Exam 4 Flashcards
Natriuretic VS Diuretic
Natriuretic = increase Na+ secretion (increase water secretion)
Diuretic = increases urine volume
(all natriuretics are diuretics but not all diuretics are natriuretics)
4 main targets of diuretics:
1) Membrane transport proteins
2) water permeable segments of nephron
3) enzyme inhibition
4) interference with hormone receptors
2 main regions of kidney:
Cortex (outer section)
Medulla (inner section)
Parts of nephron:
Renal corpuscle (bowman’s capsule and glomerulus)–> proximal convoluted tubule (S1 and S2)–> Descending limb of loop of henle–> Ascending limb of loop of henle–> Distal convoluted tubule–> collecting duct
Glomerulus
arterial capillary network in the bowman’s capsule
What happens with RBC and WBC at the glomerulus?
they do not cross over into the nephron unless there is damage to the glomerulus
Most common reason for diuretic use:
Peripheral or pulmonary edema related to CHF, kidney disease, hepatic cirrhosis, or idiopathic edema
Non-edematous uses for diuretics:
HTN
Renal Stones
Hypercalcemia
Diabetes Insipidous
5 Classes of diuretics:
Carbonic Anhydrase Inhibitors (CA-I) Loop diuretics Thiazides Potassium sparing Agents that alter water excretion
Rate of excretion
Rate of exertion= filtration rate + secretion rate - reabsorption rate
Low sodium effect on nephron
increases NO and prostaglandin –> dilates afferent arteriole–> increases filtration
Increased sodium effect on nephron
signals ATP synthesis–> increased adenosine –> constricts afferent arteriole–> decreases filtration
What is the purpose of two capillary beds in the nephron?
The capillary bed at the renal corpuscle exchanges glomerular filtrate.
The other capillary bed is all along the nephron and exchanges O2 and CO2 as well as reabsorption and secretion of things that were not filtered at the renal corpuscle.
How much filtrate is there per day?
180grams (80% is reabsorbed at the proximal convoluted tubule
Vasa Recta
area of capillary beds around the loop of henle that exchange O2 and CO2.
Juxtaglomerular apparatus (JGA) is made up of..
..macula densa cells of the distal tubule and juxtaglomerular cells along the afferent arteriole.
what signals the arterioles in the nephron to constrict or dilate?
Na+
Renin response to 2 things:
-Stretch receptors in the afferent arteriole.
(decrease stretch in AA–> renin released–> activates angiotensin/aldosterone system–> allows reabsorption of water)
-Beta agonism
Things that regulate GFR:
- Renal auto-regulation
- Neural regulation (direct nerve input into JGA)
- Hormonal regulation (sympathetic nervous system: beta receptors increase renin release and alpha receptors on vessels)
The Proximal Convolute Tubule (PCT) absorbs how much filtrate?
80%
Things that are reabsorbed in PCT:
NaHCO3 NaCl Glucose Amino acids Organic solutes K+ H2O
What is secreted in the S2 segment of the PCT?
Drugs that are too big to filter through the glomerulus
Uric acid, NSAIDS, Diuretics, antibiotics
Molecular targets in PCT:
NHE3 (Na+H+ exchanger type 3)
Carbonic Anhydrase
Drugs that effect PCT:
- Carbonic Anhydrase Inhibitors (CA-I) blocks NaHCO3 reabsorption which decreases H2O reabsorption
- Caffeine weakly blocks Adenosine receptors causing dilation of AA and increased GFR. Caffeine also blocks NHE3.
Blood osmolality:
290-310mOsm/kg
Loop of Henle (L of H): osmotic gradient
at deepest part of loop, 1200mOsm/kg
Descending limb of L of H:
Water leaves to balance osmolarity.
Ascending limb of L of H:
- Impermeable to water
- Ions leave to balance osmolarity.
