PHARM final Flashcards
Corticosteriod endogenous
Cortisol or Glucocorticoids regulate the metabolism of carbohydrates, fats, and proteins to increase levels of glucose for body energy!
- relives
Corticosteriod exogenous
A primary reason for using Aerosolized Glucocorticoids is to minimize adrenal, or HPA axis suppression, by minimizing the dosage and localizing the site of tx.
- inhibit
corticosteriods intrinsic/extrinsic
Body cannot distinguish between endogenous and exogenous
Administration of glucocorticoid drugs raise body’s level of hormones
Inhibits hypothalamus and pituitary glands, which decreases adrenal production
beclomethasone dipropinate HFA
Qvar redihaler
Flunisolide hemihydrate HFA
Aerospan
Fluticasone propinate
- Flovent HFA
- Flovent diskus
-Armonair respicklick
Fluitcasone furoate
arnuituy ellipta
budenoside
- pulmicort flexhaler
- pulmicort respules
Mometasone furoate
- asmanex twisthaler
- asmanex HFA
ciclesonide
alvesco
fluticasone propinate/salmaterol
- advair diskus
- wixela inhub
- advair HFA
- Airduo respiclick
budesonide/formoterol fumarate HFA
symbicort
mometasone furoate/formoterol fumarate HFA
dulera
fluticasone furoate/vilanterol
breo ellipta
fluitcasone furoate/umeclidinium bromide/vilanterol
treglegy ellipta
mast cells
(a type of WBC; aka: Mastocyte or Labrocyte): Connective tissue cells that contain heparin and histamine released during inflammatory and allergic reactions. When mast cells detect a germ or virus, they set off an inflammatory (allergic) response by releasing a chemical called histamine. This response protects your body from germs and infections.
Heparin: extracted from tissues rich in mast cells remains the ideal rapid anticoagulant in clinical practice.
Histamine: makes blood vessels expand and the surrounding skin itchy and swollen.
eosinophils
They attack and kill parasites andcancer cells, and help with “allergic responses”.
basophils
These small cells seem to sound an alarm when infectious agents invade your blood. They secrete chemicals, such as histamine, a marker of allergic disease, that help control the body’s immune response.
t-lymphocytes
They create antibodies to fight against bacteria, viruses, and other potentially harmful invaders
neutrophils
They kill and digest bacteria and fungi. They are the mostnumerous type of WBC and your first line of defense when infection strikes.
macrophages
A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells
Diurnal steroid cycle
Production of body’s own glucocorticoids follows rhythmic cycle; a daily rise and fall termed diurnal or circadian rhythm
- Cortisol levels are highest in the morning at 8 a.m.
Alternate-day steroid therapy
Mimics natural diurnal rhythm by giving steroid drug early in the morning when normal tissue levels are high
Suppression of the HPA system occurs at the same time it normally would with the body’s own steroid!
Inflammation
=the response of vascularized tissue to injury
Produces redness, swelling, heat, and pain
Triple response:
Redness: Local dilation of blood vessels, occurring in seconds
Flare: Reddish color several centimeters from the site, occurring 15 to 30 seconds after injury
Wheal: Local swelling, occurring in minutes
Asthma
- mast cells, eosinophils, lymphocytes, macrophages, neutrophils, epithelial cells
- inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing in night or early morning
- HYPERRESPONSIVENSS to various stimuli
Asthma
Chronic inflammation of the Aw wall causing airflow limitation and hyperresponsiveness to various stimuli
The Mast Cells and the Eosinophils are considered the be the major effector cells of the inflammatory response, regardless of whether the asthma is allergic or non-allergic
During an Asthmatic response: Aw smooth muscle contracts (bronchospasm), increased microvascular leakage and Aw wall swelling, mucus secretion, and remodeling of the Aw wall over the long term
In an Acute phase attack: pts experience wheezing, breathlessness, chest tightness, and cough
Treatment with anti-inflammatory agents such as glucocorticoids is important to reduce basal level of Aw inflammation, Aw hyperresponsiveness and predisposition to acute episodes of obstruction
Asthmatic reactions are Biphasic
Early asthmatic response caused by Immunoglobulin E (IgE)
After an insult, IgE activates Mast Cells which release inflammatory mediators such as Histamine, the Aw’s immediate response is Bronchospasm
Response peaks at 15 minutes
Late-phase reaction caused by Mast Cell mediators and release of Cytokines
- Response occurs after ~ 6-8 hours
- Can last up to 24 hours
Aerosolized steriods effect (systemic)
- Adrenal insufficiency may occur after transfer from systemic to inhaled steroids – Weaning may be required to allow recovery of the Adrenal Cortex and HPA Axis function
