Pharmacology of common renal diseases

Renal and Cardiovascular drugs Acute renal failure; AFR :

syndrome of rapid decline in renal function; BUN and Cr
Clinical pharmacology of drugs used in ARF :
obstruction of renal arteries : related HT, CV disorders

(ACE inhibitors; enalapril and ARB; losartan)

Supaporn Kansenalak : supaporn.p@psu.ac.th prerenal azothemia; BUNCr ratio diminish : depend on

Department of Pharmacology
Faculty of Science underlying disorders : volume repletion quickly
Prince of Songkla University
( h ld be
(should b d
decrease iin the
th dose
d of
f di
diuretic
ti and/or
d/

liberalized sodium intake)

Nephron
ARF related g
glomerulonephritis
p and vaculitis :

treated with immunosuppressive agents

acute tubular necrosis; ATN : focused on either

conversion of oliguric to nonoliguric renal failure or

treatment of established ATN; loop diuretics or mannitol
isoosmololity
y
dil ti segmentt
diluting
Chronic renal insufficiency; CRI
result from disorders; HT
HT, DM,
DM polycystic kidney disease,
disease
collagen-vascular diseases : decline in renal function
required diuretic treatment; loop diuretics hyperosmolality

4
3
 V1 versus V2 vasopressin receptors mediated
mannitol : osmotic diuretics
pressor versus antidiuretic responses
Vasopressin
p receptor
p agonists
g

: acetazolamide
: HCTZ synthetic 8-L-arginine vasopressin and desmopressin

: spironolactone
V1-selective agonist : contraction of GI smooth muscle;
: furosemide postoperative
p p ilieus, abdominal distention
: vasoconstriction of splanchnic arterial vessel;
esophageal
p g varices
ADH antagonist : tolvaptan V2-selective agonists; desmopressin :
: amirolide,
amirolide triamterene water conservation and release blood coagulation
Summary of the site and mechanism of action of diuretics. Three important features of this
summary figure are worth special note. 1. Transport of solute across epithelial cells in all nephron factors; central diabetes insipidus; DI, nocturnal
segments involves highly specialized proteins, which for the most part are apical and basolateral
membrane integral proteins.
proteins 2.
2 Diuretics target and block the action of epithelial proteins involved enuresis nocturnal polyuria,
enuresis, polyuria bleeding disorders
in solute transport. 3. The site and mechanism of action of a given class of diuretics are
determined by the specific protein inhibited by the diuretic. CA, carbonic anhydrase; MR,
mineralocorticoid receptor; MRA, mineralocorticoid receptor antagonist; Aldo, aldosterone. 6

Vasopressin receptor antagonists JNC-7 : 2003

(The seventh report of the Joint National Committee on Prevention,
V1a-selective antagonist; relcovaptan : dysmenorrhea, Detection, Evaluation and Treatment of high Blood Pressure)

preterm
t llabor,
b R
Raynaud
d s syndrome
d Classification Ps; SBP Pd; DBP Lifestyle Initial drug therapy
(mmHg) (mmHg) modifications without with
V2-selective;
se ect e; lixivaptan,
aptan, tolvaptan
to aptan and V1a/V2-selective
se ect e Compelling indications

Normal < 120 and < 80 encourage no drug drugs for

antagonists : heart failure, cirrhosis, hyponatremia, indicated compelling
indications
Prehypertension 120-139 or yes
brain edema, nephrotic syndrome, glaucoma, 80-89
Hypertension 140-159 or Yes Thiazides for drugs for
SIADH; Syndrome of Inappropriate Secretion stage 1 90-99
0 most
most. ll
compelling
May consider indications.
others or
of Antidiuretic Hormone combination Other anti-
BP drugs (diu,
(diu
Hypertension 160 or 100 yes 2 drugs ACEI) as
combination needed.
stage 2
for most
8

7 8
Management of hypertension 1. Diuretics
1 Lifestyle modifications : BP,
1. BP enhanced drug efficacy natriuretic
t i ti effect
ff t and
d vasodilation
dil ti : HCTZ;
HCTZ monotherapy
th
and decreased cardiovascular risks alkalosis, glucose, LDL, uric acid and impotence
restricting
i i sodium
di consumption
i : low
l salt
l diets
di
2. Postsynaptic adrenergic receptor antagonist
The Dietary Approaches to Stop Hypertension; DASH diet
prazosin (selective 1-blockers) : reflex tachycardia
: consume a diet rich of fruits, vegetables
atenolol and metoprolol (selective 1-blockers), propranolol
(K+, Ca22+) and low fat dairy products
bradycardia, cold extremities, bronchospasm
reduction in body weight
3 Direct vasodilators
3.
increased physical activity
3.1 arteriolar vasodilators : hydralazine and minoxidil
restr ct on of ethano
restriction nta e
ethanol intake
lupus syndrome & B6-resposive polyneuropathy (hydralazine),
restriction of smoking
hypertrichosis (minoxidil)
l
relaxation
10

