Disclaimer:   This   reviewer   only   serves   as   a   guide   to    

studying  certain  topics.  Some  details  may  be  inaccurate.  
4.   b-­‐blockers  (metoprolol,  atenolol)  –  
You  should  still  read  the  book  as  reference.  
decrease  HR  à  reduced  CO  =  reduced  
 
fluid  volume  
Section  3  
Antihypertensive  Drugs   decrease  renin  (b2)  secretion  à  
  deactivate  RAAS  =  reduced  fluid  
Hypertension  –  elevated  blood  pressure   volume  &  wall  tension  
   
Regulation  of  arterial  pressure   5.   Calcium-­‐channel  blockers  
1.   Sympathetic  ANS   (amlodipine,  nifedipine,  diltiazem,  
a.   Cardiac  output  =  stroke  volume  x   verapamil)  –  block  L-­‐type  Ca2+  channel  
heart  rate   à  arterial  vasodilation  =  reduce  wall  
b.   Peripheral  vascular  resistance   tension  
c.   Venous  return    
d.   Venous  tone   6.   Direct  vasodilators  =  reduce  wall  
e.   Contractile  force  of  the  heart   tension  
  a.   Activates  K+  channel  (minoxidil,  
2.   Renin-­‐angiotensin-­‐aldosterone-­‐ diazoxide)  –  relax  arterial  wall  
system  (RAAS)   b.   Releases  nitric  oxide  (nitrates)  –  
angiotensinogen  -­‐-­‐-­‐r________-­‐-­‐à   relax  arterial  wall  
angiotensin  I  -­‐-­‐-­‐ACE-­‐-­‐à  angiotensin  II     c.   Activates  D1  receptors  
  (fenoldopam)–  vasodilation    
*ACE  –  angiotensin-­‐converting    
enzyme   7.   a2-­‐agonist  (methyldopa,  clonidine)  –  
  inhibitory  =  reduce  wall  tension  
Angiotensin  II  activates:    
a.   Vasoconstriction   8.   a1-­‐blockers  (prazosin,  terazosin)  =  
b.   Sympathetic  outflow   reduce  wall  tension  
c.   Aldosterone  à  Na+  and  water    
retention  (Na+  is  exchanged  for   9.   Centrally-­‐acting    
K+)   a.   Blocks  storage  of  NE  in  vesicles  –  
  reserpine  
Blood  pressure  increases  by:   b.   Blocks  the  release  of  NE  –  
1.   Increased  fluid  volume     guanethidine,  guanabenz,  
2.   Increased  wall  tension   guanadrel  
   
Drug  Classes  used  in  HTN   *Methyldopa,  minoxidil  are  prodrugs  
1.   Diuretics  (hydrochlorothiazide,    
furosemide)  –  prevents  Na+  &  water   Adverse  effects:  
reabsorption  =  reduced  fluid  volume   1.   Ion  imbalances  (e.g.  hypokalemia,  
  hypercalcemia)–  see  section  4  
2.   ACE  inhibitors  (enalapril,  captopril)  –   Diuretics  
blocks  conversion  of  angiotensin  I  to   2.   Dry  cough,  flushing,  hyperkalemia  –  
angiotensin  II  =  reduced  fluid  volume   ACEI  
(blocking  aldosterone),  reduced  wall   3.   Hyperkalemia  –  ARBs  
tension  (block  sympathetic  outflow  &   4.   Orthostatic  hypotension–  a1-­‐blockers  
vasoconstriction)   5.   Reflex  tachycardia,  salt  &  water  
  retention  (due  to  drop  of  BP)  –  
3.   Angiotensin-­‐receptor  blockers   nifedipine,  nitrates,  direct  
(valsartan,  telmisartan)  –  blocks   vasodilators,  a1-­‐blockers  
angiotensin  II  receptors  =    

 
  

