decrease DBP> SBP ⬆️HR ⬆️SV ⬆️CO ⬇️SVR side effects: increase SNS activity- reflex tachycardia, angina, increase renin, increase volume > take with diuretic and caution with coronary disease tachyplylaxis lupus like syndrome

why BB and diuretic taken with hydralazine?

causes increase SNS- reflex tachy, increase renin to preserve heart rate and limit SNS

arterial vasodilators:

hydralazine and minoxidil

direct arterial (little venous)

minoxidil

MOA: hyperpolarize cell by K efflux into vascular smooth muscle > vasodilation

minoxidil

orally active and 90% absorbed in GI tract

minoxidil

treats severe htn due to venovascular disease, renal failure, transplant rejection:

minoxidil

hypertrichosis

minoxidil

minoxidil onset and DOA:

1 hour and 4 hours

minoxidil MOA:

hyperpolarize with K of vascular smooth muscle > vasodilation

5 side effects of minoxidil:

⬆️SNS activity: ⬆️HR, ⬆️renin = weight gain, retention, edema> will need BB and diuretic hypertrichosis pulm htn pericardial effusion tamponade EKG: flat/inverted t wave

why is a BB and diuretic given with minoxidil:

⬆️SNS activity- ⬆️HR and ⬆️renin

facilitate forward left ventricle flow in AR, MR, HF

peripheral vasodilators

3 uses of peripheral vasodilators:

1. facilitate forward LV flow in AR, MR, HR 2. controlled hypotension in OR 3. HTN crisis

ganglionic blocker > blacks autonomic nervous system

trimethaphan

relaxes captaincies vessels

trimethaphan

will ⬆️HR due to parasympathetic blockade (not reflex)

trimethaphan

causes mydriasis, ⬇️GI activity, urinary retention:

trimethaphan

3 ⬇️ of trimethaphan:

⬇️ BP, CO, SVR

trimethaphan class, MOA, 4 side effects:

peripheral vasodilator ganglionic blocker> blocks autonomic nervous system causes: increase heart rate, mydriasis, decrease GI activity, urinary retention

spontaneous release of nitric oxide

nitroprusside

requries a-line:

nitroprusside

phototoxicity

nitroprusside

coronary steal risk:

nitroprusside

attenuates hypoxia vasoconstriction

nitroprusside

cyanide toxicity

nitroprusside

thiocyanate toxicity

nitroprusside

dose of nitroprusside (3)

controlled htn: 0.3-0.5 mcg/kg/min (dont exceed 2) htn crisis bolus: 1-2 mcg/kg gtt: 0.3 - 10 mcg/kg/min (max dose no longer than 10 min)

MOA of nitroprusside:

SNP reacts with oxyhemoglobin (RBC) > methemoglobin > releases unstable radical (5CN) and nitric oxide NO is in RBC still> crosses plasma membrane into vascular smooth muscle cell > guanalayte cyclase > ⬆️cGMP > inhibit Ca > vasodilation 5CN> 1CN reacts with methgb > cyanomethoglobin (nontoxic) > remaking 4CN metabolized in kidney > liver over 3-7 days by Rhodanese> thiocyanate

fate of cyanide:

5CN> 1CN reacts with methgb > cyanomethoglobin (nontoxic) > remaking 4CN metabolized in kidney > liver over 3-7 days by Rhodanese> thiocyanate

cyanide metabolized by who, so what, where and length?

rhodanese in kidney to thiocyanate over 3-7 days

nitroprusside onset and DOA

immediate 8min

nitroprusside treats: 5: goal:

1. htn crisis 2. controlled htn 3. MR/AR 4. CHF 5. severe heart failure goal: decrease afterload

lacks effect on non vascular smooth muscle and cardiac muscle

nitroprusside

7 negative effects of nitroprusside

1. baroreceptor reflex ⬆️HR 2. coronary steal (no with MI)- diversion of blood flow away from ischemic area 3. ⬆️CBF and ICP (no with Neuro patients) 4. attenuation of hypoxia vasoconstriction 5. ⬆️GMP= inhibit platelet aggregation- ⬆️bleeding time 6. renal toxicity (renal metabolism) 7. toxicity

nitroprusside caution using in patients with: 4

Neuro pregnancy renal MI

coronary steal

diversion of blood flow away from ischemic area nitroprusside causes this

suspect cyanide toxicity with what drug, rate, and 4 symptoms

nitroprusside greater than 2mcg/kg/min over long period tachyphylaxis or increase dose requirement tissue anoxia, anaerobic metabolism, lactic acidosis

treatment of cyanide toxicity:

1. DC SNP 2. 100% oxygen despite normal sat 3. sodium bicarbonate to correct acidosis 4. sodium thiosulfate 150mg/kg IV over 15 min (sulfur donor to convert cyanide> thiocyanide severe toxicity: sodium nitrate 5mg/kg converts hgb> methgb with converts cyanide to cyanomethoglobin

sodium thiosulfate dose:

tx cyanide toxicity due to nitroprusside 150mg/kg IV over 15 min

sodium nitrate dose:

treats severe cyanide toxicity due to nitroprusside 5mg/kg

thiocyanate toxicity sx:

