Exam 3 Flashcards
(318 cards)
1
Q
What are the segments of the Nephron ?
A
Bowman’s Capsule (Glomerular capsule & capillary work)
PCT (Proximal Convoluted Tubule)
Loop of Henle (Thick , Thin, Ascending & Descending)
DCT (Distal Convoluted Tubule)
2
Q
what is the Definition of a Diuretic?
A
Increases urine volume
3
Q
What is the definition of Natriuretic?
A
Increases sodium ion secretion = increases water secretion due to osmosis
4
Q
What are the main targets of Diuretics
A
Membrane transport proteins
Water permeable segments of the nephron
Enzyme inhibition
Interference with hormone receptors
5
Q
Interference with the aldosterone receptor will have what effect?
A
Increase urine output with diuretics
6
Q
What are the three principal activities of nephrons in producing urine ?
A
Filtration
Reabsorption
Secretion
7
Q
How many nephrons does the kidney contain ?
A
800,000 - 1 Million
8
Q
What is the primary function of the Glomerulus ?
A
Filtration
9
Q
Where are the glomeruli found ?
A
ONLY in the cortex
10
Q
What is glomerular filtration ?
A
Movement of fluids from the blood into the bowman’s capsule
11
Q
What is reabsorption and where does it mainly take place?
A
Selective transfer of essential solutes and water back into the blood
80% of reabsorption takes place in the Proximal Tubule (PCT)
12
Q
Where are the Macula Densa located ?
A
In the Juxtaglomerular Apparatus
13
Q
What are the three things that make up the Juxtaglomerular Apparatus
A
JG Apparatus includes macula Densa , Juxtaglomerular cells , and extraglomerular mesanginal cells
14
Q
Where is the Juxtaglomerular Apparatus ?
A
At the vascular pole of the renal corpuscle
15
Q
What is the osmolality in reference to the kidneys ?
A
the number of dissolved substances
Anything dissolved in a liquid that is contributing to the osmotic pressure of that fluid
16
Q
What does the Macula Densa Monitor?
A
the osmolality and volume of the fluid in the DCT
17
Q
Where does the information from the Macula Densa get transferred to ?
A
To the JG Cells
18
Q
What kind of cells are the Juxtaglomerular Cells ? What can they do?
A
Modified epithelial cells that act like smooth muscle
located in the afferent arteriole
They can contract to limit amount of fluid coming into the capillaries
19
Q
What controls the Glomerular Filtration Rate (GFR) ?
A
Directly controlled by the JGA (Juxtaglomerular Apparatus)
20
Q
What is GFR (Glomerular Filtration Rate)?
A
The rate at which the glomerulus is actually filtering the blood
Controlled by JGA
21
Q
How is the GFR regulated?
A
- Adjust blood flow
- Alter capillary surface area
- Control arteriole diameter
External force or diet increases GFR by increasing BP -> sensed by Macula Densa Cells and referred to JGA (1)
The information then decreases NO output to contract JG cells, decreasing blood flow through glomerulus, returning us to baseline.
22
Q
What are the three types of regulation our body has that affect our kidneys ?
A
Renal autoregulation
Neural Regulation
Hormonal Regulation
23
Q
What is the process of Renal Auto-regulation ?
A
Kidneys regulating how much pressure is coming into the glomerulus to ensure the kidneys aren’t damaged.
This happens through regulation of GFR
Process: External force or diet increases GFR by increasing BP -> sensed by Macula Densa Cells and referred to JGA (1)
The information then decreases NO output to contract JG cells, decreasing blood flow through glomerulus, returning us to baseline.
24
Q
What is Neural Regulation ?
A
Activation of the sympathetic nervous system —> Releases NE and Epi —> Act at JGA cells —-> Increases Renin secretion
25
What is hormonal Regulation ?
Release of different hormones to regulate blood flow in the glomerulus.
26
What are the main things the Proximal Tubule Reabsorbs naturally (without diuretics) ?
Sodium Bicarbonate (NaHCO3) , glucose, amino acids, potassium, water , organic solutes.
27
What are the Proximal Tubule targets for diuretics ?
NaCl, NaHCO3, and Caffeine
28
Where do Carbonic Anhydrase Inhibitors work and the MOA ?
block NaHCO3 reabsorption in the proximal tubule =
Excess bicarb loss
Messes with pH - older drugs - not as popular
29
Why does Caffeine make us urinate and where in the kidney does this happen?
Weakly blocks adenosine receptors in PCT (Na+ receptors)
30
What exchanger do we have in the Proximal Tubule ?
NHE3
Sodium - Hydrogen counter-current exchanger
Swaps sodium (IN) for hydrogen (OUT) in lumen for urine
From urine to interstitium
31
What is the NHE3 process ?
NHE3 starts —> H+ binds to bicarbonate to form carbonic acid (H2CO3) —> Carbonic Anhydrase (enzyme) interacts with carbonic acid to form H2O and CO2 —> CO2 diffuses into membrane and is reattached to water inside the tubule —> then add more CA to re-convert into carbonic acid and then into bicarbonate.
