Coagulation cascade: extrinsic, intrinsic and common pathways differentiation

Video animation contents:

• Intrinsic pathway
• Extrinsic pathway (endothelium exposure to VIIa factor).
• Common pathway

Extrinsic, intinsic and common pathways

Hemostasis overview

The following animation depicts the process of hemostasis after endothelial damage (vasoconstriction, platelet adhesion, activation, interaction between coagulation factors and thrombin activation).

Hemostasis

Coagulation cascade learning module

This tutorial features interactive exercises and animations that help understand the role of coagulation cascade factors and physiological hemostatic processes.

It highlights clinical disorders on intrinsic and extrinsic pathways, with a special section overviewing Von Willebrand’s disease.

Clotting cascade learning module

Coagulation factors commented

This animation focuses exclusively on the coagulation cascade factors and its sequence of activation. It emphasises biochemical and laboratory aspects.

Coagulation factors

The animation below depicts the Jak-Stat signalling pathway mechanism:

As mentioned above, there are some expectations on the future of JAK STAT pathway in pharmacology:

JAK2 Inhibitors

Despite the success of imatinib mesylate in the treatment of CML, the genetic basis of the other major myeloproliferative disorders (polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis) has, until recently, remained obscure. It is now apparent that a common activating mutation in JAK2 (V617F) underlies the aberrant signaling and proliferation in most cases, although how one mutation leads to this spectrum of disorders remains unclear. The V617F mutation is found in the pseudokinase domain of JAK2, and disruption of this autoinhibitory region leads to unchecked activity of the kinase. Cells containing the JAK2 V617F mutation are growth inhibited and undergo apoptosis in response to specific JAK2 inhibitors in vitro. Thus, JAK2 inhibitors are under development for the treatment of polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

Source: Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy: D. Golan et al. LWW. 2007

Related links

Series Introduction: JAK-STAT signaling in human disease. Christian W. Schindler. J. Clin. Invest. 109(9): 1133-1137 (2002)

JAK-STAT signaling in asthma. Alessandra B. Pernis and Paul B. Rothman. J. Clin. Invest. 109(10): 1279-1283 (2002)

NRTIs mechanism

Nucleoside analog reverse transcriptase inhibitors (NRTIs) are nucleoside analogues that act as competitive inhibitors of HIV-1 reverse transcriptase. As shown in the animation, these drugs compete with nucleoside triphosphates for access to reverse transcriptase.

All NRTIs lack a 3-hydroxyl group; thus, their incorporation into a growing DNA chain results in its termination. They require intracytoplasmic activation via phosphorylation by cellular enzymes to the triphosphate form. Most have activity against HIV-2 as well as HIV-1.

NRTIs mechanism of action

List of NRTIs

• Zidovudine or azidothymidine (AZT) (also called ZDV): first approved drug in its class.
• Didanosine (ddI): second FDA-approved drug for the treatment of HIV infection.
• Tenofovir (TDF): first nucleotide analog. It has significant drug interactions.
• Lamivudine (3TC): also used in the treatment of HBV infection.
• Emtricitabine (FTC): acts as an inhibitor of HBV and HIV transcriptase.
• Abacavir (ABC): a guanosine analog.

Animations depicting mechanisms of other antiretrovirals

• HIV protease inhibitors
• HIV fusion inhibitors

References

Katzung, B. “Basic & Clinical Pharmacology”, 11th Edition. Mc Graw Hill Medical: 2009

Recommended reading

• The Sanford Guide to HIV/AIDS Therapy 2010
• Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (2009)
• HIV Essentials 2010
• HIV Diversity and Antiretroviral Resistance: Epidemiology, Recombination, HAART

About the animation author

.Dr. Gary Kaiser is a Professor of Microbiology at The Community College of Baltimore County, Catonsville Campus located in Baltimore, Maryland. Make sure you visit his excellent microbiology website: The Grapes of Staph.

.

Watch animation

They approach the following topics related to the neurobiology of drug addiction.