9 10

3.2 arteriolar & venular vasodilators : Na nitroprusside Renin angiotensin aldosterone system
hypertensive crisis
angiotensinogen
ADR : excessive hypotension, cyanide accumulation, renin *aliskiren
methemoglobinemia, decomposed to light angiotensin I
enalapril
p ** angiotensin converting enzyme; ACE
4 Renin angiotensin aldosterone inhibitors
4.
angiotensin II *** losartan kininogen
4.1 direct renin inhibitors; DRI : aliskiren vasoconstriction kallikrein
4.2 ACE inhibitors : enalapril aldosterone release kinins; bradykinin
enalapril ** kininase II; ACE
4.3 angiotensin receptor blockers; ARB : losartan; AT1
Na
N & H2O reabsorption
+ b ti i
inactive
ti peptides
tid
first-line therapy in hypertension stage 1, 2
with DM,
DM left ventricular hypertrophy blood volume * Direct renin inhibitors;; DRI
ADR : hyperkalemia, IUGR, angioedema, dysgeusia ** ACE inhibitors; ACEI
BP *** Angiotensin
g receptor
p blockers; ARB
and
d dry
d cough
h ((common side
id effect)
ff t)
11 12
5. Calcium channel blockers : Organic nitrates and Ca2+ blockers : main drugs; vasodilators
Nifedipine Verapamil
Nifedipine, Verapamil, Diltiazem blockers : 3rd drug; slow HR and hence metabolic demand
-blockers
blocked voltage-gated L-type calcium channels Nitroglycerin : smooth muscle of vein (main) and artery

first-line therapy for hypertension stage 1, 2 : denitration at smooth muscle nitric oxide; NO
(diuretics or -blockers
blockers are contraindication)
: stimulated guanylyl cyclase **
sildenafil; Viagra, vardenafil, tadalafil
ADR : flushing, constipation, insulin release (verapamil)
GTP cyclic
y GMP GMP
Antianginals : angina pectoris O2 demand O2 supply guanylyl**
cyclase phosphodiesterase; PDE

primary symptom of ischemic heart disease activate p

protein kinase G smooth muscle relaxation
(veins >>> arteries) venodilation
stable, unstable and prinzmetals (vasospastic) angina
ADR : throbbing headache (most common), orthostatic
1. vasodilators : organic nitrates & Ca2+ channel blockers
hypotension, tachycardia ?, erythema at site
2 cardiac depressants :
2. Ca2+ channel blockers & blockers
-blockers
and
d methemoglobinemia
h l bi i ((nitrites)
i i )
14

13 14

P h h
Pathophysiology
l of
f cardiac
d performance
f : CHF
preload : usuallyy in CHF
p
: blood volume & venous tone

reduction of high filling pressure : salt restriction

and diuretics, vasodilators (nitroglycerin)

afterload : in CHF ( arteriolar tone)

contractility : decreased ( cardiac output)
heart rate : 1st compensation mechanism

15 16
 Molecular mechanism of digitalis
Drugs used in congestive heart failure; CHF
1. ; positive inotropic agents 18

dopamine drugs : dopamine, dobutamine (B1-agonist)

non-adrenergic
d drugs
d : cardiac
d glycosides;
l d d
digitalis
l

2
2. ; diuretics : loop diuretics; furosemide
;

3. ; vasodilators :
nitrovasodilators : nitroglycerin, selective 1-blockers;

prazosin, ACE inhibitors; enalapril

17

17 18

Mechanism of action : cardiac glycosides Sinoatrial node; SA action potential : phase 4, 0, 3

Myocytes; cardiac cells Non pacemaker action potentials : Phase 4,
Non-pacemaker 4 0,
0 1,
1 2,3
23
inhibition of Na+, K+-ATPase : intracellular Na+ overload Phase 4 : resting membrane potential
Ca2+ efflux Na+-Ca2+ exchanger Phase 0 : rapid depolarization
Ca2+ influx voltage-gated
g g L-type
yp calcium channel
Na+ inward; influx
Ca2+ SR Ca2+-ATPase; SARCA2 Phase 1 : initial/ partial repolarization
Ca22+

SR
Ca22+
opening of a special type
ryanodine receptor (RyR) intracellular Ca2+, of K+ channel
intracellular Ca2+ interacted with troponin C and activated Phase 2 : plateau repolarization
interaction between actin and myosin that resulted in
Ca22+ inward
sarcomere shortening contractility .. cardiac output Phase 3 : repolarization
Digitalis : contractility and heart rate
K+ efflux; outward
19 20
 Phase 1 (Ca2+ in; Na+ channel closed; K+ out)
PR interval : conduction through AV node,
node QRS duration :

Phase 0 (Na+ in) Phase 2 Phase 3 (K+ out)

ventricular depolarization, ST interval : ventricular
(Ca2+ in)
Phase 4 (resting) Phase 4 (resting)
repolarization, QT interval : ventricular depolarization

and
d repolarization
l i ti

p g PR interval : disturbance of AV node conduction,,

prolonged

prolonged QRS duration : blocked in conduction pathway

through ventricles (bundle of His), prolonged ST interval :

atrial depolarization : P wave,

wave ventricular depolarization : ischemic damage of heart,
heart QT interval (prolonged action

QRS complex and T wave : ventricular repolarization potential; AP) : varied with heart rate

21 22

Mechanism of action of antiarrhythmic drugs

Four ways to reduce the rate Class Basic Mechanism Comments

of spontaneous discharge in I Na+- channel blockade reduced phase 0 slope and peak of
action potential; AP
automaticity IA - moderate moderate reduction in phase 0 slope;
slope
p of f phase
p 4 increased APD and ERP
IB - weak small reduction in phase 0 slope;
threshold potential reduced APD; decreased ERP
maximum
i di
diastolic
t li potential
t ti l IC - strong pronounced reduction in phase 0
action potential duration, APD slope; no effect on APD or ERP
II blockade
-blockade blocked sympathetic activity;
reduced heart rate and conduction
III K+-channel blockade y repolarization;
delayed p phase
p 3
and thereby increased APD and ERP
IV Ca2+-channel blockade blocked L-type calcium channel;
23
most effective at SA and AV nodes;
23 reduced heart rate and conduction
 Class IA : quinidine, procainamide, disopyramide
procainamide (common) : arrhythmias during acute MI
cinconism,
cinconism hypotension (quinidine),
(quinidine)
reversible lupus erythematosus (procainamide)

Class IB : lidocaine (IV), mexilitine, tocainide (oral)

lidocaine
lid i (d(drugs of
f choice)
h i ) : acute
t ventricular
t i l arrhythmias
h th i