This is relayed to the next transporter to reabsorb bicarbonate , sodium and water naturally
32
what is Acetazolamide and how does it work ?
Blocks Carbonic Anhydrase enzyme (CA) which lowers o r stops NHE3 activity - BICARB WASTING and K+ Wasting
Primarily block NaHCO3 reabsorption in the PCT
Increasing sodium, bicarbonate in the urine for excretion - water will follow the urine so this also increases water in urine. Waste HCO3 and lowers body pH
33
Why are Carbonic Anhydrase Inhibitors not used as diuretics as often ?
Due to its toxic build up effects by wasting Bicarb and K+ depletion - Can lead to acidosis
Drug name: Acetazolamide
Can be used, but not often now as diuretic
Can be used for acute mountain sickness - targets CA in the CNS
34
What is the Osmolality of the kidney Medulla?
Cortex - 300 mOsm/kg
Medulla - 1200 mOsm/kg
Increase is due to reabsorption of sodium - its in the medulla first
35
Where does Mannitol work?
Primarily in the PCT (because this is where we Reabsorb our sodium)
technically all throughout the entire nephron
Contributes to osmolality of urine
36
MOA of Mannitol ?
As water follows Na+ , mannitol concentrations increases
= increases osmolality — prevents further reabsorption of water
37
What is the S2 segment of the Proximal Tubule ?
Straight segment (S2)
Secretion of larger substances in luminal fluid
(Urine acid, NSAID’s, Diuretics, ABXs etc.. )
38
What are the parts of the loop of henle and what happens there ?
Descending
- water reabsorption to balance hypertonic medullary interstitium
Ascending
-active transport of NaCl - NaKCC2 (1Na, 1K+, and 2Cl-) from urine into loop
-charge difference drives cations out of urine and back into system (This is how Mg++ and Ca++ are Reabsorbs )
39
What’s the role of the descending loop of henle in the Counter Current Medullary Gradient ?
Descending loop of henle reabsorbs water to balance out the increased sodium concentrations of the kidney medullas
As its descending deeper into the medulla sodium concentrations reach 1200 mOsm/kg
40
What’s the role of the ascending loop of henle in the counter current medullary gradient ?
As the Ascending loop of henle ascends out the medulla into the cortex, its membrane becomes impermeable to water only allowing NaCl to leave
This increases water concentrations in the ascending loop which decreasing or balancing out NaCL
41
What are the strongest diuretics and where to they work?
Loop Diuretics
They work by selectively inhibiting NaCl reabsorption at the thick ascending limb (TAL)
( Where its impermeable to water loss)
42
What are the benefits of Loop diuretics ?
Do not develop acidosis
Puts patient closer to alkalotic state
43
What is the most efficacious diuretic ?
Loop Diureitcs
- Furosemide (Sulfonamide)
- cannot be given to those with sulfa allergy
44
Where does Furosmide target ?
Loop diuretic
Targets NaKCC2 transporter = More Na in the lumen to be put out in the urine and water will follow
- not absorbing Na leads to less absorption of Cl- and K+ = decreasing positive potential of lumen = decreasing Mg++ and Ca++ absorption (lost in the urine) must monitor this with long term use
45
What’s the biggest difference between Loop diuretics and Carbonic Anhydrase Inhibitors ?
Will not loose Bicarb with loop diuretics
-will loose K+, Mg+ , and Ca+ due to polarity change in lumen
46
Overall toxicity of Loop Diuretics ?
ALLERGIES - sulfa allergy
47
What’s the one loop diuretic that is not sulfa based and would be safe for a patient with a sulfa allergy ?
Ethacrynic acid
48
Where is the Distal convoluted tubule ?
After the ascending loop of henle back in the cortex
49
What happens in the distal convoluted tubule ?
Usually back to balanced osmolality of 300 mOsm/kg
-Little water movement
-Some sodium absorption via NCC co-transporter (Na, and Cl-)
Target for THIAZIDES
PTH works here
50
What is the MOA of Thiazides ?
Inhibit NaCl transport (NCC) in DCT (Distal convoluted tubule)
some inhibition of CA
Can all be given orally
Also sulfonamides - avoid with sulfa allergy
Not as efficacious as loop diuretics
SOME loss of Bicarb and K+
Prototype drug: Hydrochlorothiazide
51
How do we see most movement of fluid with diuretics?
Poly- Pharmacy
Ex : thiazides and loop diuretics - works synergistically to move lots of fluid by targeting different areas
52
What parts comprise the collecting tubule?
Leaving the nephron
Collecting tubule first then Collecting duct
NOT apart of the nephron
53
Where is the final site for sodium reabsorption ?
Collecting tubule
54
What area can we concentrate our urine ?
Collecting duct
- very dark yellow here Due to water absorption
55
Where is the most important site for potassium secretion ?
Collecting tubules
56
What kind of cells do we have at the collecting tubule and what do they do ?
Principal cells and intercalated cells
- Principal - sodium reabsorption based on aldosterone activity
- intercalated - buffers?
