antiHTN Flashcards
what effects BP
CO and SVR
What effects CO
HR and SV
what effects SVR
direct innervation
circulating regulators
local regulators
what effects SV
contractility and preload
what effects preload
venous tone
intravascular volume
what de/increased HR
D: PSNS I: SNS, catecholamines HTN drugs that effect here: B-antagonists CCB
Catecholamines effect
contractility HTN drugs that effect here: B-antagonists, CCB venous tone HTN drugs that effect here: alpha 1 antagonist ACEI ARB Nitroprusside
what effects intravascular volume
Na/H2O retention I: by SNS, aldosterone, ADH D: natriuretic peptide HTN drugs that affect here: Diuretics ACEI ARB
what causes Direct innervation of SVR
Alpha 1
so then for HTN drugs would want
alpha 1 antagonist or alpha 2 agonists
what Circulating regulators effect SVR
Increased by catecholamines, ATII HTN drugs that effect this would be alpha 1 antagonist alpha 2 agonist ACEI ARB
what Local regulators effect SVR
Decreased by NO, prostacyclin, adenosine, H Increased by endothelin, ATII HTN drugs that effect this would be: endothelin antagonist Nitroprusside ACEI ARB
tx guidelines
normal
tx thresholds
> 120/80 than than should initiate “lifestyle modifications”
Tx when
140/90 without DM or kidney d
130/80 with DM or kidney disease (bc of end organ damage)
first-line therapy is
thiazide diuretic UNLESS “compelling indication”
most pts will requires at least 2 meds to reach this goal
Compelling indications 7
- Heart Failure: Thiazide and either bblocker, ACEI, (those 2 first pick) or ARB, aldosterone antagonist
- MI:?no thiazide? bblocker (first choice) ACEI, aldosterone antagonist
- High CVD risk: Thiazide, bblocker, ACEI, CCB
- DM: Thiazide, then 1st choice ACEI, then bblocker, ARB, CCB
- chronic kidney disease:? thiazide? ACEI or ARB
- recirrent stroke prevention: Thiazide, ACEI
- Isolated systolic HTN; Thiaside, CCB
HTN emergency 2 types
HTN urgency or Crisis
HTN Urgency
DPB >120 with evidence of progressive end organ Damage
BUN and creat increasing
Goal: decreased DBP to 100-105 within 24hrs: Clonidine
HTN Crisis
DBP> 120 with evidence of end organ FAILURE
Goal: decreased DBP 100-105 ASAP: nitroprusside, NTG, Labetalol, Fenoldapam
Renin secreted by
Juxaglomerular apparatus
Renin results in
vasoconstriction, Na retention–increased intravascular volume
goal of renin
is aimed at maintaining tissue perfusion through increased extracellular fluid volume
Renin-angiotensin system is synergistic with…
SNS by increasing the release of NE from sympathetic nerve terminals
Renin-angiotensin system pathway
BP falls stimulates kidney to release renin
renin converts angiotensinogen (from liver) to angiotensin I
ACE converts angiotensin I to angiotensin II
ATII causes vasoconstriction (increased afterload) and stimulates the secretion of aldosterone
**Aldosterone increased Na and H2O retention causing an increase in Preload
Angiotensin II acts where (4) which each cause what?
Adrenal cortex: aldosterone–increased Na reabsorption
Renal proximal tubule: increased Na reabsorption
Renal efferect arterioles: vasoconstriction
Hypothalamus: thirst, increased ADH secretion
ACE inhibitors
first line therapy for?
more effective in… bc..
renin-angiotensin system blockers
first line therapy: HTN, CHF, Mitral regard
More effective in DM pts
Delay progression of renal disease
main action of ATII are at what receptors? which has stronger effects?
