Drugs that increase urinary output

Two major applications

Treatment of hypertension

Mobilization of edematous fluid, which prevents renal failure

High ceiling (loop)—(furosemide)

Thiazide—(hydrochlorothiazide)

Osmotic—(mannitol)

Potassium-sparing: two subdivisions:

Aldosterone antagonists (spironolactone) and Nonaldosterone antagonists (triamterene)

Mechanism of action: Acts on the ascending loop of Henle to block reabsorption

Pharmacokinetics: Rapid onset

Therapeutic Uses: Pulmonary edema, Edematous states, Hypertension

Hyponatremia, hypochloremia, and dehydration

 Hypotension, Loss of volume

Relaxation of venous smooth muscle

Hypokalemia, Ototoxicity

Hyperglycemia, Hyperuricemia

Use in pregnancy

Impact on lipids, calcium, and magnesium

Digoxin

Ototoxic drugs

Potassium-sparing diuretics

Lithium

Antihypertensive agents

Nonsteroidal anti-inflammatory drugs

Most widely used Action—distal convoluted tubule

Peaks 4-6 hours

Essential hypertension

Edema

Diabetes insipidus

Hyponatremia, hypochloremia, and dehydration Hypokalemia

Use in pregnancy and lactation-Enters breast milk

Hyperglycemia

Hyperuricemia

Impact on lipids, calcium, and magnesium

Blocks aldosterone in the distal nephron 

 Retention of potassium Increased excretion of sodium

Hypertension

Edematous states

Severe heart failure

 Primary hyperaldosteronism

Hyperkalemia

Benign and malignant tumors

Endocrine effects

Thiazide and loop diuretics

Agents that raise potassium levels

Disrupts sodium-potassium exchange in the distal nephron

 A direct inhibitor of the exchange mechanism

Decreases sodium reuptake

Inhibits ion transport

Hypertension

Edema

Hyperkalemia

Leg cramps

Nausea Vomiting (rarely)

Dizziness

Blood dyscrasias

Prophylaxis of renal failure

Reduction of intracranial pressure

Reduction of intraocular pressure

Edema

Headache

 Nausea Vomiting

 Fluid and electrolyte imbalance

Filtered at the glomerulus

 Undergo limited reabsorption

 Promote osmotic diuresis

Cause-hyperventilation

 Treatment-rebreathe CO2-laden expired breath

Causes: Retention of CO2 secondary to hypoventilation -Depression of the medullary respiratory center -Pathologic changes in the lungs

Treatment: Correct respiratory impairment; Infusion of sodium bicarbonate if severe

Causes: Excessive loss of gastric acid

Administration of alkalinizing salts

Treatment: Solution of sodium chloride plus potassium chloride

Causes: Chronic renal failure Loss of bicarbonate during severe diarrhea, Metabolic disorders, Methanol and certain medication poisoning

Treatment: Correcting the underlying cause of acidosis Alkalinizing salt if severe

Primarily by the kidneys

Influenced by extracellular pH

Insulin has a profound effect on potassium level

Most common cause is treatment with a thiazide or loop diuretic

Adverse effects on skeletal muscle, smooth muscle, blood pressure, and the heart

Potassium salts

 Oral potassium chloride

 Intravenous potassium chloride

Contraindication to potassium use

Severe tissue trauma

 Untreated Addison’s disease

 Acute acidosis

 Misuse of potassium-sparing diuretics

 Overdose with IV potassium

Treatment: Withhold foods that contain potassium Withhold medicines that promote potassium accumulation

Management: Counteract potassium-induced cardiotoxicty

Lower extracellular levels of potassium

Infusion of sodium bicarbonate

Diarrhea

Hemodialysis

 Kidney disease

 Prolonged intravenous feeding

 Chronic alcoholics

Hypermagnesemia

Arteries

Arterioles

Capillaries

Venules

Veins

9% in the pulmonary circulation

7% in the heart

84% in the systemic circulation

Average adult, 5 L/min

 Cardiac output = heart rate × stroke volume

Myocardial contractility

Cardiac afterload

Cardiac preload

Preload: End-diastolic volume or end-diastolic pressure

Afterload: arterial pressure

Systemic filling pressure

Auxiliary muscle pumps

Resistance to flow between peripheral vessels and the right atrium

 Right atrial pressure

force of contraction depends on the length of muscle fibers of the heart wall.

