Pharm Test 3 Flashcards
in general, diuretics decrease bp by
decreasing blood volume by increasing urinary volume
why is carbonic anhydrase not recommended as a front line diuretic?
because of it’s toxicity: decreases K+ and lowering the body pH by wasting HCO3
where does mannitol work?
throughout the entire nephron but primarily in the proximal convoluted tubule
mannitol contributes to the _______ of the urine
osmolality
what kind of diuretic is mannitol?
osmotic
what is an osmotic diuretic?
A drug that is going to affect the osmolality of the fluid that’s in the nephron.
what is osmolality?
the number of dissolved particles that are in a solution.
what is a normal body osmolality?
300mOsm/kg
what is the osmolality of the renal cortex?
300 mOsm/kg
what is the osmolality of the kidney as we descend into the renal medulla?
It increases as high as 1200mOsm/kg
why is the osmolality so high in the renal medulla?
as we’re reabsorbing the sodium, before it gets into the blood stream, it goes into the medulla first.
what is an impermeable solute?
a solute that cannot be reabsorbed from the nephron back into the blood.
how does mannitol work?
It is a sugar alcohol that increases the osmolality of the inside of the nephron. Since it’s more concentrated in the nephron water stays in the nephron and goes into the medulla to be excreted.
what is the s2 segment of the nephron?
The fairly straight portion of the proximal tubule before it reaches the loop of Henle. It has special transporters that can transport much larger substances into the urine.
why don’t we have water leaving in the ascending portion of the loop of Henle? what kind of transport do we have instead?
because this section is water impermeable
Na+ leaving via the NKCC2 pump in order to balance the osmolality in the nephron.
what kind of ion movement happens in the thick ascending limb of the loop of Henle?
NKCC2 pumps Na+, K+ and 2 Cl- INTO the Thick Ascending Limb
K+ leak channels leak K+ OUT of the thick ascending limb into urine
this positive efflux pushes
Ca++ and Mg++ INTO the Thick ascending limb
Na+/K+ ATPase pumping Na+ OUT of the Thick ascending limb
K+Cl- cotransports both OUT of the Thick ascending limb into the interstitium.
which part of the loop of Henle is permeable to water? Which direction does water go?
the descending portion
water leaves the nephron to try and balance out the really high osmolality in the renal medulla
what is moving in/out of the collecting tubule?
water leaves
where do loop diuretics work? How?
the thick ascending limb. It blocks the NKCC2 pump so more sodium stays in the urine. water follows.
which electrolytes get depleted or less absorbed when using loop diuretics?
Na+
K+
Cl-
Mg++
Ca++
what is the difference between loop diuretics and carbonic anhydrase inhibitors?
Loop diuretics don’t effect bicarb
what is toxicity of loop diuretics?
allergic reactions. Loop diuretics are Sulfonamides.
what is the only loop diuretic that is not a sulfonamide?
Ethacrynic Acid
why is there less water movement in the distal convoluted tubule?
because the osmolality in the renal cortex is closer to 300mOsm/kg which is balanced
What kind of electrolyte movement can we expect in the distal convoluted tubule?
Na+ and Cl- going INTO the Distal Convoluted Tubule
Ca++ leak channels INTO the DCT thanks to parathyroid hormone
Na+/K+ ATPase pumping sodium OUT of the DCT
NCX pumping Na+ IN and Ca++ OUT of the DCT
Ca+/H ATPase pumping Ca++ OUT and H+ INTO the DCT
what do thiazide diuretics target?
the NCC
Na+ and Cl- co transport into the DCT
it also gets rid of a little bit of bicarb
what is the prototype thiazide drug?
hydrochlorothiazide
which diuretics are sulfonamides?
loop and thiazides
thiazides don’t work as well as _____
loop diuretics
When combining diuretics, you want to combine what types?
drugs that work on different parts of the nephron.
where is the final site in the kidney that sodium can be reabsorbed?
the collecting tubule
where in the kidney is the most important site for K+ secretion?
the collecting tubule
where is aldosterone released from?
the adrenal cortex
we have sodium reabsorption in the collecting tubule d/t
aldosterone being released in response to low bp. aldosterone binds to the receptor inside the collecting tubule and increases the activity of ENaC
what is ENaC?
a sodium transporter pulling sodium out of the urine and into the collecting tubule
what are the principal cells responsive to in the collecting duct of the kidney?
aldosterone
what is the normal without drugs movement of Cl-, Na+, and K+ in the collecting tubule?