57
How and where does Cl- naturally drive out ?
Paracellular route of the Collecting tubules
-naturally collecting tubule brings in more Na than it allows K+ out (ENaC channel) this builds up a more negative (-) charge in the lumen-urine which increases the driving force for Cl- to leave - it does so through paracellular route
58
How do upstream diuretics affect downstream ?
Upstream diuretics result in excess Na+ in the collecting tubule
Upstream diuretics: CA Inhibitors, Loop Diuretcs, Thiazides - ALL block sodium reabsorption
- as more sodium comes in, more potassium leaves. (WASTING)
- Acetazolamide blocks NaHCO3 which further increases the net negative charge and increases K+ driving force to leave.
59
What is potassium wasting ?
Increasing the driving force of K+ to leave the cell specifically in the Collecting Tubule due to the decreased or inhibited reabsorption of sodium from upstream diuretics ( CA inhibitors, Loop diuretics, thiazides)
CA inhibitors (acetazolamide) also blocks the reabsorption of bicarbonate which increases K+ driving for even more
60
Where does aldosterone naturally work ?
At the collecting tubule
-secreted by Adrenal cortex
- increases Na+ and water reuptake via ENaC
- increasing blood volume and pressure
61
Potassium SPARING Diuretics ?
Spironolactone and Amiloride
62
How does Spironolactone work ?
Blocks aldosterone receptors
-slows down ENaC channel and increases Na in lumen with water too
-does not increase driving force of K+ = potassium sparing
63
How does AMILORIDE work?
Inhibition of Na+ flux through ion channels in luminal membrane
- also does not increase driving force of K+ wasting
64
Clinical uses for potassium sparing diuretics ?
Mineralcorticoid excess - overproducing aldosterone
CONN’s syndrome
CHF
Nephrotic syndrome
Use of other diuretics and low potassium
65
When do we not want to give potassium sparing diuretics ?
Patient taking potassium - Hyperkalemia - renal disease
Liver disease
66
What is the very bottom of the nephron ?
Collecting duct
67
What is the very bottom of the nephron ?
Collecting duct
68
What diuretic acts at the collecting duct (bottom)?
ADH (Vasopressin)
-increases water reabsorption
69
How does ADH work at collecting duct ?
Increases water reabsorption
Binds to receptors —> activates -cAMP —-> induces aquaporins to migrate to the surface side of lumen-urine (apical membrane) —> allow water to flow down its concentration gradient into the interstitium.
70
Where is the apical membrane ?
Membrane separating lumen-urine from collecting tubule
71
What is the antagonist of ADH and what does it do ?
Conviaptan
- decreases BP by blocking the production and migration of aquaporins by blocking receptor
- potassium sparking as well
72
What kind of drugs work on the entire tubule ?
Osmotic diuretics
73
Which loops are freely permeable to water ?
PCT and descending loop of henle
74
What is the use for mannitol ?
Intracranial pressure - primarily
Anytime you want to clear out the kidneys
-acute hemolysis , radiocontrast agents, removal of renal a toxins
75
What is mannitol (chemically ) ?
A sugar - alcohol
D - Glucose
76
ADME of Mannitol
Cannot be taken orally
Induces diarrhea
Not metabolized
Glomerular filtration 30-60 mins
No absorption - no secretion
Counters osmotic Force - increase urine volume - reduces Na reabsorption
77
Toxicity of Mannitol or Osmotic Diuretic ?
Extracellular volume expansion (congestion and hyponatremia prior to diuresis)
Dehydration
ACUTE Hypernatermia and Hyperkalemia
Hypunatremia with renal failure
78
How does Mannitol Crystalize ?
It’s a sugar solution that can precipitate and crystallize
- administer with in-line filter with high concentrations (>20%)
79
Most common reason for diuretic use ?
Peripheral or pulmonary edema
-CHF, kidney disease, hepatic cirrhosis, idiopathic edema
80
Non-edematous reasons for diuretics ?
HTN
Hypercalcemia
Urinary casts
Renal stones
Rhabdomyolysis
Diabetes Insipidus
81
What is Diabetes Insipidus ?
Insufficient ADH
-polydipsia ( thirst )
-polyuria
82
How do we treat DI and why ?
THIAZIDE Diuretics
Further depletion to decrease GFR
Increases NaCl reabsorption in PCT
(Due to Macula Densa sensing depletion )
83
MOA of Paradoxical effect of thiazides on Neurogenic Diabetes Insipidus?
Thiazides decrease tubular sodium reabsorption —> increases urinary excretion of Na+ —> decreases extra cellular volume —-> increases proximal sodium and water reabsorption —> decreasing distal delivery of Na+ and water —> decreases urine output .
(Increases sodium in DCT and decreasing delivery to distal segments - decreasing UO )
84
What determines airway resistance ?
Airway diameter
ANS input
- Greatest resistance is in medium bronchi
85
What’s the difference between the bronchi and bronchioles ?