Overdoses of class I antiarrhythmic drugs

sodium lactate (reverse drug-induced arrhythmias)

sympathomimetics (reverse drug-induced hypotension)

26

25 26

Class II : atenolol, metoprolol, propranolol, timolol essential hypertension

losartan
very short acting in acute arrhythmias : esmolol (only IV)
(ARB)
commonly used as prophylactic drugs in MI patients
Class III : K+ channel blockade : amiodarone, bretylium
A i d
Amiodarone : blocked
bl k d NNa+, K+, Ca
C 2+
2 channels
h l and
d -receptor

A. Renin (( aliskiren;; DRI))
sotalol : used in supraventricular & ventricular tachycardia
B. Bradykinin (enalapril; ACEI)
ADR : postural hypotension (bretylium), Torsade de pointes
C
C. Aldosterone (spironolaction;
( K+ sparing diuretics))
D. Angiotensin II ( : losartan; ARB)
: chronic
h i amiodarone
i d therapy
th : pulmonary
l fibrosis,
fib i
peripheral neuropathy (common), thyroid dysfunction
NLE1 2556 : mechanism : selective AT1 inhibitors
Class IV : Ca2+ blockers; verapamil (oral, IV), diltiazem
AV nodal reentry; nodal tachycardia
27 28
 55 2 wk enalapril 50 PE: pansystolic murmur, fine
amlodipine hypertension 2 PE: crepitation in both lower digoxin (digitalis, cardiac
lungs are clear
glycosides) furosemide (loop diuretics)
glycosides),
A. Chest X-ray ( PE: lungs are clear) digoxin
B. Dextromethorphan ( cough suppressants) A. preload ( nitroglycerin : venodilation)
C. Inhaled corticosteroids (
(
) B. afterload ((vasodilators : amlodipine,
p , pprazosin,, enalapril)
p )
D. Reduced amlopdipine dosage ( SE : dry cough) C. contractility ( agonist : dopamine,
E. enalpril ( : common SE) epinephrine)
A. Na+, K+ ATPase inhibition ( : .)
NLE1 2556 : SE of ACEI NLE1 2556 : contractility tachycardia
plasma
l b d ii
bradyninin Pt.
Pt heart failure)
29 30

25 brain tumor urine 10L/24 hr 60 DM 3 FBS 140-160, HbA1C 7.8%

investigated : BUN 40, Cr 1, Na+ 120, K+ 3.6, Cl- 120, HCO3- 130 hypertension+dyslipidemia BP 140/90
vasopressin (desmopressin; ADH) 150/90 mange

A. Amlodipine (.)
A Serum
A. S bicarbonate
bi b t ( HCO3-
( acetazolamide)
t l id ) B. HCTZ ( DM)
B. Serum potassium ( K+ sparing diuretics) C. Atenolol (..)
(..)
C. Serum creatinine ( thiazide GFR) D. Enalapril ( lifestyle
D Serum chloride (
D. ( diuretics Na+ & Cl-) modifications )
E. Serum osmolality ( : H2O reabsorption) E. Lifestyle modifications ( HbA1C
, BP )
NLE1 2556 : ADH agonists NLE1 2556 : managementt off hhypertension
t i
31 32
 25 asthma corticosteroids 2-3
55 & furosemide

salbutamol ( (loop diuretics)
agonists),
ago s s), cchlorpheniamine
o p e a e (a (antihist),
s ), bbromhexine
o e e
(expectorants), dextromethorphan (cough suppressants)
(tremor) SE
A. Na+ ( Na+ diuresis)
A. Salbutamol ( : SE tremor) B
B. ( hypokalemia)
K+ (
B. Chlorpheniamine ( SE : sedation) C. Ca2+ (hypocalsemia. Cramp)
C Bromhexine
C. B h i ( ( )) D. Mg2+ (hypomagnesemia arrhythmia)
D. Corticosteroids ( ..)
E. Dextromethorphan (..) NLE1 2556 : SE of loop diuretics : alkalosis
NLE1 2556 : common SE of selective 2 agonists)
33 34

Vasoactive substance 25 (schizophrenia) haloperidol

(typical antipsychotics) SE
AA. Kinin
Ki i (
( bradykinin
b d ki i : peripheral
i h l vasodilation)
dil i ) cloxapine (atypical antippsychotics)
SE

B. Renin ( RAAS : vasoconstriction)
C. Dopamine ( : renal vasodilation D receptors) A. Wt. gain ( SE : cloxapine)
A
A. Angiotensin (AT II : vasoconstriction) B. DM (
( SE
) )
B. Vasopressin (V1a agonists : vasoconstriction) C. Extrapyramidal effect (SE of high potency : haloperidol)
D. Agranulocytosis ( : common SE : cloxapine)
1 agonists
NLE1 2556 : main action D agonists E. Postural hypotension ( SE of medium potency)
NLE1 2556 : common SE of atypical antipsychotics
35
36
Neuroleptic
p drugs
g Antipsychotic sgents
Classification 1. Phenothiazines