• Methamphetamine actions on dopamine vesicles.
• LSD action on serotonin receptors.
• Heroin effects on opioid receptors .
• How marijuana interacts with the cannabinoid system and its receptors.
• Activation of the GABA-A ionotropic receptor by alcohol.
• Cocaine action on dopamine reuptake.

This blog has a related post that explains nicotine addiction mechanism through a 3-D video animation.

Some clinical uses of IV vancomycin include treatment of infective endocarditis and sepsis caused by MRSA. Since vancomycin is poorly absorbed,  it is used only in treatment of enterocolitis caused by C. difficile.

Vancomycin adverse effects include skin flushing (red-man syndrome), fever, chills and phlebitis at the infusion site. Ototoxicity and nephrotoxicity must be kept in mind when treating patients that are receiving other drugs.

Mechanism of action

As you can see in the animation below, vancomycin binds to the pentapeptides of the peptidoglycan monomers and prevents the transglycosylation step in peptidoglycan polymerization. This weakens the cell wall and damages the underlying cell membrane.

About the animation author

Dr. Kaiser enjoys riding his Harley-Davidson Low Ride

.

.

Dr. Gary Kaiser is a Professor of Microbiology at The Community College of Baltimore County, Catonsville Campus located in Baltimore, Maryland. Make sure you visit his excellent microbiology website: The Grapes of Staph.

.

.

.

References

Golan, David E (editor). “Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy”, 2nd edition. LWW: 2008.

Harvey, R; Champe, P (series editors). “Lippincott illustrated reviews: Pharmacology”, 4th edition. LWW: 2009.

Gilbert, D; Moellering R (editors) “Sanford Guide to Antimicrobial Therapy”, 39th edition. Antimicrobial therapy: 2009

Hauser, A. “Antibiotic Basics for Clinicians: Choosing the Right Antibacterial Agent”.1st edition. LWW:2007

Gallagher, J. “Antibiotics Simplified”. 1st edition. Jones & Bartlett Publishers: 2008

Transcript of the video narration:

“Although nicotine can interact with a variety of receptor at numerous tissues, it is its interaction with specific receptors in the brain that creates the dependence associated with smoking.

Within the midbrain, nicotine interacts with the alpha 4 beta 2 nicotinic acetylcholine receptor. Acetylcholine is the natural ligand for this receptors. However, nicotine also an acetylcholine receptor agonist, has a higher affinity for the α4β2 (alpha 4 beta 2) receptors. Located on postsynaptic neurons, these receptors are comprised by two α4 and three β2 subunits that form a channel for transporting ions through the membrane.

When two molecules of nicotine or another ligand engage binding sites within the ionotropic receptor, the ion channel is activated. Looking into the receptor, we see that it is closed, but activation by ligand triggers channel opening for the passage of calcium, sodium and potassium ions.This generates action potentials to the reward area of the brain. Here, the impulse stimulates the release of neurotransmitters including dopamine. Dopamine triggers additional signaling events that stimulate the reward circuit generating short feelings of well-being, increased attention and improved mood. Every time tobacco is used, dopamine levels surge. However, nicotine is eliminated rather rapidly, causing dopamine levels to decline. The result: a craving for more nicotine.

With continued use, α4β2 (alpha 4 beta 2) nicotinic receptors undergo complex adaptive changes including up regulation and desensitization. Over time, these and other downstream changes contribute to a stronger need for nicotine stimulation to achieve the rewards of smoking.”

Digoxin is indicated in the treatment of atrial fibrillation, atrial flutter and heart failure (currently it is not a first line treatment).

This excerpt explains digoxin effects on cardiac contractility and autonomic regulation of the electrophysiologic properties of the heart.

From: Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 2nd edition. D.Golan

Digoxin

Digoxin is a selective inhibitor of the plasma membrane sodium pump.