- Recurrence of allergic inflammation after cessation
- Acute Asthma may occur after transfer from systemic to inhaled steroids
- HPA suppression is Minimal or Absent on small doses; Increases with High Doses (dose-dependent)
- Growth restriction in children (dose-dependent)
aerosolized steriods effect (local)
Most common
1. Oropharyngeal fungal infections; aka: Candidiasis (Oral “Thrush”)
2. Dysphonia (hoarseness and changes in voice quality)
Less common:
1. Cough, bronchoconstriction
2. Incorrect use of MDI (inadequate dose)
What to do:
1. Use minimal dose
2. Use reservoir
3. “Rinse mouth after use”
steriod use in asthma
Clinical use of inhaled corticosteroids in “addition to” first-line β-agonist reduces morbidity and Aw hyperresponsiveness, decreased exacerbations, and improved FEV1
steriod use in COPD
Reduces symptoms, exacerbations, and mortality
Neutrophils predominate in COPD
steriod effect on WBC count
Demargination (don’t adhere): Causes depletion of neutrophil stores reducing their accumulation at inflammatory sites and in exudates
Overall increase in WBC count
Constriction of microvasculature to reduce leakage of cells and fluids into inflammatory sites
steriod effect on B-receptors
β-adrenergic agents are the most potent inhibitor of mast cell release!
Steroids restore responsiveness to β-adrenergic stimulation
Steroid action is slow, but the sooner steroids are given, the sooner the pt begins to respond to β-adrenergic drugs!
Steroids enhance β-receptor stimulation by increasing the number and availability of β-receptors on cell surfaces and by increasing the affinity of the receptor for β-agonists
inflammatory response
- Increased vascular permeability:
An exudate is formed in surrounding tissues - Leukocytic infiltration:
- White Blood Cells (WBC) emigratethrough capillary walls (diapedesis)in response to attractant chemicals (chemotaxis) - Phagocytosis:
- White cells and macrophages (in lungs) ingest and process foreign material such as bacteria - Mediator cascade:
- Histamine and chemoattractant factors are released at the injury site
- Various inflammatory mediators are generated
aerosolized corticosteriods
“targets” inflammation in the Aw with a smaller dose “reducing systemic side effects!”
Complementary interaction between Glucocorticoids and β-adrenergic Agonists (LABAs)
Steroids increase β2-adrenergic receptor transcription
Inhaled corticosteroid therapy can provide partial protection against the development of tolerance!
Intranasal steriods
Used for treatment of allergic or inflammatory nasal conditions and seasonal or perennial allergic or nonallergic rhinitis and to prevent reoccurrence of nasal polyps
nonsteriol indications
- Cromolyn-like drugs (aka: “Mast Cell” Stabilizers)
- Antileukotrienes
- Monoclonal antibodies
B2-antagonists
blovcks or inhibits beta 2 receptors
controllers
= to maintain exacerbations
- inhaled corticosteriods
- oral corticosteriods
- cromolyn sodium
- LABA
- leukotriene modifiers
- sustained-release thephylline
- muonoclonal antibodies
relivers
= relieve symptoms
- SABA
- systemic corticosteriod
- inhaled anticholinergic bronchodilators
extrinsic asthma (allergic)
Depends on allergy, atopy (environment)
Intrinsic asthma (non-allergic)
Shows no evidence of sensitization to common inhaled allergens (inside)
mast cell stabilizers
cromolyn sodium
antileukotrienes
- zarfirlukast
- montelukast
Cromolyn sodium
= Prophylactic aerosolized agent in the treatment of Asthma to prevent inflammatory responses often used in infants and young children
Anti-Asthma agent; Anti-Allergy agent; Mast Cell Stabilizer
- Prevents (inhibition of…) “Mast Cell degranulation” blocking the release of chemical mediators of inflammation
Pentamidine
type: anti-fungal
indication: active against pneumocytsis jiroveci, the organism for pneumocytsis jiroveci pneumonia
trade name: NebuPent
form: dry powder
Reconstituted with 6 mL of sterile water (Not saline - can cause precipitation)
Respirgard II Nebulizer (1-2 um)
pentamidine MOA/side effects
When given by Aerosol, Pentamindine reaches significantly higher concentration in the lung than when given via IV
MOA= UNKNOWN
Cough and bronchial irritation (36% of patients in one study)
Shortness of breath (SOB
Bad taste (bitter or burning) of aerosol impacting in oropharynx
Bronchospasm and wheezing (11% of patients
Spontaneous pneumothoraces
Conjunctivitis
Rash
Neutropenia (Neutrophil WBC)
Pancreatitis
Renal insufficiency
Dysglycemia (hypoglycemia and diabetes)
Digital necrosis in both feet
Appearance of extrapulmonary P. jiroveci infection
pentamidine preventing airwat effects
Pretreat with β-adrenergic bronchodilator
Can reduce or prevent local airway reaction!