1 high potency : high extrapyramidal symptom effects

1. blocked postsynaptic D2-receptors
receptors at mesolimbic pathway
antipsychotic effect : positive signs
: fluphenazine
p : haloperidol
p : p
pimozide
blocked postsynaptic D2-receptors at
2. medium potency : high atropine-like effects
ch m
chemoreceptor
c pt triger
t i zone;
n ; CTZ : antiemetic
nti m tic effect
ff ct
: chlorprothixene : clozapine : risperidone
blocked postsynaptic D2-receptors at nigrostriatal
3 low potency : high sedative effects
3.
pathway : extrapyramidal symptoms; EPS
: chlorpromazine : thioridazine : quetiapine
blocked postsynaptic D2-receptors at tubuloinfundibular

pathway : galactorrhea

37 38

Atypical antipsychotic drugs

70
atrial fibilation
warfarin
Serotonin dopamine antagonist; SDA
(oral anticoaggulants) 1
Clozapine Risperidone,
Clozapine, Risperidone Quetiapine
drug interaction
other side effects : EPS
negative symptoms D2 antagonist A. Terbinafine ( .SE )
B. Griseofulvin
G f ( SE
( S )
blocked 5HT2 > D2-receptors
C. Caspofungin ( ..)
Risperidone, and Quetiapine : less EPS D. Ketoconazole ( : enzyme inhibition DI)
Clozapine : agranulocytosis,
agranulocytosis weight gain E Amphotericin B (
E. (



) )
NLE1 2556 : azole antifungal agents
39 40
 55 recurrent ventricular arrhythmia 5 MI digitalis furosemide (loop
increased ESR pulmonary diuretics digitalis toxicity
function diffuse lung capacity
capacity, CXR diffuse interstitial
pneumonia A. Hypokalemia (

A. Atenolol ( Class II : blockers) Na+, K+ ATPase)
B. Verapamil ( ( Class IV : Ca2+ blockers) B. Hypocalcemia
C. Propranolol ( Class II blockers) C. Metabolic alkalosis
D. Amiodarone ( : SE of class III K+ blockers) D. Hyponatremia
E. Procainamide ( Class I Na+ blockers) E. Hypochloremia
NLE1 2556 : serious SE of amiodarone, peripheral NLE1 2556 : hypokalemia diuretics
neuropathy,
th ththyroid
id ddysfunction
f ti h t ffailure
heart il : di
digitalis
it li
41 42

20 amphetamine
nonselective blockers

A. Thyrotoxicosis ( ) amphetamine
B. Type I DM ( hypoglycemia) A Apicac (
A. (
)
)
B. Atropine ( organophosphate poisoning)
C Renauld
C. Renauld phenomenon ( ( 2 : vasoconstriction)
C. Naloxone ( overdose of morphine)
D. Second degree AV block ( 1 : bradycardia)
D. (
D NH4Cl (
E. COPD ( 2 : bronchospasm)
)
D. NaHCO3 ( D)
NLE1 2556 : contraindication of nonselective blockers
NLE1 2556 : indication of acid forming salts :
amphetamine toxicity
43 44
 50 DM 20 BP 160/100
70 hypertension
yp
140 albumine +1, sugar +1 engorged neck vein, cardiomegaly, hepatomegaly
hypertension
CHF


A. Enalpril ( compelling indication of HT with DM) A. Aspirin ( . CAD)
B. Propranolol ( HT stage 1) B. Enalapril ( vasodilators afterload)
C Prazosin (
C. (
HT stage 2) C Abfleximab (
C. ( NSAID)
D. Spironolactone ( HT stage 1) D. Nifedipine ( Ca2+ blockers HT)
E. Streptokinase ( venous thrombosis)
NLE1 2556 : compelling indication of HT
NLE1 2556 : drugs used in heart failure : inotropic
ventricular hypertrophy agents, diuretics, vasodilators, blockers
45 46

60

lidocaine ((class IA))
nitroglycerin
antiarrhythmic drugs

A K+ channel
A. h l blockers
bl k (( class
l III : amiodarone)
id )
A. Venous capacitance (.. ) B. Na+ channel blockers ( class I : quinidine etc.)
B. Cardiac preload ( : venodilation) C. Ca2+ channel blockers ( class IV : verapamil)
C Cardiac afterload (
C. (
vasodilators) D adreceptor
D. d t blockers
bl k (( class
l II : atenolol)
t l l)
D. Heart rate ( digitalis) E. Adenosine receptor blockers ( Mg2+,
E. Contractility ( Ca2+ blockers, digitalis etc.)
blockers) NLE1 2556 : mechanism of Class I antiarrhythmic drugs
NLE1 2556 : site of action : vein >>>> artery
47 48
 hypertension ACEI (enalapril) CCB
ventricular
hypertrophy (amlodepine, verapamil)
A HCTZ (
A. (
HT stage 1 : )

B. Enalpril ( : ventricular hypertrophy) A CXR (
A. ( :
investigated infection,
infection pus fluid)
C. Propranolol ( Ht stage 1 : )
B. PFT ( : )
D Prazosin (
D. (
HT stage 2)
E. Nifedipine ( Ht stage 1 HCTZ, C. discontinue ACEI ( : common SE : dry cough
propranolol) bradykinin )
NLE1 2556 : compelling indication : ACEI NT 55 : common SE of ACE inhibitors

49 50

65 essential hypertension
yp losartan 55 2
(ARB) enalapril amlodipine 2
PE: lungs are clear

A. renin ( : aliskiren; DRI) A. chest x-ray ( : PE : lungs are clear infection, air, exudate)
B bradykinin (
B. ( : enalapril
plasma bradykinin) B dextromethorphan (
B. ( : cough suppressants)
C. aldosterone ( block AT receptor adrenal gland C. inhaled corticosteroids ( : )
aldosterone release) D. reduced amlodipine dosage ( SE : pedal
edema, flushing)
A angiotensin II (
A. ( : enalapril angiotensin synthesis) E. enalapril ( : plasma bradykinin
// )
NT 55 : mechanism of ARB
NT55 :


