Pharmacology Flashcards
What is the 60/40/20 rule for body water?
60% of body weight is total body fluid
40% of BW is intracellular fluid
20% of BW is extracellular fluid
What are the 2 compartments within ECF?
Intravascular—>blood (7% of BW/25% of ECF)
Extravascular—>interstitial fluid (75% of ECF)
Where and how does diuretics work on? ICF or ECF? and it is equivalent to?
Force renal output—>shrink intravascular volume (ECF)—>decrease CO—>decrease BP
Equivalent to decrease Na intake
Total body fluid increase or decrease as ones ages?
Decrease from 75% of BW to 50% (most shrinkage occurs in ECF)
Is the osmolarity of ICF and ECF same or different?
Same
What are the equations for BP or CO?
BP = TPR x CO CO = HR x SV
How large are the CO going through kidneys/RBF/RPF/GFR?
20% of CO perfuses the kidneys
1/2 of RBF is RPF
20% of RPF is GFR (125 ml/min)—>filtration fraction (FF)
Is there urine production if RBF is zero?
NONE
What happened when you drink a lot of water or sodium?
ECF expands—>increase renal output of water and sodium
In healthy individual, renal output of Na matches?
Dietary intake of Na
Edema is a shift of fluid from ___ to ___?
Intravascular to extravascular
Hydrostatic pressure does? oncotic pressure does?
Push fluid out of the capillaries/push fluid into the capillaries
The ultrafiltrate of glomerulus has similar composition to plasma except?
Without protein
What is the equation for excretion? and what is the fraction of excretion of water and Na(FEwater/FEsodium)?
Excretion = filtration - reabsorption + secretion
1%
___ and ___ of kidney are impermeable to water, which results in?
Thin and thick ascending limb—>reabsorb solute w/o water—>dilute the tubular fluid (osmolarity decreases)
___ drives the solute transport and maintain the counter current multiplication
Thick ascending limb
The clearance rate of ___ is the GFR? and it is similar to endogenous __?
Inulin (amount filtered = amount excreted)/creatine
What does it mean when FEwater > or
> 1%—>positive water balance
negative water balance
Fractional reabsorption is = ?
1 - FE
Is sodium ever secreted in the kidney?
Never
Aldosterone increase __ reabsorption and ___ secretion?
Na/K
We have normally a high or low K diet? which results in?
High K diet/aldosterone secretes K into the tubule
How does hypokalemia happens during alkalosis?
Proton comes out of the cells and K goes into the cell—->increase K secretion in kidneys
The faster the flow through the collecting duct, the ___ of the rate of secretion of K into the tubule
Higher
If creatine excretion is going up, what does that tell you about the GFR?
It is going down (kidney is sick)
Reabsorption of Na increases or decreases as Na goes from Loop of Henle to the Collecting duct? and what happens if a diuretics is used?
Decrease/diuretics blocks Na reabsorption—>different part of the tube will try to compensate by reabsorbing more Na
Na reabsorption is coupled with ___ in the late distal tubule and early collecting duct?
K secretion
Diuretics (non K sparing) cause hyper/hypokalemia?
Hypokalemia
What drives the Mg and Ca from the tubular fluid into the blood at thick ascending limb of loop of Henle? what if you block the Na/K/Cl channel with a diuretics?
The positive (+7) voltage difference in the tubular fluid created by the Na/K/Cl channel--->push Mg and Ca out of the tubular fluid Increase Mg and Ca in the tubular fluid for excretion
What does it mean when U/P (urine osmolarity over plasma osmolarity) >1 or
> 1—>urine is hypertonic—>free water clearance is negative—>kidney is retaining water
urine is hypotonic—>free water clearance is positive—>kidney is eliminating water
ADH increases when plasma osmolarity rises or falls?
Rises
What transporter is responsible for Na reabsorption in early distal tubule? and what blocks it?
Na-Cl cotransporter/thiazide diuretics
ADH acts on what parts of the kidney?
Late distal tubule and collecting duct
When you eat a lot of Na, your ADH is high or low?
Low
In the late distal tubule and collecting duct, increase ADH results in?
Increase Na reabsorption—>increase Na/K ATPase on the blood side of the luminal cell—>increase intake of K into the cell—>increase secretion of K out of the cell into the tubular fluid
Conductance equals to ?
1/resistance
Can AP opens an inactivated gate?
No
Which phase does the heart muscle contracts?
The plateau phase of the AP
What is the AP of pacemaker cells in the SA and AV node that is different from the rest of the heart muscle cells?
Slow response AP
Hypo/hyperkalemia causes hyper/depolarize?
