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.

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

Propofol -Intravenous Anesthetics

- A nonbarbiturate anesthetic
- It is very lipid-soluble, acts rapidly and has a short recovery time.
- It is associated with less nausea and vomiting than some of the other IV anesthetics.
- Propofol is very similar to thiopental in its effects on the cardiorespiratory system.
- It does not have any analgesic properties but lowers the dose of opioid needed when the two agents are used in combination.

- The most significant adverse cardiovascular effect associated with propofol administration is hypotension. It should be used with caution in patients with cardiac disease.

Streptomycin

Streptomycin was the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus.

Streptomycin cannot be given orally, but must be administered by regular intramuscular injection.

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

DIAGNOSIS

Affective disorders:
I. unipolar depression – depression alone
bipolar affective disorder – alternating II. bipolar affective disorder – alternating depression and mania

Diagnosis is based on 

At least five of the following for 2 weeks
I. Depressed mood most of the day
II. Markedly diminished interest or pleasureII. Markedly diminished interest or pleasure
III. Significant weight loss or weight
IV. Insomnia or hypersomnia
V. Psychomotor agitation or retardation
VI. Fatigue or loss of energy
VII. Feelings of worthlessness or excessive guilt
VIII. Diminished ability to think or concentrate, 
IX. Recurrent thoughts of death

Underlying biological basis for depression is a deficiency of the monoamine neurotransmitters  norepinephrine and/or serotonin in the brain.