Toxicology- Lyon- Exam 1, Lecture 3 Outcomes (PART 3)

how does the sympathetic nervous system contribute to blood pressure?

increasing heart contractions and causing vasoconstriction to increase blood pressure

what systems are involved in the normal physiologic controls the body uses to control blood pressure?

Vascular, cardiac, renal, endocrine and nervous systems

what systolic/diastolic levels are considered hypertensive?

systolic greater or equal to 130

diastolic greater or equal to 80

what is the role of the kidney in the renin-angiotensin-aldosterone system RAAS?

senses low blood pressure and releases renin into circulation to start RAAS cascade

what drugs discussed in lecture act on the sympathetic nervous system and act as sympatholytics?

beta-blockers

anti-hypertensives (anti-HTN) act primarily on what 3 systems to decrease BP?

1) sympathetic NS

2) The RAAS system (or directly on kidney)

3) smooth muscle of vasculature (ca2+ channel blockers)

when the heart is unable to pump enough blood to meet the needs o the body, this is called...

heart failure- reduced CO

If a patient is going through heart failure, what kind of symptoms would stem from a stressed sympathetic nervous system reacting to this failure?

tachycardia, decreased exercise tolerance, muscle fatigue, edema, cardiomegaly, etc.

what are the 4 main TYPES of drugs used to treat heart failure?

1) sympatholytics

2) diuretics

3) ACE inhibitors and ARBs

4) Vasodilators

What type of medication is contraindicated for heart failure? TQ

Calcium channel blockers! (exacerbates heart failure)

what is another name for sympatholytics and what do they do?

adrenergic receptor antagonists

they block or prevent sympathetic signaling

Beta-1 receptors normally stimulate what in the body?

beta-2 receptors normally stimulate what in the body?

1- cardiac and kidney stimulation to increase HR, contractility and conduction velocity

2- relaxes bronchial, uterine and peripheral vasculature in smooth muscle. stimulate glycogenolysis in liver to increase blood sugar

Beta-1 antagonists (blockers) do what? TQ

DECREASE contractile force of ctx and HR

block renin secretion and decrease formation of angiotensin II

Beta-1 Blockers have what effect on HTN

decrease blood pressure by decreasing CO, HR and BV.

What medication is commonly prescribed with CHF to decrease energy demands on the heart, reduce RAAS and help with arrhythmia?

beta blockers

(by reducing sympathetic stimulation)

How do beta blockers "help" with angina symptoms?

- decreasing heart needs, therefore decreasing oxygen demand

-prevent coronary vasospasm

overall decreasing ischemia and pain!

Differentiate between Non-selective beta blockers (1st gen) and selective beta blockers (2nd gen).

non-selective BB- block BOTH beta 1 and beta 2 receptors and lead to more side effects.

selective- only block 1 receptor and are considered cardio-selective. (used in HTN, angina, CHF and arrhythmias)

what are the general adverse effects of ALL beta blockers (either first gen or second gen)?

- HypOtension and bradycardia

- fatigue and insomnia

-erectile dysfunction

- can increase TGs and decrease HDL

T/F: it is important to tell patients to get off beta blockers quickly because it's dangerous to be on them long term.

FALSE: NEVER tell patients to stop taking beta blockers abruptly. may lead to MI or sudden death.

which adverse effects are specific to non-selective (2nd gen) beta blockers?

-bronchoconstriction in asthmatics and COPD

-peripheral vasoconstriction

-hypoglycemia in diabetics

patients with which lung conditions should not be on beta blockers?

asthma or COPD bc they cause bronchoconstriction

patients with which vascular conditions should not be on beta blockers?

raynaud and peripheral vascular disease due to them causing vasoconstriction

Why should diabetics not use 2nd gen beta blockers?

potentially causes hypoglycemic state bs beta 2 blockers decrease blood sugar levels in conjunction with DM medications

What are the main interactions with beta blockers

- NSAIDS

- any herb or supplement that lowers BP

-anti diabetic herbs and supplements

what nutrient depletions are attributed to the use of beta blockers?