SE of ACE inhibitors; enalapril)
51 52

50 PE: pansystolic murmur, fine 25 10
crepitation in both lower ( heart failure) digoxin , L/24hr. investigation: BUN 40, Cr 1.0, Na+ 160, K+ 3.6, Cl- 120, HCO3-
furosemide (OK)
digoxin 30
vasopressin (ADH; desmopressin)
A. preload ( : furosemide)
B afterload
B. ft l d (
( :
arteriolar
t i l vasodilators)
dil t ) A serum bicarbonate
A. bi b t ( CAI serum HCO3-)
( :
C. contractility ( : digoxin contractility) B. serum potassium ( : K+ sparing diuretics : spironolactone)
D. beta receptor ( : -agonist : epi, iso, dopamine) C. serum creatinine ( : SE of thiazides BUN)
E. Na+/K+ ATPase inhibitor ( : contractility D. serum sodium ( : action of diuretics)
heart rate heart failure) E. serum osmolality ( osmolality
)
NT55 : mechanism of digitalis; cardiac glycosides
NT55 : effect
ff t off vassopressin;
i ADH
53 54

25 asthma
corticosteroid 2-3

pulmonary edema
(
(
salbutamol ( agonist), chlorpheniramine (antihistamine), furosemide; loop diuretics) (sure)
bromhexine (expectorants), dextromethorphan (cough suppressant)


(tremor)

side effect A. acetazolamide ( : SE : )
B. furosemide ( : case CHF drug of choice for

pulmonary edema loop diuretics : SE : ototoxicity)

A. lb t l (
A salbutamol (
side ff t 2 agonist)
id effect i t)
B. bromhexine ( : SE ) C. spironolactone ( : SE : gynecomastia, menstrual disturbance)
C. corticosteroid ( : SE : ) D Hydrochlorothiazide (
D. ( : SE : impotence
HT)
D. chlorpheniramine ( : SE : sedation)
E. dextromethorphan ( : SE )
NT55 : SE : ototoxicity of loop diuretics)
NT55 : SE of 2 agonist : tremor, tachycardia)
55 56
 55



Vasoactive substance
blood vessel
flurosemide (loop diretics) A. Kinin ( : bradykinin systemic)

B. Renin ( :


)
A. Na+ ( : diuresis) C. Dopamine ( DA receptor )
B. K+ ( alkalosis action
D. Angiotensin ( : ATII )
potential )
2+
C. Ca ( : hypocalcemia E Vasopressin
E. V i (
( :
V1A receptor
t )
)
muscle contraction cramp) p)
2+
D. Mg ( : arrhythmia)
NT55 : dopamine BP (1 stimulation)
NT55 : hypokalemia
57 58

25


haloperidol (high potency : high EPS) CHF digitalis (digoxin)
toxicity
SE clozapine (medium potency; atypical)
SE
A. enalapril ( : renal insufficiency : hyperkalemia)
A. weight gain ( : SE convertional antipsychotics) B. verapamil ( class IV antiarrhythmics
B. diabetes mellitus ( : SE low potency antipsychotics)
)
C. extrapyrimidal effect ( : SE high potency) C. furosemide ( hypokalemia : digitalis toxicity)
D. agranulocytosis ( SE clozapine) D. metoprolol ( : CHF)
E postural hypotension (
E. SE
low/ medium
potency) Compre55 : drug interaction CHF
NT55 : SE clozapine

59 60
 (suckling reflex)

2









A. cortisol (( : stress hormone adrenal ggland))
A. oxytocin ( :
IV infusion : induction labor at term)
B. oxytocin ( milk ejection : suckling reflex : stimulated
B. ergotamine ( : ergot alkaloid CNS effects
modified myoepithelium contraction)
C. dinoprostone ( : PGE2 therapeutic abortion)
C. estrogen ( : myometrium contraction)
D. methylergonovine ( ergot alkaloid
D. progesterone ( : myometrium relaxation
postpartum or post abortion
maintain pregnancy)
E. prostaglandin ( : PGE2 and PGF2 myometrium
Compre55 : therapeutic use of oxytocic drugs
contraction))
Compre55 : oxytocic drugs
milk production
prolactin hormone)
61 62

Nifedipine (verapamil, diltiazem; CCB)

enalapril, simvastatin,
propanolol, verapamil, paracetamol
A cell SA node (
A. ( : prototype
vessel)

B. cell macula densa ( : ) A. enalapril ( : SE : hyperglycemia hyperkalemia)
C. cell
autonomic ganglian ( : nicotinic receptors) B. simvastatin ( : antilipidemia SE : hepatotoxicity, myopathy)
D. skeleton muscle ( : C NMJ) C. propranolol ( : Pt. DM)
E. vascular smooth muscle ( dihydropyridine D. verapamil ( insulin release : hyperglycemia)
vessel)) verapamil
p and diltiazem : heart E. pparacetamol (( : ))
verapamil GI : constipation)
Compre55 : contraindication antihypertensive agents
Compre55 : mechanism of Ca2+ channel blockers

63 64

5 1
A. epinephrine ( : vasoconstrictors : BP) 1 ()
B NO (
B. ( nitric
i i oxide
id : vasodilation
dil i guanylyl l l cyclase
l 1


cyclic GMP vasodilation nitroglycerin)
C. endothelin ( : protein that constrict vessel) A
A. (
( :

)
)
D. ATII ( : vasoconstrictor ACE enalapril) B. (
E. PGE ( : PGE2 vasodilation PGE1 )
)
C. ( :
)
C
Compre55
55 :
nitroglycerin
it l i D.
(
( : )
)