There is no cartilage in the bronchioles - more likely to contract
86
What stimulates the bronchioles to contract ?
The vagus nerve via the ANS
87
What dilates the bronchioles?
Sympathetic nervous system activation
88
Obstructive disorders?
Asthma
Chronic Bronchitis
Emphysema
89
Can you grow out of asthma ?
Yes 30-70% of children grow out of it
90
What does a Histamine challenge test ?
Forced expiratory volume
Symptom free asthma adults - significant drop in forced expiratory volume
91
What is the hygiene hypothesis ?
We’ve been dirty humans for millions of years, couple hundred years ago we decided to be clean, now our bodies dont react the same
Get a dog
92
Asthma airway description
Widespread narrowing of the airways
- partially due to contraction of airway smooth muscle
- mucosal thickening
- mucus plugs
- wheezing, breathlessness , chest tightness, coughing late at night and early mornings
93
How do you diagnose Asthma ?
FEV1 ( Forced ecxipiratory testing over 1 second )
Or
PEF ( Peal Expiratory Flow)
94
How is the FEV1 test performed?
Using a flow meter - you check how much a patient can blow out in 1 second
Then administer histamine or methacholine (can lead to asthma attack)
FEV1 will fall significantly if they are asthmatic
95
Does Peak Expiratory flow increase or decrease as we age normally ?
INCREASES until about age 30-35
96
Does dead space increase to decrease with age in the lungs ?
Increased
97
Asthma treatment
Beta adrenergic and anti-inflammatory
98
What causes Asthma ?
genetics ( over 25 genes implicated)
Atopic *extrensic* - allergy
99
Type 1 allergic response process
Allergen —> inhaled —> dendritic cells interact with allergen —> present them on the surface of their cells with MHC2 receptor ( this activates inflammatory response) —> migrates to closest T-Helper 2 Cell —> releases interleukin 4 —> activates B-cells —> turn into plasma cells (produce antibodies) and memory cells (remember it forever) —> produces antibodies IGE —> bind to mast cells (Airway and intestinal tract) —-> antibody is then stuck to mast cells
100
Where does Dupixent act on the allergy pathway ?
Inhibits IL4 and B-cells
101
when do we have mast cell degranulation ?
Usually after second exposure to allergy
102
What leads to muscular contractions and cellular leakage in allergy or asthma reactions ?
Leukotrienes and histamine ( both GPCR’s)
103
what’s the reason for the early reaction decrease in FEV
Histamines, PGD2s, LTC4
104
What is the secondary reaction of an allergen due to ?
Leukotrienes - can happen several hours later
105
Histamines are generally more associated with what ?
More allergy than asthma
106
What is the arachadonic acid pathway ?
Pro-inflammatory pathway
107
What happens in the late response and when ?
2-8 hours
Sustained broncho-constriction
PDG2, Histamine, LTC4 AND cytokines
Proteases , neutrophils,
108
Is mucus good or bad ?
Good traps allergens and helps get rid of them
109
What dictates the viscosity of mucus ?
Water to glycoproteins
When it dries out it increases the viscosity making it harder to get out
110
Parasympathetic Neural Control of airways includes which nerve ?
Vagus nerve - maintains normal resting tone of airway smooth muscle
111
Airways are innervated by what ?
parasympathetic, sympathetic, and NANC
112
Parasympathetic activation stimulates what in the airways and has what effect ?
M3 receptors - Contracts airways
113
Sympathetic activity activates what receptor and produces which response in the airways?
B2 - Relaxation/ Dilation
114
What causes and asthma attack ?
Allergens, viral and bacterial infections, irritants ,medications, exercise, GERD, anxiety and stress
Activates Sympathetic and followed by Parasympathetic
115
What is Croup?
Acute laryngotraceobronchitis after viral infection
Common in young children
Seal - like bark
Self-limiting condition
116
What’s more severe asthma or COPD ?
COPD
117
COPD definition ?
Combination of chronic bronchitis and emphysema
118
What is emphysema ?
Permanent enlargement of the gas - exchange airways accompanied by destruction of alveolar walls without obvious fibrosis
119
Sympathomimetics in Asthma
Adrenergic agonist - B2
Relaxes airway
Helps cilia and
120
Epinephrine in asthma
SQ or inhaled
Maximum bronchodilation
Can increase HR
Also affects B2 - vasoconstricts = decreased laryngeal edema
121
Short Acting Beta 2 Agonist (SABA)
B2 selective
Albuterol
Terbutaline
122
LABA (Long acting)
salmeterol and formoterol
Last 12 hrs
Slowly release
123
Why do metered valve oral inhalation B agonist deliver more medication than dosed?
80-90% deposited in mouth or pharynx - only 20% getting to where it needs to be
124
Methylxanthines include what ?
Theophylline, Theobromine , Caffine
125
Theophylline MOA
PDE Inhibitor
Inhibits phosphodiasterase
126
The more we purify theophylline the more what ?
The More toxic it becomes
127
Muscarinic Antagonist for COPD or severe hyper re-activity diseases
Ipratropium
128
Can tea treat asthma ?
