Thiopental 

- A barbiturate that is generally used to induce anesthesia.
- The temporal course of effects from induction to recovery depends almost entirely upon progressive redistribution.
- Metabolic degradation or excretion during anesthesia is negligible, except in the case of methohexital.
- The barbiturates produce minimal analgesia.
- Respiratory depression may be pronounced.
- Cardiac output is reduced while total peripheral resistance is increased.
- It does not sensitize the heart to catecholamines.
- It may cause bronchiospasm, especially in asthmatics.
- It is contraindicated in acute intermittent porphyria.

 Sympathomimetics

Beta-Adrenergic Agonists

Beta1-adrenergic agonists (dopamine, dobutamine, prenalterol, xamoterol) have been used to treat acute and chronic heart failure, but have limited usefulness in chronic CHF because of their arrhythmogenic effects, short duration of action, the development of tolerance, and necessity of parenteral administration

Dopamine (i.v.) is used in acute heart failure (cardiogenic shock) to increase blood pressure and increase cardiac output

• It has a short half-life (1 min)
• At high doses dopamine has potent peripheral vasoconstrictor effects (alpha-receptor stimulation), in addition to its inotropic effects
• Low dose dopamine has a renal artery dilating effect and may improve sodium and water excretion in patients refractory to loop diuretics
• When systolic pressure is greater than 90 mm Hg, nitroprusside can be added to reduce ventricular filling pressure and reduce afterload
• i.v. furosemide should also be administered to reduce edema

Levodopa and ibopamine, analogs of dopamine that can be administered orally, have been shown to improve symptoms in some patients, but can exhibit arrhythmogenic side-effects and tachyphylaxis

Dobutamine is a somewhat selective beta1-adrenergic agonist that lacks vasoconstrictor activity and causes minimal changes in heart rate

• It is frequently added to nitroprusside when blood pressure is adequate to increase cardiac output
• It is administered as an i.v. infusion to treat acute severe heart failure
• It has a short half-life (2.4 min) and is only used on a short-term basis, although long-term beneficial effects on cardiac function have been noted
• After 72 hours of therapy, tolerance can develop to dobutamine necessitating switch to other inotropic support (e.g. milrinone)
• Dobutamine can enhance AV conduction and worsen atrial tachycardia

Prenalterol and xamoterol are partial beta1-adrenergic agonists that may simultaneously stimulate beta1-receptors and block the receptors from stimulation by endogenous catecholamines, thereby protecting against beta1-receptor down-regulation

Procoagulant Drugs:

Desmospressin Acetate

• Is a synthetic analogue of the pituitary antidiuretic hormone (ADH).

• Stimulates the activity of Coagulation Factor VIII

• Use for treatment of hemophilia A with factor VIII levels less than or equal to 5%, treatment of hemophilia B or in clients who have factor VIII antibodies. Treatment of severe classic von Willebrand's disease (type I) and when an abnormal molecular form of factor VIII antigen is present. Use for type IIB von Willebrand's disease.

COAGULANTS

An agent that produces coagulation (Coagulation is a complex process by which blood forms clots).

ANTICOAGULANTS

An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting.

Anticoagulants:

Calcium Chelators (sodium citrate, EDTA)

Heparin

Dalteparin Sodium (Fragmin) -Low molecular-weight heparin

Enoxaparin - Low molecular-weight heparin

Tinzaparin Sodium  - Low molecular-weight heparin

Warfarin

Lepirudin - recombinant form of the natural anticoagulant hirudin: potent and specific Thrombin inhibitor

Bivalirudin - analog of hirudin: potent and specific Thrombin inhibitor

Procoagulants:

Desmopressin acetate

Antiplatelet Drugs:

Acetylsalicylic Acid, Ticlopidine, Sulfinpyrazone, Abciximab , Clopidogrel bisulfate

Fibrinolytic Drugs:

Tissue Plasminogen Activator (t-PA, Activase), Streptokinase (Streptase),

Anistreplase, Urokinase

Antagonists:

Protamine sulfate, Aminocaproic acid

Pharmacological agents used to treat blood coagulation disorders fall in to three major categories:

1. Anticoagulants: Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of arterial thrombi and thromboembolic clots.

2. Antiplatelet agents: Substances that reduce the adhesion and aggregation of platelets.

3. Fibrinolytic agents: Substances that promote the destruction of already formed blood clots or thrombi by disrupting the fibrin mesh.

Serotonin or 5-hydroxytryptamine (5-HT)

It is a neurotransmitter, widely distributed in the CNS, beginning in the midbrain and projecting into thalamus, hypothalamus, cerebral cortex, and spinal cord. CNS serotonin is usually an inhibitory neurotransmitter and is associated with mood, the sleep-wake cycle.

Serotonin is thought to produce sleep by inhibiting CNS activity. 

In the blood, 5-HT is present in high concentration in platelets (regulator of platelets function) and also high concentration in intestine

Pharmacological effects:

Smooth muscles. 5-HT stimulates the G.I smooth muscle; it increases the peristaltic movement of intestine.
Serotonin contracts the smooth muscle of bronchi; 

Blood vessels. If serotonin is injected i.v, the blood pressure usually first rises, because of the contraction of large vessels and then falls because of arteriolar dilatation. Serotonin causes aggregation of platelets. 

Specific agonists

- Sumatriptan a selective 5-HT1D used in treatment of acute migraine.
- Buspirone a selective 5-HT1A used in anxiety.
- Ergotamine is a partial agonist used in migraine. It acts on 5-HT1A receptor.

Nonspecific 5-HT receptor agonist

o Dexfenfluramine used as appetite suppressant.

Specific antagonists

o Spiperone (acts on 1A receptor) and
o Methiothepin (acts on 1A, 1B, 1D receptors)

Osmotic diuretics

An osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium. They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate.

Mechanism(s) of Action

1.    Reduce tissue fluid (edema) 
2.    Reflex cardiovascular effect by osmotic retention of fluid within vascular space which increases blood volume (contraindicated with Congestive heart failure) 
3.    Diuretic effect

o    Makes H2O reabsorption far more difficult for tubular segments insufficient Na & H2O capacity in distal segments
o    Increased intramedullary blood flow (washout)
o    Incomplete sodium recapture (asc. loop). this is indirect inhibition of Na reabsorption (Na stays in tubule because water stays) 
o    Net diuretic effect: 
    Tubular concentration of sodium decreases 
    Total amount of sodium lost amount increases 
    GFR unchanged or slightly increased

Toxicity

Circulatory overload, dilutional hyponatremia,  Hyperkalemia, edema, skin necrosis

Agents
Mannitol