AT1 and AT2 receptors which belong to gprotein coupled receptors
AT1effects> AT2 effects
AT1 receptor effects
generalized vasoconstriction- especially in the afferent arterioles of renal glomeruli
Increased NE release
Proxima tubular reabsorption of Na
Secretion of aldosterone from adrenal cortex
AT2 receptor effects
are subtle
ACEI MOA and site of action
block the conversion of ATI to ATII through an interaction with the zinc ion of ACE (peptidyl-dipeptidase), preventing conversion of ATI to II
Site of action: ACE endothelium
ACE inhibitors drugs 9
Captopril- capoten Enalapril- vasotec Ramipril- altace Benazepril- lotensin Lisinopril- zestril, prinivil Moexipril- univasc Quinapril- accupril Fosinopril- monopril Trandorapril- mavik
ACE inhibitors pharm effects and uses
fall in arterial pressure, reduced cardiac load
(more arterial than venous)
For: HTN, Cardiac failure, postMI, diabetic neuropathy, CRI
ACE inhibitors SE
*Prolonged hypotension intra-op (prohibit taking on the A.M of surgery Granulocytopenia *Angioedema Proteinuria *Persistent Cough (increased bradykinin which causes vasodilation) Hyperkalemia
ACE inhibitors contraindications
renal artery stenosis
Renal artery stenosis patients may develop Renal failure due to efferent arteriole constriction
Captopril, dose, kinetics, SE
ACEI prototype
Dosage 12.5-25mg q 8hrs
Onset 15mins
Short plasma half-life (E1/2 time 2hrs)
Decreases SVR, does not interfere with sympathetic outflow.
Side effects: rash, loss of taste, NSAID antagonize its effects, hyperkalemia, angioedema.
Enalapril
ACEI
IV preparation
Compared to captopril it lacks a sulfhydryl group (H-S-CH2) thus does not cause the rash and renal insufficiency caused by captopril
Lisinopril
ACEI
Administered in a active form and excreted unchanged in the kidney
Angiotensin II Receptor Blocker (ARBs) MOA
Competitive binding to inhibit the action of angiotensin II at its receptor
By blocking the vasoconstrictive actions of angiotensin II without effecting ACE activity
results in decreased peripheral vasoconstriction
At the AT1 receptor
ARBs SE
Side effects similar to ACE inhibitors
less cough noted
No effect on ACE
No significant bradykinin accumulation
ARB contraindications
renal art stenosis
pregnancy
ARB drugs 8
Losartan-hyzaar, cozaar Valsartan- diovan Irbesartan- avalide, avapro Candesartan- atacand Telmisartan- micardis Eprosartan- teveten Olmesartan- benicar Tasosartan- verdia
arterial vasodilators
minoxidil
hydralazine
Hydralazine MOA, dose, peak
arterial vasodilator
phthalazine derivative
activates guanylate cyclase (which synthesized cGMP to GTP, which signal to relax)
produces Direct relaxant effecy on vascular smooth muscle
arteries>veins
Calcium ion transport in vascular smooth muscle
Dosage 2.5-10mg IV
peaks 10-20m, can last up to 6 hrs
Hydralazine kinetics
Extensive hepatic first pass metabolism Onset 15 minutes give slowly Elimination 1⁄2 time 3 hours After IV < 15% appears unchanged in the kidney
Hydralazine SE
Reflex tachycardia DBP reduced >SBP Decreased SVR Increase HR, SV, CO Tolerance and Tachyphylaxis Sodium and H20 retention Angina with EKH changes Clinically used in combination with BB and diuretic- Limits the increased SNS activity
Minoxidil MOA, use
arterial vasodilator
Directly relaxes the arteriolar smooth muscle little effect on venous capacitance
increase influx of K into vascular smooth resulting in hyperpolarization and vasodilation
orally activated
Use: tx most severe forms of HTN due to:
renovascular disease
renal failure
transplant rejection
-also used in combo with BB and diuretics
Minoxidil kinetics
90% oral dose absorbed from GI tract
peak levels in 1 hr
e1/2t 4hrs
10% unchanged in urine
Minoxidil SE
Marked increase in
heartrate CO
Increased plasma concentration of NE and Renin
Compensatory retention of Na and H20
Weight gain
Edema
hypertrichosis
Pulmonary HTN
Pericardial effusion or cardiac tamponade
Can have abnormal EKG
flat or inverted T wave, increased voltage of the QRS complex
Peripheral vasodilators
utilized for
facilitate forward LV in AR, MR, or HF
controlled hypotension in OR- a techinque, will have less bleeding, goal MAP<70, however must avoid myocardial ischemia, cerebral ischemia-blindness (ex, used for ENT, near clips)
Tx HTN crisis
Peripheral vasodilators drug names 8
Nitroglycerin (NTP) Nitroprusside (SNP) Isosorbid Dipyridamole Papaverine Trimethaphan Diazoxide Adenosine
Sodium Nitroprusside (SNP) MOA
Direct acting , nonselective peripheral
vasodilator
Relaxation of arterial and venous vascular smooth muscle
Lacks significant effects on nonvascular smooth muscle and cardiac muscle
SNP interacts with oxyhemoglobin
– dissociates immediately to form Methemoglobin Releasing Nitric Oxide (NO)
Nitric Oxide activates guanylate cyclase (in the vascular muscle) thus increasing cGMP
cGMP inhibits calcium entry into vascular smooth muscle but increases uptake of Ca into the sER
** Results in vasodilation via NO
Nitroprusside metabolism
Transfer of an electron from the Iron (Fe) of
oxyhemoglobin to SNP yields
metHGb and an unstable SNP radical where all 5 cyanide ions are released.