MILD cases can be treated by theophylline tea
129
What organ is monitored with theophylline ?
Hepatic function
Can also cause tremors.
130
What atropine derivative is used for COPD ?
Ipratropium bromide
131
Why would we select ipratropium bromide for asthma ?
if patient cannot tolerate pure beta agonist , No CNS affects. more used for COPD still
132
What long term medications is less effective in COPD?
Corticosteriods due to the long term chronic inflammation of the emphysema factor of COPD
133
Where is the gluco-corticoid receptor ?
inside the cytoplasm
134
What will the presence of glucocorticoids allow binding of ?
GRE Glucocortoid Response Elements
can be silencer (shut down production of genes) or enhancer (increase production of genes)
135
Increase in Annexin -1 (lipocortin-1) has what reaction ?
suppression of Phospholipase A2 - inhibiting leukocyte response of arachidonic acid complex
136
Increases in Leukoprotease inhibitor (SLP1) has what effect?
Leukoprotease Inhibitor (SLP1) will block protease enzymes released by WBC in secondary reactions
137
What is IL-10
Immunosuppressive - ANTI-INFLAMMATORY
138
What is NFkB ?
a pro-inflammatory cytokine
139
What effect will Glucocorticoids have on NFkB?
will repress them
140
Glucocorticoid effects ?
inhibit immune response by blocking transcription/translation
binds to GRE inside the cytoplasm
Increasing Annexin-1 --> this surppresses PLA2
Increasing Leukoprotease Inhibitor (SLP1)
Increasing iL-10 - antiinflammatory
and inhibiting NFkB
141
What infection comes from inhaled corticosteriods ?
Oropharyngeal candidiasis
142
Anti-IGE Monoclonal antibodies target what ?
IgE antibodies
wont activate IgE or induce mast cell degranulation
143
Whats an example of a IgE monoclonal antibody drug ?
Xolair
used for prevention - not active asthma attack
144
What drugs can be given to inhibit the Leukotriene pathways of arachidonic acid ?
Zileuton - inhibit lipoxygenase
Montelukast & Zafirlukast - inhibit binding to the receptor
145
Drug classes for both Asthma and COPD ?
SABA , LABA
Inhaled Corticosteriods
and phosphodiasterase inhibitors
146
Treatment standard for COPD ?
LABA and LAMA
long acting Beta -2 adrenergic agonist and Long acting muscarinic antagonist
147
Why are IgE less safe?
Can cause anaphylactic reaction to occur.
148
Pruritis can be what kind of reaction ?
Neuropathic or psychogenic
149
Tell me about Histamine
Mediator of allergic and inflammatory response
rapidly stored or inactivated
in vesicles inside Mast cells , neurotransmitter in the brain and in our stomach
150
How many types of histamine receptors do we have ?
Histamine 1 - 4 type receptors
151
Histamine receptors are all what ?
G-protein stimulated
152
Histamine of the Nervous system and effects ?
H1 and H3 - pain and itching
153
What is the Wheal and Flare effect ?
Histamine effects to allergen Triple response with allergy test .can lead to anaphyalactic reaction
Wheal = welt/swelling = positive test
Flare = reddness around the area
Itch due to increased nerve endings
154
Histamine in the stomach does what ?
releases Hcl
155
Anti-Histamine causes what in the CNS ?
DROWSINESS
156
Anti-muscarinic effects of H1 receptor Antagonist and which class?
Urinary retention ,
First generation
157
5HT (Serotonin) causes what ?
constriction of blood vessel , Platelet clotting Process
158
where is most of the serotonin in our body ?
90% in the gut in Enterochromaffin cells
159
Serotonin in the brain has what role ?
Mood, sleep, appetite....
160
Where is Serotonin created in the brain ?
Raphe Nuclei
circulating throughout the entire cerebral spinal fluid
161
What is the 1 Ion channel of serotonin receptor family ?
5-HT3
162
5-HT3 induces what ?
Nausea
163
Serotonin Agonist targets and the receptors ?
5-HT1A - Raphe , Hippocampus
5-HT1B - Basal ganglia
5-HT1D Brain
164
5-HT Antagonist targets ?
5-HT 2A Platelets, smooth muscle cerebral cortex
5-HT3 - sensory and enteric
165
Buspirone is used for what ?
anti-anxiety w/o drowsiness
partial agonist
166
low energy is associated with what diagnosis ?
Depression
167
High energy is associated with what diagnosis ?
anxiety
168
What causes Migranes ?
unknown for sure but related to CGRP , Sub P, trigeminal Nerves
169
Treatments of migraine ?
ASA + Caffiene, NSAIDS
triptans - 5HT agonist 1B/1D**
Ergotamine - less effective - from a poison fungus
anti-nausea and glucocorticoids
170
Where do triptans work for migraines ?
1B/1D - in cranial blood vessels - prevents dilation
treats pain and aura
171
Prevention of Migraines
Beta Blockers, Anti-depressents, anti-seizuere, BOTOX, MABs- AIMOVIG -CGRP
172
What kind of medication is AIMOVIG ?