More Na+ moves into the Collecting Tubule than K+ leaves the CT. This makes the urine net negative which drives Cl- through the cells to the interstitium
what is the movement of Cl-, Na+, and K+ in the collecting tubule when you give potassium wasting diuretics with affects on sodium?
Cl- moves through the cells to the interstitium
LOTS of Na+ moves into the Collecting Tubule (because it was blocked from being absorbed higher up)
LOTS of K+ leaves the CT (to balance out Na+)
what is the movement of HCO3-, Na+, and K+ in the collecting tubule when you give potassium wasting diuretics with affects on bicarb? (acetazolamide)
Bicarb can’t move between the cells so this makes the urine extra negative
LOTS and LOTS of Na+ moves into the Collecting Tubule (because it was blocked from being absorbed higher up)
LOTS and LOTS of K+ leaves the CT (to balance out Na+)
what drug antagonizes aldosterone in the kidney?
Spironolactone
why is spironolactone K sparing?
because you block aldosterone in the collecting tubule. This blocks Na+ reabsorption which makes the urine more Positive so K+ stays within the collecting tubule.
what drug is similar to Spironolactone and how does it work?
Amiloride
it blocks the ENaC pump
what is Conn’s syndrome?
an increase in aldosterone production d/t a tumor or hyperplasia. this works as a diuretic
would use a K+ sparing diuretic
what is a contraindication to taking a K+ sparing diuretic?
pt is taking K+ supplements
toxicity of K+ sparing drugs
hyperkalemia
what is the antidiuretic hormone in the collecting duct?
vasopressin
what does vasopressin do in the kidneys?
increases cAMP which moves aquaporin channels to the cell wall so that water can rush into the collecting duct and then the interstitium.
why would a patient not produce ADH?
possibly d/t their blood pressure being too high already
what drug blocks the receptor for ADH?
Conivaptan a K+ sparing diuretic
What is Mannitol normally used for?
to decrease ICP
to promote removal of renal toxins
Describe 2 drugs that reduce potassium loss during sodium diuresis.
Potassium sparing diuretics:
Block aldosterone receptors (spironolactone)
Inhibition of sodium flux through ion channels in luminal membrane (amiloride)
List the potential side effects of mannitol
Extracellular volume expansion d/t rapidly distributed fluids to extracellular compartments. This can lead to congestion and hyponatremia prior to diuresis.
Dehydration
Hypernatremia
Hyperkalemia
In patients with renal failure - hyponatremia
What is the major application for acetazolamide?
Used in acute mountain sickness because blocks carbonic anhydrase in CNS
What is the major application for thiazides?
diuretic when K+ needs to be preserved
What is the major application for loop diuretics?
Most efficacious diuretic, used for fluid overload, especially when K+ wasting is okay
What is the major application for potassium sparing diuretics?
Useful in patients with hypokalemia
Most useful in states of mineralocorticoid excess (result in overproduction of aldosterone)
Primary - over produce aldosterone
Conn’s syndrome
Pituitary gland tumor
Results in Ectopic ACTH production
Secondary
CHF
Nephrotic syndrome
Use of other diuretics that waste potassium
What are the toxicities associated with acetazolamide?
K+ depletion
Acidosis
What are the toxicities associated with thiazides?
allergic reaction.
sulfonamide
What are the toxicities associated with loop diuretics?
allergic reaction.
sulfonamide
What are the toxicities associated with potassium sparing diuretics?
Hyperkalemia
What is diabetes insipidus?
insufficient ADH which leads to excessive thirst and urination.
What is one of the treatments for neurogenic Diabetes insipidus?
Thiazide diuretics.
