A. Sympathetic Nervous System Depressants

1. Antagonists

Both α-adrenoceptor antagonists and β-adrenoceptor antagonists are useful  antihypertensives.

• α-blocker                     Prazosin, phentolamine, phenoxybenzamine
• β-blocker                     Propranolol ,Metoprolol, atenolol
• α/β-blocker                  labetalol

2. Sympathetic depressants

a. Examples of peripherally acting agents include

• reserpine This agent interferes with the storage of norepinephrine
• quanethidine This agent interferes with the release of norepinephrine
• trimethaphan This agent blocks transmission through autonomic ganglia.

b. Examples of Centrally acting agents include

• alphamethyldopa
• clonidine. These agents act by decreasing the number of impresses along sympathetic nerves.

Adverse Effect

include nasal congestion, postural hypotension, diarrhea, sexual dysfunction, dry mouth. sedation and drowsiness.

B. Directly Acting Vasodilators

Act on vascular smooth muscle cells independently of adrenergic nerves and adrenergic receptors.

Relaxation of vascular smooth muscle which leads to a decrease in peripheral vascular resistance.

Sites of action of vasodilators are many. For example

 Calcium Channel Blocker’s  MOA

. Decrease automaticity & conduction thru SA & AV nodes

. Decreased myocardial contractility

. Decreased peripheral & coronary 

smooth muscle tone = decrease SVR

Potassium channels activators

minoxidil, cause vasodilation by activating potassium channels in vascular smooth muscle.

An increase in potassium conductance results in hyperpolarization of the cell membrane which is associated with relaxation of smooth muscle.

Nitrovasodilators, such as sodium nitroprusside,

Increase in intracellular cGMP. cGMP in turn activates a protein kinase. Directly-Acting Vasodilators are on occasion used alone but more frequently are used in combination with antihypertensive agents from other classes (esp. a β-blocker and a diuretic.)

Rofecoxib

Inhibit prostacyclin(PGI2) in vascular  endothelium , letting TXA2 act freely and  promote platelet aggregation. 

used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhea

Higher incidence of cardiovascular thrombotic  events.

Not used due to increase risk of heart attack, stroke

Types of Neurons (Function)

•There are 3 general types of neurons (nerve cells): 

1-Sensory (Afferent ) neuron:A neuron that detects changes in the external or internal environment and sends information about these changes to the CNS. (e.g: rods and cones, touch receptors). They usually have long dendrites and relatively short axons. 

2-Motor (Efferent) neuron:A neuron located within the CNS that controls the contraction of    a muscle or the secretion of a gland. They usually have short dendrites and long axons. 

2-Interneuron or association neurons: A neuron located entirely within the CNS in which they form the connecting link between the afferent and efferent neurons. They have short dendrites and may have either a short or long axon.

Gastric acid neutralizers (antacids)

Antacids act primarily in the stomach and are used to prevent and treat peptic ulcer. They are also used in the treatment of Reflux esophagitis and Gastritis.

Mechanism of action: 

Antacids are alkaline substances (weak bases) that neutralize gastric acid (hydrochloric acid) they react with hydrochloric acid in the stomach to produce neutral or less acidic or poorly absorbed products and raise the pH of stomach secretion.

Antacids are divided into systemic and non-systemic.

• Systemic antacids (e.g. sodium bicarbonate) are highly absorbed into systemic circulation and enter body fluids. Therefore, they may alter acid–base balance. They can be used in the treatment of metabolic acidosis. 

Non-systemic: they do not alter acid–base balance significantly, because they are not well-absorbed into the systemic circulation. They are used as gastric antacids; and include:

• Magnesium compounds such as magnesium hydroxide and magnesium sulphate MgS2O3. They have relatively high neutralizing capacity, rapid onset of action, however, they may cause diarrhoea and hypermagnesemia.

• Aluminium compounds such as aluminium hydroxide. Generally, these have low neutralizing capacity, slow onset of action but long duration of action. They may cause constipation.

• Calcium compounds such as. These are highly effective and have a rapid onset of action but may cause hypersecretion of acid (acid - rebound) and milk-alkali syndrome (hence rarely used in peptic ulcer disease). 

Therefore, the most commonly used antacids are mixtures of aluminium hydroxide and magnesium hydroxide . 

Thrombolytic Agents:

Tissue Plasminogen Activator (t-PA, Activase)

t-PA is a serine protease. It is a poor plasminogen activator in the absence of fibrin. t-PA binds to fibrin and activates bound plasminogen several hundred-fold more rapidly than it activates plasminogen in the circulation.

Streptokinase (Streptase)

Streptokinase is a protein produced by β-hemolytic streptococci. It has no intrinsic enzymatic activity, but forms a stable noncovalent 1:1 complex with plasminogen. This produces a conformational change that exposes the active site on plasminogen that cleaves a peptide bond on free plasminogen molecules to form free plasmin.

Urokinase (Abbokinase)

Urokinase is isolated from cultured human cells.Like streptokinase, it lacks fibrin specificity and therefore readily induces a systemic lytic state. Like t-PA, Urokinase is very expensive.

Contraindications to Thrombolytic Therapy:

• Surgery within 10 days, including organ biopsy, puncture of noncompressible vessels, serious trauma, cardiopulmonary resuscitation.

• Serious gastrointestinal bleeding within 3 months.

• History of hypertension (diastolic pressure >110 mm Hg).

• Active bleeding or hemorrhagic disorder.

• Previous cerebrovascular accident or active intracranial bleeding.

Aminocaproic acid:

Aminocaproic acid prevents the binding or plasminogen and plasmin to fibrin. It is a potent inhibitor for fibrinolysis and can reverse states that are associated with excessive fibrinolysis.

Uses of NSAIDs

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions, such as cancer and cardiovascular disease.

NSAIDs are generally indicated for the symptomatic relief of the following conditions.

rheumatoid arthritis, osteoarthritis, inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome), acute gout, dysmenorrhoea, metastatic bone pain ,headache and migraine, postoperative pain, mild-to-moderate pain due to inflammation and tissue injury, pyrexia, renal colic

Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation; an indication useful in the management of arterial thrombosis and prevention of adverse cardiovascular events.