MAB's - CGRP
173
Triptan toxicity with MAOi's and SSRi's can lead to what ?
Serotonin syndrome
174
What are symptoms of Serotonin Syndrome ?
HTN, tremors, hyperthermia, hyper active bowel sounds, mydriasis agitation , coma
175
What are treatments of Serotonin Syndrome ?
Sedation with benzo's, paralysis , intubation & ventilation
176
What symptoms do serotonin syndrome , malignant hyperthermia, and neuroleptic malignant syndrome ?
HTN and hyperthermia
177
What causes Serotonin Syndrome ?
anything that increases Serotonin and other drugs
like st johns wart
178
What treats Neuroleptic malignant syndrome ?
Diphenhydramine ( Benadryl)
179
What treats Malignant Hyperthermia ?
Dantrolene - a muscle relaxent
180
What causes MH ?
the continued opening of RyR receptors
181
What Serotonin drugs were used to treat obesity ?
5-HT2 AGONIST - Fen-Phen - withdrawn
5-HT2c agonist - Lorcaserin -withdrawn
182
Why was Fen-Phen and Lorcaserin removed from the market ?
side effects of arrythmias
183
What does obesity lead to ?
metabolic syndrome- increases pressure and risk of diabetes and cardiovascular disease
184
What are newer non-serotonin weight loss drugs ?
GLP-1 - Liraglutide
GI Lipase inhibitor - Orlistat
185
What are some serotonin antagonist drugs?
Phenoxybenzamine
cyproheptadine
186
What the actions of serotonin antagonist drugs?
surppess 5-HT2
187
What receptor does zofran work on ?
5-HT3 inhibitor
only ion channel
188
Study of ondesteran has been shown to limit what after spinal anesthesia ?
decreased nausea and blood pressure
189
Dopamine has how many receptors and what kind?
D1-5
ALL metabotropic
190
D1 receptors are found where ?
postsynaptic
191
D2 receptors are where ?
Pre-synaptic and autoreceptors
192
NIgrostriatal is used for ?
motor movement
193
Mesolimbic system controls what ?
addiction and reinforcement
194
Mesocortical pathway controls what ?
working memory and planning
195
Depression facts
fourth highest cause of disability worlwide
women are more affected (2x as often as men)
196
Anxiety facts
women are still twice as likely
197
SAD is what ?
Seasonal Affective disorder - depression with less sun
198
Major classes of Anti-depressants
SSRi's - Selective serotonin reuptake inhibitors
SNRi's - NE reuptake inhibitors
TACs - Tricyclic antidepressants
MAOi's - Monamine Oxidase inhibitors
199
Which anti-depressent has the most side effects ?
MAOi's
200
All anti-depressents increase what ?
monamine neurotransmitter levels within the synapse
201
SSRi's MOA ?
inhibition od SERT (serotonin transporter)
increases serotonin in the synapse
202
SSRi's drugs
Przac, Celexam Paxil, Zoloft, Lexapro
203
SNRi's MOA
inihibit SERT and NET
204
TCA's MOA /
inhibit SERT, NET m and some anticholinergic effects
205
MAOi's MOA ?
used for refractory depression unresponsive to other meds
Rarely used due to lethal drug interactions
206
What MAOi is irreversible ?
NARDIL - Phenelzine
207
Anti-depressent sites of action
SSRi- SERT
TCA's - SERT, NET - widespred surppression of nervous system
MOAi's-
208
What do all MAOi's have a risk of ?
SUICIDE
especially with younger people
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Newer Anti-depressants
Wellbutrin , Sunosi
210
NDRi's MOA
inhibits NE and DA reuptake
used for depression, ADHD, GAD. and daytime sleepiness
211
Benzodiazapines MOA and concerns
suppress anxiety
sedative - impaired cognitive function
212
Alternative Treatments for depression/anxiety
Psychotherapy - talk therapy
Electroconvulsive therapy
St. John's Wort
213
What is the top selling botanical product in the US ?
St Johns worts
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What is the idea behind electroconvulsive therapy ?
resetting chemical pathways in the brain
215
NDRi have no effect on what neurotransmitter ?
no effect on Serotonin !
216
Definition of Seizures ?
abnormal discharge of cerebral neurons
217
What can GABA do to Glutamate
GABA can shut down glutamate
218
What two neurons mainly control brain activity ?
GABA and Glutamate
219
What is trephening ?
drilling into the skull to prevent seizures , no longer used
220
Other old treatments of Seizures ?
trephening
cupping
herbal remedies
animal extracts
221
Anti-seizure medications main MOA ?
voltage - operated ion channels and excitatory synaptic function
ion channels
GABA and Glutamate targets
222
Which Ions are targeted with anti-seziure medications ?
Na+
K+
Ca++
223
Inhibition with anti-seizure medications include what ?
enhancing inhibition of GABA
inhibiting excitation (Glutamate)
224
What are the three classifications of Seizures ?