Hypokalemia—>hyperpolarize (increase threshold)
Hyperkalemia—>depolarize (decrease threshold)
Threshold potential depends on?
Resting membrane potential/Na current availability/cell size
Resting membrane potential depends on which ion?
K
What is the level of hyperkalemia affect the excitability?
Moderate—>increase excitability
Severe—>decrease excitability (too much depolarization—>decrease K conduction)
What is effective/relative/functional refractory period?
Effective—>can’t be stimulated with an AP
Relative—>can be stimulated but need a bigger AP
Functional—>combination of effective and relative
Heart muscle cells and pacemaker cells depends on what ions for AP?
Heart muscle cells—>Na
Pacemaker cells—>Ca
Which cell has faster conduction speed, heart muscle or pacemaker cells?
Heart muscle cells
Sequence of conduction in the heart
SA node—>AV node—>purkinje fibers
Cardiac contract is dependent on?
AP duration
Tackycardia increases or decreases CO?
Decreases
Stretching sarcomere length increase ___ but over stretching causes?
Increase contractility/decrease in contractility
SV = ?
end diastolic volume - end systolic volume
Ejection fraction = ?
SV/EDV
How does diuretics work?
Increase urine output by decreasing active reabsorption of the solutes
Initial affect—>maintenance of the new baseline (body fights back)
Which kind of diuretics mimic diabetes insipidus? and how does it work?
Aquaretics—>decrease the ability of ADH to increase the water permeability of the late distal tubule and collecting duct
How does saluretics work?
Decrease solute reabsorption
How does osmotic diuretics work?
Raise osmolarity of tubular fluid—>oppose water reabsorption
What are diuretics used for?
HTN/edema/hyper or hypocalcemia or kalemia
Where is bicarb reabsorbed in the kidney?
Proximal tubule
What is the affect of loop diuretics on water regulation of the kidney?
Keeping the osmolarity of the urine close to that of the plasma—>decrease both + and - free water clearance—>takes the pt longer to get rid of/conserve water when he is volume overloaded/dehydrated
Thiazide diuretics only affect + or - free water clearance?
+
Which has a higher chance to cause hyponatremia, loop or thiazide diuretics?
Thiazide diuretics
What diuretics work on proximal tubule?
Carbonic anhydrase inhibitor/osmotic diuretics/aminophylline
Excess glucose is like what kind of diuretics?
Osmotic
What diuretics work on thick ascending limb?
Loop
What diuretics work on early distal tubule?
Thiazide
What diuretics work on late distal tubule/collecting duct?
K sparing/vaptans
How is bicarb and Na reabsorbed in the proximal tubule and what block this?
Na comes in and H+ goes out to the lumen—>bicarb + H+ becomes carbonic acid—>then disassociate into H2O and CO2—>CO2 comes into the cell and combine with water to form carbonic acid and then disassociate into H+ (goes out again) and bicarb—>bicarb is transported into the blood/carbonic anhydrase inhibitor (carbonic anhydrase facilitate the disassociation and association of bicarb and carbonic acid)
What is carbonic anhydrase does to ammonia excretion?
Decrease ammonia excretion—>causes hepatic encephalopathy
Which loop diuretics does not have a sulfamoyl group?
Ethacrynic acid
How does the body counter the increase of Na excretion created by diuretics?
Decrease GFR (decrease filtering load of Na)
How does hypokalemia happens with loop diuretics?
Late distal tubule and collecting duct trying to compensate for excess Na in the tubular fluid by reabsorbing Na—>increase K secretion—>hypokalemia
Thiazide decrease or increase Ca reabsorption and results in?
Increase/prevent Ca stone in the tubules
What is the pathology of nephrogenic diabetes insipidus?
Collecting duct and late distal tubule fail to response to ADH
What does Li do to the distal tubule and the collecting duct? what is used to treat that?
Make them fail to response to ADH (like diabetes insipidus)/K sparing—>might need to decrease Li dosage
Why do loop and thiazide diuretics cause hyponatremia?
Decrease + free water clearance
Response to volume contraction/expansion happen only at what part of the kidney?
Distal tubule and collecting duct
Where in the kidney do amiloride and triamterene secreted into the tubular fluid?
Proximal tubule
High or low Na diet is needed for spironolactone to work?
Low Na diet—>volume contracted—>ADH is released
Does the activity of spironolactone depends on GFR/tubular secretion and con.?
No (act inside of the cell)
Can we use diuretics for renal disease and nephrotic syndrome? and what should we be aware?
Yes/need to increase dose of diuretics
Hypokalemia can be an indication for ___ and ___?
