the airway.
Oral Systemic Corticosteroids
Systemic effect; take time to work, but work more quickly than ICS, bc they’re more potent.
This is why only used for exacerbations and short period of time.
What are the oral systemic corticosteroids?
Predinisone (oral tablet)
Prednisolone (oral liquid)
Methylprednisone (oral or parenteral IV, IM)
Dexamethosone (Oral or parenteral IV, IM).
What are the systemic corticosteroid side effects?
Adrenal suppression - exogenous steroids lower their secretions; start to shut down. If dose is less than a week, you don’t need to taper it off. However, if dosed for longer, you must taper off so the adrenal glands start working again.
Effects seen more with chronic dosing; not short-course therapy.
IMMUNOSUPRESSION - leads to secondary infections.
Growth supression
Dermal thinning
Hypertension
Muscle weakness
Patient in ER for asthma exacerbation, what can you do?
Send them home with 5 days of corticosteroids. Stop at the end, no taper needed.
Dose is less than a week, which is why no taper dosing is needed.
A patient with a bad exacerbation might have 3 to 4 days inpatient and 5 going home. How do you dose this?
Need to taper off this dose to prevent the withdrawal that leads to adrenal insufficiency.
Step 1 Asthma Treatment
SABA PRN
Exercise induced bronchospasm.
They have a known trigger, so use beforehand to prevent from occurring.
Step 2 Asthma Treatment
More symptoms, want to add a controller therapy - ICS.
Step 3 Asthma Treatment
Can add LABA or increase ICS.
Step 4 Asthma Treatment
Med dose ICS and LABA
Step 5 Asthma Treatment
High dose ICS and LABA
May add omaxilizumab.
Keep journal of symptoms and nighttime awakenings.
Spacers
Open tube that extends inhaler away from patients mouth
Valve holding chambers
have a one way valve that do not allow patient to exhale into the device
What does a nebullizer do?
Aerosolizes drug.
Compressor with tubing, put drug into a cup, turn on compressor and the air will cause the aerosolization of albuterol to occur.
Downsides to nebulizer?
In six month old, putting a mask with nebulizer is easy, because they’re passively breathing it in.
Downside: more medicine is absorbed, which causes more systemic side effects.
Nebullizer ADR
2 puffs = 180mcg of albuterol
Neb: inhale for 15 mins = 2.5 to 5 mg
Inhale more, so you get jittery, increased HR, potassium shift inwards.
Benefit: helps noncompliant patient get doses in.
Nebullizer Benefit
Help patient get the dose in.
Particle size is important. If its too big, you end up swallowing it. If its too small, you can exhale it.
“Goldy Lock’s” size to get to lungs where it will work.
If patient inhales inappropriately, too fast or too slow, what can you use?
Spacers and valve holding chambers; removes needs for coordinated activity.
Drug is held in chamber and patient can breathe it in more controlled (if you go too fast, it whistles).
MDI with chamber vs. Nebulizer treatment
Equal efficacy, no additional toxicity with MDI.
Inhaler Technique
Take cap off and shake inhaler to “prime” it (takes 3-4 puffs).
Breathe it all out, when you start to inhale actuate inhaler so you have the best airflow down to lungs for drug to go. Hold for 10s and breathe out as normal.
How do you instruct patient on frequency of inhaler use?
Don’t use multiple puffs in succession, bc puff needs time to work ~30 seconds
First dose opens up smooth muscle of bronchioles, so second dose can penetrate even deeper.
When a patient is on ICS, what do you tell them to do afterwards?
rinse mouth and spit
avoids thrush
COPD
Chronic damage being done to lungs over time; effects aren’t completely reversible like they are with asthma.
Accelerated decline in FEV1 over time. Can be asymptomatic for long period of time as lungs start declining. More symptoms will appear as it progresses (graph).
When not airing, need transplant.
What causes COPD?
smoking
alpha 1 antitrypsin deficiency
pollution
What type of med is used for Acute COPD?
For rescue inhaler, start with b2 agonist to relieve acute symptoms.
What type of med is used for Chronic COPD?
Long acting cholinergic or beta agonist. Spireva.
