Tag: Potassium Channel Openers

Potassium Channel Openers

POTASSIUM CHANNEL OPENERS

Q. 1

A 38 year old woman being treated for hypertension and diabetes has the sudden onset of swelling and tenderness of the wrists and knees. On examination she is febrile and flushed. A friction rub can be heard at the left lower sterna border. Which of the following drug is most likely the cause of these findings?
 A Metformin
 B Hydralazine
 C Minoxidil
 D Nitroprusside
Q. 1

A 38 year old woman being treated for hypertension and diabetes has the sudden onset of swelling and tenderness of the wrists and knees. On examination she is febrile and flushed. A friction rub can be heard at the left lower sterna border. Which of the following drug is most likely the cause of these findings?
 A Metformin
 B Hydralazine
 C Minoxidil
 D Nitroprusside
Ans. B

Explanation:

Hydralazine

Drug  induced  lupus  refers  to  a  form  of  lupus caused by medication, it causes some symptoms similar to those of SLE (arthritis, rash, fever, and chest pain, but no kidney involvement ) that go away when the drug is Stopped common medications that may cause drug-induced lupus include hydralazine (Apresoline), procainamide (Procan, Pronestyl), methyldopa (Aldomet), quinidine (Quinaglute), isoniazid (INH), and some anti-seizure medications such as phenytoin (Dilantin) or carbamazepine (Tegretol) compications are more common in females. It is also more common in ‘slow acetylators’ since the metabolism of hydralazin is reduced in these patients.


Q. 2

Which of the following is true about diazoxide except 

 A

K+ channel opener

 B >Can be used as antihypertensive agent
 C >Causes severe hypoglycemia
 D >Used in insulinoma
Q. 2

Which of the following is true about diazoxide except 

 A

K+ channel opener

 B >Can be used as antihypertensive agent
 C >Causes severe hypoglycemia
 D >Used in insulinoma
Ans. C

Explanation:

Causes severe hypoglycemia [Ref : Harrison 17/e p 2564, 2355; Katzung II/e p. 180; Lawrence 10/e p. 424, 621; KDT 6/c p 274, 548, 554]

Diazoxide

  • Diazoxide is a direct acting arteriolar dilator.
  • Diazoxide causes arteriolar dilatation with little effect on veins.

Diazoxide prevents smooth muscle contraction and relaxes the arterioles

  • Diazoxide is a potassium channel activator which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions. This switches off voltage gated calcium ion channel which inhibits the generation of action potential.

When used as an intravenous antihypertensive agent diazoxide causes excessive hypotension.

  • Diazoxide was formerlyused as an intravenous bolus dose for the at of hypertensive emergencies.
  • But the dangers of excessive hypotension are now recognized to outweigh the benefit, and its emergency use is obsolete.
  • Hypotension due to diazoxide has resulted in stroke and myocardial infarction.

–      The reflex sympathetic response due to hypotension can provoke angina, electrocardiographic evidence of ischemia and cardiac failure in patients with ischemic heart disease and diazoxide should be avoided in this situation.

Diazoxide produces hyperglycemia by increasing insulin secretion, therefore it is used to treat various forms of hypoglycemia

  • Diazoxide activates the same potassium channel in the pancreatic islet cells that is blocked by sulfonylureas.
  • SullOnylureas close the potassium channels and increase insulin secretion whereas diazoxide opens the potassium channel in pancreatic islet cells and decrease insulin secretion.
  • Due to its hyperglycemic action it is a useful drug for patients with chronic hypoglycemia from excess endogenous insulin secretion, either from an iselt cell tumour (insulinoma) or islet cell hyperplasia.

According to Lawerence

  • Diazoxide stimulates the ATP dependent r channel that is blocked by the sulphonylureas. Therefore its chronic use  as an antihypertensive agent is precluded by the development of diabetes. Indeed its use in therapeutics should now be confined to rare indication of treating hypoglycemia due to islet cell tumour (insulinoma).
  • Diazoxide is chemically related to thiazide diuretics. But in contrast to the structurally related thiazide diuretics, diazoxide causes renal salt and water retention.

Q. 3

Which of the following agent decreases cardiac afterload?