Molecular target in L of H:
NKCC2
Na+K+2Cl- transporter
Drugs that effect L of H:
Thick ascending limb: loop diuretics inhibit NKCC2 transporter
Distal Convoluted Tubule (DCT) absorption:
- very little H2O and Na+ movement
- Active Ca++ reabsorption by parathyroid hormone (PTH)
Molecular target in DCT:
NCC
Na+Cl- transporter
Drugs that effect DCT:
Thiazides inhibit NCC.
also very limited effect on carbonic anhydrase in PCT
What happens at the collecting tubule in the presence of a diuretics that blocks NaCl upstream?
(ex of this kind of diuretic)
There is an increases in NaCl reaching the CT–> more Na+ moves into cell–> creates a more negative gradient–> pushes Cl- out of tubule
(ex: Loop diuretics and thiazides)
What happens at the collecting tubule in the presence of a diuretic that blocks NaHCO3 upstream?
(ex of this kind of diuretic)
More NaHCO3 is reaching the CT–> more Na+ moves into cell creating a negative gradient–> HCO3- collects creates a more negative gradient–> K+ leaves the cell and enters the tubule to balance the charge
(ex: Acetazolamide)
Aldosterone
- secreted by adrenal cortex
- Increases water and Na+ reuptake at ENaC
- Increase blood volume and pressure
Antidiuretic Hormone (ADH)
aka Vasopressin
- Increases water reabsorption
- Binds to receptor on CT wall–> stimulates adenylyl cyclase–> produces cAMP–> causes vesicles with aquaporins to fuse to cell wall–> water flows into cell from lumen side
Acetazolaminde: drug class
Diuretic: Carbonic Anhydrase Inhibitor
Acetazolaminde: Targets
inhibits carbonic anhydrase in the PCT
block 80% of HCO3 reabsorption
Highly K+ wasting
Acetazolaminde: clinical uses
Glaucoma
Alkalinization of urine for drug trapping
Metabolic alkalosis
Acute motion sickness
Acetazolaminde: Toxicity
Depletion of blood buffering capacity (risk for metabolic acidosis)
Kidney stones
Furosemide: Drug class
Loop diuretic
Loop diuretics: targets
Inhibit NKCC2 in the TAL of the loop of henle
blocks NaCl reabsorption
increases loss of K+, Mg++, Ca++
Furosemide: precautions
Sulfa allergy
Hydrochlorothiazide: Drug class
Thiazide diuretic
Thiazides: targets
Inhibit NCC in the DCT
blocks NaCl reabsorption
K+ wasting
Thiazides: precautions
Sulfa allergy
Spironolactone: Drug class
Potassium sparing diuretic
Aldosterone receptor antagonist
Spironolactone: targets
Blocks aldosterone receptors in collecting tubule (which decreases reabsorption of Na)
Amiloride: Drug class
Potassium sparing diuretic
Amiloride: targets
inhibits Na+ flux through ion channels in luminal membrane
Potassium sparing diuretics: clinical uses
Primary: Conn’s syndrome and Ectopic ATCH production
Secondary: CHF and Nephrotic syndrome
Mannitol: Drug class
Osmotic Diuretic
Mannitol: Clinical uses
to decrease ICP
Osmotic diuretics: precautions
Hypernatremia in healthy patients
Hyponatremia in renal impaired patients
Hyperkalemia
Use in-line filter, mannitol can crystalize
Conivaptan: Drug class
ADH antagonist (diuretic)
Vasopressin (desmopressin): Drug class
ADH agonist (decreases diuresis)
COPD=
bronchitis + emphysema
Asthma
1) Airway hyper reactivity (causes constriction)
2) Inflammation
3) Mucosal thickening
Eosinophils vs Neutrophils
Eosinophils more associated with Asthma
Neutrophils more associated with COPD
Emphysema
hyperinflation of alveoli which leads to damage to cell membrane, destruction of alveoli, and/or development of scar tissue along the alveoli
FEV1
Forced expiratory volume
A way to measure bronchial hyper-reactivity
Fall in FEV for 1 second after administration of histamine or methacholine
PEF
Peak expiratory flow
Max flow of forced expiration
Early vs late response in asthma:
Early response is a Type1 hypersensitivity like reaction (Histamine, Leukotriene, PG)
Late response is due to inflammation (eosinophils, cytokine)
Histamine
- Released during mast cell degeneration.