Cardiac myocytes exposed to digoxin extrude less sodium, leading to a rise in intracellular sodium concentration. In turn, the increase in intracellular sodium concentration alters the equilibrium of the sodium–calcium exchanger: calcium efflux is decreased because the gradient for sodium entry is decreased, while calcium influx is increased because the gradient for sodium efflux is increased. The net result is a rise in the intracellular calcium concentration. In response to this rise, the SR of the digoxin-treated cell sequesters more calcium. When the digoxin-treated cell depolarizes in response to an action potential, there is more Ca²⁺ available to bind troponin C, and tension development during contraction is facilitated.

In addition to its effects on myocardial contractility, digoxin exerts autonomic effects through its binding to sodium pumps in the plasma membranes of neurons in the central and peripheral nervous systems. These effects include inhibition of sympathetic nervous outflow, sensitization of baroreceptors, and increased parasympathetic (vagal) tone. Digoxin also alters the electrophysiologic properties of the heart by a direct action on the cardiac conduction system. At therapeutic doses, digoxin decreases automaticity at the AV node, prolonging the effective refractory period of AV nodal tissue and slowing conduction velocity through the node. These combined vagotonic and electrophysiologic properties underlie the use of digoxin in the treatment of patients with atrial fibrillation and rapid ventricular response rates; both the decreased automaticity of AV nodal tissue and the decreased conduction velocity through the node increase the degree of AV block, and thereby decrease the ventricular response rate.

In contrast to its effects at the AV node, digoxin enhances automaticity of the infranodal (His–Purkinje) conduction system. These divergent effects at the AV node and His– Purkinje system explain the characteristic electrophysiologic disturbance of complete heart block with accelerated junctional or accelerated idioventricular escape rhythm (referred to as “regularized” atrial fibrillation) in patients with digoxin toxicity.

Digoxin is commonly marketed under the trade names Lanoxin, Digitek, and Lanoxicaps

First, a video that analyzes the factors that affect drug distribution: protein binding, molecular weight and lipid solubility.

Authors: Nelson Caetano, Dr. Jef Bratberg. University of Rhode Island

A transcript of the explanatory text:

Unbound drug passes freely through blood vessels and is distributed into the rest of the body. Protein bound drug is trapped within the vessel and is therefore unable to reach its intended sight of action.

Small drug molecules can freely diffuse out of the blood vessel while large drug molecules are confined to the plasma. Heparin is a good example of a drug like this.

Lipid solubility of a drug is a major component in determining its distribution, particularly on the brain. The blood brain barrier prevents the crossing of polarized molecules from capillaries to brain neurons.

The slides below are part of a lecture I give about pharmacokinetics. I chose the slides that explain the meaning of the different values of volume of distribution.

A drug that has a volume of distribution near the plasma volume (e.g. 5 liters) is a drug distributed mainly in the intravascular space. A drug with a very high volume of distribution ( hundreds of liters) should guide us to think that is a drug that bind very strongly to a particular tissue.

