Heparin:

• Inhibits blood coagulation by forming complexes with an α2-globulin (Antithrombin III) and each of the activated proteases of the coagulation cascade (Kallikrein, XIIa, XIa, IXa, Xa, and Thrombin). After formation of the heparin-ATIII-coagulation factor, heparin is released and becomes available again to bind to free ATIII.
• Blocks conversion of Prothrombin to Thrombin and thus inhibits the synthesis of Fibrin from Fibrinogen.
• Inhibits platelet function and increases vascular permeability. May induce moderate to severe thrombocytopenia.
• Is prescribed on a “unit” basis.
• Heparin is not effective after oral administration and is generally administered by intravenous or subcutaneous injection. Intramuscular injections should be avoided.
• Heparin does not cross the placenta and does not pass into the maternal milk.
• is contraindicated in any situation where active bleeding must be avoided.

Ulcerative lesions, intracranial hemorrhage, etc.

Overdosage:

• Simple withdrawal.

• Protamine sulfate: Highly basic peptide that binds heparin and thus neutralizes its effects.

Immunosuppressive antibodies can be classified mainly into monoclonal and polyclonal antibodies, targeting specific components of the immune system.

1. Monoclonal Antibodies:

   • Basiliximab: Targets the IL-2 receptor on T cells, inhibiting T-cell activation. It is FDA approved for use in renal transplantation to prevent acute rejection.

   • Alemtuzumab: Targets CD52, a protein found on the surface of mature lymphocytes. It is used for treating chronic lymphocytic leukemia and as an induction agent in kidney transplantation.

   • Rituximab: Targets CD20 on B cells, leading to B-cell depletion. It is used in various conditions, including non-Hodgkin lymphoma and rheumatoid arthritis.

   • Daclizumab: Targets the IL-2 receptor (CD25) and is used in renal transplantation to prevent acute rejection.

   • Eculizumab: Targets complement component C5, inhibiting the complement cascade. It is used in conditions like paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

2. Polyclonal Antibodies:

   • Rabbit Antithymocyte Globulin (rATG): A polyclonal antibody that targets multiple T-cell surface markers, leading to T-cell depletion. It is used as an induction agent in kidney transplantation and for treating acute rejection.

   • Equine Antithymocyte Globulin (eATG): Similar to rATG, it targets T cells and is used in transplantation settings.

3. Mechanisms of Action:

   • Depletion of Immune Cells: Many antibodies work by depleting specific immune cell populations (e.g., T cells or B cells) to reduce the immune response against transplanted organs or in autoimmune diseases.

   • Blocking Activation Signals: Some antibodies block key receptors involved in T-cell activation, preventing the immune response from being initiated.

   • Inhibition of Complement Activation: Antibodies like eculizumab inhibit the complement system, which can contribute to tissue damage in antibody-mediated rejection.

4. Clinical Applications:

   • Organ Transplantation: Antibodies are commonly used to prevent rejection in kidney, liver, and heart transplants.

   • Autoimmune Diseases: They are also used in treating conditions like rheumatoid arthritis, lupus, and multiple sclerosis.

5. Potential Side Effects:

   • Infections: Due to immune suppression, patients are at increased risk of infections.
   • Allergic Reactions: Some patients may experience allergic reactions to antibody therapies.
   • Infusion Reactions: These can occur during the administration of monoclonal antibodies, leading to symptoms like fever, chills, and hypotension.

Angiotensin

It is generated in the plasma from a precursor plasma globulin. It is involved in the electrolyte balance, plasma
volume and B.P

Angiotensin I:
Renin is an enzyme produced by the kidney in response to a number of factors including adrenergic activity (β1-
receptor) and sodium depletion. Renin converts a circulating glycoprotein (angiotensinogen) into an inactive material angiotensin-I. It gets activation during passage through pulmonary circulation to angiotensin II by (ACE). ACE is located on the luminal surface of capillary endothelial cells, particularly in the lungs & also present in many organ (e.g brain).

Angiotensin II:
Is an active agent, has a vasoconstrictor action on blood vessels & sodium and water retention

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.)

Gabapentin (Neurontin): newer; for generalized tonic-clonic seizures and partial seizures (partial and complex)

Mechanism: unknown but know doesn’t mimic GABA inhibition or block Ca currents

Side effects: dizziness, ataxia, fatigue; drug well-tolerated and no significant drug interactions

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.