+
6.   Bradycardia,  AV  block  –  diltiazem,   Cortical   Na   Na   K+-­‐sparing  
collecting   reabsorption   channels   diuretics  
verapamil,  b-­‐blockers   duct  (CCT)  
+
coupled  to  K   (ENaC),  K  
7.   Positive  Coomb’s  test,  hemolytic   +
&  H  secretion   channel,  H+  
transporter,  
anemia  –  methyldopa  
aquaporins  
8.   Lupus-­‐like  symptoms  –  hydralazine   Medullary   Water   Aquaporins   Vasopressin  
9.   Major  depression  –  reserpine   collecting   reabsorption   antagonists  
duct  (MCT)   under  
10.  Hyperglycemia  –  diazoxide   vasopressin  
11.  Hirsutism  –  minoxidil   control  
12.  Mask  the  symptoms  of  hypoglycemia    
in  diabetic  treatment  –  b-­‐blockers   Class:  
13.  Fetal  renal  toxicity,  aggravation  of   1.   Carbonic  anhydrase  inhibitors  –  
acute  renal  failure  –  ACEI,  ARBs   acetazolamide,  brinzolamide,  
14.  Bronchoconstriction  –  nonselective  b-­‐ dorzolamide  
blockers   2.   Thiazide  diuretics  –  
15.  Cyanide  poisoning  after  prolonged   hydrochlorothiazide  (HCTZ),  
use  –  nitroprusside   chlorthalidone  
16.  Rebound  hypertension  on  abrupt   3.   Loop  diuretics  (high-­‐ceiling  diuretics)  
withdrawal  –  clonidine   –  furosemide,  torsemide,  ethacrynic  
17.  Rebound  tachycardia  on  abrupt   acid  
withdrawal  –  b-­‐blockers     4.   K+-­‐sparing  diuretic  –  amiloride,  
  triamterene,  spironolactone  
Section  4   5.   Osmotic  diuretics  –  mannitol  IV  
Diuretics   6.   Vasopressin  antagonists  –  conivaptan,  
  tolvaptan  
 
Uses:  
1.   Hypertension  
2.   Glaucoma  –  acetazolamide,  mannitol  
3.   Reduce  intracranial  pressure  –  
mannitol  
4.   Treatment  of  syndrome  of  
inappropriate  ADH  secrection  (SIADH)  
–  demeclocycline  
5.   Treatment  of  potassium  wasting  
associated  with  thiazides/loop  –  K+  
 
 
B.  Katzung,  Basic  &  Clinical  Pharmacology  12th  ed.,  2012  
sparing  diuretics    
Fig  4.1  Segments  of  the  nephron   6.   Treatment  of  hyperaldosteronism  –  
  aldosterone  antagonists  
Segment   Function   Transporter     Drugs    
Proximal   Reabsorption   Na/H   Carbonic   Drug  Class   MOA   Adverse  effects  
+ + 2+
convoluted   of  Na /K /Ca   (NHE3),   anhydrase  
2+ Carbonic   Inhibits  carbonic   Metabolic  acidosis,  
tubule   &  Mg ,  85%   carbonic   inhibitors  
anhydrase   anhydrase   alkalinization  of  urine  
(PCT)     NaHCO3   anhydrase   2+
inhibitors     (precipitate  Ca  
Thick   Active   Na/K/2Cl   Loop   (acetazolami
+
stones),  low  K    
ascending   reabsorption   (NKCC2)   diuretics   de)  
+ + -­‐
limb  of   of  Na /K /Cl ;   + 2+ 2+
Loop   Inhibits  NaKCC2     Low  K ,  Ca ,  Mg ,  
Henle  (TAL)   secondary  
diuretics   elevated  blood  sugar,  
absorption  of  
2+ 2+ (furosemide)   hyperlipidemia,  
Ca  &  Mg    
ototoxicity,  
Distal   Active   Na/Cl  (NCC)   Thiazides   sulfonamide  allergy,  
convoluted   reabsorption   metabolic  alkalosis  
+ -­‐
tubule   of  Na  &  Cl ,   + 2+
2+ Thiazide   Inhibits  NCC   Low  K ,  Mg ,  high  
(DCT)   Ca   2+
diuretics   Ca ,  elevated  blood  
reabsorption  
(HCTZ)   sugar  &  uric  acid,  
under  PTH  
hyperlipidemia,  

 
  

metabolic  alkalosis,   a.   Increase  preload  –  diastolic  filling  

sulfonamide  allergy  
+
K -­‐sparing   a.  Inhibits  Na+  
+
HyperK ,  metabolic  
pressure  
diuretics     influx  (ENaC)  –   acidosis,   b.   Increase  afterload  –  large  artery  
  triamterene,   gynecomastia,   stiffness  or  arterial  blood  pressure  
  amiloride   antiandrogenic  effects  
  c.   Increase   contractility   –  
b.  Antagonizes   sympathetic  activation    
aldosterone  -­‐  
sprinolactone,  
(__  receptors)  
eplerenone    
Osmotic   Remains  in  the   Hypo/hyperernatremia   Goals  of  Treatment:  
diuretics   lumen  “holds”  
(mannitol)   water  
1.   Increase   oxygen   supply   –   coronary  
*All  diuretics  may  cause  hyponatremia,  hypotension  and   vasodilation  
dehydration   •   nitrates  
*In   mannitol,   hyponatremia   occurs   when   water   is   •   calcium-­‐channel  blockers  
withdrawn   from   the   cells,   hypernatremia   occurs   when  
water  is  excreted  out  in  the  urine  
(CCB)  
  2.   Decrease  oxygen  demand  –  decrease  
Drug  interaction:   cardiac   workload   by   decreasing  
Furosemide   +   aminoglycosides   =   increase   contractility,  preload  and  afterload  
ototoxicity   •   b-­‐blockers  
Furosemide  +  NSAIDs  =  reduced  diuretic  effect   •   nitrates  
K+-­‐sparing   diuretics   +   __________   =   •   CCB  
hyperkalemia    
GINT   MOA:  
          1.   Nitrates  –  release  of  nitric  oxide  à  
Section  5   venodilation,  arteriolar  and  coronary  
Anti-­‐Angina  Drugs   vasodilation  
  Ø   nitroglycerin,  isosorbide  
Ischemia  to  cardiac  muscles  =  angina  pectoris   mononitrate  (ISMN),  
(chest  pain)     isosorbide  dinitrate  (ISDN),  Na  
  nitroprusside,  amyl  nitrite  
Heart   receives   oxygenated   blood   during    
_______________  (systole  or  diastole?)   2.   b-­‐blockers  –  blocks  sympathetic  
Imbalance   of   oxygen   supply   &   demand   =   activation  reducing  cardiac  workload  
ischemia   –  prolonged  diastole  (decreased  HR),  
  decrease  contractility  
PRELOAD   AFTERLOAD  
 