Why don’t you use LABA on asthmatic by itself?
Increased mortality rate; you need an ICS to start and then add a LABA.
If COPD patient symptoms aren’t controlled with a long acting cholinergic or long acting beta agonist - What do you prescribe?
Consider combination therapy.
May add theophyline or ICS added.
Asthma corticosteroids are initiated more early on than in COPD patients.
In COPD treatment, what else is added in conjunction with the medications?
oxygen therapy
Why do we use drugs for cessation of smoking?
Nicotine is addictive; drugs used will try to replicate components, such as the dopamine pathway or nicotinic receptors itself.
When people cut off nicotine cold turkey, they have withdrawals and lowered receptors. This is why we need drugs to stimulate during process.
What drugs are used with cessation of smoking?
Buproprion (Zyban)
Nicotine transdermal (Patch)
nicotine polacrilex (Gum)
nicotine spray or inhaler
Vareniciline (Chantix)
Nitroglycerin tablets - sublingual.
Buproprion Sustained Release use?
Sustained release; long-acting drug. Stimulates “reward” pathway in the brain, dopamine, to decrease withdrawal effects of smoking.
Buproprion MOA?
Nicotine indirectly activates epinephrine and dopamine in CNS.
Bupropion micmics these effects because it inhibits the uptake of norepinephrine and dopamine; increasing dopamine helps bc nicotine isn’t stimulating the pathway anymore.
Alternative uses of buproprion?
Used for weight loss.
Who do you avoid giving buproprion to?
Patients with seizure disorder - run risk of seizure threshold being decreased and causing seizures.
Don’t want them on other drugs that increase norephineprine; no monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressant (TCA).
Its an antidepressant, so it can interact with antidepressants - usually work by seratonin reuptake inhibitors.
How long does it take buproprion to work?
7 to 12 weeks
What are nicotine replacement agents used for?
Taper the nicotine dose, which is healthy since they’re not inhaling tar or other carcinogens.
Nicotine is activating receptor, so do not want smoking on top of this or increases risk of toxicity!
Patient education about nicotine patch?
Make sure patient removes old patch before putting a new one on; don’t want to experience toxicity.
Leave on for 12 hours and then take off.
Who is nicotine replacements bad for?
Cardio patients, bc it may cause tachyarrythmia or hypertension.
Will affect antihypertensives
Vareniciline (Chantix) MOA
Newest drug
Partial nicotine receptor agonist; it binds to receptor and activates, but not to the same degree (partial).
If you smoke while on drug, it binds more tightly than nicotine and prevents it from activating. Can smoke on this drug and taper off to just this drug.
Vareniciline (Chantix) ADR
Vivid dreams, nausea, sleep disturbance
Black box warning for neuropsychiatric events, like depression and SI. If your patient has a history of that, this isn’t a good drug for them.
What immunizations are important for COPD?
Annual influenza - if they get flu, they’d get a bad bacterial superinfection.
Pneumococcal vaccine - more at risk for pneumococcal infections. Want to avoid.
START OF CARDIOLOGY CARDS
START OF CARDIOLOGY CARDS
Infective Endocarditis - What is it?
Bacterial infection on lining of heart or valve itself. Colonies of bacteria like to settle on valve.
Who is at risk for infective endocarditis??
What happens if you can’t treat it with abx?
Older patients > 60 yrs, male patients, IVDA, those with poor dental hygiene which leads to hematogenous spread, and valvular heart disease.
If you can’t treat with antibiotics, you need a valve replacement.
What is the pathogenesis of infective endocarditis?
A thrombus is formed on an abnormal endothelial surface, where vegetation can start. Bacteria in blood colonizes here and starts proliferating.
Why is it difficult to treat infective endocarditis?
Difficult to penetrate through and get a full kill of all the bacteria. This is a concentrated core of bacteria to penetrate.
6-12 weeks of treatment
What are the most causative bugs of infective endocarditis?
Mainly gram positives!
S aureus
Enterococci
HACEK
Gram negatives in immunocompromised
What is HACEK?
Haemophilus aphrophilus Actinobacillus actinomycetemcomitans Cardiobacaterium hominis Eikennella corrodens Kingella kingae
They live in the mouth. Common bugs of endocarditis.
