Exam 7 - Antihypertensives & Renal Pharm Flashcards
Hypertension
- Systolic > 140 mmHg
- Diastolic > 90 mmHg
- 30% incidence
Prehypertension
120-139 / 80-89
Stage I HTN
140-159 / 90-99
Stage II HTN
> 160 / >100
Primary HTN
- Essential HTN
- Idiopathic
- Most common
- 90%
Secondary HTN
- caused by specific disease
- valve disease / coarcation of aorta / pregnancy
Diagnosis of HTN
- Repeated and reproducible measurements
- at least 3 over several weeks / organ damage
HTN risk factors
- Advanced age
- DM
- Obesity
- Family history
- Stress
- Smoking
- Poor diet
- Lack of activity
HTN complications
- Stroke/Ischemic heart heart disease (leading causes of death)
- LV hypertrophy
- Aortic aneurysm
- Arrhythmias
- End organ damage
- especially kidneys / eyes
Blood Pressure
BP = CO x PVR
- so antihypertensives either drop CO and/or PVR
Four ways of controlling BP
- Arterioles resistance
- Venule capacitance
- Cardiac output
- Volume via kidneys
CO and PVR control
- Barroreceptor reflex
- Renin-Angiotensin-Aldosterone system
Barroreceptors
- rapid, moment to moment changes
- in aortic arch and carotid sinuses
Renin-angiotensin-aldosterone system
- baroreceptors release renin if BP drops
- renin converts angiotensinogen to angiotensin I
- Angiotensin I to Angio II via ACE
- Angio II constricts..drops GFR…increases aldosterone
- aldosterone increases Na absorption…more volume
- BP goes up
(Look at chart in slides)
Combo therapy
- more than one drug used to treat HTN
- minimize side effects
- monotherapy can be used if mild HTN
Recommended HTN treatment strategy
Start with:
- Thiazide diuretic
- ACE inhibitor
- Angiotensin receptor blocker (ARB)
- Ca channel blocker
Diuretics
- lower BP by reducing volume
- safe
- inexpensive
- first line drug choice
- used in combo therapy
Thiazide diuretic drugs
- Hydrochlorothiazide
- Chlorthalidone
- Indapamide
Thiazide diuretic mechanism
- inhibit Na/Cl cotransporter in distal tubule
- increase Na/H2O excretion…drops volume
- increase NaCl excretion
Thiazide diuretic uses
- useful in combo therapy
- Not effective in renal failure…metabolized by kidney
- not recommended in pregnancy
Can cause: - hypokalemia
- hyperuricemia
- hyperglycemia
Loop diuretic drugs
- Furosemide (LASIX)
- Bumetanide (BUMEX)
Loop diuretic mechanism
- inhibit Na/K/2Cl transporter in ascending limb
- blocks reabsorption
- decrease RVR
- increase RBF
- fast acting
- increase Na excretion
- increase K excretion
- increase Cl excretion
Loop diuretic uses
- Works well in renal failure
Causes: - hypokalemia
K sparing diuretic drugs
- Spironolactone
- Eplerenone
K sparing diuretics mechanism
- Aldosterone receptor antagonist
- more Na/H2O into collecting duct
- reduces K loss in urine
- used in combo therapy w/ thiazides to reduce K loss
- increase Na excretion
- increase K retention
B blockers
- block B1/B2 receptors
- decrease sympathetic outflow
- drop CO / HR / contractility
- inhibit renin release from kidney
B1 selective drugs
- Acebutolol
- Atenolol…for HTN
- Bisoprolol
- Esmolol (BREVIBLOCK)….use in OR….short acting
- Metoprolol…for HTN
Nonselective B blockers
- Propanolol
- Nadolol
- don’t use w/ COPD
- ALL B blockers Nonselective at high doses
A/B blockers
- Carvedilol… for heart failure
- Labetalol….OK for pregnancy HTN
B blocker adverse effects
- Bradycardia
- Hypotension
- Fatigue
- Insomnia
- Sexual dysfunction
- Altered lipid panel…high LDL…low LDL…high triglycerides
B blocker cautions
- do not stop abruptly ….angina / MI / death
- tapered off over weeks
B blockers in IV form
- Esmolol
- Metropolol
- Propanolol
ACE inhibitor drugs
- Benazepril
- Captopril
- Enalpril
- Lisinopril
ACE inhibitor mechanism
- blocks ACE
- No Angio I to Angio II
- drops Angio II levels
- causes vasodilation
- increases bradykinin
- reduces aldosterone…decrease in Na/H2O retention
ACE and bradykinin
- ACE breaks down bradykinin
- bradykinin increase NO / prostacyclin
- both vasoconstrictors
ACE inhibitor uses
- good for patients with diabetic nephropathy
- decrease progression and albuminuria
- common following MI
Chronic use can: - drop in BP
- LV hypertrophy regression
- better LV healing after MI
ACE inhibitor adverse effects
- dry cough…main reason to get off
- rash
- fever
- altered taste
- hypotension
- hyperkalemia
- fetal malformations