Antihypertensives
Item Number: 11201   correct answer: 4  category: Antihypertensives
1.   Gynecomastia, hyperkalemia, and menstrual abnormalities are potential adverse
effects associated with:
A.  amiloride
B.  captopril
C.  triamterene
D.  spironolactone
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11218   correct answer: 2  category: Antihypertensives
2.   Diuretics which may result in hyperkalemia when used in a patient also
receiving potassium supplementation include:
A.  amiloride
B.  mannitol
C.  triamterene
D.  bumetanide
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11220   correct answer: 1  category: Antihypertensives
3.   Metabolic alkalosis may be a complication of the administration of:
A.  hydrochlorothiazide
B.  bumetanide
C.  furosemide
D.  acetazolamide
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11244   correct answer: 2  category: Antihypertensives
4.   Beta blockers which are relatively cardioselective include:
A.  metoprolol
B.  pindolol
C.  atenolol
D.  timolol
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11288   correct answer: 2  category: Antihypertensives
5.   Reflex tachycardia is not likely to occur during therapy with:
A.  clonidine
B.  diazoxide
C.  reserpine
D.  minoxidil
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11308   correct answer: 3  category: Antihypertensives
6.   Beta blockers which may be less likely to produce CNS-related adverse effects
include
A.  metoprolol
B.  nadolol
C.  timolol
D.  atenolol
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11316   correct answer: 4  category: Antihypertensives
7.   Guanadrel is pharmacologically similar to:
A.  clonidine
B.  guanabenz
C.  methyldopa
D.  guanethidine
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11335   correct answer: 1  category: Antihypertensives
8.   Adverse effects associated with guanethidine include:
A.  orthostatic hypotension
B.  enhanced sensitivity to sympathomimetics
C.  diarrhea
D.  sedation
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11340   correct answer: 2  category: Antihypertensives
9.   Adverse effects associated with hydralazine include:
A.  reflex tachycardia
B.  hypertrichosis
C.  lupus syndrome
D.  orthostatic hypotension
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11341   correct answer: 2  category: Antihypertensives
10.   Risk factors associated with increased risk of toxicity during captopril
therapy include:
A.  bilateral renal artery stenosis
B.  congestive heart failure
C.  systemic lupus erythematosus
D.  female gender
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 684   correct answer: 4  category: Antihypertensives
11.   Diazoxide, a drug used for treatment of hypertensive crises, is most closely
related to:
1. nitrofuran
2. sulfonamides
3. dopamine antagonists
4. thiazide diuretics
5. nitrates

Item Number: 807   correct answer: 2  category: Antihypertensives
12.   Which of the following drugs is(are) known to induce hyperuricemia and
occasionally to bring about an acute gouty attack?
1. salicylates (6 grams per day)
2. chlorothiazide
3. phenytoin
4. spironolactone
5. All of the above

Item Number: 1186   correct answer: 4  category: Antihypertensives
13.   Undesirable side effects of reserpine include:
1. bradycardia
2. postural hypotension
3. diarrhea
4. All of the above
5. None of the above

Item Number: 1858   correct answer: 3  category: Antihypertensives
14.   Propranolol may cause all of the following EXCEPT:
1. bradycardia
2. bronchiolar constriction
3. hyperglycemia
4. reduced myocardial contractility
5. prevention of the dilation of vessels caused by circulating epinephrine

Item Number: 2883   correct answer: 5  category: Antihypertensives
15.   Alpha methyldopa has been used successfully in the control of hypertension.
Side effects include all of the following, EXCEPT:
1. positive direct Coomb’s test
2. diarrhea
3. hemolytic anemia
4. fever
5. nephrotic syndrome

Item Number: 3538   correct answer: 3  category: Antihypertensives
16.   A 48-year old salesman with known hypertension complains of a decreasing
annual income, a loss of “drive”, and a depressed outlook on life. His blood
pressure is normal on medication. The antihypertensive drug most likely to be
the cause of his new complaints is:
1. hydralazine
2. alpha methyldopa
3. reserpine
4. hydrochlorothiazide
5. guanethidine

Item Number: 6258   correct answer: 1  category: Antihypertensives
17.   Side effects of medications are often responsible for a patient not complying
with the prescribed drug regimen.  An agent which has somnolence as a primary
side effect is:
1. methyldopa
2. hydralazine
3. guanethidine
4. 1,2
5. 1,3

Item Number: 6259   correct answer: 4  category: Antihypertensives
18.   One of the mechanisms for ‘resistance” to an antihypertensive drug regimen is
a retention of salt and water and an increase in extracellular fluid volume.
Agents which have been shown to cause retention of salt and water include:
1. methyldopa
2. clonidine
3. guanethidine
4. All of the above
5. 1,2

Item Number: 6273   correct answer: 4  category: Antihypertensives
19.   Clonidine hydrochloride lowers blood pressure by reducing sympathetic tone.
It is believed to act by inhibiting sympathetic outflow from the vasomotor
center in the medulla.  A potentially serious adverse reaction that has been
reported is:
1. ventricular fibrillation
2. anaphylaxis
3. irreversible nephrotoxicity
4. withdrawal syndrome resembling hypertensive crisis
5. systemic lupus erythematosus

