Fentanyl (Sublimaze)

• Related chemically to meperidine.
• Approximately 80 times more potent than morphine.
• Duration of action very short (t1/2 20 min).
• Used mainly following general anesthesia.
• Neurolept analgesia: Fentanyl & Droperidol (Innovar)
• fentanyl in analgesic (2-10 µg/kg), or anaesthetic (30-100 µg/kg) doses seldom causes significant decreases in blood pressure when given alone, even in patients with poor LV function
• hypotension following fentanyl is mostly due to bradycardia and can be prevented by the use of anticholinergics, sympathomimetics or agents such as pancuronium this is more likely to occur in patients with high pre-existing sympathetic tone
• hypertension is the commonest disturbance with high dose fentanyl anaesthesia, usually accompanying intubation, sternotomy, or aortic root dissection

Classification

I) Esters

 1. Formed from an aromatic acid and an amino alcohol.

 2. Examples of ester type local anesthetics:

 Procaine

Chloroprocaine

Tetracaine

Cocaine

Benzocaine- topical applications only

2) Amides

 1. Formed from an aromatic amine and an amino acid.

 2. Examples of amide type local anesthetics:

Articaine

Mepivacaine

Bupivacaine

Prilocaine

Etidocaine

Ropivacaine

Lidocaine

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. 

Dextromethorphan  
O-methylated dextrorphan,  Excellent oral antitussive,  No analgesic effect,  No GI effects,  No respiratory depression

Loop (High Ceiling) Diuretics

Loop diuretics are diuretics that act at the ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

Agent: Furosemide

Mechanism(s) of Action

1.    Diuretic effect is produced by inhibit of active 1 Na⁺, 1 K⁺, 2 Cl^-  co-transport (ascending limb - Loop of Henle). 
o    This produces potent diuresis as this is a relatively important Na re-absorption site.

2.    Potassium wasting effect 

a.    Blood volume reduction leads to increased production of aldosterone 
b.    Increased distal Na load secondary to diuretic effect 
c.    a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting (same as thiazides but more likely)

3.    Increased calcium clearance/decreased plasma calcium 

o    secondary to passive decreases in loop Ca++ reabsorption.
o    This is linked to inhibition of Cl^- reabsorption.
o    This is an important clinical effect in patients with ABNORMAL High Ca⁺⁺
 

Roxithromycin

It is used to treat respiratory tract, urinary and soft tissue infections. Roxithromycin is derived from erythromycin, containing the same 14-membered lactone ring. However, an N-oxime side chain is attached to the lactone ring.

Roxithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Legionella pneumophilae.

When taken before a meal, roxithromycin is very rapidly absorbed, and diffused into most tissues and Phagocytes Only a small portion of roxithromycin is metabolised. Most of roxithromycin is secreted unchanged into the bile and some in expired air