-The greater the stretch of cardiac muscle, the greater the force of contraction. 

- if increase in volume of blood entering heart,  ventricular wall stretches causing the cardiac muscle to contract more forcefully.

Arteriole pressure

Angiotensin-Converting Enzyme Inhibitors

mechanism of action

Angiotensin-Converting Enzyme Inhibitors

Adverse effects

Explain the normal physiologic process being impacted upon with ACEI’s In response to low B/P, decreased blood volume, decreased sodium, or decreased renal perfusion.

Renin is produced and converts angiotensinogen to angiotensin 1

Angiotensin 1 is converted to angiotensin 2 by ACE

Angiotensin 2 attaches to blood vessels causing

vasoconstriction, which raises B/P by increasing total peripheral resistance (tpr); water and sodium are retained (increasing blood vol.)

       angioedema (swelling face, lips; dyspnea)  [>bradykinin]

                        Dry hacking cough (from angioedema)

 Inhibitors of CYP3A4

Angiotensin II Receptor Blockers

Therapeutic Uses:

hypertension

heart failure

diabetic neuropathy

MI

stroke prevention

migraine

Angiotensin II Receptor Blockers

adverse effects

angioadema/cough (rare)

fetal harm

renal failure

Calcium Channel Blockers do what?

Name the consequences of blockade

Prevent calcium ions from entering cells which decreases HR, contractility force and conduction velocity

Regulate contraction of vascular smooth muscle

(no significant effect on veins)

...on the heart:

Myocardium

SA/AV node

Coupling of cardiac calcium channels to beta1-adrenergic receptors

Nondihydropyridines- act on arterioles AND THE HEART (verapamil and diltiazem)

Dihydropyridines- act on arterioles (nifedipine)

Hemodynamic:

vasodilation

decreased arteriole pressure

increased coronary perfusion

Th. uses:

angina pectoris, essential HTN, cardiac dysrhythmias and migraine

constipation

facial flushing

dizziness

headache

adema of ankles/feet

gingiva hyperplasia

heartblock

interactions:

digoxin

beta-adrenergic blocking agents

toxicity:

severe hypotension

bradycardia and AV block

V-tahcydysrhythmias

actions:

blocks calcium channels in heart and blood vessels

th. uses:

angina pectoris

hypertension

cardiac dysrhythmias

Nifedipine:

actions and th. uses

actions:

vasodilation by blocking calcium channels; net effect-> lower BP, increased HR and contractile force

th.uses:

angina pectoris, hypertension and investigational use for migraines and to supress preterm labor

adverse effects:

flushing, headache, perpheral adema, gingival hyperplasia and reflex tachy

ineractions:

beta-adrenergic blockers

essential HTN

hypertensive crisis

angina pectoris

heart failure

MI

pheochromocytoma

peripheral vascular disease

pulmonary arteriole hypertension

produce controlled hypotension during surgery

postural hypotension

relflex tachy

expansion of blood volume

mech of action :

fastest acting antihypertensive agent MUST GIVE SLOWLY- IV

venous/arteriole dilation

used in hypertensive emergencies (rapid onset)

adverse effects:

exessive hypotension

cyanide poisoning

thiocyanate poisoning

normal 120/80

preHTN 120/80 - 139/89

HTN 140/90

stage 2 HTN when systolic an diastolic BP fall into different categories- >160/92

primary HTN:

unknown cause, chroninc-progressive, older blacks/mexicans/postmenopausal women/obese, treated but not cured (lifelong), referred to as essential hypertension

secondary HTN:

can ID cause, possible to treat the cause directly, sometimes curable

Heart: MI, heart failure, angina pectoris

Kidney disease

Stroke

weight loss, sodium restriction, DASH eating plan, alcohol restriction, aerobic exercise, smoking cessation and maintainence of potassium/calcium intake

sympathetic baro-receptor reflex

RAAS

renal reg. of BP

CO is dertmined by:

PR is determined by:

CO: 

HR

contractility

venous return

blood volume

PR:

arteriolar constriction

Stage C Heart Failure

HF symptoms, structural heart disesae,

4 goals: correct pulmonary/peripheral adema

prevent remodeling from getting worse

improve quality of life

prolong life

antidysrhythmics

calcium channel blockers

NSAIDs

diuretics

ACEI's

ARBs

beta blockers

vasodilators

cardiac glycosides (digoxin)

1 .How does Digoxin work on the heart?

2. What is the adverse effect?

3. what might be a symptom of digoxin toxicity?

1. increases heart contractility and CO

2. severe dysrhythmias

3. yellow halos around lights

anorexia

nausea

vomiting

fatigue

impulse arises above ventricle

atrial flutter and fib

sustained supraventricular tachy -SVT

Ventricular dysrhythmias are chracterized by:

sustained ventricular tachy

venrticluar fib

ventricular premature beats

Digoxin-induced vent-dysrhythmias

Torsades de-pointes

Adenosine effects on heart and ECG:

Therapeutic use?

decreases automaticity in SA node

slows conduction through AV node

prolongation of PR interval

Th. use- termination of paroxysmal SVT

Close to the heart and as fast as possible

what happens to the heart rhythm after giving adenosine?

How many doses can be given?

Brief asystole (up to a minute)

3 doses can be given

Adenosine adverse effects:

sinus brady

dyspnea

hypotension

facial flushing

Chracteristics of chronic stable angina:

treatments:

...predictable

emotional excitement

large meals

cold temps

coronary artery disease

treatments:

increase cardiac O2 supply/decrease O2 demand

Which classes of drugs would you use to treat angina?

What is the most common reason for angina?

First administer a vasodilator, then a beta-blocker.

Occlusion

organic nitrates

beta-blockers

calcium channel blockers

variant angina (Prinzmetal's; vasospastic)

pathophysiology:

treatment:

th. agents

path: coronary artery spasm

Tx: increase cardiac O2 supply

th. agents: calcium channel blockers

    organic nitrates

If unstable angina is not treated what will happen?

unstable angina:

path:

Tx:

th. agents:

Path:angina symptoms at rest

new-onset exertional angina

intesifying of existing angina

Tx: maintain O2 supply/decrease O2 demand

th. agents:  anti-ischemic therapy, antiplatelet therapy and anticoagulant therapy 

Nitroglycerin is an ____________ and a ________.  It can be given every _______ minutes up to _______ times.

Organic nitrate

vasodilator

five min

three times

Nitroglycerin

adverse effects:

adverse effects:  headache, orthostatic hypotension, reflex tachy

How is Nitroglycerin administered?

Why is it put in a dark bottle?

How can the pt tell if the pill is still good?

pill form

topical

sprays

IV

It is put in a dark bottle b/c light will break it down.  The pt can tell the pill is ok if it tingles in the mouth.

Heparin uses:

is it fast acting or slow acting?

pulmonary embolism

stroke evolving

massive deep vein thrombosis

Heparin is fast-acting.

Hemorrhage

Heparin-induced thrombocytopenia

Hypersensitivity reactions

What is the lab called to measure clotting time?

Activated Partial Thromboplastin Time aPPT

Low-molecular-weight-heparin:

meaning?

therapeutic uses:

adverse effects:

Fractionated: composed of molecules that are shorter than those in unfractionated heparin.

Th. uses: prevention of DVT post-op, tx of existing DVT, prevention of ischemic complications

adverse effects:

bleeding, immune-mediated thrombocytopenia

expensive

Fondaparinux (Arixtra)

frac or unfrac?

Th. uses?