- Induces smooth muscle contraction/bronchospasm.
- Causes mucosal edema/secretions due to dilation of vasculature
4 Histamine receptors
H1- lungs
H2- GI system
H3- CNS
H4- CNS
H1
Bronchoconstriction
vasodilation
Diphenhydramine: Drug class
(Benadryl)
Antihistamine
H1 inverse agonist
Diphenhydramine: Clinical use
Type 1 Hypersensitivity reactions
very limited use in asthma
Leukotrienes
Slow reaction
released during mast cell degeneration.
released from lungs during inflammation.
Causes same things that histamine causes only slower.
Prostaglandins
Potent bronchoconstriction.
Enhance histamine effect.
Short duration of action.
Which prostaglandin contributes the most to bronchoconstriction?
PGD2
Thromboxane (TXA2)
Produced when COX has its effect on arachidonic acid.
Constricts blood vessels.
T-Helper cells type 2 (TH2)
-Release cytokines that attract additional WBC (eosinophils) to the area, increasing the inflammatory response.
Eosinophils stimulate IgE production
Sympathetic activity on bronchiolar smooth muscle:
Relaxes
Beta2
no direct nerve innervation
Parasympathetic activity on bronchiolar smooth muscle:
Constricts
Muscarinic 3
direct nerve innervation
Epi for treatment of asthma: drug class
Sympathomimetic agent
Beta2 agonist
non-selective alpha and beta
Epi for treatment of asthma: precautions
B1 activity as well (tachycardia, arrhythmias, worsening angina)
Beta2 agonists
- Relax airway SM
- Inhibit microvascular leakage
- Increase mucociliary transport.
Short term asthma tx.
can cause tremors
Isoproterenol: Drug class and clinical use
Sympathomimetic agent
Beta2 agonist
non-selective
Short term asthma tx
Isoproterenol: precautions
arrhythmias
UK study- increased mortality
Terbutaline: Drug class and clinical use
Sympathomimetic agent
Selective Beta2 agonist
Short term asthma tx
Salmeterol/Formotorol: Drug class and clinical use
Sympathomimetic agent
Selective Beta2 agonist
longer term asthma tx (12hr effect)
(Can develop tolerance)
Albuterol: Drug class and clinical use
Sympathomimetic agent
Selective Beta2 agonist
Short term asthma Tx
Theophylline: Drug class and clinical use
Methylxanthine
Short term asthma tx
Methylxanthine: MOA
- Main: Inhibit PDE
- Inhibit adenosine receptors
- anti-inflammatory action
Theophylline: precautions
Positive chronotrope and inotrope
arrhythmia
N/V
Theophylline: dose and toxicity
Dose: 5-20mg/L
Toxic: >20mg/L
Atropine: Drug class and clinical use
M3 antagonist
Short term asthma tx
M3 antagonists: MOA
Compete with ACh at H3-R
- Block contraction of airway SM
- Block mucous secretion
Ipratropium Bromide: Drug class and clinical use
M3 antagonist (more selective than atropine)
Short term asthma tx and COPD tx
Tiotropium: Drug class and clinical use
M3 antagonist
Longer term asthma tx and COPD tx
Ipratropium Bromide VS Tiotropium
both have NO CNS effects and NO B2 activity
Tiotropium last longer (24hr)
Black Haw, Evening primrose, and Feverfew
contains mild amount of theophylline (asthma tx)
Corticosteroids: MOA
- Inhibit production of cytokines
- Inhibit lymphocytic, eosinophilic airway mucosal inflammitory
Corticosteroids: precautions
Increased risk for osteoporosis
Stunts growth in children
Inhibit immune response (Oropharyngeal candidiasis)
Prednisone: Drug class
Corticosteroid
Fluticasone: Drug class
Corticosteroid
Mast cell Stabilizers
Prevent mast cell degranulation (prophylactic).