Parasympatholytic (Ipratropium!)
Shown to prevent bronchoconstriction!
Small particle size
Reduces airway impaction and increases alveolar deposition and targeting!
Ribavirin
type: antiviral
indication: RSV, influenza viruses, herpes simplex virus
trade name: virazole
form: powder, SPAG-2 (Nebulizer)
ribavirin MOA/ side effects
= It does not prevent the attachment or penetration of RSV into the cell, which may explain why it merely reduces the severity of illness rather than prevent or abolish it altogether.
Pulmonary: Deterioration of pulmonary function and worsening of asthma or COPD; pneumothorax, apnea, and bacterial pneumonia
Cardiovascular: Cardiovascular instability, including hypotension, cardiac arrest, and digitalis toxicity
Hematological: Effects on blood cells have been reported with oral or parenteral administration but not with aerosol use
Reticulocytosis (excess of young erythrocytes in circulation) has been reported with aerosol use
Dermatological/topical: Skin irritation, rash, eyelid erythema, and conjunctivitis
RSV with other problems
Children infected with RSV results in either Bronchiolitis or Pneumonia (PNA)
Tobramycin
- antibiotic
- managment of chronic pseudonomonas aeruginosa infection in CF
- liquid/dry
Blocks protein synthesis in bacteria and causes cellular death
Bactericidal
Improved pulmonary function
- Reduced need for IV antipseudomonal antibiotics and hospitalizations
May affect nebulizer performance
Environmental contamination
Incompatibility with other drugs
cystic fibrosis meds and treatment
Tobramycin (TOBI) : chronic P. aeruginosa infection in CF patient
Aztreonam (Cayston) : chronic P. aeruginosa infection in CF patient
- antibiotics, bronchohygiene, PFT, peak flow
Endogenous
Produced inside body
- relieves
Exogenous
Outside product going inside of body (medicine)
- inhibits
activated mast cell
mulitvalent antigen cross-links bind IgE antibodies, casuing degranulation
resting mast cell
resting mast cell granules contian histamine and other inflammatory mediators
prophylactic
alternative to ICS
zafirlukast
accodate
- nonsteriod antiasthma
- leukotriene receptor antagonists
montelukast
singulair
- nonsteriod antiasthma
- leukotriene receptor antagonists
cell mediated
t lymphocytes mediate immune respone by several mechanisms, including cytotoxiticy and secretion of cytokinese (helper-T)
antibody-mediated
antibodies are serum globins modified specifically to combine and react with an antigen (IgE)
cromolyn sodium
can assist in suppressing a cough
- anti-sickle cell effects
prophylactic use only –> NOT treating acute bronchospasms
leukotrienes
= potent bronchoconstrictors
- airway edema
- mucus secretion
- ciliary beat inhibition
- recruitment of other inflammatory cells
Antileukotriene
BLOCK:
- cell sources of leukotrines
- biochemical pathways
- leukotriene production
zileuton
inhibits 5-LO enzyme
1-5um
last 5-6 generations
- effect of aersol particle size on area of preferential desposition within the airway
bronchi conducting zone
5-10 generation
gram stain
= bacteria stain differently depending on the structural componets of their cell wall
+ = purple
- = pink
acid fast stain—acid fast bacilli (AFB)
rapidn diagnosis of TB
gram positive bacteria
- MRSA
- VISA
- VRSA
- pencillin-resistant streptococcus pneumoniate
- VRE
gram negative bacteria
- MDR nonenteric bacilli (PA, SM, A)
- third generation cephalosporin
- ESBLA producing ecoli and klebsiella
- ampicillin resistant haemophilus
- carbapanemase-producing enterobacteriaceae
bacteriostatic
drug that inhibit the growth of bacteria but do not kill them
bacteriocidial
drug that kills the bacteria
penicillin (B-lactams antibiotic)
MOA= inhibit cell wall synthesis
- bactericidal (kills bacteria)
Adverse reactions:
- hypersensitivty
- hematological reactions
- GI disturbances
CNS toxicity
cephalosporins (antibiotic)
MOA= inhibit bacterial cell wall synthesis
- bactericidal (kills bacteria)
- has activity against MRSA
Adverse reactions:
- hypersensitivty
- minor GI complaints
- hypoprothrombinemia
TB meds
= airbourne isolation
- Isoniazid (bactericidal)
- Rifampin/Rifabutin (bactericidal)
- Pyrazinamide (bactericidal)
- Ethambutol (bacteriostatic)
- Streptomycin
Acyclovir and valacyclovir (antiviral)
= Zovriax
MOA= Terminate viral replication
Clinical uses:
– Herpesvirus family
– Epstein-Barr virus (EBV)
– Cytomegalovirus (CMV)
– Varicella-zoster virus (VZV) - causes chickenpox and herpes zoster (shingles)
Adverse reactions:
– Neuropathy
– Burning, irritation if used topically