Endocarditis therapy sequence
Therapy needs to be geared towards culture since you’re treating for several weeks.
Start with empiric coverage and then you scale down.
What does the empiric coverage for infective endocarditis target?
MRSA, MSSA, Streptococci, and Enterococci
Prefer bactericidal abx - leads to a better kill and gets rid of vegetation.
Good initial choice for infective endocarditis empiric therapy?
Vancomycin
Good gram positive and MRSA.
Tx may be needed for six weeks or longer.
Start patient with infective endocarditis on vancomycin, but cultures come back for Viridans streptococci and Streptococcus bovis.
What do you use to treat?
They’re PCN susceptible, so use PCN G 4-6x a day or a 24hr infusion to make sure you’re above MIC.
Alternatives: Ceftriaxone, Vancomycin (if can’t recieve cephalosporin or PCN), and Gentamycin.
Why is gentamycin used for infective endocarditis?
Gram positive synergy - one of the few cases an aminoglycoside is used to kill gram positives.
Giving a cell wall killer like PCN or ceftriaxone loosens up the cell wall so Gentamycin can get in to inhibit protein synthesis at ribosome.
Gentamycin MOA?
Whats it normally used for?
Inhibits protein synthesis at the ribosome. Bactericidal.
Normally used for gram negatives.
What’s a big benefit to using gentamycin in gram positive synergy?
It can shorten the therapy time in half and be very cost effective.
Gentamycin ADR
Don’t want to accumulate too much drug because of renal toxicity and otoxicity.
Start patient with infective endocarditis on vancomycin, but cultures come back for Streptococcal species.
What do you use to treat?
Mostly PCN sensitive. Have to follow cultures.
If susceptible to ceftriaxone and not PCN, treat with ceftriaxone.
Start patient with infective endocarditis on vancomycin, but cultures come back for Enterococci.
What do you use to treat?
Use synergy combination of gentamicin
PLUS penicillin, ampicillin, or vancomycin.
Generally resistant to PCN.
Start patient with infective endocarditis on vancomycin, but cultures come back for MSSA.
What do you use to treat?
MSSA is treated by nafcillin, oxacillin, cefazoline +/- gentamicin.
MRSA is treated with vanco.
What are antistaphyloccocal PCNs?
nafcillin
oxacillin
dicloxacillin
Start patient with infective endocarditis on vancomycin, but cultures come back for HACEK…..
What do you use to treat?
Treated by ceftriaxone, ampicillin-sulbactam, or ciprofloxacin.
How are IVDA different from normal endocarditis cases?
They inject particulate matter which can damage tricuspid valve, introduce skin flora, and use of saliva.
What are the common bugs in endocarditis for an IVDA?
S aureus for more than half the cases.
Followed by streptococci, enterococci, fungi and gram negatives.
First line treatment for IVDA endocarditis?
Vanco for empiric coverage
Why are prosthetic heart valves more difficult to treat?
Antibiotics may fail because they can’t penetrate “foreign body”.
Often requires surgery, esp MRSA
Patient came in with symptoms of endocarditis. You know they have a prosthetic heart valve, what do you use to treat it?
Triple drug regimen - targets staphylococcus!
Vancomycin
Gentamicin
Rifampin - add it as the last agent to avoid resistance
Rifampin ADR
orange-red tears, urine, feces, sweat
Why is Rifampin used for a patient with infective endocarditis and a prosthetic valve patient?
It has a unique ability to kill staph that adheres to foreign material.
Rifampin resistance is possible.
How do we acknowledge this during treatment of infective endocarditis?
Add it as the last agent in the three drug regimen.
If you use it first, resistance develops more quickly.
Rifampin MOA
Inhibits bacterial RNA polymerase by blocking RNA transcription.
Rifampin - other use?
tuberculosis
Rifampin Drug Interaction
SUPER IMPORTANT
It induces CYP enzymes like 3A4 so you see decreased level of other drugs.
CYP3A4 is responsible for metabolism of half of all drugs.
Endocarditis prophylaxis
By giving prophylaxis abx prior to bacteremia, you can prevent it from starting off in first place.
