1.  Diuretics

2.  Sympatholytics (Antiadrenergics)

• Alpha 1 Blockers
• Centrally acting Alpha 2 Agonists
• Beta Adrenergic Blockers
• Combination Alpha & Beta Blockers

3.  ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors)

4.  CCBs (Calcium Channel Blockers

5.  ARBs (Angiotensin II Receptor Blockers)

6.  Direct-Acting Vasodilators

  Sympatholytics (Antiadrenergics)

• Alpha 1 Blockers
• Centrally acting Alpha 2 Agonists
• Beta Adrenergic Blockers
• Combination Alpha & Beta Blockers

prazosin (Minipress) 

prototype Anti-adrenergic or adrenergic antagonists

Selective alpha 1 blockade causes dilation of arterioles & veins

(alpha1 adrenergic blocker)

HTN, BPH

Orthostatic hypotension, tachycardia

clonidine (Catapres)

Anti-adrenergic or adrenergic antagonists

Indirect acting alpha 2 agonists prototype

Acts in CNS.  Selective activation of alpha 2 receptors, which decreases sympathetic outflow to blood vessels and heart; results in bradycardia, decr cardiac output (CO), decr BP

HTN

Severe cancer pain

Rare rebound HTN with drug withdrawal

Drowsiness

Dry mouth 

Withdraw drug slowly over 2-4 days

generally free of serious side effects

effects kidneys more than lopressor

propanolol (Inderal) 

most important Anti-adrenergic or adrenergic antagonists

beta-adrengergic blockers nonselective prototype

blocks beta 1 and beta 2 receptors; results in decreased HR, net effect is decr. CO; highly lipid soluble

Also suppresses rennin secretion

metoprolol (Lopressor) 

Anti-adrenergic or adrenergic antagonists

cardioselective prototype

Selective blockage of beta 1 receptors of heart; results in decreases in HR, renin secretion

Preferred for pts with asthma or diabetes; HTN, angina, heart failure, MI

Bradycardia, decreased cardiac output, AV block, rebound tachycardia (withdraw drug slowly), heart failure

carvedilol (Coreg) 

Anti-adrenergic or adrenergic antagonists

combination alpha and beta blockers prototype

Combination alpha & beta blocker; dilates blood vessels

HTN, MI

Orthostatic hypotension, tachycardia Rare rebound HTN with drug withdrawal

Drowsiness

Dry mouth 

Withdraw drug slowly over 2-4 days 

Bradycardia (hold for HR <60 and SBP <100

Block Na+ and Cl- reabsorption (and thus H2O); results in Na+, Cl-, H2O excretion

4 major categories:

·       High ceiling loop diuretics (furosemide)

·       Thiazide diuretics (HCTZ)

·       Osmotic diuretics (mannitol)

enalapril (Vasotec) 

Drugs Acting on the RAAS

angiotensin-converting enzyme inhibitors (ACEI) prototype

ACE Inhibitor; decr levels of angiotensin II and incr levels of bradykinin; causes arteriole vasodilation, decr blood volume

HTN, heart failure, MI, prevent or reverse pathophysiologic effects on heart & kidney ; prevent MI, stroke, death in high risk CV pts

losartan (Cozaar) 

Drugs Acting on the RAAS

angiotensinII receptor blockade (ARB) prototype

HTN, MI, diab. Nephropathy, MI, CVA prevention 

Angioedema—NEVER give again if this develops (med may increase bradykinin synthesis)

eplerenone (Inspra) 

Drugs Acting on the RAAS

selective aldosterone antagonists prototype

Selective blockade of aldosterone receptors; causes K+ retention, Na+ and H2O excretion, decreased BP and decr blood volume

HTN, heart failure

Hyperkalemia (hold for K+ > 5.0)

Caution with ACEI or ARB or decr. Renal function

Contraindications: K+ supplement, salt sub, K+ sparing diuretics

Interactions: Increased med levels if given with erythromycin, verapamil, fluconazole; 5X if given with ketoconazole; med + lithium = incr lithium lvls

diltiazem (Cardizem) 

CCBs

non-dihydropyridines prototype

Blocks Ca++ channels in heart and blood vessels; dilates arterioles to decr BP and incr coronary perfusion; AV node blockade decr HR and AV node conduction (MOST IMPORTANT EFFECT); decr myocardial contractility

Angina, HTN, atrial flutter, atrial fib, PSVT

Dizzy, HA, ankle & foot edema, eczematous rash in elderly

Nifedipine (Procardia) 

CCB

dihydropridines prototype

Vasodilation causes decr BP; increased coronary perfusion; activates baroreceptor reflex to incr HR

(No suppressant effects on HR, AV conduction or contractility)

HTN, angina of effort, vasospastic angina, investigational for migraines & preterm labor

Reflex tachycardia; dizzy, flushing, rash, peripheral edema, HA, gingival hyperplasia

Interactions: Beta blockers prevent reflex tachycardia

apresoline (Hydralazine)

Direct-Acting Vasodilators

prototype

Selective dilation of arterioles to decrease SVR (afterload), decr BP; also increases HR and increases myocardial contractility by reflex mechanisms

HTN, hypertensive crisis, angina, short term use in HF, pheochromocytoma, pulm artery hypertension, PVD

Headache, dizzy, postural hypotension, reflex tachycardia, SLE, increased blood volume

anticoagulant

prototype

 rapid acting (in minutes); helps antithrombin III inactivate thrombin, factor Xa & others to suppress fibrin formation

Since fibrin forms framework of thrombi in veins, esp useful for VTE prophylaxis; pulmonary embolus, evolving CVA or MI, massive DVT, open heart pts, renal dialysis, DIC

Bleeding is complication in 10% of pts

Treat overdose with PROTAMINE SULFATE.