No direct effect on airway SM
Mast Cell Stabilizers: Drug examples
Cromolyn
Nedocromil
Anti-IgE monoclonal antibodies
Bind to antibody on mast cell and prevent degranulation
Omalizumab
Anti-IgE monoclonal antibody
1dose/wk injection
prophylactic
Leukotriene pathway inhibitor: MOA
2 ways:
1) inhibit 5-lipoxygenase
2) inhibit receptor binding
Montelukast: Drug class and clinical use
Leukotriene pathway inhibitor
Long term asthma tx
Montelukast: MOA
inhibits leukotriene receptor binding
Tx for ASA induced asthma:
leukotriene pathway inhibitor
Autacoid groups
(means they have their effect locally)
Histamine, serotonin, PG, leukotrienes.
1st generation H1 antagonists:
Bendryl, phenergan, dramamine
2nd generation H1 antagonists:
Claritin, Allegra, Zyrtec
Buspirone
5HT1A agonist
GAD, OCD, anti-anxiety
Triptans
5HT1B/D agonist Migraine HA prevent blood vessel dilation and stretch non-prophylactic Serotonin syndrome
Ondansetron
Zofran
5HT3 antagonist
SSRIs
Prozac
Zoloft
Inhibit SERT
SNRIs
Cymbalta
Pristique
Inhibit SERT and NET
TCAs
Elavil
Inhibit SERT, NET, and have anticholinergic effects
MAOIs
Nardil
refractory depression
Pheytoin: clinical use
Dilatin
partial, tonic-clonic
Pheytoin: MOA
Modification of ion conductance
Enhance inhibitory-GABA
Inhibit excitatory-Glutamate
Highly protein bound
Pheytoin: AE
Nystagmus diplopia sedation gingival hyplasia hirsuitism
Pheytoin: levels
Therapeutic: 10-20mcg/ml
Toxic: 30-50mcg/ml
lethal: >100mcg/ml
Carbamazepine: clinical use
Tegretol (TCA)
Partial(drug of choice) , TGN, BiPolar
Carbamazepine: MOA
Modification of ion conductance
Enhance inhibitory-GABA
Inhibit excitatory-Glutamate
Induces hepatic enzymes
Carbamazepine: AE
Diplopia
ataxia
can develop tolerance (induces hepatic enzymes, decrease in half life over time)
can speed up break down of drugs
Phenobarbital: clinical use
Barbituate
DOC in infants
partial
GTCS
Phenobarbital: MOA
sedation
Enhances inhibitory-GABA
Induces hepatic enzymes
Phenobarbital: AE
Can worse other seizures (absence, drop, or infantile)
can speed up breakdown of drugs (tolerance)
severe resp. depression
Lamotrigine: clinical use
partial and absence seizures
Lamotrigine: MOA
Modification of ion conductance
GABA analogs: Drugs
Vigabatrin
lyrica
GABA analogs: clinical use
adjunct
partial
neuralgia
Infantile spasms
Ethosuxamide: clinical use
Absence seizures DOC
Ethosuxamide: MOA
Modification of ion conductance
Ethosuxamide: AE
GI
lethargy
Valproic Acid: clinical use
Depakene
generalized seizures (except TC)
bipolar
migraine
Valproic Acid: MOA
Modification of ion conductance
Enhance inhibitory-GABA
Inhibit excitatory-Glutamate
Valproic Acid: AE
DISPLACES PHENYTOIN Inhibits metabolism of some drugs GI sedation tremor hepatotoxicity
Benzodiazepines: clinical use
status epilepticus (Diazepam)
Benzodiazepines: MOA
Enhance inhibitory-GABA
Diazepam: half life/duration
Long half life (20-100H) short duration (30min)
