Beta Blockers And Diabetes Type 2 Short Notes

Why β-blockers are to be avoided in diabetics?

 

1. Propranolol + insulin oral antidiabetics: When diabetics on insulin also receive
propranolol:

• b-blockade masks tachycardia which is the first warning signal of hypoglycemia.
• b-blockade delays the recovery from hypoglycemia by preventing glycogenolysis induced by sympathetic stimulation (acting through b₂ receptors).
• This may be avoided by using b₁-selective blocker

Read And Learn More: Pharmacology Question And Answers

2. Both propranolol and verapamil → mycardial depression:

• Propranolol + verapamil → more myocardial depression → avoid

3. β-blockers + catecholamines:

Hence, it is safer to use plain local anesthesia in such patients.

4. β-blockers + digitalis + verapamil: All depress AV conduction and together may cause cardiac arrest.

5. Enzyme inducers: Like rifampicin → ↑ metabolism → ↓ ↓ plasma levels of propranolol.

6. NSAIDs counter the antihypertensive effects of b-blockers.

β-blockers Diabetics Atenolol:

• Selective a₁ – blocker
• Longer-acting—given once daily
• Less lipid soluble—does not cross BBB, hence no CNS side effects
• No side effects on lipid profile

β-blockers Diabetics Uses:

• Commonly used in hypertension and angina (see Compare and Contrast: Propranolol and atenolol).
• Dose: 25–100 mg daily

Propranolol and Atenolol:

β-blockers Diabetics Esmolol:

• Selective a₁-blocker
• Ultra short-acting—t½–8 minutes
• Rapid-acting
• Used IV
• Safer (due to short action) in critically ill patients and useful in emergencies (due to rapid action) when immediate b-blockade is needed.

Uses of Esmolol:

In supraventricular and other arrhythmias, perioperative hypertension, and to reduce myocardial work done and tide over acute myocardial ischemia.

Dose: 0.1–0.2 mg/kg/min infusion.

Cardiac Uses:

1. Hypertension: In mild to moderate hypertension—used alone or with other antihypertensives. b-blockers are particularly suitable for combination with drugs that produce tachycardia.

2. Angina pectoris: Prophylaxis of exertional angina—both the severity and frequency are reduced. They reduce both cardiac work and O2 demand.

3. Cardiac arrhythmias: Both ventricular and supraventricular arrhythmias respond. Sotalol has additional antiarrhythmic effects. Depression of AV conduction and membrane-stabilizing effects help.

4. Myocardial infarction (MI): Intravenous b-blockers in acute MI may limit the size of the infarct and also prevent ventricular arrhythmias. In patients who have recovered from MI, long-term treatment with b-blockers prolongs survival.

5. Congestive cardiac failure: Though b-blockers have a negative inotropic effect when carefully used, they can reduce the risk of sudden death and prolong survival on long-term use.

6. Obstructive cardiomyopathy: b-blockers are found to be beneficial.

7. Pheochromocytoma: Propranolol + a-blockers before surgery to control hypertension.

8. Dissecting aneurysm of the aorta: Propranolol helps by reducing aortic pulsations.

Noncardiac Uses:

9. Thyrotoxicosis: Propranolol controls symptoms and provides symptomatic relief in thyrotoxicosis; it is used as an adjuvant in a thyrotoxic crisis or thyroid storm as it quickly affords symptomatic relief.

10. Glaucoma: Timolol used topically is the first line treatment in glaucoma. Betoxalol, levobunalol, carteolol and metipranolol can also be used in glaucoma. The fall in IOP is sustained and even if 1 or 2 doses are missed, there is no sudden rise in IOP.

11. Prophylaxis of migraine: Propranolol reduces the frequency and severity of migraine.

12. Anxiety: Propranolol prevents the acute panic symptoms seen in public speaking, examination, and other such anxiety-provoking situations. Performance in musicians can be improved when taken prophylactically. Tremors, tachycardia, and other symptoms of sympathetic overactivity are suppressed.

13. Cirrhosis: b-blockers may help by reducing the portal venous pressure by about 40%.

14. Esophageal varices: In bleeding varices, nadolol + isosorbide mononitrate → prevent rebleeding by inducing splanchnic vasoconstriction and reducing cardiac output.

15. Alcohol withdrawal: Reduce the central sympathetic overactivity → ↓ symptoms of alcohol withdrawal.

Contraindications To Β-Blockers

CCF: b-blocker → prevents an increase in heart rate and cardiac output → may be dangerous in patients with CCF → should be used cautiously and only in selected patients.