 A

Nicorandil

 B

Glyceryl trinitrate

 C

Isosorbide dinitrate

 D

None

Q. 3

Which of the following agent decreases cardiac afterload?

 A

Nicorandil

 B

Glyceryl trinitrate

 C

Isosorbide dinitrate

 D

None

Ans. A

Explanation:

Nicorandil reduces afterload and preload, while in the coronary circulation it dilates both the large epicardial and smaller resistance vessels. Because Nicorandil is an anteriolar dilator and hence primarily decrease after load.

Hydralazine and minoxidil reduce afterload by relaxing arteriolar smooth muscle. The venodilators and diuretics are used to decrease preload. The venodilators include nitroglycerine and isosorbide dinitrite. Drugs that reduce both prelod and afterload include nitroprusside, prazosin, ACE inhibitors and angiotensin II receptor blockers.

Quiz In Between


Q. 4

Preferred drugs in clinical situations associated with hypertensive emergencies:

a) Nitroprusside is preferred in aortic dissection
b) Phentolamine is the first choice in adrenergic crisis
c) Hydralazine is preferred in eclampsia
d) Nitroglycerin is best in acute left ventricular failure
e) Nicardipine in case of cerebrovascular accidents
 

 A

All true

 B

c,d,e-True & a,b-false

 C

a,e-True & b,c,d-False

 D

a,b,d, e-True & c-False

Q. 4

Preferred drugs in clinical situations associated with hypertensive emergencies:

a) Nitroprusside is preferred in aortic dissection
b) Phentolamine is the first choice in adrenergic crisis
c) Hydralazine is preferred in eclampsia
d) Nitroglycerin is best in acute left ventricular failure
e) Nicardipine in case of cerebrovascular accidents
 

 A

All true

 B

c,d,e-True & a,b-false

 C

a,e-True & b,c,d-False

 D

a,b,d, e-True & c-False

Ans. A

Explanation:

Nitroprusside is prefered in aortic dissection, Phentolamine in aortic crisis, Hydralazine in eclampsia, nitroglycerine in hypertension associated with LV Failure and nicardipine in CVA

Ref: Harrisons, Edition18 , Page – 2058

 


Q. 5

One of the following statements about hydralazine is not true –

 A

It causes direct relaxation of blood vessels

 B

It causes dilatation of both arteries and veins

 C

Postural hypotension is not a common problem

 D

It increases plasma rennin activity

Q. 5

One of the following statements about hydralazine is not true –

 A

It causes direct relaxation of blood vessels

 B

It causes dilatation of both arteries and veins

 C

Postural hypotension is not a common problem

 D

It increases plasma rennin activity

Ans. B

Explanation:

Ans. is ‘b’ i.e., It causes dilatation of both arteries and veins

o Hydralation is a potent vasodilator

o It acts as a vasodilator by directly acting on arterioles. It has negligible effect on veins.

o There is also renin release with secondary salt and water retention.

o Postural hypotension is not a prominent action because of little action on veins; venous return and cardiac output are not reduced.


Q. 6

Which of the following is a K+ channel opener?

 A

Nifedipine

 B

Minoxidil

 C

Enalapril

 D

Atenolol

Q. 6

Which of the following is a K+ channel opener?

 A

Nifedipine

 B

Minoxidil

 C

Enalapril

 D

Atenolol

Ans. B

Explanation:

Ans. is ‘b’ i.e., Minoxidil

K+ channel openers are minoxidil, diazoxide and nicorandil.

Quiz In Between


Q. 7

Diazoxide acts by –

 A

Increasing insulin release

 B

Inhibiting insulin release

 C

Inhibiting insulin release

 D

Inhibiting glucagon release

Q. 7

Diazoxide acts by –

 A

Increasing insulin release

 B

Inhibiting insulin release

 C

Inhibiting insulin release

 D

Inhibiting glucagon release

Ans. B

Explanation:

Ans. is ‘b’ i.e., Inhibiting insulin release

  • Diazoxide inhibits insulin release from P-cells and causes hyperglycemia.

o Its action on ATP sensitive IC channel is opposite to that of sulfonylureas —> opening (activation) of IC channels –> Hyperpolarization —> inhibition of insulin release.

o Other actions which contribute to hyperglycemia

a)      peripheral utilization of glucose

b)       Release of catecholamines

It is used in insulinoma.