Renal artery stenosis/hyperaldosteronism
Should you treat a younger HTN pt more aggressively or conservatively?
Mosre aggressively
HTN can causes LV hypertrophy, which is called ___?
End organ disease
What are the 5 factors associated with cardiac disease?
Smoking/diabetes/cholesterol/family history/HTN
How does alpha receptor decreases BP?
Alpha receptor—>vasoconstriction
Block alpa—>decreases peripheral resistance
What are the 3 factors that stimulate renin release?
Low CO/low volume/sympathetic tone (NE and epi)
Potency of diuretics in descending order?
Loop>thiazide>K sparing
What causes the dry cough from ACEI?
Bradykinin (prevent breakdown)
Why can’t you use dihydropyridine Ca channel blocker for anti-angina?
It causes reflex tachycardia—>increase O2 demand—>worsen angina
Couple Ca channel blocker with ___ to lessen leg edema
Diuretics
Which Ca channel blocker decrease HR/AV node conduction/contractility?
Non-dihydropyridine
Primary mechanism of beta blockers?
Reduce CO
For otherwise healthy pt with HTN, give what first?
ACEI—>get cough—>switch to ARB
For obese pt with HTN, give what first?
Thiazide
Is the airway obstruction reversible for asthma? and it is driven by TH_ cells?
Yes/TH2
Are allergen is only type of substance that can cause asthma?
No, cold air and exercise can also cause asthma
Beta 2 binds to Gs or Gi protein?
Gs
Most beta 2 agonist is a mix of R and S isomer, which isomer exerts beta 2 agonist effects?
R
How is long acting beta 2 agonist long acting?
Highly lipid soluble and binds to a 2nd site
How does paradoxical bronchospasm occurs?
Prolonged use of beta 2 agonist
Which M receptor is responsible for the effect of antimuscarinic agents on COPD?
M3
What is the first line treatment for chronic stable COPD?
Tiotropium
What is the mechanism of methylxanthine?
Inihibit breakdown of cAMP—>increase intracellular cAMP—>bronchodilation
Roflumilast mechanism?
Inhibit PDE4—>prevent neutrophil migration
When to use anti-inflammatory corticosteroid for COPD? what is the risk for?
For severe COPD with frequent exacerbation/pneumonia
Steroid sensitivity can be restored with low dose of ?
Theophylline
Which way is better for delivery, metered dose or dry powder?
Dry powder (no need to coordinate)
What is the first line treatment for persistent asthma?
Inhaled corticosteroids
What to give for COPD and asthma exacerbation?
Corticosteroid/short acting beta 2 agonist/antibiotics for COPD
Shear stress on the coronary vessels causes vaso__?
Vasodilation
Is angiographic test a diagnostic test for heart ischemia?
No/test to show the presence of coronary narrowing
What happens to the extracellular K level during ischemia and how does it happens?
Extracellular K level goes up/increase K leak outwards during AP
What happens to the extracellular phosphate/lactate/fatty acid?
Increases (MI causes symp activation—>increase fatty acid)
What is systolic injury current (subendocardial injury) and what does that cause on EKG?
Shortening of AP in ischemic cells—>ischemic cells are more negative than normal cells—>positive current flow from normal cells to ischemic ones/ST depression on EKG
What is stress test used for and what is the goal?
Diagnosis of ischemia/85% of max HR
If baseline EKG is not normal then what should be added to diagnose ischemia?
Echo and nuclear tracers
If the pts can not exercise, what should you do to diagnose ischemia?
Use dobutamine (beta 1 agonist) to stimulate the heart like it is exercising/use vasodilator to create perfusion mismatch and then detect using radioactive tracer
Why clopidogrel is not used for long term use?
Stronger than aspirin—>more risk for bleeding (except for severe vascular disease pts)
Which antiplatelet drugs can be used for pt with liver dysfunction?
Ticagrelor
What is the box warning for ticagrelor?
Aspirin maintenance dose has to be under 100mg
Which substance does ACE help degrading?
Bradykinin
How does hyperkalemia caused by ACEI?
Decrease aldosterone
How does beta blocker causes decreased exercise tolerance?
Not be able to reach high HR and CO
Affect of nitrate on cardiac function?
Increase myocardial O2 supply/venous dilation—>decrease preload
Difference between the 1st and 2nd gen dihydropyridines?
1st gen has negative inotropic effect (decrease heart contractility) and reflex tackycardia/2nd gen does not have those (less reflex tacky)
Non-dihydropyridines have negative ___ effect
Inotropic (decrease contractility)
What is the definition of congestive heart failure?
Inability to pump blood at a rate that required to supply tissues (inability for the heart to keep up)
What are class I to IV of heart failure?