Bradycardia: b-blockers should be avoided in patients with bradycardia.

• b-blockers are contraindicated in heart block because they depress AV conduction.
• To be avoided in bronchial asthma and COPD. If needed, a cardioselective b-blocker may be used with caution.
• Should be avoided in diabetics—discussed under drug interactions.

Drugs Used In Treatment Of Glaucoma

Glaucoma is a chronic, progressive optic neuropathy often associated with increased intraocular pressure (IOP). The constant rise in IOP (ocular hypertension) can damage the optic nerve leading to permanent blindness.

Glaucoma can be acute congestive and chronic simple glaucoma.

Glaucoma Treatment:

Acute congestive glaucoma: Also called narrow angle glaucoma—the objective is to quickly reduce the IOP till surgery or other measures are followed. A combination of drugs is preferred.

• Injection mannitol (20%) — 1.5 – 2g/kg or glycerol (10%) act by osmotic activity → reduce IOP
• Acetazolamide, a carbonic anhydrase inhibitor—reduces the formation of aqueous humor
• Cholinergic—miotics open the trabecular meshwork and ↑ drainage of aqueous humor.
• Pilocarpine with physostigmine (anticholinesterase) is used as eye drops
• b-blocker—timolol/betaxolol eye drops
• a-agonists—apraclonidine 1% eye drops
• PG analog—latanoprost eye drops may be added.

Open-angle or chronic simple glaucoma:

• It is slow in onset and needs long-term treatment.
• It is considered a genetically predisposed condition with hypertension, myopia, and a family history of glaucoma as risk factors.
• Drugs are used to reduce the IOP.

Glaucoma  Drugs used are:

1. Prostaglandin analogs:

• These are now considered the first-line drugs in chronic simple glaucoma. Latanoprost is a prodrug of PGF2a.
• It increases the outflow of aqueous humor probably by relaxing the ciliary muscle.
• It can be used as an adjuvant to other drugs.
• Bimatoprost, travoprost and unoprostone are similar to latanoprost.

2. β-blockers:

• Topical b-blockers like timolol are the first-line drugs in glaucoma.
• They reduce aqueous humor formation by blocking the b₂ – receptors in the ciliary body.
• Since they do not cause miosis, there is no associated headache or brow ache which are due to spasms of the iris and ciliary muscles.
• The reduction in IOP is smoother and constant.
• However, even when used as eye drops, b-blockers may be absorbed systemically.
• Hence, b₁-selective agents like betaxolol are preferred particularly in asthmatics and even these should be used carefully.
• Prolonged use of B-blockers may result in heart block and CCF, particularly in the elderly

3. Adrenergic agonists:

• Epinephrine, dipivefrin, apraclonidine, and brimonidine may act on the ciliary body to reduce aqueous humor formation or act by reducing ciliary blood flow (b₁).
• They also reduce uveoscleral outflow. Corneal penetration of adrenaline is poor, and not preferred. It can also cause conjunctival blanching followed by hyperemia.
• Dipivefrin, a prodrug of adrenaline penetrates the cornea and is converted to adrenaline. It is better tolerated and longer acting than adrenaline—used as an adjuvant.

• Apraclonidine is an analog of clonidine which has higher topical than systemic activity. It is used following surgical corrections like iridotomy.
• Brimonidine is more b₂ – selective and has higher lipophilicity than apraclonidine.
• Ocular side effects (b₁) are milder.
• Used as an alternative to other drugs and as an adjuvant.

4. Cholinergic drugs:

• Miotics like pilocarpine and physostigmine improve the drainage of aqueous humor by constricting the pupil and opening the iridocorneal angle.
• They may be used in acute congestive glaucoma and open-angle glaucoma for short periods to lower the IOP.

5. Carbonic anhydrase inhibitors:

• Production of aqueous humor requires active transport of bicarbonate ions.
• Inhibition of carbonic anhydrase decreases aqueous humor formation by enhancing bicarbonate loss.
• Acetazolamide and methazolamide are given orally but are poorly tolerated.
• Topical agents like dorzolamide eye drops are now available.
• These can also be combined with b-blockers and miotics.

6. Osmotic agents:

• 20% mannitol/10% glycerol injected IV exerts osmotic effects and draw fluid from the eye.
• These are used for rapid reduction of IOP in acute congestive glaucoma along with other drugs