Q. 8

Which of the following is true about diazoxide except

 A

K+ channel opener

 B

Can be used as antihypertensive agent

 C

Causes severe hypoglycemia

 D

Used in insulinoma

Q. 8

Which of the following is true about diazoxide except

 A

K+ channel opener

 B

Can be used as antihypertensive agent

 C

Causes severe hypoglycemia

 D

Used in insulinoma

Ans. C

Explanation:

Ans. is ‘c’ i.e., Causes severe hypoglycemia

  • Diazoxide causes hyperglycemia. not hypoglycemia (see above explanation)
  • Diazoxide acts mainly by inhibiting the release of insulin by activating K+ channels.
  • Therefore, it is used in insulinoma.

Diazoxide has been used as antihypertensive agent, especially in hypertensive emergencies. However, it can cause excessive hypotension which may precipitate stroke and MI. Therefore, its use in hypertensive emergencies is obso­lete now.


Q. 9

8 year old child presented with altered sensorium and seizure on examination BP was 180/120. Correct statements –

 A

Sodium nitroprusside drips

 B

Cause of hypertension is essential hypertension

 C

IV labetolol, hydralazine, and diazoxide are given

 D

a and c

Q. 9

8 year old child presented with altered sensorium and seizure on examination BP was 180/120. Correct statements –

 A

Sodium nitroprusside drips

 B

Cause of hypertension is essential hypertension

 C

IV labetolol, hydralazine, and diazoxide are given

 D

a and c

Ans. D

Explanation:

Ans. is ‘a’ i.e., Sodium nitroprusside drips; ‘c’ i.e., IV labetolol, hydralazine, and diazoxide are given

Treatment of hypertensive crisis

  • It is important to select an agent with a rapid and predictable onset of action and to monitor BP carecully as it is being reduced.
  • Intravenous administration is often preferred.

o Because too rapid reduction in BP may interfere with adequate organ perfusion, a stepwise reduction should be planned.

i)   The pressure should be reduced by about 1/3 of the total planned reduction during.first 6 hours.

ii)    The remaining amount is reduced over the following 48-72 hours.

o Aggressive parentral therapy is idicated -i

1)   In most hypertensive emergencies the drug of choice are IV labetalol or sodium nitropruside or sublingual nifedipine.

2)    If hypertension is less severe hydralazine or diazoxide can be used.

3)   Furosamide is give IV to initiate diuresis.

4)   Because fluid balance must be controlled carefully, intake is limited to urine output plus insensible loss.

5)    Seizures may be treated with IV diazepam.

When a hypertensive crisis is under control, oral medications replace the parentral medications.

Quiz In Between


Q. 10

Alopecia areata is treated by-

 A

Minoxidil

 B

Tranquilizers

 C

Whitfields oinment

 D

Parenternal penicillin

Q. 10

Alopecia areata is treated by-

 A

Minoxidil

 B

Tranquilizers

 C

Whitfields oinment

 D

Parenternal penicillin

Ans. A

Explanation:

A. i.e. Minoxidil


Q. 11

A Patient Presented with loss of patch of hair as shown in the image 

Best Line of Management ?

 A

Minoxidil

 B

Whitfields oinment

 C

Parenternal penicillin

 D

Topical Antifungal Agents

Q. 11

A Patient Presented with loss of patch of hair as shown in the image 

Best Line of Management ?

 A

Minoxidil

 B

Whitfields oinment

 C

Parenternal penicillin

 D

Topical Antifungal Agents

Ans. A

Explanation:

Diagnosis Alopecial areata . 

Management – Minoxidil


Q. 12

All are arteriolar dilators except ‑

 A

Hydralazine

 B

Minoxidil

 C

Nitrates

 D

Nifedipine

Q. 12

All are arteriolar dilators except ‑

 A

Hydralazine

 B

Minoxidil

 C

Nitrates

 D

Nifedipine

Ans. C

Explanation:

Ans. is ‘c’ i.e., Nitrates 


Q. 13

What treatment can be given in this type of hair loss?

 A

Antifungal

 B

Multivitamins

 C

Steroids

 D

Minoxidil

Q. 13

What treatment can be given in this type of hair loss?