Penciclovir and Famciclovir (antiviral)
= Famvir
MOA= Interfere with viral DNA synthesis and replication
Clinical uses:
– Genital Herpes Simplex Virus (HSV) and VZV
Adverse reactions:
– Considered well tolerated
– Occasional nausea, vomiting, diarrhea, headache
– Rare: neutropenia
Ganciclovir and Valganciclovir
= cytovene
MOA= Terminates viral DNA synthesis and replication
Clinical uses:
– HSV, VZV, CMV
Adverse reactions:
– Bone marrow suppression
– Headache, nausea, rash, fever, and liver transaminase elevations
Cififovir
= Vistide
MOA= Inhibits viral replication
Clinical uses:
– Herpesvirus, EBV, CMV
Adverse reactions:
– Dose-dependent nephrotoxicity
– Neutropenia, fever, headache, emesis, rash, diarrhea
Foscarnet
= Foscavir
MOA= Inhibits viral replication
Clinical uses:
– Herpesvirus, EBV, CMV
Adverse reactions:
– Dose-dependent nephrotoxicity
– Neutropenia, fever, headache, emesis, rash, diarrhea
Amanradine and Rimantadine
= Symadine/Flumadine
MOA= – Inhibit viral replication and assembly
– May inhibit uncoating of influenza virus
Clinical uses:
– Active against influenza A virus
Adverse reactions
– Well tolerated
– CNS: tremor, insomnia, light-headedness, seizure, cardiac arrhythmias, agitation
Oseltamivir and Zanamavir
= Tamiflu/Relenza
MOA= Inhibits influenza A and B neuraminidase
– Prevents virus from leaving host cells
Clinical uses:
– Treatment of Influenza A and B infection
Adverse reactions :
– Nausea and vomiting in first two days of therapy
Common cold
A nonbacterial upper respiratory tract infection (URI), usually characterized by mild general malaise and a runny, stuffy nose, symptoms include sneezing, cough and possibly a sore throat or some chest discomfort
Signs/symptoms of cold
Sign/Symptom –> Cold
Fever –> Rare
Chills –> None
Cough –> Present
Headache –> Rare
Fatigue –> Mild
Myalgia –> None or slight
Nasal congestion –> Common
Sneezing –> Common
Sore throat –> Common
Cold remedies
- Sympathomimetics
⁃ For decongestion
-pseudoephedrine (sudafed) - Antihistamines
⁃ To reduce (dry) secretions - Expectorants
⁃ To increase mucus clearance - Antitussives
⁃ To suppress cough reflex
Sympathomimetic (adrenergic) decongestants
= Adrenergic agents act to reduce swelling and relieve nasal congestion based on the “α-stimulation” causing vasoconstriction causing the decongestant effect
Antihistamines
- Occur “naturally” in the body and are contained in tissue mast cells and blood basophils
- Important mediators of local inflammatory response with effects of smooth muscle contraction, increased capillary permeability, and dilation, itching, and pain
Wheal-and-flare reaction (aka: triple response) which causes:
– Local redness, welt (wheal) formation, and reddish-white (flare) border
Effects of antihistaminic
– Blocks the increased vascular permeability, pruritus, and bronchial smooth muscle constriction
– Treats allergic disorders such as rhino-conjunctivitis or allergic rhinitis
Alternative to antihistamines for rhinorrhea = Ipratropium Bromide nasal spray
H1 receptors
- Located on nerve endings, smooth muscle, and glandular cells
- Involved in inflammation/allergic reactions, produce wheal/flare reactions, bronchoconstriction, mucus secretion, and nasal congestion and irritation
H3 receptors
- Located primarily in the CNS
- May be auto receptors for cholinergic neurotransmission in airway
Mucokinetic
= medication that increases ciliary clearance of respiratory mucus secretions
Mucolytic
= medication that degrades polymers in secretions
- classic are INEFFECTIVE for the therapy of ariway diseases and NOT recommended
Stimulants
= Increase production and presumably the clearance of mucus secretions
- Guaifenesin
Expectorants
= Facilitate removal of mucus from the lower respiratory tract
MOA:
- Vagal gastric reflex stimulation
- Absorption into respiratory glands to directly increase mucus production
- Topical stimulation with inhaled volatile agents
- Organidin (Iodinated Glycerol), an expectorant that appears safe and effective when used in cases of Chronic (obstructive) Bronchitis
Mucolytic
= Lysing or mucolytic action
- Dornase Alfa
Expectorant agents
- Iodine products
- Guaifenesin (Glycerol Guaiacolate) (aka: Robitussin or Mucinex)
- Topical agents (i.e., vaporizers)
- Parasympathomimetics (Cholinergics)
cough suppressants (antitussives)
=Treatment of nonproductive, irritating, dry, and hacking coughs
* Expectorants stimulate mucus production
* Cough Suppressants depress the cough reflex
MOA= Depress the cough center in the medulla