It depletes the patient further and leads to decreased urinary output overall.
what are the symptoms of asthma?
wheezing, breathlessness, chest tightness, coughing, and symptoms increased at night and early morning
what are the factors involved in asthma?
- Airway inflammation causing obstruction
- Increased responsiveness of trachea and bronchi to various stimuli
- Widespread narrowing of airways
- Contraction of airway smooth muscle
- Mucosal thickening
edema, cellular infiltration - Mucous plugs
- Involves WBC’s and epithelial cells
- Reversible
What is the hygiene hypothesis?
We are more clean now than we used to be as primal humans so our body attacks its own cells rather than other pathogens
Causes of asthma attack: allergens, respiratory infections, irritants, certain meds, exercise, GERD, and anxiety/stress
what are the symptoms of Croup
seal-like barking cough
If viral: rhinorrhea, sore throat, and fever
What is COPD?
Chronic bronchitis + Emphysema
the most severe of obstructive disorders.
what are the symptoms of bronchitis?
Hypersecretion of mucus and chronic productive cough that lasts for at least 3 months of the year and for at least 2 consecutive years
what are the symptoms of emphysema
dyspnea and wheezing
what are the factors involved in croup
Acute laryngotracheobronchitis
Can be from a viral infection that causes the airway to become hyperreactive
common in young children
what are the factors involved in bronchitis
Inspired irritants increase mucus production and the size and number of mucous glands
The mucus is thicker than normal
what are the factors involved in emphysema?
Abnormal permanent enlargement of the gas-exchange airways accompanied by destruction of alveolar walls without obvious fibrosis
Loss of elastic recoil
Distended alveoli cause less efficient gas exchange
what are severe cases of croup treated with?
nebulized epinephrine
Why do smokers have a nasty cough, especially in the morning?
It decreases cilia so they have a harder time moving mucous in the airway
what is the most common chronic disease in children?
asthma
what is the FEV1?
Bronchial hyperreactivity test.
A positive test is when there is a marked fall in forced expiratory volume over 1 second provoked by inhaling increasing concentrations of histamine or methacholine.
Monitor to make sure that they don’t have an asthma attack during this
What is PEF?
Peak expiratory flow
Maximum flow of forced expiration
What is the maximum amount of expiration that they can force out of that flow meter?
Describe the immune response to allergens as it pertains to dendritic cells
found in the mucosa/lining of respiratory tract, they interact with the allergen & they swallow it up and break it down.
Also referred to as antigen presenting cells since they are now going to present the antigen on the surface of their cells/cell membrane with an MHC II receptor (receptor that activates certain inflammatory cells in the immune system)
It then migrates to the closest lymph node and presents it to a T-Cell
Describe the immune response to allergens as it pertains to T cells
Helper T cells are activated in the case of an allergen reaction to an innocuous substance such as pet dander or dust mite feces.
The helper T cell releases interleukin IV and the interleukin IV (Dupixent blocks IL4 here) activates the B cells that produce antibodies
Describe the immune response to allergens as it pertains to B cells
cells that produce antibodies and turn into plasma cells and memory cells (long lived and can have a significant reaction next time that pathogen is encountered)
Describe the immune response to allergens as it pertains to plasma cells
antibody producing factories that recognize this specific allergen as foreign
In an allergic response, these antibodies are a specific subtype called IgE
IgE antibodies bind to the surface of mast cells
Describe the immune response to allergens as it pertains to mast cells
Found in the connective tissues that line the airway and the gastrointestinal tract.
Big sacks of histamine, leukotrienes and prostaglandins.
On the first exposure of an allergen, Plasma cells place Ige antibodies on mast cells marking it for future exposure.
Upon second exposure, the allergen binds to Ige and you have mast cell degranulation. It opens and spills out histamine, leukotrienes and prostaglandins which gives you allergic response symptoms.
Describe the immune response to allergens as it pertains to neutrophils
release proteases(break down proteins) and cytokines (signaling compound to control the rate of activity)
Causes both smooth muscle constriction and vasodilation causing leakiness of the vessels= tissue swelling
Describe the immune response to allergens as it pertains to eosinophils
same response as neutrophils
What kind of autocoids are released when you have an asthmatic response?
less histamine and more leukotriene and prostaglandin
what are the mediators released in the early stages of asthma?
