Class III Potassium Channel Blockers

Prolong effective refractory period by prolonging Action Potential

Treatment: ventricular tachycardia and fibrillation, conversion of atrial fibrillation or flutter to  sinus rhythm, maintenance of sinus rhythm
– Amiodarone (Cordarone) – maintenance of sinus rhythm
– Bretylium (Bretylol) 
– Ibutilide (Corvert) 
– Dofetilide (Tykosyn) 
– Sotalol (Betapace) 

 Amiodarone 
- Has characteristics of sodium channel blockers, beta blockers, and calcium channel blockers 
- Has vasodilating effects and decreases systemic vascular resistance 
- Prolongs conduction in all cardiac tissue 
- Decreases heart rate 
- Decreases contractility of the left ventricles 

Class III - Adverse Effects 
- GI- Nausea vomiting and GI distress 
- CNS- Weakness and dizziness
- CV-Hypotension, CHF, and arrhythmias are common. 
- Amiodarone associated with potentially fatal Hepatic toxicity, ocular abnormalities and serious cardiac arrhythmias. 

Drug – Drug Interactions
These drugs can cause serious toxic effects if combined with digoxin or quinidine. 
 

Ibuprofen

used to relieve the symptoms of arthritis, primary dysmenorrhoea, fever; and as an analgesic, especially where there is an inflammatory component.

Indications

rheumatoid arthritis, osteoarthritis, juvenile rheumatoid arthritis, primary dysmenorrhoea

fever, relief of acute and/or chronic pain states in which there is an inflammatory component

MOA

inhibition of  cyclooxygenase (COX); thus inhibiting prostaglandin synthesis.

Sympatholytics And Alpha Adrenergic Blockers 

Types 
1.    Alpha 1-receptor blockers: prazocin,doxazocin. 
2.    Centrally acting alpha 2- agonists: methyldopa, clonidine. 
3.    Peripherally acting adrenergic antagonists: reserpine. 
4.    Imidazoline receptor agonists: rilmenidine, moxonidine. 
 
Advantages 

- Alpha1- receptor blockers and imidazoline receptor agonists improve lipid profile and insulin sensitivity. 
- Methyldopa: increases renal blood flow. Drug of choice during pregnancy. 
- Reserpine: neutral metabolic effects and cheap. 

Indications: 

- Diabetes mellitus: alpha1- receptor blockers, imidazoline receptor agonists. 
- Dyslipidemia: alpha 1- receptor blockers, imidazoline receptor agonists. 
- Prostatic hypertrophy: alpha 1- receptor blockers. 
- When there is a need for rapid reduction in blood pressure: clonidine. 

Side Effects 

- Prazocin: postural hypotension, diarrhea, occasional tachycardia, and tolerance (due to fluid retention). 
- Methyldopa: sedation, hepatotoxicity, hemolytic anemia, and tolerance. 
- Reserpine: depression, lethargy, weight loss, peptic ulcer, diarrhea, and impotence
- Clonidine: dry mouth, sedation, bradycardia, impotence, and rebound hypertension if stopped suddenly. 

Considerations 
- Prazocin, methyldopa, and reserpine should be combined with a diuretic because of fluid retention. 

Direct Arterial Vasodilators 

Types: hydralazine, diazoxide, nitroprusside, and minoxidil

Laxatives and cathartics (purgatives)

Constipation is a common problem in older adults and laxatives are often used or overused. Non drug measures to prevent constipation (e.g. increasing intake of fluid and high–fiber foods, exercise) are much preferred to laxatives.

Laxatives and cathartics are drugs used orally to evacuate the bowels or to promote bowel elimination (defecation). Both terms are used interchangeably because it is the dose that determines the effects rather than a particular drug. For example, Castor oil laxative effect = 4ml while Cathartic effect = 15-60ml

The term laxative implies mild effects, and eliminative of soft formed stool. The term cathartic implies strong effects and elimination of liquid or semi liquid stool. 

 Laxatives are randomly classified depending on mode of action as:
 
1. Bulk-forming laxatives: are substances that are largely unabsorbed from the intestine.
They include psyllium, bran, methylcellulose, etc. When water is added, the substances swell and become gel-like which increases the bulk of the faecal mass that stimulates peristalsis and defecation.

2. Osmotic laxatives such as magnesium sulphate, magnesium hydroxide, sodium phosphate, etc. These substances are not efficiently absorbed and cause water retention in the colon. The latter causes increase in volume and pressure which stimulates peristalsis and defecation.

Lactulose is a semisynthetic disaccharide sugar that also acts as an osmotic laxative. 
Electrolyte solutions containing polyethylene glycol(PEG) are used as colonic lavage solutions to prepare the gut for radiologic or endoscopic procedures

3. Stimulant (irritant) laxatives: these are irritant that stimulate elimination of large bowel contents. Individual drugs are castor oil, bisacodyl, phenolphthalein, cascara sagrada, glycerine, etc. The faeces are moved too rapidly and watery stool is eliminated. Glycerine can be administered rectally as suppositories.