One of these cyanide ions reacts with metHGb to form cyano-methemoglobin (nontoxic)
the remainder are metabolized In the liver and kidney converted to thiocyanate
Nitroprusside toxicity
Toxicity: occurs due to the effects of high plasma concentrations of thiocyanate
– Cyanide Toxicity
can occur at rates >2ug/kg/min for long periods
Suspect when the pt starts demonstrating resistance to hypotensive effects or a previous responsive patient who is unresponsive (tachyphylaxis) at rates >2-10 ug/kg/min
May precipitate tissue anoxia, anaerobic metabolism, and lactic acidosis (if lactate levels >10 – see CNS dysfunction, mental status changes-sz)
Caution in pregnancy
Cyanide levels
SNP
plasma lactate concentrations of >10 mM, which correlates with blood cyanide concentra- tions of > 40 mcgM
clinical toxicity appear to exceed 40 mcgM, and deaths have been reported with cyanide concentrations of > 77mcgM
SNP toxicity tx
Immediate discontinuation of SNP
100%02 administration despite normal oxygen saturation
Sodium bicarbonate to correct metabolic acidosis
Sodium thiosulfate 150mg/kg over 15 minutes
Sodium thiosulfate Acts as a sulfur donor to convert cyanide to thiocyanate
– Sodium nitrate 5mg/kg if severe toxicity
Converts hemoglobin to metHgb which coverts cyanide to cyanometHemoglobin
Thiocyanate toxicity SNP
Rare as thiocyanate is cleared by the kidney in 3-7 days
Less toxic than cyanide
Symptoms include:
– N/V, tinnutis, fatigue, CNS hyperreflexia, confusion, psychosis, miosis
seizure and coma
SNP methomoglobinema
Rare
Should be considered as a differential diagnosis in patients with impaired oxygenation despite adequate cardiac output and arterial oxygenation
SNP phototoxicity
SNP should be mixed with 5% glucose in water and be protected
◆ With continuous exposure to light SNP is converted to aquapentacyanoferrate in the presence of light and the release of hydrogen cyanide
◆ Wrap the solution and tubing in foil or dark plastic bag
SNP dose
.3ug/kg/min - 10ug/kg/min IV
– Max dose: should not be infused for greater that 10 minutes
– Immediate onset
– Short duration of action
– Requires continuous IV administration to maintain therapeutic effect
– Extremely potent: use A-line
SNP cv effects
Direct venous and arterial vasodilation, decreased venous capacitance due to venous return
Baroreceptor mediated reflex responses increased HR
↓SBP, ↓SVR,↓PVR, ↑contractility, causes an intracoronary steal in areas of damage associated with MI
SNP: CNS, pulm and blood effects
increase CBR, ICP
attenuation of hypoxic vasoconstriction?
increased in intracellular GMP- inhibit platelet aggregation and bleeding time.
SNP clinical uses
Controlled hypotension:
0.3-0.5ug/kg/min not to exceed 2 ug/kg/min
– Hypertensive crises:
infusion 1-2ug/kg IV can be given as bolus
– Cardiac disease:
decreases LV afterload, benefits management of MR or AR, CHF, and heart failure.
Consider coronary steal