Focal Aware
Focal Imparied Awareness
Focal to bilateral tonic-clonic
225
What are drop attacks ?
Atonic or tonic seizures
226
SIMPLE Focal Seizures have what kind of discharge ?
minimal
does NOT affect consciousness or awareness
EEG may be normal
227
COMPLEX focal Seizures
affect level of consciousness
may become unresponsive/loss of consciousness
228
Generalized Seizure brain activity ? And affect on animals?
begin over entire surface of brain
patients have AURA
animals can note these
229
Absent seizures are ?
generalized - petite mal
stare into space - wake up with no notice of seizure
230
Tonic versus Atonic
TOnic - muscles suddenly contract/stiffen
Atonic - loss of muscle tone
231
Clonic and Myoclonic seizures
make body jerk like it is being shocked
232
Phenytonin (Dilantin)
oldest non-sedative drug - most effective
Alters Na+, K+, and Ca+
Fosphenytonin - more soluble prodrug of phenytonin
233
Seizure drug classifications
focal seizures and Generalized tonic - clonic seizures
234
Benefit of Fosphenytonin ?
Can be given IV and IM - Phenytoin cannot
235
Why is Phenytonin so toxic ?
very highly protein bound - can increase free form phenytonin if given with other drugs
LONG Half life 12-36 hr
236
Therapeutic Phenytonin levels ?
therapeutic = 10-20 mcg/ml
Free = 1-2.5 mcg/ml
toxic = 30-50 mcg/ml
lethal = >100 mcg/ml
237
Phenytonin competes with albumin binding with which drugs ?
Carbamaepine, Sulfonamides, Valproic Acid
238
Carbamazepine is effective in what ?
Trigeminal Neuralgia
239
What drug class does Carbamazepine belong to ? what else can it be used for ?
TCA - depression and Bipolar disorder as well as seizure treatment
240
Trigeminal Neuralgia signs and symptoms ?
Lightning , shocking, aching, burning , tingling, stabbing , crushing, throbbing, on ONE side of the face
241
Carbamazepine half life
initall dose 36 hours, then 20 hours after continuous therapy
242
Lacosamide (Vimpat) efficacy ?
near equal efficacy at different doses
targets Na+ channels
focal seizures
243
Phenobarbital availability ?
SEDATIVE - Oldest and currently available - safest - SEDATIVE
unknown MOA - Maybe enhances GABA
Drug of choice for babies
244
What drug has been tried on every seizure type ?
Phenobarbital
245
What seizure is phenobarbital not useful for ?
generalized seizures, absence , atonic attacks, or infantile spasms
246
Lyrica is used for what ?
FOcal Seizures - popular
247
Which anti - seizure medication can a patient get high off of ?
GABApentin
248
Oral medication for generalized seizures , that inhibits calcium channels ?
ETHOSUXIMIDE
Ca+ channel inhibition
249
Most widely used drug for seizures ?
VALPORIC ACID
250
Broad specturm AED is what ?
used for many seizures - VALPORIC ACID - DEPAKENE
251
Valporic acid has what effect on phenytonin ?
displaces pheytoin from proteins
252
Benzodiazepines used for seizures ?
Valium
Ativan
Klonopin
for status epilepticus, absence
depresses ALL CNS levels- increases GABA
253
Infantile Spasm treatment ?
developmental disorder
palliative treatment with prednisone and GABA analog
254
Diagnosis of Seizures ?
History - patient or eyewitness
physical / neuro exam
EEG
255
Most common form of status epilepticus ?
Generalized tonic-clonic
life threatening
256
Low Ketogenic diet does what for children ?
decreasing carbs/glucose source to decrease frequent firing of neuronal excitation
257
Status Epilepticus treatment
IV anti- seizure medicatons
Diazepam/Lorazepam
fosphenytoin
Phenobarbital for unresponsive
258
Surgical treatment of status epilepticus ?
Craniotomy - resection of epileptic foci
259
Lamictal (Lamortrigine)
Ion channel blocker for focal seizures
260
GABA analogs
Gabapentin , pregabalin , vigabatrin
increase GABA
adjunct, neuralgia, infantile spasms
261
What narcotic stimulates seizure activity ?
DEMEROL (meperidine)
262
Sedative -Hypnotics cause what ?
deep sleep / hypnosis
263
Sedative classifications ?
Benzo's
Barbituates
Sleep aids
Anxiolytics
Ethanol
264
Sedative - Hypnotic MOA ?
inhibition at all levels of CNS
increase flow through ion channel (Cl-)
increased channel opening time (Cl-)
265
Hypnosis effects care categorized as ?
desirable
decreased time to sleep
increases stage 2 NREM sleep
less desirable
decreased REM
Decreased stage 4 NREM slow-wave sleep
266
newer sedative - hypnotics have less effects where ?
on deep sleep
267
REM or NREM
Rapid eye movement
non-rapid eye movement sleep
268
REM is what ?
close to being awake
269
Which stage of sleep is more "restful"?
REM
associated with dreaming
270
Flumazenil reverses what ?
