Sympatholytics (Antiadrenergic Agents)

PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent 

It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension. 
It increases the cardiac output and decreases the total peripheral resistance.

It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.

Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.

ERGOT ALKALOIDS

 Ergotamine is an  important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.

METHYSERGIDE

It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine. 

SUMATRIPTAN

It is a potent selective 5-HT 1D  receptor agonist used in the treatment of migraine.

PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1  receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.

TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½

DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.

TAMSULOSIN
It is uroselective α1A  blocker and has been found effective in improving BPH symptoms.

Other drugs used for erectile dysfunction

Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.

Hydromorphone

• About 8-10 times more potent than morphine when given intravenously.
• Slightly shorter duration of action.
• More soluble than morphine, thus higher concentrations may be injected if necessary.
• Better oral/parenteral absorption ratio than morphine, but not as good as codeine or oxycodone.

• It is used for the treatment of moderate to severe pain

Ketorolac

Mechanism of action

primary action responsible for its anti-inflammatory/antipyretic/analgesic effects is inhibition of prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX). Ketorolac is not a selective inhibitor of COX enzymes

Indications: short-term management of pain

Contraindications

hypersensitivity to ketorolac, and against patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis).

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. 

Antiemetics

 Antiemetic drugs are generally more effective in prophylaxis than treatment. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting centre, dopamine receptors, chemoreceptors trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination of these.
 
 Drugs used in the treatment of nausea and vomiting belong to several different groups. These include:
 
1. Phenothiazines, such as chlorpromazine, act on CTZ and vomiting centre, block dopamine receptors, are effective in preventing or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy).
They are generally ineffective in motion sickness.
Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines

2. Antihistamines such as promethazine and Dimenhyrinate are especially effective in prevention and treatment of motion.

3. Metoclopramide has both central and peripheral antiemetic effects. Centrally, it antagonizes the action of dopamine. Peripherally metoclopramide stimulates the release of acetylcholine, which in turn, increases the rate of gastric. It has similar indications to those of chlorpromazine.

4. Scopolamine, an anticholinergic drug, is very effective in reliving nausea & vomiting associated with motion sickness.

5. Ondansetron, a serotonin antagonist, is effective in controlling chemical-induced vomiting and nausea such those induced by anticancer drugs. 

6. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties

Neurolept Anesthesia
An antipsychotic agent such as droperidol plus an opiate analgesic agent such as fentanyl or sufentanil. This latter agent is approximately eight to ten times more potent than fentanyl.