Narcotics:
– i.e., Codeine, Hydrocodone
Nonnarcotic:
– i.e., Dextromethorphan and Benzonatate
Diphenhydramine Hydrochloride
Benadrly
Flu (influenza)
= Caused by the Influenza virus and associated with symptoms of fever, headache, general muscle ache, and extreme fatigue or weakness. Onset of symptoms is usually rapid
Sign/Symptom –> Influenza
Fever –> Typical, high
Chills –> Typical
Cough –> Nonproductive, may be severe
Headache –> Prominent
Fatigue –> Early, severe
Myalgia –> Usual, may be severe
Nasal congestion –> Occasional
Sneezing –> Occasional
Sore throat –> Occasional
API alpha-1 antitrypsin (a1-AT)
= treatment of congenital a1-AT deficiency which leads to emphysema
α1-AT deficiency
= diseased state
α1-proteinase inhibitor
= deficient protein
α1-Antitrypsin Deficiency
= A genetic defect that can lead to development of severe Panacinar Emphysema
- Accounts for ~ 2% of all emphysema in the United States
Pathogenesis of Emphysema
= process of alveolar wall destruction
Centrilobular emphysema
occurs in the upper lobes
Panacinar
= involves all lung fields, primairly in the bases
Emphysema
= the alveoli at the end of the bronchioles of the lungs are destroyed
- permenant enlargement and destruction of air sacs
- destruction of A-C membrane
- air trapping/hyperinflation
Nicotine
- The affinity of Nicotine stimulates acetylcholine (neurotransmitter) receptors
- Causes HTN, tachycardia, and peripheral vasoconstriction.
- Also binds to receptors in the CNS which causes respiratory stimulation, tremors, convulsions, nausea, and emesis
nictoine withdrawls
- Craving for nicotine
- Nervousness
- Irritability
- Anxiety
- Drowsiness
- Sleep disturbance
- Impaired concentration
- Increased appetite with weight gain
Drugs for nictoine withdrawls
- Bupropion (Zyban) —> first line
- Varenicline (chantix) –> first line
- Clonidine (catapres) –> antihypertensive second line
Nitric oxide (NO)
= a product of endothelial cells, in the respiratory tract, and acts as a Nitrovasodilator
- pulmonary vascular relaxation
= use in neonates with hypoxic respiratory failure to reduce pulmonary artery pressure and increase oxygenation in newborns with PPHN (up to 14 days of tx)
NO risks
= Risks of methemoglobinemia and elevated Nitrogen Dioxide (NO2) increase at concentrations > 20 ppm (in the bloodstream)
Neuromuscular Blocking Agents (NMBAs)
= Drugs that cause skeletal muscle weakness or paralysis, preventing movement ¨Paralytics or Muscle Relaxants¨
- Produce their effect at the neuromuscular junction by interfering with Ach
Non depolarizing agents (antagonists) –> slow to act
= block Ach receptors without activating them, by preventing thebinding of Ach, nondepolarizing agents block the depolarizing effects of Ach, thereby preventing muscle contraction)
Depolarizing agents (agonists) –> no action
= bind to Ach receptors and cause sustained postsynaptic membrane depolarization; the postsynaptic ending becomes refractory and unexcitable, resulting in flaccid muscles)
depolarizing NMBAs drug
succinlycholine
nondepolarizing NMBAs drugs
- Cisatracurium
- Pancuronium
- Rocuronium
- Vecironium
Clincial use of NMBAs
- Facilitate Intubation
- Obtain muscle relaxation during surgery; particularly to the thorax and abdomen
- Enhance patient-ventilator synchrony
- Reduce intracranial pressure (ICP) in intubatedpatients with uncontrolled ICP’s
- Reduce O2 consumption
- Terminate convulsive status epilepticus and tetanus refractory to other therapies
- Facilitate procedures and diagnostic studies
- Keep pts immobile (i.e., trauma patients)
Dendrites
= collect information from other neurons
Synaptic cleft
= the small gap seperates the transmitting and receiving neurons
Neurotransmitters
= stored in the axon terminal
Transmitting neuron
= releases neurotransmitter into synaptic cleft
Neurotransmitter
= bind to the receptors in the plasma membrane of the receiving cell
Depolarization
= action potential occurs
Repolarization
= Membrane potential returns to baseline (resting state)
- Ach is broken down and inactivated by acetylcholinesterase (AChE), thus returning it to the resting state
NMBA vent
= require muscle relaxation are pts with severe asthma, reduction of oxygen consumption in PTs with difficult-to-manage conditions, like ARDS, and PTS requiring “uncomfortable” modes of ventilations
Succinylcholine
- depolarizing agent
- Paralysis in 60–90 seconds with a clinical duration from 10 to 15 minutes
- No agents that reverse their blockade
- Ideal for patients requiring intubation!