NT55 :

benzene,
b lilindane)
d )
65 66

70 atrial fibrillation warfarin 45 enalapril

1 drug ( ACE inhibitors)
interaction A. renin ( : renal blood flow, angiotensionogen)
A. terbenafine ( : antifungals azole : enzyme inhibitors) B. bradykinin (OK : inactive form)
B griseofulvin (
B. ( :

azole : enzyme inhibitors) C AT I (
C. ( : renin action
aliskiren : DRI )
)
C. caspofungin ( : antifungals azole : enzyme inhibitors) D. AT II ( : ACE AT I AT II,
D. ketoconazole ( azole : imidazole ACE iinhibitors
hibit
AT II)
CYP3A4 : enzyme inhibitors) E. angiotensinogen ( : protein renin, aliskiren)
E. amphotericin B ( : antifungal antibiotics SE :
nephrotoxicity, blood dyscrasia
enzyme inhibitors) NLE1 2556, NT2011 :
NT55 : azole antifungal agents enzyme inhibitors drug (enalapril : ACE inhibitors : angiotensin II)
i t ti
interaction
B : bradykinin
67 68





HIV amphotericin
p B (( antifungal
g antibiotics))
A. acetylcysteine ( : mucolytics )
B dextromethorphan (
B. ( cough suppressants) A alteration cell membrane permeability (
A. ( : bind with
C. pseudoephridine ( : decongesants; -agonist) ergosterol : pore/ channel.. loss of membrane permeability)
D. CPM ( : chlorphenilamine antihistamines B ergorsteroll synthesis
B. h i (( : synthetic
h i azole l antifungals
if l
) : 14--sterol demethylase)
C. DNA synthesis ( : flucytisine : antimetabolites)
NT2011 :
NT 2011 : mechanism of amphotericin B
Indication : drug of choice : systemic mycoses; Cryptococcosis
ADR : nephrotoxicity, bone marrow depression

69 70

Synthetic antifungal agents : azoles : 40

antipsychotics
1

Imidazole : ketoconazole, miconazole, clotrimazole
Triazole : Itraconazole,
Itraconazole Fluconazole
Fluconazole, Posaconazole A haloperidol (
A. ( : high potency : high EPS)
Isavuconazole, Voriconazole (lower ADR) B. chlorpromazine ( : low potency : high sedative)
C. risperidone ( : atypical low EPS : medium potency :
Mechanism : inhibited 14--sterol demethylase enzyme high atropine-like effect)
Indication : chronic mucocutaneous candidiasis D. clozapine ( agranulocytosis and weight gain)
y
: systemic mycoses
y and dermatomycoses
y
ADR : inhibited CYP3A : enzyme inhibitors NT 2011 : side effect of atypical antipsychotics :
(gynecomastia menstrual irregularity)
(gynecomastia, serotonin dopamine antagonists; SDA
: drug-induced hepatitis

71 72
 schizoid
haloperidol (
( conventional X &
typical antipsycotics)



A. inhibit postsynaptic ( : orthostatic hypotension) (Sarcoptes scabiei) :
B. inhibit postsynaptic D2 ( : typical antipsychotics)



C. inhibit postsynaptic H1 ( : sedation : side effect)
D. inhibit postsynaptic M1 ( : CVS : side effect) : benzene benzyl benzoate,
E inhibit postsynaptic 5HT2 (
E. ( : atypical group : ggamma benzenehexachloride; GBH ((lindane),)
risperidone, cloxapine) precipitated sulfur, crotamiton; Eurex and
thiabendazole cream
typical/ convertional antipsychotics
73 74

70


(heart
classic angina
hypertension
failure) engorged neck vein, cadiomegaly,
hepatomegaly
congestive heart failure (OK) A verapamil (
A. ( main drug in AP : unstable & variant
HT) vasodilators
A. aspirin ( : NSAID : antithrombotics, antiplatelets) B. isorbide dinitrate ( : angina

HT)
B. enalapril ( : ACE inhibitors (vasodilators : C. propranolol ( 3rd drug in AP HT : cardiac
corrected heart failure decreased compression)
afterload
afterload, antihypertensive agents) y
D. hydralazine (( : reflex tachycardia
y AP))
C. abfliximab ( : NSAID : selective COX2)
NLE1 2556,
2556 NT 2008 : drugs compelling indication; JNC7
76

75 76
 Na+ : 130-146, K+ 3.2-4.6, Cl- 98-108, HCO3- 23-29
MI ?
? PVC prematuret ventricular
t i l contraction??
t ti ??
A. lidocaine ( acute ventricular arrhythmias 65

ischemia; MI)

BP 140/90 mmHg
B. propanolol ( : prophylaxis of MI) serum electrolyte Na+ 129, K+ 3.0 (), Cl- 90
C. quinine ( : malaria quinidine : class IA ??) HCO3- 32 () mEq/L
( )
NT 2008 : Pt. MI PVC A. enalapril; ACE inhibitors ( : hyperkalemia; K+ )

g
B. spironolactone; aldosterone antagonist (( : K+ )
C. propranolol; -adrenergic blockers ( : lab)
D HCTZ; thiazide diuretics (
D. (
alkalosis)
2+
E. verapamil; Ca channel blockers ( : lab)
77 78

77 78

58
Cardiac glycosides : digitalis (digoxin, digitoxin)
congestive heart failure

(stable angina) /


A. -adrenoceptors ( : -agonist)
A. nitroglycerin; organic nirates ( : acute attack; sublingual)
B. cardiac output ( : ? ?)
B. metoprolol; 1 blockers ( : AP; selective 1-blockers)
C. isosorbile dinitrate; organic nitrates ( : AP) C.
K+ channel ( : Class III : ammiodarone)
D. aspirin (gr I; 81 mg); NSAID ( ( :
prophylaxis recurrent MI) D. phosphodiesterase ( : PDE inhibitors)
E. hydralazine; systemic vasodilators ( reflex E. Na+, K+-ATPase
t h di
tachycardia O2 demand
d d ) ( : force heart rate )

79 80

79 80
 48
50


148/90 mmHg


200/140 mmHg (hypertensive
A. hydrochlorothiazide ( : hyperglycemia) crisis)
i i )