PUMP   3.   CCB  –  coronary  and  arteriolar  
vasodilation  by  blocking  the  L-­‐type  
  Ca2+  channel  of  smooth  (e.g.  
 
dihydropyridines)  and  cardiac  (e.g.  
CONTRACTILITY  =  strength  of  the  PUMP  
  diltiazem,  verapamil)  muscles    
Fig  5.1  Schematic  diagram  of  the  cardiac  workload    
  Adverse  effects:  
Causes:   1.   Nitrates  –  orthostatic  hypotension,  
1.   Decrease  oxygen  supply     tachycardia,  throbbing  headache,  
a.   Formation  of  atheromatous   tolerance  after  8-­‐10  hours  (maintain  
plaques  (as  seen  in  stable  angina)   nitrate-­‐free  period),  cyanide  poisoning  
b.   Vasospasm  (as  seen  in  variant   after  prolonged  use  
angina  or  Prinzmetal’s  angina)    
2.   Increase  oxygen  demand  =  increase   2.   b-­‐blockers  –  may  trigger  coronary  
cardiac  workload   vasospasm,  (see  others  from  previous  
sections)  

 
  

  Absolute  refractory  period  –  phase  0  to  1st  

3.   CCB  –     half  of  phase  3  
a.   Nifedipine  –  hypotension,  reflex   Relative  refractory  period  –  2nd  half  of  phase  3  
tachycardia     to  phase  4  
b.   Diltiazem,  verapamil  –  heart    
failure,  AV  blockade     ECG  tracing  
c.   verapamil  –  flushing,  constipation     P  wave  –  atrial  depolarization  
  QRS  complex  –  ventricular  depolarization  
Drug  interaction:   T  wave  –  ventricular  repolarization  
Nitrates  +  phosphodiesterase  inhibitors  (e.g.   PR  interval  –  conduction  time  from  atrium  to  
sildenafil,  valdalafil)  =  severe  hypotension   ventricle  
  QT  interval  –  duration  of  ventricular  action  
Section  6   potential  
Anti-­‐arrhythmic  Drugs   QRS  –  intraventricular  conduction  time  
   
What  is  the  timing  of  systole  and  diastole  in  
relation  to  ECG  tracing?  
 
Mechanisms  of  arrhythmia  
1.   abnormal  automaticity  
2.   abnormal  reentrant  conduction  
 
Classification:  
I.   Na+  channel  blockers  –    
IA.  Prolong  the  action  potential  (AP)  –  
B.  Katzung,  Basic  &  Clinical  Pharmacology  12th  ed.,  2012  
  procainamide,  disopyramide,  
  quinidine  
 
IB.  shorten  the  AP  in  some  cardiac  
tissues  –  lidocaine,  mexelitene  
 
IC.  Have  no  effect  on  AP  duration,  
increase  QRS  duration  –  flecainide  
 
II.   b-­‐blockers  –  sotalol,  propranolol,  
esmolol  
  •   PR  interval  is  prolonged,  
Katzung  &  Trevor’s  Pharmacology  Examination  and  Board  Review  9 th  ed.,  2009  
suppression  of  abnormal  
 
pacemakers,  reduction  of  
Action  potential  phases  
cAMP  à  reduce  Na+  &  Ca2+  
Phase  0  –  upstroke  
currents  
Open  fast  Na+  channel  
•   Some  with  local  anesthetic  
Phase  1  –  early  fast  repolarization  
effect  (block  Na+)  
Close  Na+  channel,  opening  Ca2+  channel  
 