Angiotensin II Recepter Blockers (ARBs)
- Candesartan
- Eprosartan
- Irbesartan
- Losartan
- Telmisartan
- Valsartan
ARB mechanism
- Block angio II receptors
- produce vasodilation
- block aldosterone secretion…lowers BP and Na/H2O retention
- DOES NOT increase bradykinin
ARB uses
- good for DM / HF / Chronic kidney disease
- adverse effects like ACE inhibitors…but less cough
- put on ARB if ACE inhibitors don’t work
- DO NOT combine with ACE inhibitors
- Teratogenic…fetal malformations
Renin inhibitors
- Aliskiren
Renin inhibitor mechanism
- directly inhibits renin
- drops Na/H2O retention
- as effective as other methods
- NO NOT combine worth ACEi or ARB
Renin inhibitor adverse effects
- diarrhea
- cough
- DO NOT use in pregnancy
Ca channel blockers
- blocks Ca into heart cells / smooth muscle cells
- smooth muscle relaxation
- dilates MAINLY arterioles
- initial or add on therapy
Alpha 1 blocker drugs
- Doxazosin
- Prazosin
- Terazosin
Alpha 1 blocker mechanism
- decrease PVR
- decrease BP
- relaxes venous and smooth muscle
- causes reflex tachycardia / orthopedic hypotension
- Na/H2O retention increases….so used with diuretic
- NOT used as initial treatment
Clonidine
- Alpha 2 agonist
- drops sympathetic outflow…drops PVR and BP
- relaxation of venules
Clonidine adverse effects
- dry mouth
- sedation
- constipation
- rebound HTN if stopped abruptly
Methydopa
- Alpha 2 agonist
- similar to clonidine
- HTN during pregnancy
- also Labetol OK for pregnancy
Vasodilator drugs
- Hydralazine
- Minoxidil
- Nitroprusside
- Nitroglycerin
Hydralazine
- releases NO from endothelium
- mainly on arteries
- reflex stimulation of heart… causes angina / MI / HF
- increases renin…Na/H2O retention
- must be used w/ beta blocker AND diuretic
- OK for pregnancy
- Can cause Lupus at high doses…autoimmune disease
Minoxidil
- Hyper-polarization of smooth muscle…contraction less likely
- Mainly in arteries
Minoxidil side effects
- severe tachycardia…dose dependent
- palpitations
- angina
- headache
- sweating
- hypertrichosis…hair growth
- used w/ beta blocker and diuretic
Nitroprusside
- dilates arteries/veins by releaseing NO
- drops PVR and venous return
- rapid onset/offset…IV infusion…used in emergencies
- lasts 5 min
Nitroprusside side effects
- Accumulation of cyanide
- only use 3 days
- arrhythmias
- excessive hypotension
Nitroglycerin
- common in OR / on CPB / after CPB
- bolus or IV drip
- decreases BP and SVR
- dilates coronary vasculature
- good for coronary spasm / air in coronaries
HTN on pump
- adjust flow
- check anesthetic depth
- increase isofluorene
- drugs
Proximal convoluted tubule
Reabsorbed:
- 100% of glucose, proteins, metabolites
- 65% Na, H2O, Cl, K, bicarb
Secreted:
- H
- organic acids/bases
- catecholamines
- drugs/toxins
Descending loop
Reabsorbed:
- 20% H2O
Ascending loop
- impermeable to H2O
Reabsorbed:
- 25% Na, Cl, K
- Ca, bicarb, Mg
Secreted:
- H
Early distal
- impermeable to H2O
Reabsorb:
- 5% Na, Cl, K
Late distal / Collecting tubule
Reabsorb:
- H2O if there is ADH
Principal cells:
- reabsorb Na
- secrete K
Intercalated cells:
- reabsorb/secrete K, bicarb, H
Collecting duct
Reabsorb:
- 10% Na, H2O (if ADH)
- urea
Secrete:
- H
Common uses for diuretics
- HTN
- Edema from:
- CHF / liver cirrhosis / corticosteroid therapy / bad renal
Ascites
Swelling in abdomen
Thiazide diuretics characteristics
- most widely used
- acts on distal tubule
- all have same Emax….but different potencies
- low ceiling diuretics
- effective orally
- 1-3 weeks for BP drop
Thiazide diuretics mechanism
- blocks Na/Cl transporter
- enter lumen via proximal tubule…act on distal
- compete with organic acids to enter proximal
Thiazide diuretics actions
- Increased excretion of Na and Cl
- hyperosmolar urine…UNIQUE to thiazides…don’t change pH
- Loss of K
- high Na = more K secretion later in tubule…continual loss
- Loss of Mg
- supplementation required
- Ca retention
- due to increased PTH in distal…good for bones
- Reduced PVR
- less volume = less CO…overtime volume comes up but PVR stays low
Thiazide therapeutic uses
- HTN: drug of choice / minor diuretic effect / PVR low
- HF: loops are drug of choice / thiazide is supplement
- Hypercalciuria: idiopathic / good for kidney stones
- Diabetes Insipidus: substitute for ADH
Thiazide diuretics adverse effects