Diurectics
= Main purpose is to eliminate “excess fluid” from the body
- Drugs that increase the excretion of solutes and water by directly increasing urine output (UOP)
- Reduce extracellular fluid volume (ECFV) in order to decrease Blood Pressure (BP) “or” rid the body of excess interstitial (tissue) fluid
Osmotic diuretics
= Mannitol (Aridol), Glyerin, Isosorbide, & Urea
- Mannitol is preferred because of its lowest toxicity
- Mannitol is the preferred agent because of lower toxicity
- Treat and prevent Acute Renal Failure (ARF)
Carbonic anhydrase inhibitors (CAIs)
= Acetazolamide, methazolamide, dichlorphenamide
Main indication:
- Effectively decrease intraocular pressure in glaucoma
- Lower HCO3– in mountain sickness
- Treat Metabolic Alkalosis
- Increase urine pH in cystinuria
* Considered to be very weak diuretics
= increased flow of alkaline urine
Adverse effect= Hypokalemia (K+)
Loop diuretics
= Furosemide (Lasix), Bumetanide (Bumex), Torsemide (Demadex), Ethacrynic Acid
* Most potent diuretics called “High-ceiling” diuretics
Main indications:
- HTN, CHF, ARF, CRF, Ascites, and Nephrotic Syndrome
- Acute pulmonary edema, hypercalcemia (Ca++), renal transplant, and to enhance urinary excretion of chemical toxins
Adverse effects= may cause dose-related ototoxicity, consisting of tinnitus and clinical or subclinical hearing loss; most ototoxicity is reversible!
Thiazide diuretics
= Chlorothaizidem hydrochlorothizide, chlorthalidone
= First line therapy for mild HTN
- CHF, Idiopathic Hypercalciuria (Ca++)
Other uses:
- Nephrogenic diabetes insipidus (next slide), CRF
Adverse effect= increase in serum glucose; some case of DKA have been reported
Potassium-sparing diuretics
= Spironolactone (Aldactone), Eplerenone (Inspra)
Main indications:
- Most commonly used for Cirrhosis and Ascites
Other uses:
- Pt’s with elevated aldosterone
- May cause Hyperkalemia (K+), which is a more life-threatening situation than K+ depletion
Potassium-sparing diuretics
= Triamterene and Amiloride
Triamterene
⁃ Blocks Na+ channels in the collecting ducts
⁃ Short acting, but requiring multiple doses
* Poor choice for patients with liver dysfunction
Amiloride
⁃ Blocks Na+ channels in the collecting ducts
⁃ Moderately long half-life
* Coadministration of K+ supplements as well as renal dysfunction, may cause Hyperkalemia (K+), which is a more life-threatening situation than K+ depletion
Nephron
= functional unit of the kidney
- maintains homeostasis between the internal volume and electrolyte status and the influences of the environment, diet and intake)
- Kidneys can not regenerate new Nephrons
- Renal injury, disease, and aging are associated with a gradual decrease in the number of Nephrons
Cardiac output through renal system
= 20% of total blood flow through the nephron (~ 130 mL/min) is filtered through the Glomerulus
- < 1% is excreted as urine
Normal adult output = 30-60 mL/hr
Common electrolytes
= Fundamental function of the Kidney is the control of buffering substances, especially, HCO3– !