Histamine
leukotrienes
prostaglandins
tryptase
Cause swelling and constriction and rush of WBC’s to further the allergic reaction
What are the mediators released in the late stages of asthma?
2-8 hours later
Leukotrienes
Histamine
Mucus production is the body’s defense against irritants and microorganisms
Produced by
goblet and epithelial cells
List the primary pathways of the arachidonic acid cascade, and its main products.
Arachidonic acid produces
LOX pathway- produces leukotrienes
COX pathway- produces prostaglandins
What are the ANS effects on airway diameter
Normal: slightly closed off resting airway tone d/t parasympathetic vagal stimulation.
In asthma:
Greatest resistance is in medium bronchi d/t further airway constriction
Describe the 2 broad categories of treatment for asthma and COPD
Short-term relievers: sympathomimetics
Contraction of smooth muscle → beta agonists
Long term controllers: corticosteroids
Edema and cellular infiltration → anti-inflammatory agents
Antihistamines have small benefit in asthma
List the major classes of drugs used in asthma and COPD.
Short term relievers:
* Beta agonists-Epi, isoproterenol, albuterol, salmeterol/Formotorol
- anti-muscarinic- IV atropine, Inhaled. Ipratropium bromide
- Methylxanthines- Theophylline(strong tea)
Long term controllers:
* Steroids-Prednisone, fluticasone
- monoclonal antibodies- Omalizumab
- Leukotriene antagonists: Lipoxygenase inhibitors- Montelukast
Receptor inhibitors
can use anti-IgE monoclonal antibodies. This targets portion of IgE that binds to mast cells and does not activate IgE already on mast cells.
What is the most effective treatment for COPD, how does it work?
A methylxanthine called Theophylline.
Phospho Diesterase inhibitor (PDE) to relax smooth muscle in the airways, is anti-inflammatory, and inhibits adenosine receptors
What is found in concentrated tea that can help COPD patients?
Theophylline
What are anti muscarinic drugs used in COPD?
Atropine
Ipratropium bromide(atrovent)- more selective than atropine
Tiotropium(Spiriva)- longer lasting
Describe the mechanisms of action of sympathomimetics used in asthma
Relax airway smooth muscle
And…
Inhibit some substances from mast cells
Inhibit microvascular leakage
Increase mucociliary transport
Describe the mechanisms of action of corticosteroids used in asthma
Inhibits immune response by blocking transcription/translation
- steroid enters cell binds to glucocorticoid receptor (GR) and moves to nucleus
- Through Transactivation binding of the activated GR homodimer to a glucocorticosteroid response element (GRE) in the promoter region of steroid-sensitive genes leads to the transcription of genes encoding anti-inflammatory mediators.
- Through Transrepression the glucocorticoid receptor–corticosteroid complex interacts with large co-activator molecules with intrinsic histone acetyltransferase (HAT) activity
- thus switching off expression of the inflammatory genes that are activated
what is a side effect of corticosteroids?
may increase osteoporosis and stunt growth rate in children
oropharyngeal candidiasis
Identify treatment considerations for specific patients with mild asthma and/or COPD
Beta receptor agonist on an as needed basis
Identify treatment considerations for specific patients with moderate asthma and/or COPD
Inhaled corticosteroid - different depending on the severity of the symptoms
Oral leukotriene receptor antagonist
Identify treatment considerations for specific patients with frequent asthma and/or COPD
inhaled corticosteroids
Identify treatment considerations for specific patients with severe asthma and/or COPD
inhaled corticosteroids
Anti-IgE antibody
Oxygen
beta-2 agonist (nebulizer)
Systemic steroids- Prednisone, Methylprednisone
Intubation
Mechanical ventilation
What is Trelegy/ ellipta?
anti-inflammatory steroid, anticholinergic, and beta 2 agonist
used for COPD
What is the Asthma progression?
