Warfarin (Coumadin):

• The most common oral anticoagulant.
• It is only active in vivo.
• Warfarin is almost completely bound to plasma proteins. -96% to 98% bound.
• Warfarin is metabolized by the liver and excreted in the urine.
• Coumarin anticoagulants pass the placental barrier and are secreted into the maternal milk.
• Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism.

• Bleeding is the most common side effect and occurs most often from the mucous membranes of the gastrointestinal tract and the genitourinary tract.

Oral anticoagulants are contraindicated in:

• Conditions where active bleeding must be avoided, Vitamin K deficiency and severe

hepatic or renal disease, and where intensive salicylate therapy is required.

Oxycodone  
About equal potency to morphine. Very effective orally.

It is combined with aspirin or acetaminophen for the treatment of moderate pain and is available orally

Oxycodone is a semisynthetic compound derived from thebaine, with agonist activity primarily at mu receptors.

Ketoprofen

It acts by inhibiting the body's production of prostaglandin.

CARDIAC GLYCOSIDES

Cardiac glycosides (Digitalis)

Digoxin

Digitoxin

Sympathomimetics

Dobutamine

Dopamine

Vasodilators

α-blockers (prazosin)

Nitroprusside

ACE-inhibitors (captopril)

Pharmacology of Cardiac Glycosides

1. Positive inotropic effect (as a result of increase  C.O., the symptoms of CHF subside).

2. Effects on other cardiac parameters

1) Excitability

2) Conduction Velocity; slightly increased in atria & ventricle/significantly

reduced in conducting tissue esp. A-V node and His-Purkinje System

3) Refractory Period; slightly ^ in atria & nodal tissue/slightly v in ventricles

4) Automaticity; can be greatly augmented - of particular concern in ventricle

3. Heart Rate

-Decrease due to 1) vagal stimulation and 2) in the situation of CHF, due to improved hemodynamics

4 Blood Pressure

-In CHF, not of much consequence. Changes are generally secondary to improved cardiac performance.

-In the absence of CHF, some evidence for a direct increase  in PVR due to vasoconstriction.

5. Diuresis

-Due primarily to increase in  renal blood flow as a consequence of positive inotropic effect (increase CO etc.) Possibly some slight direct diuretic effect.

 Mechanism of Action of Cardiac Glycosides

Associated with an interaction with membrane-bound Na+-K+ ATPase (Na-K pump).

Clinical ramifications of an interaction of cardiac glycosides with the Na⁺ K pump.

I. Increase levels of Ca⁺⁺, Increase therapeutic and toxic effects of cardiac glycosides

II. Decrease levels of K⁺ , Increase toxic effects of cardiac glycosides

Therapeutic Uses of Cardiac Glycosides

• CHF
• CHF accompanied by atrial fibrillation
• Supraventricular arrhythmias

 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

Cells of the Nervous System 

1-Neurons (Nerve Cells):function units of the nervous system by conducting nerve impulses, highly specialized and amitotic. Each has a cell body (soma), one or more dendrites, and a single axon. 
• Cell Body: it has a nucleus with at least one nucleolus and many of the typical cytoplasmic organelles, but lacks centriolesfor cell division. 

• Dendrites:Dendrites and axons are cytoplasmic extensions (or processes), that project from the cell body. They are sometimes referred to as fibers. Dendrites (afferent processes) increase their surface area to receive signals from other neurons, and transmit impulses to the neuron cell body. 

• Axon: There is only one axon (efferent process) that projects from each cell body.        
It carries impulses away from the cell body.

2-Glial cells: do not conduct nerve impulses, but support, nourish, and protect the neurons. They are mitotic, and far more numerous than neurons. 

Astrocyte: A glialcell that provides support for neurons of the CNS, provides nutrients regulates the chemical composition of the extracellularfluid.

• Oligodendrocyte: A type of glialcell in the CNS that forms myelin sheaths.

• Microglia:The smallest glialcells; act as phagocytes (cleaning up debris) and protect the brain from invading microorganisms.

• Schwann cell:A cell in the PNS that is wrapped around a myelinatedaxon, providing one segment of its myelin sheath.