If you have a patient with prosthetic heart valve, history of infective endocarditis, or a structural vulnerability - How can you prevent infective endocarditis?
Prophylaxis beforehand, especially before dental procedures. Broncoscopy, tonsillectomy, etc.
Mouth can spread into the blood stream.
How are endocarditis prophylaxis administered?
30-60 mins prior to procedure
Amoxicillin PO
If PCN allergy, use cephalexin, clindamycin, azithromycin.
What types of patients with infective endocarditis get the triple drug regimen?
Prosthetic Heart Valves
What is acute rheumatic fever?
Nonsuppurative complication of pharyngeal infection. Occurs 2-3 weeks following pharyngitis.
Causes arthritis, carditis, nodules, erythema marginatum.
What bug causes rheumatic fever?
Group A streptococcus
What are three parts of treatment for rheumatic fever?
Antibiotic therapy
HF management
Anti-inflammatory therapy
Patient with Acute Rheumatic Fever, what antibiotics are appropriate?
Amoxicillin and PCN
Eliminate Group A Strep carriage
How do you treat carditis if it develops from ARF?
Aspirin to help deal with anti-inflammatory effect. Helps relieve symptoms.
Treat CHF
Valve surgery
How do you treat arthritis and fever if they occur from ARF?
Continue aspirin until symptoms are resolved.
If it doesn’t work, you can use glucocorticoids to manage inflammation, i.e. prednisone.
Typical American Diet consists of ___ triglycerides and ____ cholesterol.
100g triglycerides a day
250mg of cholestrol
How are triglycerides and cholesterol digested?
Triglycerides and cholesterol are incorporated into chylomicrons.
When chylomicrons are metabolized, the ratio of triglycerides and cholestrol change as we go along.
Dietary cholesterol is ingested in GI tract - how?
Emulsified by bile acids; the bile salts are sent to biliary tract, which contains cholesterol as well. Can reabsorb cholesterol in biliary tract.
Cholesterol is absorbed into GI tract and then hits the liver first.
Drugs work at second site to prevent reabsorption.
Lipase FXC
Hydrolyzes triglycerides in the core of the chylomicron. As time goes on, triglycerides go down as they’re being converted to cholesterol.
Chylomicron - describe triglyceride and cholesterol balance.
A big portion of triglycerides, but as metabolism continues, you have higher cholesterol.
LDL and HDL come from chylomicrons.
Triglycerides FXC
Synthesize cell membranes, hormone synthesis, and are disposed as bile salts.
Enterohepatic recirculation
When things are kicked out of biliary tract and reabsorbed through GI tract.
Birth control, antiepileptics, and other drugs do this to increase their half life.
What’s converted to triglycerides?
Carbohydrates and fatty acids
What’s excreted from liver?
VLDL - higher portion of cholesterol, but made of triglycerides
As metabolism goes on, TG is converted to cholesterol esters.
- lipoprotein
- lipase
LDL
Bad cholestrol, lead to artheriosclerosis and plaque formation.
LDL is removed by?
LDL receptor, found in liver. How we metabolize and get rid of LDL.
More LDL receptors in liver, the more that is cleared from blood stream, which is good.
As triglycerides are more metabolized, what to they turn into?
LDL
Where is cholesterol metabolized?
Liver
ApoB-100
Protein on surface of LDL that interacts with the receptor.
Important for catabolism of LDL.
Low Density Lipoprotein
Main focus for medications.
Have a half life of 1-2 days. ApoB interacts with LDL. Patients might not express LDL receptor or ApoB, which leads to high cholestrol since they can’t metabolize it.
If you have a lot of cholesterol in blood stream, what happens?
Liver gets saturated, LDL receptors down regulate or less expressed.
Lower LDL receptors leads to atherosclerosis. Will start making plaques in arteries.
LDL receptor action
Take LDL into liver to make amino acids, bile salts, and recycles the receptor to put on surface of hepatocyte to take another LDL.
Too much cholesterol in liver or blood, there’s less LDL receptors. Why?
There’s enough choleserol so you don’t want to metabolize anymore.