Adverse effects:

fractionated synthetic anticoagulant

th. uses: 

prevent DVT post-op,

tx of acute PE (w/ warafin)

adverse effects:

bleeding

pts weighing less than 50kg

thrombocytopenia

spinal or epidural hematoma

What is the oral anticoagulant?

What is its antidote?

Warafin (Coumadin)

vit K is antidote

Warafin therapeutic uses:

adverse effects:

th. uses:

long-term prophylaxsis of thrombosis-

prevent venous thrombosis and pulm embolism

prevent thromboembolism in pts w/ synth heart valves

prevent thrombosis during atrial fib

adverse effects:

hemorrhage

fetal hemorrhage and tertatogenesis during preg

use during lactation

Drugs that...

increase/decrease anticoagulant effects, promote bleeding, Heparin, aspirin and acetaminophen

-some antibiotics can make you bleed (cephalosporin)

Aspirin is used to do what?

when might aspirin be given urgently?

prevent platelets from sticking togther

MI, clot

Most effective drugs for lowering chloesterol:

Therapeutic uses:

 what are the nonlipid beneficial CV actions:

Statins (Lipitor) (Zocor)

th. uses: hypercholesterolemia, prevent primary/secondary CV events

nonlipid benefits:

bone formation

reduce risk for CV events

Statins adverse effects:

headache

rash 

GI disturbances

myopathy/rhabdomyolysis (rare)

hepatotoxicity (rare)

What is the benefit of niacin?

adverse effects?

niacin raises HDLs

adverse effects:

flushing

GI disturbances

hepatotoxicity

hyperglycemia

gouty arthritis

Bile-Acid Binding Resins

adverse effects:

how do these resins affect the liver?

adverse effects:

constipation

decreased uptake of fat soluble vitamins

does not directly do anything to the liver.

Fibric Acid Derivatives (Fibrates) (gemfibrozil, Lopid)

Therpeutic uses:

Adverse effects:

th. uses: reduces levels of plasma triglycerides (VLDLs)

adverse effects:

rash

gastrointestinal

gallstones

myopathy

hepatoxicity (works through the liver)

Ezetimibe (Zetia)

Mech of action:

Th. uses:

adverse effects:

interactions:

mech:

inhibit cholesterol absorption

th. use:

reducing total cholesterol, LDL chol., apolipoprotein B

adverse effects:

myopathy

rhabdomyolosis

hepatitis

pancreatitis

thrombocytopenia

interactions:

statins, fibrates, bile-acid sequestrants, cyclosporine

Iron adverse effects:

 drug interactions:

adverse effects:

constipation

toxicity

staining of teeth (elixir)

interactions:

antacids

tetracycline

Ascorbic acid

 Iron binds w/ calcium

What is required to absorb B12?

What if a person lacks this?

Intrinsic factor

if no intrinsic factor, then you must bypass the gut; if you cannot bypass the gut, then you must give pt intrinsic factor.

what might a chemo pt receive to improve his/her immunity?

What is epogen?

who might abuse it?

how can you create the same effect natuarlly?

Epogen uses:

adverse effects:

uses:

anemias of chronic renal failure

HIV pts taking zidovudine

chemo induced anemia

anemia in pts facing surgery

 adverse effects:

hypertension

autoimmune pure red cell aplasia

CV events

neupogen uses:

adverse effects:

uses:

cancer

severe chronic neutropenia

adverse effects:

therapeutic effects are enhanced

systemic effects are minimized

relief of acute attack is rapid

metered dose inhalers (MDIs)

dry-powder inhalers (DPIs)

nebulizers

types of quick relief asthma meds

when are these drugs not enough to control asthma?

short acting beta-agonists

systemic corticosteroids (IV/Pill/inhale)

anticholinergic agents

the drugs are not enough to control asthma if they are used more than 3 times per week.

inhaled corticosteroids -no systemic se

long-acting beta agonists

leukotriene antagonists

fewer systemic se (but lungs are absorpative)

quick acting

non-invasive

effective

begin to inhale just prior to drug admin; continue slow inhalation -use a spacer so more med gets to lungs

hold breath as long as possible

wait 2 minutes b/t puffs (at least 30sec)

clean mouth piece!