- Sodium
- Potassium
- Chloride
- Bicarb
- Hydrogen
- Calcium
- Magnesium
Cerebral edema
= swelling caused by abnormal accumalation of fluid in intercellular spaces of body
- TREAT WITH OSMOTIC DIURETICS
Synergistic effect
= effect of two chemicals on an organism is greater than effect of either chemical individual
- Most common combination of diuretics is Loop and Thiazide!
Midbrain
= Functions as a relay station for information traveling “to and from” the Cortex
- Also integrates and modulates autonomic (involuntary system) functions, which occur primarily in the hypothalamus (involuntary eye movement)
Brainstem (medulla)
= Control area for autonomic (involuntary system) functions such as breathing and cardiovascular control, and alertness
Hypothalamus
= controls various homeostatic functions such as body temp, respirations, and heart beat
- directs horomone secretions of the pituitary
Antidepressants
= drugs that can alter levels of certain neurotransmitters within the brain, in particular norephinephrine and serotonin
- SSRI first line medical treatment
Antipsychotics
= increase dopamine in the brain
- help with hallucinations and abnormal thought process
Benzodiazepines
= (CNS depressants) used to reduce anxiety
- Little effect on cardiac function!
- Excellent induction agents when providing general anesthesia
- Prevent “unpleasant recall” during uncomfortable interventions
- Terminate seizures and elevate seizure threshold
- Can be used as a Somnific (promotes sleep)
- Alprazolam (Xanax)
- Diazepam (Valium)
- Lorazepam (Ativan)
- Midazolam (Versed)
Adverse effect:
= may augment respiratory depression induced by opioids
Barbiturates
= oldest groups of sedative drugs
Ultra-short acting barbiturates are used for:
- Anesthesia induction –> Thiopental, Thiamylal, Methohexital
- Hypnotics (sleep aid meds) –> Pentobarbital, Secobarbital
- Seizures –> Phenobarbital
Adverse effects:
- Because of their toxic potential and rapid development of tolerance,
- Intentional or accidental overdose (OD) results in respiratory arrest and cardiovascular collapse
- Depress neuron activity in the brain control center
- High risk of addiction and abuse
Opaites
= moderate to severe pain by binding to opioid receptors in the brain and spinal cord
Drugs:
- Morphine, Codeine, Fentanyl, Heroin, Hydrocodone (Norco, Vicodin), Hydromorphone (Dilaudid – 5-10 times stronger than Morphine), Oxycodone, Tramadol
Adverse effects:
- Tolerance develops rapidly and withdrawal is very painful and
unpleasant
- High enough doses result in loss of consciousness and respiratory
arrest
Alcohol
= In excess alcohol behaves like a general anesthetic by depressing ALL BRAIN AREAS resulting in the loss of voluntary muscle control and consciousness
- Toxic Levels 400–600 mg/dl (0.4 – 0.5%) blood alcohol level=Respiratory arrest
Withdrawls:
- Delirium Tremens (DT’s)
– hyperthermia, increased BP, muscle twitching, hallucinosis, and seizures
– If seizures occur, mortality from DT’s is 5% to 10%
Pain scale
= fifth vital sign
- many factors that alter pt responses: physiologic, social, and psychological
- Won-Baker face pain rating scale
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
= frequently used to treat moderate pain
= Aspirin is a salicylate; OTC analgesic and cold remedy
- May cause gastric irritation and ulceration
- Renal injury can result from prolonged use and high doses
- Inhibit platelet aggregation which compounds the problem of GI bleeding
= Acetaminophen (Tylenol)
- In large doses may cause lethal hepatic (liver) necrosis
* OD of Acetaminophen reversed with N-Acetylcysteine!