Item Number: 6274   correct answer: 4  category: Antihypertensives
20.   Propranolol produces most of its important effects by antagonizing the beta
adrenergic effects of catecholamines released by sympathetic nerve stimulation
or from the adrenal medulla. It therefore results in all of the following
EXCEPT:
1. negative inotropic effect on the heart
2. bronchoconstriction
3. lowering plasma renin activity
4. hyperglycemia
5. negative chronotropic effect on the heart

Item Number: 7929   correct answer: 3  category: Antihypertensives
21.   The antihypertensive agent most likely to increase cardiac output is:
1. chlorothiazide
2. reserpine
3. hydralazine
4. alpha-methyldopa
5. guanethidine

Item Number: 8117   correct answer: 1  category: Antihypertensives
22.   An agent which produces its antihypertensive effect by blocking autonomic
ganglia, thus lowering the sympathetic tone of blood vessels, is:
1. trimethaphan
2. diazoxide
3. phenoxybenzamine
4. reserpine
5. alpha-methyldopa

Item Number: 8236   correct answer: 1  category: Antihypertensives
23.   The most useful drugs in the long-term treatment of essential hypertension
are:
1. thiazide diuretics
2. osmotic diuretics
3. mercurial diuretics
4. carbonic anhydrase inhibitors
5. xanthine diuretics

Item Number: 8321   correct answer: 5  category: Antihypertensives
24.   Antihypertensive agents that act primarily at arterioles include:
1. hydralazine
2. minoxidil
3. diazoxide
4. nitroglycerin
5. 1,2,3

Item Number: 8332   correct answer: 1  category: Antihypertensives
25.   Antihypertensive agents have different modes of action. The expected
onset of action of IV nitroprusside is:
1. seconds
2. several minutes
3. 15 to 30 minutes
4. several hours
5. 12 to 24 hours

Item Number: 8354   correct answer: 4  category: Antihypertensives
26.   Antihypertensive agents must be used with caution.  The medical condition for
which methyldopa is most contraindicated is:
1. renal insufficiency
2. coronary insufficiency
3. mental depression
4. liver disease
5. asthma

Item Number: 8364   correct answer: 2  category: Antihypertensives
27.   Antihypertensive agents must be used with caution. The medical condition for
which hydralazine is most contraindicated is:
1. renal insufficiency
2. coronary insufficiency
3. mental depression
4. liver disease
5. asthma

Item Number: 8375   correct answer: 3  category: Antihypertensives
28.   Antihypertensive agents must be used with caution. The medical condition for
which reserpine is most contraindicated is:
1. renal insufficiency
2. coronary insufficiency
3. mental depression
4. liver disease
5. asthma

Item Number: 9618   correct answer: 5  category: Antihypertensives
29.   Reduced tissue levels of norepinephrine may result from long-term treatment
with:
1. guanethidine
2. reserpine
3. alpha-methyl-tyrosine
4. All of the above
5. 1,2

Item Number: 11387   correct answer: 1  category: Antihypertensives
30.   Propranolol is a potent blocker of beta-adrenergic sympathetic activity. It
has been found to be detrimental, however, in patients with:
1. bronchial asthma
2. hypertension
3. hyperthyroidism
4. atrial fibrillation
5. ventricular arrhythmias

Item Number: 13199   correct answer: 4  category: Antihypertensives
31.   It is important to understand the mechanism of action of the various drugs
used in the treatment of hypertension. The antihypertensive action of
propranolol involves all of the following EXCEPT:
1. decreased stroke volume
2. inhibition of renin release
3. central nervous system effect
4. depletion of catecholamines
5. decreased heart rate

Item Number: 13202   correct answer: 4  category: Antihypertensives
32.   It is important to understand the side effects of the various antihypertensive
agents. Drugs such as guanethidine that block the function of postganglionic
adrenergic neurons may produce all of the following EXCEPT:
1. orthostatic hypotension
2. bradycardia
3. retrograde ejaculation
4. constipation
5. dry mouth