B. ppropranolol
p (( : Pt. DM)) A. furosemide ( : thiazides: 1st in HT stage 1, HT stage 2,
C. hydralazine ( : HT stage 2 ) drug of choice for pulmonary edema; CHF)
D enalapril (
D. ( drug compelling indication B. prazosin ( : 1-blockers : HT stage 2)
DM & ventricular hypertrophy C. enalapril ( : ACEI HT with ventricular hypertrophy, DM)
) D sodium nitroprusside (
D. ( BP
E. verapamil ( : insulin release hyperglycemia) hypertensive emergency)
E verapamilil (
E. ( :
HT withith asthma,
th elderly)
ld l )
compelling
p g indication in JNC7 81

81 82

25
hydrochlorothiazide
(HCTZ) triamterene



A HCTZ
A.
triamterene

A. propranolol ( : CVS drugs : antiBP, AP, antiarrhythmics) ( : alkalosis)
B. furosemide ( heart and respiratory B HCTZ alkalosis
B. lk l i triamterene
ti t (( : triamterene
ti t
diseases renal dis. loop diuretics) hyperkalemia alkalosis)
C. verapamil ( : Ca2+ blockers : CVS drugs) C. triamterene hyperglycemia HCTZ ( : )
D enalapril (
D. ( : ACE inhibitors : CVS drugs) D. HCTZ acidosis triamterene ( : )
E. nitroglycerin ( : organic nitrates : antianginals) E. triamterene ( : K+ sparing diuretics :
alkalosis HCTZ)

83 84

83 84
 metabolic acidosis


A. loop diuretics ( alkalosis) metabolic alkalosis

B. ( : diabetic ketoacidosis) A. potassium chloride ( : replaced K+ alkalosis)
C. anaerobic gglycolysis
y y B. sodium citrate ( HCO3-
( : alkalosis)
( : wastes acidosis) C. sodium bicarbonate ( : HCO3- alkalosis)
D. alcoholism ( : wastes D. furosemide ( : alkalosis)
acidosis)
E. mannitol (( : acid-base balance
E. uremia ( : wastes products Pt. with volume overload)
ketoacidosis)
85
diuretic 86
85 86

barbiturate (weak acid)

(heart
(h t ffailure
il :

acute pulmonary edema) CHF
A
A. (
( : salts )
)


B. ( : )
A. mannitol ( : CHF volume load)
C
C. ( H+ )
( : )
B. hydrochlorothiazide ( : antiBP, onset )
D. ( : barbiturate
C. furosemide (
( loop diurtics with prompt onset :
urine base)
drug of choice of acute pulmonary edema)
E. ( : strong base : irritation)
NT 2008 : acute pulmonary edema
CHF NT 2008 : Henderson
Henderson-Hasselbalch
Hasselbalch equation
weak acid
87
alkaline urine : ionized form 88
87 88
 20 55 recurrent ventricular



? arrhythmia 5

increased
A. ( : systemic BP ) ESR pulmonary function diffuse lung capacity
B. ( : O2 x-ray diffuse interstitial pneumonia
intracranial pressure


volume)
C. ( : B) A. atenolol ( : -blockers choice C)
(
D
D. (
osmotic B. verapamilp (( : ADR ,, constipation)
p )
osmotic diuretic; mannitol : dehydration intracranial p.) C. propranolol ( : -blockers choice A)
E. vasoconstrictors ( : systemic BP D amiodarone (
D. ( class III :
ventricular
intracranial pressure) arrhythmia pulmonary fibrosis, thyroid dysfunction)
E procainamide
E. i id ( ( : class
l IA syndromed similar
i il tto SLE)
NT 2008 : indication of osmotic diuretics 89
SE class III : K+ blockers : amiodarone
90

89 90

50 chronic obstructive pulmonary 46 cholesterol

disease theophylline 14



2 CPK
theophylline

A. captopril ( : ACEI : antiBP side effect)
theophylline
A. rifampin ( : enzyme inducers theophylline ) B. propranolol ( : -blockers : antiBP side effect)
B. isoniazid (( : antiTbc,, SE : pperipheral
p neuritis,, ppolymorphism)
y p ) C. nicotinic acid (( : antilipidemia
p )
C. cimetidine ( H2 blockers with enzyme D. symvastatin ( HMG CoA reductase inhibitors
inhibitors : theophylline )) : creatine kinase activity )
D. hydrochlorothiazide ( : 1st drug for HT )
E. hydrochlorothiazide ( ( : thiazide diuretics : antiBP )
)
E. pyrazinamide ( : antiTbc )
91 92
drug interaction : enzyme inhibition SE HMG CoA reductase inhibitors
91 92
 30
QRS complex

BT 38.3 C BP
A. atrial depolarization ( : P wave)


B. atrial repolarization ( : ) friction rub Lt. lower substernal border
A. hydralazine ( : SE : lupus syndrome)
C. SA node depolarization ( : atrial contraction)
B. minoxidil ( : hypertrichosis; growth of hair)
D. ventricular depolarization ( QRS complex) C. propranolol ( : tremor, bradycardia, asthma)
E. ventricular repolarization ( : T wave) D captopril (
D. ( : dry cough
cough, taste disturbance)
E. sodium nitroprusside ( : massive hypotension,
cyanide accumulation; methemoglobinemia)

AP and surface EKG 93 SE : vasodilator : hydralazine : LE like syndrome 94

93 94

50 DM and HT metformin, glipizide,

56 warfarin
HCTZ, gemfibrozil, captopril (enalapril), aspirin, propranolol
cimetidine





A. vitamine K ( : warfarin) ?
A. propranolol (
( :
antiBP
Pt. DM)
B. warfarin ( cimetidine enzyme inhibitors)
B. captopril ( : antiBP : hyperkalemia Bl glu)
C
C. warfarin (
( :
toxic effect : bleeding )
)
C. hydrochlorothiazide; HCTZ ( : 1st antiBP : hyperglycemia)
D
D. gemfibrozil (
( :
fibric acid derivative : myositis,
myositis flu
flu-liked)
liked) D. warfarin ( : enzyme inhibitions)
D. aspirin ( : thrombolytics : GI side effects) D. warfarin low aspirin ( : Pt.