Class I—>pts with cardiac disease but w/o limitation in physical activity
Class II—>cardiac disease with slight limitation
Class III—>marked limitation
Class IV—>inability to carry out physical activities w/o discomfort
___ reduce readmission with chronic heart failure pts
Exercise
LV dysfunction w/o intervention will get?
Worse (cardiac remodeling)
What is responsible for cardiac remodeling of heart failure?
neurohormonal (e.g. NE/aldosterone/angiotensin II)—>target these to prevent heart failure
What are stage A and B of development of heart failure and how to manage?
Stage A—>high risk for HF w/o structural heart disease nor symptoms—>treat underlying conditions (use ACEI or ARB)
Stage B—>structural heart disease no symptoms of HF (ACEI or ARB)
What are stage C and D of development of heart failure and how to manage?
Stage C—>structure disease with HF symptoms (ACEI/diuretics/beta blockers)
Stage D—>refractory HF (hospice)
Main effect of ACEI?
Artery and vein dilation—>increase CO and exercise tolerance
CHF/LV dysfunction, first line treatment? what about ischemic heart disease?
ACEI/aspirin, beta blockers, statin
Mechanism and benefit of angiotensin receptor blockers over ACEI?
Block angiotensin II type 1 receptor (AT1)—->usually used to replace ACEI because of the cough
Inhibit angiotensin II’s effect on symp tone—>dilate vessels
Treating HTN, use diuretics with combo of ___?
ACEI or beta blockers
___ dose of aldosterone antagonist is used for class III and IV of CHF to reduce death
Low (because the side effect of hyperkalemia)
Eplerenone does not have side effect of ___ comparing with spironolactone?
Gynecomastia
Why is beta blockers used for reduction of mortality in CHF?
Anti arrhythmic/inhibit negative cardiac remodeling
Digoxin increases intracellular ___ and ___ level and has a ___ inotropic effect?
Na and Ca/positive
What is the toxic effect of digoxin?
Cardiac arrhythmia
When is digoxin used?
For pt who is admitted into the hospital and had a previous decompensation episode
What does diuretics aim to and does it inhibit negative cardiac remodeling?
Treat symptoms/no
Low dose dobutamine stimulate ___ receptor and high dose stimualte ___ receptor?
beta 2—>vasodilation/alpha—>vasoconstriction
What is the effect of milrinone similar to?
Dobutamine—>increase HR/contractility/vasodilation
Dobutamine and milrinone, which drugs develop tolerance?
Dobutamine
Management of acute decompensated heart failure?
Diuretics for symptoms, use inotropic to improve CO and symptoms but long term worsen outcomes
Which surface protein of chylomicron activates plasma lipoprotein lipase (or CPL) that hydrolyze chylomicron?
ApoCII
Where is VLDL produced and how it is degraded?
Endogenously produced by liver/hydrolyzed from VLDL to IDL to LDL (mainly cholesterol by now)
Which ligand on the surface of LDL is responsible for taking LDL back into the liver?
Apo B100
What are the 3 effects of free cholesterol in the hepatocyte recycled by the liver from LDL?
Decrease HMG CoA reductase—>decrease cholesterol synthesis
Increase ACAT—>for storage of cholesterol esters
Decrease LDL receptor—>decrease uptake of LDL
What is the enzyme used by HDL to get cholesterol from peripheral tissues and bring them back to liver?
LCAT
How does atherosclerosis plaque developed?
Endothelial damage (HTN)—>inflammation response—>LDL deposition—>LDL oxidation—>macrophages swallow LDL—>foam cells—>smooth muscle cell joins—>plaque
Serum cholesterol increases with __?
Age
3 major risk factors for atherosclerosis?
Age/BP/smoking (decrease HDL)
3 major factors that increase HDL level?
Estrogen/exercise/alcohol
How to manage pt with moderate high lipid level?
Lifestyle and diet change first
What is the mechanism of nicotinic acid?
Lower VLDL secretion from liver and increase HDL
Fibric acid derivatives enhance ___ that stimulate ___ clearance?
LPL (or CPL)/TG-rich lipoprotein (like VLDL/chylomicron)
Possible beneficial effects of statins?
Counteract osteoporosis/cardioprotective
Statin is given with __ to have synergistic effect?
Ezetimibe
Statin should not be given with ___ due to ___?
Fibrates/increased risk of myositis
Electrolyte imbalance causes ___ and ___ waves in ECG?
U and J
What are the 2 mechanisms of arrhythmia?
Automaticity and conduction
Where is the ectopic activity usually located in the heart?