BENZO's
271
what did propofol replace?
Thiopental and methohexital
272
Additional effects of sedative hypnotics ?
Anticonvulsants
muscle relaxants
respiration and cardiac function (minimal)
273
Rate of oxidation of alcohol ?
ZERO ORDER KINETICS
independent of time and concentration
7-10g (150-220 mmol) per hour
274
Alcohol abuse is defined as ?
used in dangerous situations and despite adverse consequences
275
Alcohol dependence is defined as ?
characteristics of alcohol abuse and physical dependence on alcohol
276
Legal alcohol limits
0.08% -
Chronic drinkers can reach 0.3-0.4% and remain high functioning
277
Pathways to metabolize acetaldehyde ?
alcohol dehydrogenase
and
microsomal ethanol - oxidizing system (MEOS)
278
MEOS breaks down acetaldehyde more in which drinkers ?
chronic alcohol use
279
Alcohol dehydrogenase pathway
Ethanol is broken down by NAD and alcohol dehydrogenase = NADH --> travels to electron transport chain (ETC) wheres its used to make ATP
this increases our energy and caloric intake
280
what decreases alcohol dehydrogenase activity ?
FORMEPIZOLE -
used for toxic alcohol poisoning
281
What are the Two Main types of GABA Receptors that sedatives work on ?
GABA - A
GABA - B
282
How many binding sites are there for GABA ?
TWO
283
What happens when GABA binds to the two binding spots on its receptor ?
Opens channel , allows for Chloride influx - HYPERPOLARIZES the cell
284
Sedative - Hyponotoics potentiate inhibition where ?
At all levels of the CNS
by increasing flow through the channel or keeping the channel open longer
285
What is stage 4 of sleep ?
NREM - slow wave sleep
deepest level of sleep
286
What does a Hypnogram graph ?
stages of sleep
287
Majority of our time sleeping is spent in which stages ?
Stage1 and Stage 2
288
Alcohol sleep puts us in what stage sleep faster ?
NREM - Stage three
reach this stage faster and stay here longer
289
Alcohol sleep also give us what ?
more vivid dreams
290
Why is alcohol sleep not as "restful"?
we dont spend as much time in REM sleep
291
What is propfol prepared in?
emulsion of soy and egg
patient with allergies cannot have it
292
What is the most commonly abused drug ?
alcohol
293
How does alcohol tolerance build up ?
based on how fast we can break down alcohol
294
What is Acetaldehyde ?
toxic compound that leads to headaches, nausea, vomitting etc
295
What is Acetaldehyde broken down by ?
Aldehyde Dehydrogenase in moderate amounts
296
MEOS is developed when ?
over time and produced NADPH
297
"Beer bellies" are usually formed with which ethanol breakdown pathway ?
Alcohol dehydrogenase pathway
298
MEOS pathway requires what ?
NADPH+ as reducing agenet - reduces oxygen from water. Not producing NADH so they have less calories- less weight gain- thinner
299
What is NADH a precursor for ?
ATP - energy
300
Pain pathways with ethanol ?
GABA
Glutamate - NMDA inhibition
301
Chronic use of ethanl is associated with what progression ?
LIVER DISEASE
Alcoholic Fatty Liver
hepatitis
Cirrhosis
Liver failure
302
Tolerance , Dependence , Addication differences?
Tolerance = more drug to get inital effect
Dependence = Body is now reliant on drug (Physical )
Addiction = (MENTAL ) dopamine mental effects- will seek out drug regardless of consequences
303
Wernicke-Korsakoff Syndrome is what?
Thiamine deficiency found in chronic alcoholics - due to getting more nutrients from alcohol than food
tx: thiamine therapy
304
Average blood alcohol in fatal cases is what ?
greater than 0.4%
305
Chronic alcohol treatment ?
banana bag
thiamines, folate, magnesium , and multivitamins
306
Alcohol withdrawl syndrome symptoms ?
miild - anxitey , insomina , sweating x 1 day
severe = seizures , fever, hallucinations 1-5 days
Delirium Tremens - pateint can die
307
Naltrexone is for what ?
long acting opioid and alcohol antagonist
308
Acamprosate treats the desire for alcohol how ?
increases activity of GABA channels
usually adjunct therapy
309
Treatement of alcohol targets?
anxiety - Buspirone
Sleep problems - Ambient and lunesta
310
"Date Rap" drug is what ?
Benzodiazepines
311
Where does dupixent work ?
inhibits the release of IL4 (interleukin 4) in the immunologic pathway of allergic reactions and Asthma
312
What ion does Phenytonin inhibit ?
**Na**+ , K+, and Ca+
313
What ion does ethosuximide inhibit?
Ca+
314
What ion does Lacosimide inhibit ?
Sodium Na+
315
What ion does Phenobarbital inhibit?
increases GABA = increasing inhibition
316
What ion does carbamezipine inhibit ?
Na+
317
Which anesthetic drugs can increase seizure activity ?
Methohexital and Sevoflorane
318