If you decrease the LDL in liver, you’ll put out more LDL receptors to metabolize.
Too high LDL in liver, you express less receptors.
What is heterozygous or homozygous famlial hypercholesteremia?
Heterozygous familial hypercholesteremia - has half the normal number of LDL receptors. Cholesterol is twice the normal amount.
Homozygous familial hypercholesteremia - No functional LDL receptors. Can be as high as 1000mg/dL.
What’s the typical breakdown of serum cholesterol?
60-70 LDL
20-30 HDL
10-15 VLDL
Statins
Main go to drug for dyslipidemia. Used for cardiovascular protection.
Ezetimibe MOA
inhibits absorption of cholesterol
Statins MOA
HMG-CoA reductase inhibitors
Lovastatin Simvastatin Pravastatin Fluvastatin Atorvastatin Rosuvastatin Pitavastatin
Statins
Statins MOA
HMG-CoA reductase inhibitors
HMG-CoA reductase produces cholesterol. By blocking it, we lower LDL in hte liver. Less cholesterol in the hepatocyte causes a response where more LDL receptors are expressed to metabolize the serum LDL.
Decreased serum VLDL and IDL – Done by increasing number of receptors so more can be taken out of blood stream.
Benefits of statins
Outside of its main use, it has pleiotropic effects which are positive and don’t relate to main mechanism.
You have stabilization of plaques, which have good effects on mortality and cardiovascular death.
Frequently recommended for patients with Cardiovascular Disease - Need to be on a statin unless theres a contraindication.
Statins PK - Does it interact with any major enzymes?
Major enzymes:
CYP3A4 - statins are metabolized by it. If you inhibit CYP3A4 via FQ or macrolide, you’ll see high levels of statins and can lead to toxicity.
If a patient has a pneumonia and is on statins, can you prescribe a macrolide?
Which ones?
Macrolides inhibit CYP3A4, which lead to higher drug levels of statins in blood stream.
Patients on FQ and macrolides should be on Resuvostatin or Pitavastatin to avoid toxicity with CYP inhibition.
Dose Response Curve: Statins
Explain the concept.
Using combination therapy is good because synergism lead to better affects than drugs being used by themselves.
Ex: Statin lowers LDL but is prescribed with resin.
Statin effects on Triglycerides
The higher Triglyceride levels in blood, the better effect statins have on it.
START OF CARDIOLOGY 2 CARDS
START OF CARDIOLOGY 2 CARDS
How do statins work?
Inhibit cholesterol formation in the liver , so you produce less cholesterol in the liver. Makes hepatocytes form more LDL receptors to take it out of the blood and process through liver.
Serum lipids go down. Also have other pleiotropic effects - stabilization of plaques and prevent other cardio events.
Common Side Effects of Statins
Headache, fatigue, GI intolerance
Increase in liver enzymes (AST and ALT can rise). Usually dose dependent.
Increase dose increases risk for toxicity.
If you have a patient on statins with an increase in LFTs, what do you do?
Reduce the dose or switch to a different agent.
Rare to see liver problems by itself.
What do you measure when on statins? When?
LFT.
Beginning of therapy and a month or two after to see how they tolerate the drug.
ADR of Statins
Myalgias and myopathies; rare cases of rhabdomyolysis occur as well.
Muscle pain is a common side effect. When dosing based on cardio risk, try to run up as high as you can until patient can’t tolerate it anymore.
What is rhabdomyolysis?
Muscles are broken down; kidneys take a hit, because myoglobin goes into the blood and causes interstitial damage to their kidneys.
How do you treat rhabdo patients?
Give them fluids to dilute the myoglobin to help the kidney.
Patient ran a marathon but haven’t had any physical activity at all - What is this a sign of?
Sign of rhabdo, urine is ice tea colored.
What do you do when your patient is on statins and is experiencing impaired renal function and myopathy?
Decrease dose and do the best one they can tolerate. Avoid drug interactions.
Major drug reactions of fibrates?
Be very careful when prescribing statins and Gemfibrozil together, because it can lead to increase in statins and toxicity.
Or when you do prescribe them togetehr, lower the dose of the statin.
