2ND TRIMME PHARMACOLOGY!

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Diuretics
Thiazides Hydrochlorothiazide (HydroDIURIL) Chlorthalidone (Hygroton) Chlorothiazide (Diuril) Indapamide (Lozol) Metolazone (Zaroxolyn)	Potassium Sparing Amiloride (Midamor) Spironolactone (Aldactone) Triamterene (Dyrenium)	Loop Diuretics Furosemide (Lasix), Bumetanide (Bumex), Ethacrynic acid (Edecrin) Torsemide (Demadex)

• Chlorothiazide (Diuril)
• The thiazides act in the distal tubule to decrease sodium reabsorption (inhibits Na/Cl transporter).
• As a result of decreased sodium and chloride reabsorption, a hyperosmolar diuresis ensues.
• Delivery of more sodium to the distal tubule results in potassium loss by an exchange mechanism.
• Thiazides also promote calcium reabsorption, in contrast to loop diuretics.
• The initial decrease in blood volume followed by a longer-termed reduction in vascular resistance appear to account for the hypotensive effects of the thiazides.
•  Adverse Effects
• Potassium depletion is a potentially serious side-effect that may require potassium supplementation and/or concurrent use of potassium-sparing diuretics.
•  Hyperuricemia may occur precipitating gout. 
• The increase in systemic uric acid is due to a decrease in the effectiveness of the organic acid secretory system.
•  Diabetic patient may have difficulty in maintaining proper blood sugar levels.

 

•   Furosemide (Lasix), Bumetanide (Bumex),Ethacrynic acid (Edecrin)
• Furosemide (Lasix), bumetanide (Bumex), and ethacrynic acid (Edecrin) are "high-ceiling" loop diuretics acting primarily at the ascending limb of the loop of Henle.
• The effectiveness of these agents is related to their site of action because reabsorption of about 30 - 40% of the filtered sodium and chloride load occurs at the ascending loop.
• Distal sites are not able to compensate completely for this magnitude of reduction of NaCl reabsorption.
• Loop diuretics increase urinary Ca²⁺ in contrast to the action of thiazides.
• Loop diuretics also increase renal blood flow by decreasing renal vascular resistance.
• These drugs are rarely used in the management of hypertension because of their short duration of action and the availability of better drugs. 
• Adverse Effects
• Ototoxicity
• Furosemide (Lasix) and ethacrynic acid (Edecrin) block renal excretion of uric acid by competition with renal secretory and biliary secretory systems.Therefore these agents can precipitate gout.
• Potassium depletion.

Furosemide

 

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Sympatholytics
Centrally Active Clonidine (Catapres) Methyldopa (Aldomet) Guanabenz (Wytensin) Guanfacine (Tenex)	Adrenergic Neuron Blocker Guanadrel (Hylorel) Guanethidine (Ismelin) Reserpine	Adrenoceptor Antagonists  Labetalol (Trandate, Normodyne) (alpha & beta) Prazosin (Minipress) (alpha), Terazosin (Hytrin) (alpha)

• Clonidine (Catapres) (Sympatholytic)
• Antihypertensive:
• Clonidine (Catapres) acts in the brain, inhibiting adrenergic outflow from the brainstem. Inhibition of sympathetic outflow results in a decrease in blood pressure.
• Mechanism of action: centrally acting selective a₂ adrenergic agonist.
• Especially effective in
• management of severe hypertension or
• in renin-dependent hypertension
• Transdermal clonidine (Catapres) patch: useful for surgical patients unable to take oral formulation
• Clonidine (Catapres) reduces cardiac output (by reducing both stroke volume and heart rate) and peripheral resistance.
• Reduction in stoke volume occurs due to increased venous pooling (decreased preload).
• Clonidine (Catapres) does not interfere with cardiovascular responses to exercise.
• Renal blood flow and function is maintained during clonidine treatment.
• Clonidine (Catapres) has minimal or no effect on plasma lipids.
• Other Clinical Uses
• Analgesia--
• Preservative-free clonidine administered into epidural/subarachnoid space (150-450 micrograms)-- dose-dependent analgesia
• No respiratory depression, nausea, vomiting, delayed gastric emptying or pruritus -- effects associated with opioids
• Probable Mechanism: activation postsynaptic a₂ receptors in the spinal cord substantia gelatinosa
•  Clonidine (Catapres) & morphine: no cross-tolerance when used concurrently in neuraxial analgesia
• Side effects of neuraxial clonidine (Catapres)
•   hypotension, sedation, dry mouth
• Preanesthetic Medication:
• Oral clonidine (Catapres) (preanesthetic medication):
• Enhances intrathecal morphine + tetracaine (pontocaine) for postoperative analgesia (no increase in morphine-related side effects)
• Preanesthetic clonidine (Catapres) also:
• Reduces reflex tachycardia that may be caused by direct laryngoscopy for tracheal intubation
• Reduces intraoperative blood-pressure heart rate lability
• Reduces plasma catecholamines levels
• Significantly decreases anesthetic requirements for inhaled (MAC) and injected agents.
• Adverse Effects
• Dry Mouth (xerostomia)
• bradycardia (in patients with SA nodal abnormality)
• Withdrawal syndrome upon abrupt discontinuation (increased blood pressure, headache, tachycardia, apprehension, tremors

Clonidine