- short acting beta 2 agonist
- If symptoms are twice a month, also include a low dose inhaled corticosteroid
- If they are greater than that, combine the inhaled corticosteroid with a long acting beta 2 agonist like femoderol
- Even worse than this, combine with a leukotriene receptor antagonist
- When it is affecting lung function, then we will combine with a medium dose inhaled corticosteroid
- Last step, use IgE antibodies1.
What is an autacoid?
General term for things that are released locally and have an effect locally
NOT neurotransmitter
Examples of autacoids
histamine, serotonin, prostaglandins and leukotrienes
cause things like itchiness (pruritus)
What is the effects of Histamine in the brain?
excitatory
What does Histamine do in the stomach?
produces hydrochloric acid to digest food
why do some people itch when given morphine?
because of histamine release
Where is H1 found?
brain, smooth muscle, endothelium
Where is H2 found?
brain, heart, GI, mast cells
where is H3 found?
brain
what is the cardiovascular effects of histamine?
vasodilation causes decreased BP
Increased HR d/t reflex tachycardia
what is a secondary response of Histamine in the lungs?
bronchoconstriction
Where is serotonin found?
90% found in Gut
also a neurotransmitter
what does 5-HT do in the gut?
causes peristalsis
can lead to diarrhea
what is a precursor to melatonin?
5-HT
What does serotonin do in regards to platelets?
vasoconstricts injured blood vessels
got it’s name because it is found in “Serum” and gives vessel “tone”
what is the response of 5-HT in the respiratory system?
ACh release= constriction
hyperventilation
What is the triple response of allergy testing and mediators?
Histamine
Wheal- swelling
Flare- redness
sensory nerve endings-itchy
what are the 2 groups of H1 antihistamines?
1st Gen H1 receptor antagonists:
Systemic + CNS
Resembles antimuscarinic drugs
Effects:
Crosses BBB and has sedative effects and some Anticholinergic activity (antiemetic)
2nd Gen H1 receptor antagonists:
More systemic, less CNS
Does not cross BBB
Effects:
Less sedation because it has a lower CNS distribution
How does Epi reverse histamine effects?
works on alpha and beta NOT histamine receptors
Constricting blood vessels
Dilating airways
1st gen H1 antagonist drugs
- dramamine
- Phenergan
- Benadryl
Atarax
Chlor-Trimeton
2nd gen H1 antagonist drugs
- Allegra
- Clarintin
- Zyrtec
1st and 2nd gen Histamine antagonists have equal
efficacy
List the uses of the H2 antihistamines
Shuts down production of hydrochloric (stomach) acid
Not as effective as PPIs
Heavy OTC use
Contrast PPIs and H2 antihistamines
PPI’s have replaced H2 antihistamines
Name 2 members of PPI group
Nexium
Omeprazole
Describe platelet response all the way to fibrin clot (pharm)
- Platelets bind to damaged vessels → they aggregate →
- platelet degranulation releases serotonin → this increases tone in the blood vessel → vasoconstriction →
- so we don’t bleed out and have time to form a fibrin clot → fibrin clot forms to prevent blood loss
Where is serotonin produced?
Raphe Nuclei
What are the 3 main 5-HT agonist targets? and associated drugs?
5-HT1A Buspirone (anxiety)
5-HT1B Sumatriptan (migraines)
5-HT1D Sumatriptan (migraines)
what is the only ion channel serotonin receptor?
Where is it found?
What reflex is it associated with?
(5HT3)
Found in area postrema → area associated with nausea reflex → give ondansetron (antagonist that binds to 5HT3)
What are the 2 main 5-HT antagonist targets? and associated drugs?
(5HT 2A
Location: smooth muscle, platelets and cerebral cortex
Drugs: Phenoxybenzamine, cyproheptadine)(not on his review)
5HT 3
Location: Area postrema
Drug: ondansetron
Serotonin agonists used to be good for what?
weight loss.
No longer allowed in America
Preventatives for Migraine HA(not on his med review?)