4. Faecal softeners: they decrease the surface tension of the faecal mass to allow water to penetrate into the stool. They have detergent– like property e.g. docusate(docusate sodium, docusate calcium, and docusate spotassium. )

5. Lubricant laxatives e.g. liquid paraffin (mineral oil). It lubricates the intestine and is thought to soften stool by preventing colonic absorption of faecal water. They are used as retention enema. 

6. Chloride channel activators

Lubiprostone works by activating chloride channels to increase fluid secretion in the intestinal lumen. This eases the passage of stools and causes little change in electrolyte balances. Nausea is a relatively common side effect with lubiprostone.

Clinical indications of laxatives

1. To relieve constipation.
2. To prevent straining.
3. To empty the bowel in preparation for bowel surgery or diagnostic procedures.
4. To accelerate elimination of potentially toxic substances from the GI tract.
5. To accelerate excretion of parasite after anti-helmintic drugs have been administered. 

Use of local anesthetics during pregnancy

Local anesthetics (injectable)

Drug                                                   FDA category

Articaine                                             C

Bupivacaine                                        C

Lidocaine                                            B

Mepivacaine                                        C

Prilocaine                                            B

Vasoconstrictors

Epinephrine 1:200,000 or 1:100,000 C (higher doses)

Levonordefrin 1:20,000 Not ranked

Local anesthetics (topical)

Benzocaine                                        C

Lidocaine                                            B

RENIN-ANGIOTENSIN SYSTEM INHIBITORS

The actions of Angiotensin II include an increase in blood pressure and a stimulation of the secretion of aldosterone (a hormone from the adrenal cortex) that promotes sodium retention. By preventing the formation of angiotensin II, blood pressure will be reduced. This is the strategy for development of inhibitors. Useful inhibitors of the renin-angiotensin system are the Angiotensin Converting Enzyme Inhibitors 

First line treatment for: Hypertension , Congestive heart failure [CHF] 

ACE-Inhibitor’s MOA (Angiotensin Converting Enzyme Inhibitors)

Renin-Angiotensin Aldosterone System: 
. Renin & Angiotensin = vasoconstrictor 
. constricts blood vessels & increases BP 
. increases SVR or afterload 
. ACE Inhibitors blocks these effects decreasing SVR & afterload 
 
. Aldosterone = secreted from adrenal glands 
. cause sodium & water reabsorption 
. increase blood volume 
. increase preload 
. ACE I  blocks this and decreases preload 

Types 

Class I: captopril 
Class II (prodrug) : e.g., ramipril, enalapril, perindopril 
Class III ( water soluble) : lisinopril. 

Mechanism of Action 

Inhibition of circulating and tissue angiotensin- converting enzyme. 
Increased formation of bradykinin and vasodilatory prostaglandins. 
Decreased secretion of aldosterone; help sodium excretion. 

Advantages 

- Reduction of cardiovascular morbidity and mortality in patients with atherosclerotic vascular disease, diabetes, and heart failure. 
- Favorable metabolic profile. 
- Improvement in glucose tolerance and insulin resistance. 
- Renal glomerular protection effect especially in diabetes mellitus. 
- Do not adversely affect quality of life. 

Indications 
- Diabetes mellitus, particularly with nephropathy. 
- Congestive heart failure. 
- Following myocardial infraction. 

Side Effects  

- Cough (10 - 30%): a dry irritant cough with tickling sensation in the throat. 
- Skin rash (6%). 
- Postural hypotension in salt depleted or blood volume depleted patients. 
- Angioedema (0.2%) : life threatening. 
- Renal failure: rare, high risk with bilateral renal artery stenosis. 
- Hyperkalaemia 
- Teratogenicity. 

Considerations 
- Contraindications include bilateral renal artery stenosis, pregnancy, known allergy, and hyperkalaemia. 
- High serum creatinine (> 3 mg/dl) is an indication for careful monitoring of renal function, and potassium. Benefits can still be obtained in spite of renal insufficiency. 
- A slight stable increase in serum creatinine after the introduction of ACE inhibitors does not limit use. 
- ACE-I are more effective when combined with diuretics and moderate salt restriction. 
 

ACE inhibitors drugs

Captopril 50-150 mg       
Enalapril 2.5-40 mg
Lisinopril 10-40 mg
Ramipril 2.5-20  mg        
Perindopril 2-8  mg

Angiotensin Receptor Blocker  

Losartan    25-100 mg 
Candesartan 4-32  mg
Telmisartan 20-80 mg

Mechanism of action 

They act by blocking type I angiotensin II receptors generally, producing more blockade of the renin -angiotensin - aldosterone axis. 

Advantages 

• Similar metabolic profile to that of ACE-I. 
• Renal protection. 
• They do not produce cough. 

Indications 

Patients with a compelling indication for ACE-I and who can not tolerate them because of cough or allergic reactions.