- K depletion
- Hyponatremia
- Hyperuricemia…caution with gout
- Volume depletion…orthostatic hypotension
- Hypercalcemia
- Hyperglycemia…impaired release of insulin/tissue glucose uptake
Thiazide diuretic drugs
- Hydrochlorothiazide (HCTZ) (Microzide)
- Chlorothiazide (Diuril)…not oral…ok for pregnancy
Thiazide-like diuretics
- Chlorothalidone (Thalitone)
- Metolazone (Zaroxolyn)….more potent than others
- Indapamide
- different structure / same functions / same effects
Loop diuretics characteristics
- act on ascending loop
- high ceiling diuretics…higher doses…higher urine output
- Oral or IV
- Rapid onset, short duration…2-4 HOURS
- Limiting step: how much gets into lumen via proximal tubule
- good at removing Na and Cl from body
Loop diuretics mechanism
- blocks Na/K/2Cl transporter on luminal membrane
- downstream sites can’t compensate for increase in Na
- greatest diuretic effect
- increase RBF via prostaglandin synthesis
- this effect blocked by NSAIDS…they block loop diuretics
- increase secretion of Na / K / Ca
Loops diuretic uses
- Peripheral/pulmonary edema
- Emergency…acute pulmonary edema
- Hypercalcemia (1.2-1.4 is normal)
- Hyperkalemia (3.5-5 is normal)
- Diuretic of choice in renal failure
Loop diuretic perfusion uses
- remove extra fluid on pump
- treat hyperkalemia
- maintain urine production / renal function
Loop diuretic dose
20-40 mg bolus…lasts 2 hours in pump
Loop diuretic adverse effects
- Ototoxicity…hearing loss
- Hyperuricemia…compete with uric acid for secretion
- Acute hypovolemia
- K depletion…more exchange of Na for K in tubule
- Hypomagnesemia….on chronic use
Loop diuretic drugs
- Furosemide (Lasix)
- Bumetanide (Bumex)
- Ethacrinic acid
K sparing diuretic characteristics
- act in collecting tubule
- aldosterone antagonists… stops Na reabsorption/K secretion
- Na channel blockers
Aldosterone
- from adrenal cortex…zone glomerulosa cells
- principal cells of collecting tubule
- increase Na/K ATPase activity AND permeability of membrane Na
- increase Na reabsorption and K secretion
- important regulator of K
K sparing diuretic uses (aldosterone antagonists)
- Diuresis…given with loops or thiazides
- Secondary hyperaldosteronism
- like hepatic cirrhosis or nephrotic syndrome
- HF…prevent remodeling / decrease mortality / UNIQUE effect
- Resistant HTN…use of 3+ medications w/o BP drop
- Ascites…like with hepatic cirrhosis
- Polycystic ovary syndrome…high androgen levels
- off label use…stop steroid synthesis
K sparing adverse effects (aldosterone antagonists)
- Gynecomastia in males
- Menstrual irregularities
- Hyperkalemia…careful if on high K diet
- confusion
K sparing drugs (aldosterone antagonists)
- Sprinolactone (aldactone)
- Eplerenone (Inspra)…less endocrine effects
K sparing diuretics (Na channel blockers)
- not very effective
- in combo w/ other diuretics for k sparing effects
- increase Na secretion
- increase K reabsorption
K sparing diuretics (Na channel blockers) adverse effects
- Increase uric acid
- renal stones
- K retention
K sparing diuretics (Na channel blockers) drugs
- Triamterene (dyrenium)
- Amiloride
Carbonic anhydrase inhibitors
- much less effective than loops and thiazides
- 1st diuretic developed
Carbonic anhydrase inhibitors mechanism
- acts in proximal tubule
- drops Na uptake by dropping H levels in tubule cells
- less effective Na/H exchange
- urine pH increase
- metabolic acidosis after several days
- increase excretion of Na / K / bicarb
Carbonic anhydrase inhibitors uses
- glaucoma: less aqueous humor / pressure
- correction of metabolic alkalosis (gets rid of bicarb)
- mountain sickness
- prophylaxis…counters respiratory alkalosis
- drops pulmonary edema
Carbonic anhydrase inhibitors drug
- Acetazolamide (Diamox)
Osmotic diuretics drug
- Mannitol (osmitrol)
- IV only
Osmotic diuretics mechanism
- elevates blood osmolality…pulls in water
- elevates tubular filtrate osmolality
- filtered but not reabsorbed
- causes water excretion
- inhibits reabsorption of Na / Cl / solute
Osmotic diuretic uses
- reduce intracranial pressure
- acute renal failure…shock/drug toxicity/trauma
- will give on bypass
Mannitol dose
CPB: 0.5-1.0 g/kg
In prime: 12.5g/50ml vials in prime
- check for crystals
- use filtered needle
- may cause transient hypotension if given too fast