Item Number: 13701   correct answer: 4  category: Antihypertensives
33.   Propranolol is contraindicated in all of the following EXCEPT:
1. bronchial asthma
2. sinus bradycardia
3. second or third degree heart block
4. migraine headache prophylaxis
5. congestive heart failure

Item Number: 13713   correct answer: 4  category: Antihypertensives
34.   Which of the following diuretics has a greater antihypertensive activity?
1. hydrochlorothiazide 50 mg
2. chlorothiazide 500 mg
3. spironolactone 100 mg
4. all are equivalent antihypertensive agents
5. 1,2

Item Number: 13717   correct answer: 2  category: Antihypertensives
35.   A patient complains of headache and his blood pressure is 120/80. His
medications include hydrochlorothiazide and hydralazine. Which of the
following would seem most likely?
1. The headaches are secondary to thiazide-induced hypokalemia
2. The headaches are secondary to hydralazine therapy
3. The headaches are probably unrelated to drug therapy
4. The headaches are related to hydralazine-induced agranulocytosis
5. 1,2

Item Number: 13718   correct answer: 4  category: Antihypertensives
36.  A patient is admitted to the hospital for surgery and has been taking 2.4 mg
of clonidine plus 50 mg hydrochlorothiazide daily for several months prior to
surgery.  You would expect in this patient:
1. A low likelihood of problems if the clonidine is continued
2. A possibility of markedly increased blood pressure if the clonidine is
stopped
3. Severe postural hypotension if clonidine is discontinued abruptly
4. 1,2
5. 1,3

Item Number: 13719   correct answer: 5  category: Antihypertensives
37.   Drugs which may have their effectiveness diminished if the patient
concomitantly receives a tricyclic antidepressant include:
1. hydralazine
2. guanethidine
3. clonidine
4. 1,2
5. 2,3

Item Number: 13720   correct answer: 4  category: Antihypertensives
38.   Tachycardia is a prominent side effect of:
1. diazoxide
2. hydralazine
3. clonidine
4. 1,2
5. 2,3

Item Number: 13722   correct answer: 2  category: Antihypertensives
39.   All of the following statements concerning the use of sodium nitroprusside are
true EXCEPT:
1. it is metabolized to thiocyanate
2. it must be given by rapid IV push injection
3. it dilates both arterial and venous vessels
4. 1,3
5. 2,3

Item Number: 488   correct answer: 2  category: Antihypertensives
40.   Chronic administration of ethacrynic acid without proper electrolyte
management produces:
1. potassium retention
2. metabolic alkalosis
3. metabolic acidosis
4. excessive inhibition of carbonic anhydrase
5. respiratory alkalosis

Item Number: 578   correct answer: 3  category: Antihypertensives
41.   A diuretic agent which has been associated with hearing loss when given
intravenously is:
1. spironolactone
2. triamterene
3. ethacrynic acid
4. chlorothiazide
5. sucrose

Item Number: 579   correct answer: 1  category: Antihypertensives
42.   A diuretic agent which has a steroid-like nucleus is:
1. spironolactone
2. triamterene
3. ethacrynic acid
4. chlorothiazide
5. sucrose

Item Number: 580   correct answer: 1  category: Antihypertensives
43.   The diuretic agent which acts by inhibiting aldosterone at the distal tubular
renal cell is:
1. spironolactone
2. triamterene
3. ethacrynic acid
4. chlorothiazide
5. bumetanide

Item Number: 581   correct answer: 2  category: Antihypertensives
44.   A diuretic agent which is potassium-sparing and does not depend upon the
adrenal cortex for action is:
1. spironolactone
2. triamterene
3. ethacrynic acid
4. chlorothiazide
5. sucrose

Item Number: 583   correct answer: 4  category: Antihypertensives
45.   Which of the following diuretic agents may produce hypokalemic alkalosis but
is a very useful drug in the treatment of volume-dependent hypertension?
1. spironolactone
2. triamterene
3. amiloride
4. chlorothiazide
5. sucrose