Patient-controlled analgesia (PCA) pumps
= PRN
- Better to keep control of pain than have to regain control
- For pts on a PCA pump it is recommended a bag-mask and naloxone be available in rooms at all times
Naloxone
= Narcan, opoid antagonist
- Nasal Spray has been approved for use to combat overdoses
Cardiac output (CO)
= Amount of blood leaving the heart with each contraction per unit of time
HR x SV
Epinephrine (Adrenalin chloride)
= Alpha receptors cause vasoconstriction
- tachycardia effect
Vasopressin (Pitressin)
= for hypotension in setting of septic shock
Atropine
Anticholinergic
= symptomatic bradycardia
Adenosine
Endogenous nucleotide
= treat supraventricular tachycardia
SA node
= initiates electrical activity (pacemaker)
- generates action potential
AV node
= links activity of the atria and ventricle
Purkinje fibers
= conduction network
Sudden cardiac death (SCD)
- CPR
- minimize time to defibrillation
MEDS:
- epinephrine
- vasopressin
- atropine
- sodium BICARBONATE
- magnesium sulfate
NAVEL
- Naloxone (narcan)
- Atropine
- Vasopressin
- Epinephrine
- Lidocaine
Implantable cardioverter-defibrillator (ICD)
= used to cardiovert, terminate ventricular tachycardia (VT), and pace bradycardia
Hypertension (HTN)
- 1 billion people world wide; 1 in every 4 Americans
- more than 140/90
- Affects numerous organs (heart, brain, kidneys, eyes
- increased CVD morbidity and mortality
HTN pathophysiology
Arterial blood pressure= generate by interplay between blood flow and resistance to blood flow
Preload= volume of blood affected by venous capacitance
- increase in hypervolemia, regurgitation of cardiac valves, and heart failure 
After load= volume of blood flow affected by arteriolar capacitance
- increase in hypertension and vasoconstriction
Angiotensin-converting enzyme inhibitor (ACEIs)
= used to suppress the renin-angiotensin-aldosterone system (RAAS)
- block the conversion of Angiotensin 1 to 2
- antihypertensives
Arterial blood pressure (BP)
= blood flow and resistance to blood flow
Elevated: 120-129, less then 80
Stage 1: 130-139, 80-89
Stage 2: more than 140, more than 80
Diuretics used for HTN
= thiazide and thiazide-like agents
- mainly for vasodilation
First line agents for HTN
- Angiotensin-Converting Enzyme Inhibitors (ACEIs)
- Angiotensin II Receptor Blockers (ARBs)
- Calcium Channel Blockers (CCBs)
- Thiazide-type Diuretics
Second line agents for HTN
- α2-Agonists
- Vasodilators
- β-Blockers
- α-Blockers
- Direct Renin Inhibitors (DRIs)
- Antiadrenergics
Myocardial ischemia
= lack of blood flow to the cardiac tissue which leads to poor O2 supply
Myocardial infarction
= blood flow is completely cut off, resulting in cellular, death and necrosis 
Angina pectoris signs
- burning sensation
- Shortness of breath
- Chest tightness
PTS with angina
= should receive daily aspirin 75 to 100 mg per day to prevent MI 
Nitroglycerin= reduces myocardial oxygen demand by dilating coronary arteries of collaterals
- 2.5-9mg every 12 hours
Ranolazine (Ranexa)= chronic angina
- 500mg BID
Nitroglycerin
= acute TX or prophylaxis of angina, AMI, acute HF, HTN
ROA: oral, IV, mensch, transdermal, translimgual, sublingual
Adverse effect: tachycardia, palpitations, postural hypotension, dizziness, flushing, headache
Heparin
= anticoagulant naturally present in the secretary granules of human mass cells inhibits the conversion of fibrinogen to fibrin
- prevent unwanted clotting without an increased risk of hemorrhage  
Aspirin
= reduce platelet irrigation by the inhibition of prostaglandin production
- Increases bleeding times
Anticoagulant
= work by preventing the formation of the fibrin clot and preventing further clap formation and already existing thrombi 
Thrombolytics
Indications: PE, ischemic stroke, acute ST segment elevation MI (STEMI)
Contradictions: internal bleeding, aortic, dissection, head injury, or stroke in the last three months, HTN, and anticoagulant use
Adverse effect: major and minor bleeding
Cardiac cell contraction
= depend on free, intracellular calcium ion concentration
Sleep apnea
OSA: occurs when the muscles in the back of your throat relax
CSA: When the brain fails to transmit signals to your breathing muscles
Restless leg syndrome (RLS)
= chronic and progressive neurological disorder, characterized by unpleasant sensation and legs
- dopamine
Narcolepsy
= excessive daytime sleepiness, and sleep attacks
- sodium oxybate (xyrem)
Insomnia
= difficulty and falling asleep
- Benzos
N1 (NREM)
= lightest sleep stage
N3 (NREM)
= deepest sleep stage
REM sleep
- rapid eye movement
Tonic (persistent)= similar to N1, ECG facing increased activity in theta frequency range —> sawtooth wave
- loss in muscle strength
Circadian rhythm
= 24 hour light dark cycle critical for human health and well-being
6am —> sharpest BP
10am —> highest alertness
2100 —> melatonin secretion starts

Melatonin
= transition phase from wakefulness in arousal to high sleep propensity coincides with nocturnal rise and endogen melatonin
Neurotransmitters
= wakefulness, and EEG arousal influenced by several excitatory neurotransmitters
- Glutamate, acetylcholine, monoamines