 A

Antifungal

 B

Multivitamins

 C

Steroids

 D

Minoxidil

Ans. D

Explanation:

Ans:D.)Minoxidil.

The patient in question is suffering from Androgenetic Alopecia.Female pattern Baldness is shown in the image.

ANDROGENETIC ALOPECIA

  • Androgen hormones are clearly implicated in the pathogenesis; in particular, androgenetic alopecia is linked to high levels of dihyrotestosterone (DHT) levels
  • Treatment:Minoxidil,Finasteride.

Quiz In Between



Potassium Channel Openers

POTASSIUM CHANNEL OPENERS


POTASSIUM CHANNEL OPENERS

General MOA

  • Mainly vasodilators:
  • Causes vasodilation (mainly arterioles, negligible effect on venules) by opening potassium channels.

Adverse effect (Major):

  • Reflex tachycardia – Due to vasodilation.
  • Headache – Due to dilation of cerebral blood vessels.
  • Sodium & fluid retention – Due to compensatory mechanisms.

Important drugs:

  • Hydralazine, minoxidil, diazoxide, nicorandil & dalfampridine.

1. Hydralazine:

  • MOA:
    • Acts by vasodilation.
    • By releasing nitric oxide (NO) from endothelium.
    • NO release requires intact endothelium.
  • Metabolism:
    • Metabolized by acetylation.
    • Effect determined genetically due to presence of slow & fast acetylators.
  • Adverse effect: 
    • Drug-induced lupus erythematosus (on prolonged administration).

2. Minoxidil:

Metabolism:

  • Prodrug.
  • Activated in liver producing minoxidil sulfate (by phase II reaction).
  • MOA:
    • Minoxidil sulphate opens potassium channels.
    • Its levels unaltered in renal disease – Indicated even for chronic renal failure.
  • Uses & adverse effect:
    • As an anti-hypertensive drug.
    • Cause abnormal hair growth in females (hirsutism) – Utilized for alopecia (Alopecia areata) treatment in males.

3. Combination of Minoxidil & hydralazine:

  • Given orally for severe hypertension.

4. Diazoxide:

  • Thiazide derivative.
  • During hypertensive emergencies, as rapid i.v. injection.
  • Adverse effect:
    • Hyperuricemia.
    • Hyperglycemia (by inhibiting insulin release from pancreatic beta cells) –> leading to insulinoma.

5. Nicorandil

  • Cardioprotective potassium channel opener.
    • Causes ischemic preconditioning & coronary dilation – By activating myocardial ATP sensitive K+ channels.
    • Also possesses NO-releasing property.
  • Useful in angina.

6. Dalfampridine:

  • An oral potassium channel blocker.
  • Indication:
    • Improves walking ability in people with multiple sclerosis.

Exam Important

POTASSIUM CHANNEL OPENERS

  • Potassium channel openers are mainly vasodilators (mainly arterioles) by opening potassium channels.
  • Important potsssium channel openers include, Hydralazine, minoxidil, diazoxide, nicorandil & dalfampridine.
  • Hydralazine acts both by vasodilatation & also by releasing nitric oxide (NO) from intact endothelium.
  • On prolonged hydralazine administration, causes drug-induced lupus erythematosus.
  • Minoxidil is a prodrug activated in liver forming “minoxidil sulfate”.
  • Minoxidil sulfate opens potassium channels.
  • Minoxidil is a safer anti-hypertensive drug for chronic renal failure cases.
  • Minoxidil is useful as an anti-hypertensive drug & for alopecia treatment in males.
  • By causing abnormal hair growth as an adverse effect in females (hirsutism), minoxidil is utilized for alopecia treatment (Alopecia areata) in males.
  • Combination of Minoxidil & hydralazine is given orally for severe hypertension.
  • Diazoxide as rapid i.v injection is useful during hypertensive emergencies.
  • Nicorandil is a cardioprotective potassium channel opener, by ischemic preconditioning & coronary dilation.
  • Nicorandil activates myocardial ATP sensitive K+ channels & result in coronary dilation.
  • Dalfampridine is an oral potassium channel opener which helps improve walking ability in people with multiple sclerosis.

 

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