Item Number: 2787   correct answer: 2  category: Antihypertensives
46.   Hypercalcemia following thiazide administration is characterized by which of
the following?
1. hypercalciuria
2. hypocalciuria
3. increased serum phosphorus
4. decreased serum phosphorus
5. increased urinary phosphorus

Item Number: 2804   correct answer: 2  category: Antihypertensives
47.   The diuretic agent, furosemide, is known to produce:
1. decreased renin production and aldosterone release
2. increased renal blood flow and glomerular filtration rate
3. redistribution of blood from the renal cortex to the medulla
4. All of the above
5. 1,3

Item Number: 3241   correct answer: 2  category: Antihypertensives
48.   Complications of treatment of edema with thiazides include all of the
following EXCEPT:
1. hyperuricemia
2. hyperkalemia
3. hyperglycemia
4. hyponatremia
5. alkalosis

Item Number: 3449   correct answer: 3  category: Antihypertensives
49.   Possible consequences of chlorothiazide administration include all of the
following EXCEPT:
1. thrombocytopenia and agranulocytosis
2. jaundice, skin eruptions, and photosensitivities
3. hypoglycemia
4. hypokalemic nephropathy
5. hyperuricemia

Item Number: 3543   correct answer: 4  category: Antihypertensives
50.   Which of the following diuretics may cause hyperkalemia:
1. ethacrynic acid
2. mercurials
3. thiazides
4. triamterene
5. acetazolamide

Item Number: 3911   correct answer: 3  category: Antihypertensives
51.   The dominant action of the thiazide diuretics (e.g. hydrochlorothiazide)is to
increase the renal excretion of sodium and chloride and an accompanying volume
of water.  This results from:
1. alterations in acid-base balance
2. an indirect renal effect
3. inhibition of the tubular mechanisms of electrolyte transport
4. increased glomerular filtration rate
5. inhibition of carbonic anhydrase

Item Number: 3919   correct answer: 3  category: Antihypertensives
52.   The oral diuretics are an effective group of drugs in the treatment of
hypertension. The mechanism of action mainly responsible for the reduction of
blood pressure after 2 months of treatment is:
1. reduction in plasma volume
2. reduction in cardiac output
3. drug-induced saluresis
4. reduction in serum potassium concentration
5. effects on the neurotransmission at adrenergic ganglions

Item Number: 4308   correct answer: 4  category: Antihypertensives
53.   About 20 percent of adults in north America have arterial blood pressures
above the normal range. The aldosterone antagonist, spironolactone, has been
used to treat hypertension with some success. Side effects of spironolactone
include:
1. hyponatremia
2. azotemia
3. gynecomastia
4. all of the above
5. 1,3

Item Number: 4437   correct answer: 3  category: Antihypertensives
54.   The effectiveness of which of the following diuretics is diminished in
metabolic acidosis?
1. triamterene
2. spironolactone
3. acetazolamide
4. All of the above
5. 1,3

Item Number: 4775   correct answer: 3  category: Antihypertensives
55.  The inhibition of carbonic anhydrase in proximal renal tubular cells caused by
acetazolamide causes a loss in urine of:
1. hydrogen ions
2. glucose
3. bicarbonate ions
4. glycine
5. None of the above

Item Number: 7278   correct answer: 4  category: Antihypertensives
56.  Complications common to ethacrynic acid and thiazides include:
1. alkalosis
2. potassium depletion
3. hyperuricemia
4. All of the above
5. 1,3

Item Number: 7930   correct answer: 5  category: Antihypertensives
57.   Hypokalemia may result from all of the following EXCEPT:
1. flumethiazide
2. hydrochlorothiazide
3. chlorthalidone
4. bendroflumethiazide
5. triamterene

Item Number: 8226   correct answer: 5  category: Antihypertensives
58.   Hypochloremic alkalosis may result from prolonged use of:
1. furosemide
2. mannitol
3. ethacrynic acid
4. All of the above
5. 1,3