Phase  2  –  plateau  
III.   K+  channel  blockers  –  
Open  Ca2+  channel,  open  K+  channel  
amiodarone,  dofetilide,  ibutilide  
Phase  3  –  repolarization  
Close  K+  channel   •   Prolongs  AP  duration,  
Phase  4  –  diastole   increase  effective  refractory  
Activation  of  Na+/K+  pump,  Na/Ca  exchanger   period  (ERP)  
returning  the  Na+,  Ca2+  &  K+  to  resting    
potential  

 
  

IV.   Ca2+  channel  blockers  –  diltiazem,    

verapamil,  not  dihydropyridines   Drug  interaction:  
•   state  &  use-­‐dependendent   1.   quinidine  reduces  clearance  of  digoxin  
selective  depression  of  Ca2+   2.   hyperkalemia  excacerbates  cardiac  
current,  AV  conduction   toxicity  of  class  I  
velocity  decreased,  ERP  is   3.   Low  K+  increases  the  cardiac  effects  of  
increased   digoxin  
  4.   High  Mg2+  decreases  cardiac  effects  of  
V.   Miscellaneous  –  adenosine,   digoxin  
digitalis,  potassium,  magnesium    
•   Blocks  conduction  of  AV  node   Section  7  
–  adenosine   Drugs  Used  in  Heart  Failure  
   
*sotalol  –  class  II  &  III,  amiodarone  –  class  I  &   Heart  failure  –  inadequate  cardiac  output  
III   to  meet  the  needs  of  the  body  
   
Pharmacokinetics:   Goals  of  treatment  
1.   Lidocaine  has  high  first-­‐pass  effect   1.   Reduce  cardiac  workload  
and  metabolites  are  cardiotoxic   a.   Reduce  fluid  volume  –  ACEI,  ARBs,  
2.   Adenosine  has  short  duration  of   diuretics  
action   b.   Decrease  contractility  (for  chronic  
  heart  failure)  –  BB  
Uses:   c.   Decrease  preload  and  afterload  –  
1.   Magnesium  –  torsades  de  pointes   CCB,  nitrates,  direct  vasodilators,  
2.   Amiodarone  –  ventricular  fibrillation,   a1-­‐blockers  
ventricular  tachycardia    
3.   Digoxin  –  atrial  defibrillation   2.   Increase  cardiac  contractility  (if  
4.   Adenosine  –  supraventricular   hemodynamically  unstable)  –  digoxin,  
tachycardia   dopamine,  dobutamine,  epinephrine,  
  milrinone  
Adverse  effects:    
1.   Precipitation  of  arrhythmias  –  class  I   Line  of  treatment  
esp.  flecainide   1.   ACEI/ARBs  
2.   procainamide  –  hypotension,  lupus-­‐ 2.   b-­‐blockers  
like  symptoms   3.   diuretics  +  nitrates,  direct  
3.   quinidine  –  cinchonism  (vertigo,   vasodilators,  CCBs  
headache,  tinnitus),  autoimmune   4.   Inotropics  (dopamine,  epinephrine,  
reactions,  cardiac  depression,   dobutamine)  
torsades  de  pointes    
4.   lidocaine,  mexelitene  –  local   MOA:  
anesthetic  toxicity  (convulsions)   1.   Cardiac  glycosides  –  inhibition  of  
5.   b-­‐blockers  –  review  previous  section   Na+/K+-­‐ATPase  à  increase  cardiac  
6.   class  III  –  precipitation  of  torsades  de   contractility  and  decrease  heart  
pointes   rate  
7.   amiodarone  –  microcrystalline   2.   Amnirone,  milrinone  –  
deposits  in  cornea  and  skin,  thyroid   phosphodiesterase  inhibitor  
dysfunction,  paresthesia,  tremor,    
pulmonary  fibrosis   Review  MOA  of  other  drugs  in  previous  sections  
8.   adenosine  –  hypotension,  flushing,    
transient  chest  pain,  dyspnea   Uses:  
  b-­‐blockers,  ACEI,  ARBs  –  chronic  heart  failure  

 
  

milrinone,  amnrinone,  dopamine  –  acute  

heart  failure  
 
Adverse  effects:  
Digoxin  –  diarrhea,  arrhythmia,  confusion,  
hallucination,  nausea,  vomiting  
Milrinone,  amnrinone  -­‐  hypotension  
 
Drug  Interactions:  
1.   Quinidine  delays  reduces  clearance  of  
digoxin,  increase  digoxin  serum  levels  
2.   Hypokalemia  increases  digoxin  
toxicity  (loop  and  thiazide  diuretics)  
3.   Hypokalemia,  hypomagnesmia,  
hypercalcemia  enhances  digoxin  
effects  (vice  versa  decreases  effects)  
 
Review  previous  sections  for  adverse  effects  and  
drug  interactions  of  other  drug  class  
 
GINT