Purkinjie
Which 2 phases do pacemaker cell AP lack?
phase 1 and 2
How does early afterdepolarization occur?
Inhibit K current/inhibit Na inactivation current/increase Ca current—>another AP might be generated after depolarization
What are the 2 triggered activity of abnormal automaticity?
EAD and DAD
What are the 2 major factors that decrease conduction velocity and cause arrhythmia?
Low Na current/increase gap junction resistance
What are the 3 general mechanism for cardiac arrhythmia?
Enhanced automaticity/triggered activity/reentry
What is reentry arrhythmia?
A propagating impulse fail to die out and travel back in a circular path to re-excite the heart after refractory period is ended
What is the concept behind class I anti arrhythmic drug?
Block the unidirectional block of reentry to a full block and break the circular path of reentry
Hyper or hypokalemia causes bradycardia?
Hyperkalemia
What does sick sinus syndrome cause?
Bradycardia
What is 1st/2nd/3rd degree AV block?
1st—>prolonged PR interval
2nd: not every P wave is followed by QRS
mobitz type I—>PR interval prolongs till QRS beat is dropped (Wenchebach)
mobitz type II—>constant PR interval prolongation
3rd—>complete block (ventricular pacemaker)
What is normal PR interval?
0.12 to 0.2 s
What is hemiblock?
Block of either left anterior or posterior fascicle of left bundle branch
What causes an inverted P wave?
Beat starts from AV node then travels back to SA node/may block a sinus beat and produce compensatory pulse
What can cause prolonged QRS?
Bundle block/conduction starts in either left or right ventricle
2/3 of supraventricular tachycardia is caused by ?
AV node reentry
Paroxysmal (sudden onset and termination) is characteristics of what kind of SVT?
Atrial or junctional
How to terminate AV node reentry SVT?
Vagal tone/adenosine/beta or Ca blocker
What is Wolff-Parkinson-White syndrome?
Special kind of SVT—>higher risk for sudden death/treat with amiodarone and procainamide
More than __ PVC is defined as ventricular tachycardia
3
Difference between spontaneous and sustained VT?
Spontaneous VT—>less than 30 sec
Sustained VT—>more than 30 sec
What is torsades de pointes and how does it occur?
It is a polymorphic VT—->long QT syndrome/caused by EADs via inhibition of K current (caused by many drugs)
What is catecholamine induced polymorphic VT and what causes it and how do we treat it?
It is a one kind of PVT/defect in Raynodine receptor causes Ca overload—>DADs/beta blocker
How does CPVT usually triggered?
Exercise induced
What is atrial flutter?
Rapid atrial rate/e.g. every 4 P waves follows 1 QRS/saw tooth pattern
When is atrial flutter dangerous?
When it causes Wolff-Parkinson-White syndrome
How to manage chronic A fib?
Anticoagulant and rate control of ventricles
What are ventricular flutter/fib what do they look like on ECG?
lethal/dysfunctional ventricular contraction/no QRS or T on ECG—>just up and down waves
What does torsades de pointes ECG look like?
A sin wave
What are class I anti-arrhythmic drugs? and which one is the strongest?
Block Na—>thus phase 0/Ic is the strongest
What is special about class Ib anti-arrhythmic drug?
Block Na in ischemic tissues—>treat arrhythmia caused by ischemia
Sotalol induces ____ strongly?
LQT
Quinidine may increase ___ and interact with ___ ?
AVN transmission/Digoxin (displace it—>increase free Digoxin level)
Which class Ia drug causes lupus like syndrome?
Procainamide
Lidocaine is used for what kind of arrhythmia?
Ventricular fib/tachy
What is the oral version of lidocaine?
Mexiletine
Beta blockers decrease mortality in ___ pts?
CHF/MI
Sudden withdraw of beta block in angina pt may cause?
MI
What anti-arrhythmic drugs are strong proarrhythmic?
Class Ic and Class III
Class III drugs are mainly used for ? (except for amiodarone)
Atrial arrhythmia because of their induction of ventricular arrhythmia
Don’t use amiodarone for ___ pt?
Pregnant
Which drug causes blue gray skin?
Amiodarone
What other drugs interact with Digoxin like Quinidine?
Class IV
What antiarrhythmic drugs are contraindicated in AV block pts?
Beta blockers/Ca channel blockers/Digoxin
Adenosine does not work on ___?
Atrial arrhythmia
What are the first line treatment for acute and chronic A fib/flutter/SVT?
Non dihydropyridine/beta blocker/digoxin
What is given for unsustained VT and sustained VT?
Beta blocker/amiodarone or ICD
What is given for V fib?
Amiodarone or ICD