rinse out mouth to prevent thrush!

if they have 2 inhalers instruct to use beta agonist first, then steroid

report palpitations or chest pain

measure canister fullness: floats in water when full

keep a spare!

what is the protoype beta 2 adrenergic agonist for asthma?

how is it used in asthma?

adverse effects?

oral preparations?

prototype: Albuterol

asthma uses:

quick relief, long-term control

adverse effects:

(inhaled) tachy and tremor

(oral) excess dose, angina, tachydysrhythmias, tremor

long acting beta 2 agonist asthma med:

how long does it last?

for which type of asthma?

salmeterol, serevent

 Lasts 12 hours

For mild/moderate asthma ONLY!!! Not for acute attacks!

most effective type of steroid antiasthma relief (long term)

adverse effects:

Interventions:

fastest admin:

inhaled glucocorticoids

adverse effects:

oropharyngeal candidas (thrush)

dysphonia (hoarseness)

interventions:

gargle after each admin

spacer

fastest admin: IV then pill, then inhaler

NOT for rapid relief!

for acute asthma attacks, which form of beta 2 agonists provides the fastes relief and which form of steroid provides the fastes relief?

inhaled for beta 2 agonist

IV for steroid

advantage to inhaled corticosteroids:

actions:

adv: reduced systemic se

actions:

reduce inflammation

stabilize mast cells

restore bronchodilator response to sympathomimetics

not effective in acute attacks

takes weeks to reach th.levels

oral candida

dysphonia

how do mast cell stabilizers work to prevent an asthma attack? They are which type of med?

what is the prototype mast cell stabilizer med for asthma?

how long to reach th. levels?

not good for_____?

especially good for____?

prevent mast cells from releasing histamine; antiinflammatory

 prototype:  cromolyn sodium (intal)

takes several weeks of daily use to reach th. levels

not good for acute attacks

especially good for seasonal allergic attacks (start before season begins to build up th. level)

how are mast cell stabilizers given?

what is a popular mast cell stabilizer?

spin inhaler (capsule w/ powder)

MDI

solution for nebulizer

Tilade (nedocromil)

Cromolyn (intal)

mech of action:

route:

adverse effects:

mech: anti-inflammatory

route: inhale (nebulizer, MDI)

adverse effects:

safest of all antiasthma meds

cough, bronchospasm

for asthma, when would you use a methylxanthine (theophylline)?

therapeutic index?

use in diffcult to control asthma

very narrow th. index

what are the first line drugs of choice for the COPD pt? What is the name of the drug?

what does this do to secretions? what can you tell your pt to do to manage this?

what is the combination treatment in the COPD pt?

anticholinergics or cholinergic antagonists; ipratropium (atrovent)

 decrease and thickens secretions causing plugging- tell pt do stay hydrated

combination of a beta 2 agonist w/ the anticholinergic (combivent)

for which instances would anticholinergics/cholinergic antagonists NOT be treatment for COPD pts?

for whom else would you not give these drugs?

not for use is acute attacks

not for use in pts w/narrow angle glaucoma, BPH, bladderneck obstruction, preg: cat B

If giving epi, what must be monitored?

what can be given to help protect the heart?

watch for CV se; monitor CV activity, BP, etc.

give a beta blocker for heart protection

actions of leukotriene antagonists:

pt must be over what age ?

protoype:

broncho protection; increases broncho dilation-  for prohpylaxis and chronic treatment of asthma symptoms

REDUCES:

inflammation

edema

mucous secretions

recruitment of eosinophils and other inflammatory cells

can only be given to pts over 7 yr old

prototype: singulair (montelukast) or

accolate (zafirlukast)

5-lipoxygenase inhibitor

actions:

uses:

protoype:

contraindacated for whom?

actions:

blocks enxyme that converts arachidonic acid into leukotrienes

uses:  prophyaxis/chronic treatment of asthma

prototype: Zyflo

contra: pts w/ liver disease