What statins are not metabolized by CYP3A4?
Resuvostatin or Pitavastatin are not metabolized by CYP3A4.
What happens to statins if you have a CYP3A4 inhibitor on board?
Inhibit enzyme and metabolism, so less drug is metabolized, which increases risk for toxicity. Be cautious of it.
Contraindications of statins
Hepatic disease
Pregnancy - baby needs lipids to make cell membranes. Teratogenic.
What are some things to consider when dosing a statin? Relative CI.
Relative CI - you can get away with adjusting the dose.
Gemifibrozil, niacin, and erythromycin —- all will increase level of statins.
What statin doesn’t get metabolized by CYP3A4?
Rosuvastatin
Potavastatin
What inhibits CYP450 and lead to drug interactions with statins?
Verapimil Amiodarone Niacin Fibric acid derivatives (Gemifibrozil) Grapefruit Juice
P-glycoprotein - What does it do?
Its an efflux transporter; things abosrbed from GI tract and this is responsible for kicking things back out.
Inhibited by grapefruit juice as well. Inhibition of this can cause increase in drug levels.
CNS - blood brain barrier and PGP
Brain wants to keep toxins out, so PGP can help.
Statin - place in therapy?
First line drug for hyperlipidemia, most efficacious.
Not given to those who are pregnant or have hepatic disease.
Cholesterol absorption inhibitors - What drug?
Ezetimibe
How does Ezetimibe work?
Decrease the amount of absorption from cholesterol from your diet.
By decreasing amount of cholesterol absorbed, liver doesn’t think it has enough cholesterol. Starts producing more LDL receptors on the surface to absorb more cholesterol and LDL from the blood.
Efficacy between statins and Ezitimibe - which is more potent?
Statins are more potent and efficacious.
How do you synergistically treat hyperlipidemia?
Ezetimibe can be used in combination with statins - synergistic.
Statins work on directly producing cholesterol in the liver and Ezetimibe protects you from absorbing cholesterol from your diet.
Ezetimibe MOA
Decreases cholesterol absorbed in diet. Less cholesterol is absorbed in the liver so the liver puts out more LDL receptors to lower levels.
What does Ezetimibe do to prolong its half life?
Drugs that undergoes eneterohepatic reabsorption. – Absorbed in GI, spit out through biliary tract, and reabsorbed = gives it a longer half life.
Ezetimibe PK - Does it interact with any major enzymes?
No CYP interactions
Benefits of Ezetimibe
You can have an additional LDL reduction by 15-20% when adding a statin.
Only have to take it once a day. Enterohepatic circulation prolongs half-life.
Ezetimibe ADR
Enterohepatic circulation limits the systemic effects, may see GI upset, but minimal as far as side effects go.
May also see elevation in hepatic transaminases when used with statins!
When is Ezetimibe contraindicated?
Shouldn’t be used in breast feeding, pregnancy, children, hepatic disease, myopathy.
When combined with a statin, you may see myopathy and hepatic disease.
What are important drug interactions with Ezitimibe?
Fibric acid derivatives - increases risk of cholelithiasis and myopathies.
Bile Acid Sequestrants - work only in GI tract, so they can bind to this med and decrease the concentration.
Antacids decrease concentration and cyclosporine increases concentrations.
Fibrates - Name them.
Gemfibrozil (Lopid)
Fenofibrate (Tricor)
Bezafibrate (Bezalip)
Fibrates MOA
Activate PPAR-alpha (nuclear transcription factor), which increases fatty acid oxidation. Leads to less secretion of triglycerides, which means less VLDL is produced and decrease LDL on cell surface (VLDL is precursor). Can see increase in HDL which is protective cholesterol.
Fibrates PK - Do they interact with any enzymes?
Fenofibrate is metabolized by minor pathway in CYP3A4
Fibrates Dosing
Once daily medications lead to greater compliance. – Fenofibrate or Bezafibrate.
Why do you want to give Gemfibrozil before meals?
When you have ingestion of dietary fats, you produce the most cholesterol. This oxidation of fatty acids lead to less triglycerides being released.
Not as big of an effect as statin, but HDL increases and triglycerides decrease.