Hemorrhage, thrombocytopenia (check platelets 2-3 x/week first 3 weeks of heparin therapy), hypersensitivity, local irritation & hematoma, vasospastic reactions; long term use can cause osteoporosis.

Contraindications:  thrombocytopenia, uncontrollable bleeding, dur & after eye, brain, spinal cord surgeries, LPs, regional anesthesia

Highly cautious with pts with high likelihood of bleeding (hemophilia, peptic ulcer, severe HTN)

enoxaparin (Lovenox) 

low molecular weight heparin prototype

Shorter molecular chain than Heparin; inactivates factor Xa; less effect in inactivation of thrombin

VTE prophylaxis, DVT with or without pulm embolus; prevention of ischemic complications in unstable angina, non Q wave MI, STEMI

Advantages—as effective as unfractionated Heparin, can be given on fixed dose schedule, don’t need aPTT monitoring, can be used at home, less likely to cause thrombocytopenia

warfarin (Coumadin)

lowmolecular weight heparin

Antagonist of Vit K at synthesis sites 

Long term prophylaxis of thrombosis, prevention of pulm embolus, pts with prosthetic heart valves, atrial fib, risk of recurrent TIA & MI

Hemorrhage 

Don’t use during pregnancy or lactation

Skin necrosis, alopecia, dermatitis, fever, GI disturbances, red-orange urine

Contraindications:  thrombocytopenia, high risk for bleeding, HTN, Vit K deficiency, liver disease, alcoholism.  

Aspirin (ASA) + dipyridamole (Aggrenox)

antiplatelet prototype

ASA irreversibly inhibits cyclooxygenase and prostacyclin causing decreased platelet activity; dipyridamole also suppresses platelet

MI prophylaxis, prevention of reinfarction, stroke prevention, TIA, chronic stable angina, after coronary stent, AMI, after valve replacement

GI bleeding, hemorrhagic stroke

adenosine diphosphate receptor antagonists prototype

Irreversible blockade of ADP receptors on platelet surfaces

(for life of the platelet)

MI and CVA prevention, after stents

Similar to ASA.  Less incidence of intracranial bleeding than ASA, possible TTP

Spasm 

Involuntary contractions                 

treatment?                              

Analgesics                                                                       

Anti-inflammatory agents                                                           

NSAIDs

Valium (diazepam)

Soma (carisoprodol)

.                         Spasticity                       

     CNS disorders

treatment?

Baclofen (lioresal):

muscle relaxant

centrally-acting prototype

muscle relaxant:

centrally acting prototypes?

Baclofen (lioresal)

and carisoprodol (soma)

Management of Osteoporosis:

1.      Bisphosphonates—prototype: Fosamax (alendronate)

2.     Miacalcin (calicitonin-salmon)

penicillins

cell wall weakening agent

prototypes: Pen G, Nafcillin, Amplicillin

cell wall weakening agent

four generation prototypes. each stronger than last

gen 4: cefepime

distributes well in most tissues

excretion by renals

caution with allergies

bleeding - vit K interference

use with AAPC- c. diff.

cell wall weakening agent

prototype: vancocin

potentially very toxic

save for worst of infections: gram pos. staph a.

use as alternative to penicillin allergy patients

use with AAPC/c.diff.

use with mrsa

distributes well in all tissues except CSF

excreted by renals - monitor renal labs

SE: ototoxicity

renal toxicity

thrombophlebitis

VRE 

cell wall weakening agent

prototype: imipenem

bacteriostatic inhibitor

prototypes: tetracycline (short acting), doxycline (long acting)

broad spectrum

gram pos. and gram neg.

static only

seldom used as first line of defense

short, intermittent, long acting

decreased absorption: food, Calcium, iron, magnesium, antacids

widley distributed - not in CSF

excreted in renal and hepatic systems

SE: nvd, cramping, burning - give with food, stains teeth so dont give to preg. womn or children,exacerbation of preexisting renal diseases

used for aapc/c.diff.

bacterialcidal inhibitor

prototype: gentamicin

narrow spectrum bactericidal

commonly used as combo drug

distribution to renal and ear cells

monitor renal labs closely

unmetabolized by hepatic system

can cause tinnitus

can cause dizziness, headache, ATN proteinuria, increases BUN and Cr., ototoxicity, vertigo

inhibitors of cell wall synthesis

broad spectrum prototype

broad spectrum, widely used

effective w/gram neg. and some gram pos.

not effective w/ c.diff.

absorbed quickly but incompletely

interacts with calcium, iron, antacids

used for: URI, UTI, GI tract

concentration in urine stool bile

SE: GI upset, oral candida, tendon rupture, interacts with coumadin

selective: COX 2 inhibitors: celecoxib (celebrex)

Vioxx (Rofecoxib) was withdrawn voluntarily from the market, due to an increased risk of myocardial infarction and stroke

uses: essential hypertension, reversal of toxicity from alpha 1 agonists, benign prostatic hyperplasia

adverse rxn of alpha 1 blockade: orthostatic hypotension, reflex tachycardia, nasal congestion, inhibition of ejaculation

adverse rxn of alpha 2 bloackade: potentiation of the reflex tachycardia that can occur in response to blockade of alpha 1

uses: angina, HTN, cardia dysrhythmias, MI, HF, hyperthyroidism, migrain, stage freight, glaucoma

adverse rxn to beta 1 blockade: bradycardia, reduced CO, HF, AV heart block

adverse rxn to beta 2 blockade: bronchoconstriction, inhibition of glycogenolysis