N/V tinnitus fatigue CNS hypereflexia confusion psychosis miosis seizure coma

enzymatic release of nitric oxide

nitroglycerin

relaxes all types of smooth muscle including Pulm and GI

nitroglycerin

venous > arteriole venous capacitance vessels and large coronary arteries

nitroglycerin

involves glutathione and glutathione S-transferase

nitroglycerin

requries thio-containing compound to produce nitric oxide (inside smooth muscle cell)

nitroglycerin

high doses will cause methemoglobinemia

nitroglycerin

treats: angina cardiac failure controlled htn laparoscopic cholecystectomy

nitroglycerin

relaxes sphincter of ODDI

nitroglycerin

will allow coronary blood flow to ischemic areas with less ST elevation

nitroglycerin

tolerance especially after 24 hours

nitroglycerin

MOA of nitroglycerin

enzymatic release of NO: NTG > RNO2 in RBC > enters smooth muscle cell > S-nitrosothiol > NO > GC > ⬆️cGMP > vasodilation glutathione dependent pathway

nitroglycerin treats: 4

angina cardiac failure controlled hypotension laparoscopic cholecystectomy

laparoscopic cholecystectomy medication, dose, purpose

nitroglycerin 200mcg bolus at a time relax sphincter of ODDI

nitroglycerin controlled hypotension gtt:

4-5 mcg/kg/min less potent than SNP

less potent

nitroglycerin

effects of nitroglycerin on angina: 3

venodialtion decrease preload, R/LVEDP, myocardial oxygen requirements

decreases L/RVEDP

nitroglycerin

elimination 1/2t of nitroglycerin

1.5 min

oral nitroglycerin

isosorbid

8 positive effects of nitroglycerin

decrease: venous return, preload, L/RVEDP, stroke volume, cardiac output (no SVR change) bronchodilator relax sphincter of ODDI coronary blood flow to ischemic area

5 negative effects of nitroglycerin:

1. tolerance 2. ⬆️ CBF, ICP (no Neuro pt) 3. inhibit hypoxia vasoconstriciton 4. inhibit platelet aggregation 5. methemoglobinemia

more likely to develop methemoglobinemia

nitroglycerin

methemoglobinemia MOA and treatment drug and dose

nitrate metabolite oxides ferrous iron in hgb > methgb methylene blue: 1-2mg/kg over 5 min

methylene blue treats what and dose:

methemoglobinemia 1-2mg/kg over 5 min

oral nitrate

isosorbid

treats angina and decrease preload with heart failure

isosorbid

causes orthostatic hypotension

isosorbid

active metabolite more active than parent: isosorbid-5 mononitrate

isosorbid

isosorbid oral PO and sublingual DOA

oral po: 6 hours sublingual: 2 hours

isosorbid metabolite:

isosorbid-5-mononitrate

phosphodiesterase inhibitor MOA, treat who, caution with who, 2 drugs

inhibit phosphodiesterase> inhibit breakdown of cAMP, gAMP> vascular smooth muscle relaxation and positive inotropy in myocardial cells treat: heart failure caution: concurrent with nitrates and sexual dysfunction drugs milrinone and Amrinone

class I CCB

verapamil diltiazem

class II CCB

nifidepine nicardipine

class I and class II CCB differ by:

class I: rate control at AV node class II: arterial bed vasodilation

rate control at AV node

class I CCB

arterial bed vasodilation

class II CCB

phenylalkyamine

verapamil

derivative of papaverine

verapamil

levoisomer specific to L type Ca channels

verapamil

calcium channels are found: 6

muscle of: 1. skeletal 2. vascular smooth 3. cardiac 4. mesenteric 5. neurons 6. glandular cells

CCB MOA (not antiarrhymic):

bind to L type (slow) Ca Chanels and inactivate class I= AV node rate control class II= arterial bed vasodilation

4 adverse effects of CCB:

cancer cardiac prolong bleeding constipation

4 effects of class I CCB:

negative inotropy negative chronotropy ⬇️SA node activity ⬇️ rates of conduction impulses of AV node

effects of class II CCB:

vascular smooth muscle relaxation arterial > venous ⬇️SVR, BP nifedipine nicardipine

toxicity of CCB treatment

calcium gluconate dopamine

7 CCB drug interactions:

1. inhaled anesthetics - myocardial depression, vasodilation 2. lidocaine- toxicity 3. Dantrolene- hyperkalemia 4. NMB- potentiation 5. digoxin- decreased clearance and increase plasma Conc 6. H2 antagonist: ranitidine and cimetidine alters hepatic enzyme and increase CCB conc (slow metabolism) 7. BB- myocardial depression and bradycardia

verpamil and diltiazem with dantrolene

hyperkalemia

verapamil and diltiazem with digoxin

increase digoxin conc bc decreased clearance

first line stable angina treatment

CCB- dilates coronary artery

100

verapamil metabolite

norverapamil