Item Number: 8320   correct answer: 2  category: Antihypertensives
59.   Triamterene:
1. antagonizes aldosterone
2. can produce systemic hyperkalemia
3. is classified as a sodium-sparing diuretic
4. is of no clinical usefulness
5. interferes with the diuretic activity of spironolactone

Item Number: 8365   correct answer: 1  category: Antihypertensives
60.   Antihypertensive agents must be used with caution.  The medical condition for
which spironolactone is most contraindicated is:
1. renal insufficiency
2. coronary insufficiency
3. central depression
4. liver disease
5. asthma

Item Number: 8418   correct answer: 1  category: Antihypertensives
61.   With which of the following side effects is spironolactone most closely
identified with?
1. hyperkalemia
2. metabolic acidosis
3. metabolic alkalosis
4. hypoglycemia
5. hypokalemia

Item Number: 8822   correct answer: 3  category: Antihypertensives
62.   A diuretic which acts by inhibition of the sodium-hydrogen exchange is:
1. furosemide
2. chlormerodrin
3. acetazolamide
4. mannitol
5. triamterene

Item Number: 10292   correct answer: 2  category: Antihypertensives
63.   To achieve smooth reduction of blood pressure, all of the oral diuretics
must be administered at least once daily.  Maximum effectiveness is achieved only
after:
1. 1 to 2 weeks
2. 3 to 4 weeks
3. 5 to 6 weeks
4. 7 to 8 weeks
5. 9 to 10 weeks

Item Number: 10293   correct answer: 3  category: Antihypertensives
64.   Diuretics may reduce blood pressure through several mechanisms. The critical
effect, however, appears to be:
1. reduction of vascular smooth muscle reactivity
2. effect on autonomic control of vascular tone
3. reduction of total body sodium content
4. effect on electrolyte content of arterial tissues
5. reduction of plasma renin activity

Item Number: 11201   correct answer: 4  category: Antihypertensives
65.   Gynecomastia, hyperkalemia, and menstrual abnormalities are potential adverse
effects associated with:
A.  amiloride
B.  captopril
C.  triamterene
D.  spironolactone
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11218   correct answer: 2  category: Antihypertensives
66.   Diuretics which should not be used in a patient also receiving potassium
supplementation include:
A.  amiloride
B.  mannitol
C.  triamterene
D.  bumetanide
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 11220   correct answer: 1  category: Antihypertensives
67.   Metabolic alkalosis is a complication of the administration of:
A.  hydrochlorothiazide
B.  bumetanide
C.  furosemide
D.  acetazolamide
1. A,B,C
2. A,C
3. B,D
4. D only
5. All are correct

Item Number: 13710   correct answer: 3  category: Antihypertensives
68.    Which of the following drugs may be hazardous if give to a patient receiving
spironolactone?
1. epinephrine
2. propranolol
3. potassium chloride
4. monoamine oxidase inhibitors
5. All of the above

Item Number: 13715   correct answer: 1  category: Antihypertensives
69.   A side effect of spironolactone, when utilized to treat hypertension is:
1. hyperkalemia
2. acne
3. hypomagnesemia
4. male pattern baldness
5. bronchospasm

Item Number: 13823   correct answer: 1  category: Antihypertensives
70.   The principle site of action of furosemide is the:
1. ascending loop of Henle
2. descending loop of Henle
3. proximal tubule
4. distal tubule
5. None of the above

Item Number: 13824   correct answer: 3  category: Antihypertensives
71.   The site of action of mannitol is:
1. ascending loop of Henle
2. descending loop of Henle
3. proximal tubule
4. distal tubule
5. None of the above

Item Number: 14202   correct answer: 5  category: Antihypertensives
72.   A diuretic which is contraindicated in a patient with hyperkalemia is:
1. acetazolamide
2. chlorothiazide
3. ethacrynic acid
4. furosemide
5. spironolactone

More USMLE pharmacology questions

Mechanism of action, pharmacokinetics and properties of: Thiopental, Phenobarbital, Methohexital and Pentobarbital

Great aid to review this topic for your pharmacology test, like USMLE step 1.