Beta-blockers, CCBs, ACEi
* Help with the throbbing pain from a headache
Antidepressants - SSRIs, TCAs
Anti-seizure- valproate, topiramate
Botox
* Paralyze facial muscles so that tensed facial muscles can not cause a migraine
MAbs -Aimovig
* Aimovig - targets CGRP
CGRP plays important role in migraines
Aimovig is an anti-CGRP antibody that binds to the protein itself and prevents it from binding to its receptors.
Treatments for migraines HA
Pain: ASA, NSAIDS, ASA + caffeine, opioids (severe headache)
Triptans(on review)
Ergotamine - less effective than triptans
Anti-nausea - chlorpromazine, ondansetron
Glucocorticoids (more for prevention) - prednisone
Others:
CCB, TCAs, SSRIs, Beta blockers
Toxicity associated with Triptan
Can wear off → recurrence of migraine
Coronary vasospasm - rare
(On review) Serotonin syndrome
Mainly in pt taking triptans + SSRIs, MAOIs or St. John’s wort
Describe the action of sumatriptan
5HT receptor Agonists (1B/1D)
Prevent dilation and stretching of pain endings
what is sumatriptan used for?
Mainstay of migraine treatment
what are the contributing factors to serotonin syndrome?
MDMA, SSRIs, MAOIs, St John’s Wort, Triptans with any of the previous ones (anything that increases serotonin)
what are the contributing factors to Neuroleptic malignant syndrome
Dopamine blocking anti psychotic drugs
what are the contributing factors to malignant hyperthermia
Succs , volatile anesthetics (sevo)
Mutation of Ryr receptor → keeps it open for long → calcium efflux for longer → increased muscle cell rigidity
What are the treatments for serotonin syndrome
Sedation (benzo)
Paralysis
Intubation
Ventilation
Consider 5-HT blocker
What are the treatments for neuroleptic malignant syndrome
Diphenhydramine (parenteral benadryl)
Cooling if high temp
Benzos if needed
What are the treatments for malignant hyperthermia
Dantrolene (muscle relaxant)
Cooling
what are the 3 types of hyperthermia disorders?
serotonin syndrome
neuroleptic malignant syndrome
malignant hyperthermia
What is the mesolimbic pathway?
Pleasure and reward pathway.
can be a positive effect (addicted to exercise) or negative (addicted to drugs or gambling)
Differentiate between anxiety and depression
Depression is a lack of energy, anxiety is an excessive amount of energy.
What are the forms of Depression?
Dysthymia
Psychosis: delusionals/hallucinations
PPD
Seasonal affective disorder (SAD): decrease in melatonin
Bipolar disorder: switching from depression to anxiety
what are the forms of anxiety?
Generalized anxiety disorder (GAD)
OCD
PTSD
Social phobia
List the four categories of antidepressant medications in order of treatment severity.
- SSRIs
- SNRIs (selective serotonin-NE reuptake inhibitors)
- TCAs (named for cyclic molecule repeated x3)
- MAOIs
What is the black box warning on all antidepressants?
Can have an increased risk of suicidal ideation (first 1-2 months). Not used to dealing with increase in serotonin, norepi, dopamine
SSRI mechanism of action
Inhibitor of SERT
SNRI mechanism of action
Inhibit SERT and NET
what are SNRI’s used for?
Used for major depression and pain disorders (trigeminal neuralgia)
TCA mechanism of action
Inhibit SERT, NET, some anticholinergic effects, some effects on dopamine
Why are TCA’s less common?
They have more side effects
MAOI mechanism of action
prevent breakdown of monoamines, a lot more present in the synapse
Why are MAOI’s rarely used?
Rarely used due to lethal drug interactions (need to know everything the pt is taking, including botanical agents)
Refractory depression
List alternative therapies for depression.
- Psychotherapy - talk therapy
- Electroconvulsive therapy
Useful for BPD or other types of severe depression
Reestablish normal electrical pathways in the brain - St. John’s wort
Top selling botanical agent in the US
Don’t need a prescription
What are histamines?
fast acting establishers of allergic reaction symptoms:
mucus secretion, capillary dilation, allergic response including itching, hay fever and anaphylaxis