ASA mucous barrier :

)

drug interaction :
SE 95 drug interaction : enzyme inhibition 96

95 96
 58 congestive heart failure 50
HCTZ K+


choice

A. mannitol ( : CHF, load )
B. furosemide ( : side effect K+ ) : ACE inhibitors (captopril, enalapril)
C. acetazolamide (( : CAI : acidosis gglaucoma))
D. spironolactone ( sparing K+
common SE of ACEI renal insufficiency ( K+),
K+ sparings (triamterene amiloride)

placental blood flow (IUGR), angioedema and dysgeusia)
combination of diuretics :
additive effect
combined therapy : drug interaction of diuretics 97

97 98

60
congestive heart failure furosemide digitalis
(
( AP) isosorbide
i bid dinitrate
di it t
digitalis toxicity
(sure AP) ??
A hypokalemia (
A. ( : K+

digitalis)
A. guanylyl cyclase ( : denitration; NO cGMP
B. hyponatremia ( : Na+ : diuretic effect)
venodilation
dil ti >>> vasodilation
dil ti : preload)
l d)
C. hypochloremia ( : Cl- : diuretic effect )
B. 2-receptor ( : bronchodilators D hypocalcemia (
D. ( : Ca2+
hypercalcemia
centally 2-agonist : clonidine, methyldopa) digitalis furosemia)
C. ionized Ca2+
C ( ( : Ca2+ blockers : nifedipine) E. metabolic alkalosis ( : HCO3- digitalis)
D. 1-receptor ( : -blockers : propranolol)
drug interaction : K+
CHF
E. ACE ( : ACE inhibitors : enalapril)
mechanism
angina pectoris 99
((hypokalemia)
yp ) and digitalis
g toxicityy
99 100
 50 K+ sparing diuretics 60 hypertension enalapril
1


() A hyperkalemia (
A. ( : mechanism : aldosterone :
severe hyperkalemia ( K+) K+ aldosterone : renal insufficiency)

A. -blockers; prazosin ( : palpitation, postural hypotension) B. hypernatremia ( : Na+ )

B -blockers;
B. blockers; propranolol (
( : bradycardia,
bradycardia tremor) C. hyperuricemia
yp (( : uric acid )
C. direct vasodilators; hydralazine, minoxidil ( : LE, hypertrichosis) D. hypocalcemia ( : Ca2+ )
D. Ca2+ blockers; nifedipine, verapamil ( : flushing, constipation) E hypophosphatemia
E. h h h t i ( ( : PO42- ) )
E. ACE inhibitors; enalapril ( hyper K+)
combined therapy : drug interaction SE) SE enalapril technical term
101 102

101 102

Na+ : 130-146, K+ 3.2-4.6, Cl- 98-108, HCO3- 23-29

50
hypertension




K+= 6 (), Na+=135, Cl-


captopril amlodipine (nifedipine : anti BP)
( : K+ sparing diuretic : aldosterone
A spironolactone (
A.
A. captopril ( common side effect :
antagonist : K+ )
B. priqnerene ?? triamterene ( : C) captopril
/ )
C. amirolide (??? K+ sparing diuretic :
K+
B dose amlodipine (
B. ( : )
)

A

A
C) C. CXR ( : lung disease)
D. furosemide ( Pt. chronic renal failure) D. loratadine ( : antihistamine )
E. eplerenone ( : aldosterone antagonist : K+) E. dextromethorphan ( : : cough suppressants)

P e-103
Pt. common SE of ACEI



104

103 104
 glaucoma acetazolamide (CA inhibitors) 60




A urea (
A. ( : wastes protein) A. atenolol ( : selective 1 blockers )
B. glucose ( : osmotic diuretics (mannitol) glaucoma B. enalapril ( ACE inhibitors : common SE)
dehydrating effect intraoccular pressure) C meformin
C. f i ( ( :
antihypertensive
tih t i agents) t)
C. amino acid (( : acetazolamide)) D. verapamil ( : Ca2+ blockers : constipation
D. chloride ( : diuretics : natriuretic effect) insulin )
bi b t (
E bicarbonate
E. (
carbonic
b i anhydrase
hd E HCTZ (
E. ( : thiazide diuretics : impotence,
impotence hyperglycemia
hyperglycemia,
inhibitors : H2CO3 : inhibited HCO3- reabsorption) cholesterol, LDL )

mechanism of CAI; acetazolamide 105

common SE of ACE inhibitors 106

105 106

55 ischemic heart disease, hypertension 40

dyslipidemia JNC 7
p : K+ )),
severe heart failure ACEI ((enalapril (lifestyle modifications)

-blockers (propranolol) aldosterone antagonist A. ( : lifestyle modifications)
( i l t : spare K+)
(spironolactone B
B.

(
( : lifestyle
lif t l modifications)
difi ti )
A. hyperkalemia ( K+) ( : enalapril spironolactone) C. omega 3 ( : consume
B. hypermagnesemia ( : Mg2+) a diet rich of fruits, vegetables and low fat dairy products)
C hyponatremia (
C. ( : Na+) D. aerobic ( : lifestyle modifications)
E. ( : lifestyle modifications)
D. hypocalcemia ( : Ca2+)
E. hypophosphatemia ( : PO42-)
lifestyle modifications; JNC7 : 7
combined therapy py : drugg interaction SE)) 107

107 108