Adverse effects of fibrates
Nausea, abdominal pain, diarrhea.
BIG RISK - Cholelithiasis, can affect movement of bile acids. By inhibiting that movement, you can have gallstones.
Myopathy is also a risk. Can have synergistic effects with statins.
When are fibrates contraindicated?
Pregnancy
Hepatic or renal dysfunction
Galbladder disease
Adjust dose based on renal dysfunction.
What could happen if you prescribe fibrates to a patient on warfarin?
Warfarin - see increased anticoagulant effects, could be related to protein binding interaction.
Warfarin binds to albumin. If a fibrate drug is used, it will bind to albumin more tightly and plasma concentrations of warfarin will increase. More drug is available, so increase risks for bleeding.
What happens when you have a patient on HMG CoA reductase inhibitors (statin) and you put them on fibrates?
With gimfibrozil, will see reactions that increase levels of statins, increasing risk for toxicity.
See it in most fibrates, but highest effect in gimfibrozil.
Decrease the statin by half.
Primarily, when are fibrates used?
Primary hypertriglyceridemia
TG>1000mg/dL or low HDL.
Can add it to increase those levels.
What are bile acid sequestrants called?
Resins.
They work in the bile tract and are not systemically absorbed, which is why you can give them to children and pregnant patients :)
Bile Acid Resins MOA
By binding cholesterol and bile salts, they’re bound by resins and will be excreted in the feces.
You absorb less cholesterol from diet and spit out diet tract to prevent that from being absorbed..
Increases LDL receptors to decrease cholesterol in the blood. Not as effective as statins, but are nice bc they’re not absorbed systemically.
Why would you see some GI issues with Resins?
Cholesterol excreted in feces can lead to GI effects.
Who are Resins good for?
Children and pregnant patients!
Children and pregnant women love resins
What are the Bile Acid Sequestrants? 3C
Cholestryamine
Colestipol HCl
Colesevelam
Not absorbed, but bind cholesterol in GI tract to prevent them from being absorbed.
Dosing of bile acid sequestrants
Issues with tolerance that might come up?
Plateau effect?
Most products come as tablets; these come as bulky powders or tablets.
Patient may not tolerate as well, bc of the pulpy taste. Can mix with orange juice to mask flavor.
There’s a “plateau effect” where if you increase dose you get more ADR instead of efficacy from this.
Why should BAS be taken within an hour of meal?
That’s when you have most fat in GI tract. Galbladder is actively secreting bile salts to help emulsify.
Should give more bang for your buck.
Why do you separate bile acid sequestrants from other medications?
They can bind to other medications.
Can give a drug one hour before or two to four hours after to make sure the reaction doesn’t cause binding.
Because you don’t absorb fats in GI tract when using bile acid sequestrants, what can yo feel?
bloating, flatulence, fullness, constipation, nausea.
Because bile acid sequestrants bind to bile sats, what might you see less absorption of? Why?
Less absorption of water soluble vitamins – ADEK and folic acid. Bile salts normally help emulsify these for absorption.
Avoid this by separating medication times to one hour before or four hours after taking BAS.
What drugs can be bound up by bile acid sequestrants?
digoxin, warfarin, thyroxine, beta blockers, and thiazide diuertics
How do you avoid bile acid sequestrants from binding to other medicines?
avoid interaction by adminstering one hour before or four hours after bile acid sequestrant.
What are BAS contraindications?
High levels of triglycerides (can make it worse) and familial dysbetalipoproteinemia.
Bile Acid Sequestrant - Place in therapy
Safest drug, because no systemic side effects. Good for pregnant patient and children.
Poorly tolerated from GI standpoint.
Can use with antilypemics as well since they have a differnt mechanism of action.
Niacin
B complex vitamin; another derivative is nicotinic acid.
Used an an antilipemic.
Amide form is a niacinamide. Can cause flushing.
Why are long acting forms of niacin used?
Less likely to cause side effects and hot flashes.
Niacin products
Immediate release
Niacin supplment and Niacor
Long acting
Niacin Supplement
Extended release
Niaspan
Inositolhexiancinate
Supplements
Not well regulated by FDA.