-CoQ10 (statins also deplete this)

-melatonin (hence why an adverse effect is insomnia)

beta blocker generic names typically end with what?

-olol

Propranolol

Atenolol

metoprolol

nebivolol

varvedolol

are all types of what?

beta blockers!

Diuretics are used for which heart conditions specifically?

HTN and CHF

myocardial ischemia due to an imbalance between the heart's blood supply and oxygen demand is known as what condition?

*presents with chest pain*

angina

pharmacological tx of angina focuses on what 2 things?

1) decreasing oxygen demand by decreasing cardiac work

2) increasing oxygen delivery by increasing coronary flow

Nitrates calcium blockers and beta blockers are all used to treat what?

angina pectoris

what is the mechanism of action of diuretics

decrease the renal absorption of sodium, thus resulting in fluid loss and a reduction in blood volume. sodium leaves the body, water goes with it.

decreases BP by 10-15 mm HG ish

T/F: diuretics are typically the first drugs prescribed for either HTN or CHF to decrease edema.

FALSE- typically not the first, but added to TX with other drugs

What are the three major classes of diuretics (hint it's where they work within the kidney tubules)?

- Thiazides (work on DCT)

-Loop (work on loop of henly)

-potassium sparing (work on CD)

What is the clinical use of thiazides (a type of diuretic)?

used for HTN and CHF as first line agents.

protective against osteoporosis due to ability to decrease urinary excretion of calcium

Why would we want to prescribe thiazides to a woman with osteoporosis and CHF compared to another diuretic?

these are protective against osteoporosis due to ability to decrease urinary excretion of calcium

Loop diuretics cause a _________ of calcium but can ________ kidney stones.

LOSS; prevent

what are the adverse effects specifically of thiazide and loop diuretics? TQ (6)

which adverse effects are LOOP only?? TQ (2)

NEED TO KNOW

- Hypokalemia--> leading to metabolic alkalosis

- Hyponatremia and hypomagnesmia (mm cramps!)

-Hypocalemia (LOOP ONLY)

-HypERuricermia (secrete uric acid and lead to gouty attacks)

-hypERglycemia

--Allergic Rxns (bc of sulfide structure)

-Ototoxicity (reversible hearing damage) (LOOP ONLY)

what are the drug and herb interactions associated with thiazides and loop diuretics?

- any herb/supp meant to lower BP

-NSAIDS

-Anthroquinone glycoside laxatives (plant based) like aloe and senna

-Licorice root

-Dandelion leaf

Licorice root increase the potential for what adverse effect if taken with a thizide or loop diuretic?

hypokalemia and HTN

A male with gout may want to stay away from which diuretics?

thiazide and loop diuretics because they can cause hyperuricemia and make gout pain worse!

What nutrient depletions can be seen with thiazides and loop diuretics? (7 ish)

Which are thiazides only and which are loop only?

1- CoQ10 THIAZIDE ONLY

2-Calcium LOOP ONLY

3- Potassium

4- Sodium

5- Magnesium

6- Zinc

7- Vit C/ B1/ and B6

Diuretic generic names typically end with what?

-ide

Hydrochlorthiazide and indapamide are what type of meds?

Thiazides

Forosemide and bumetanide are which type of meds?

loop diuretics

What do potassium sparing diuretics work on/block?

sodium transporters that are affected by aldosterone, this causing sodium excretion and potassium retention.

(opposite of aldosterone!)

T/F: you can pare potassium sparing diuretics with thiazide or loop diuretics to prevent hypokalemia.

TRUE

What are the three generic potassium sparing diuretics discussed in lecture (tricky because no pattern to naming!)

-Amiloride

-Triamterene

-Spironolactone (aka mineral corticoid antagonist MCA)

Spironolactone is an anolog (look alike) to what?

aldosterone

spironolactone (diuretic) can also act as am __________ blocker, therefore it is used for what other conditions?

-androgen

PCOS/PMOS, androgenic alopecia, hirsutism and acne

what are the adverse effects of potassium sparing diuretics? TQ (4)

- HypERkalemia (may lead to metabolic acidosis)

-Androgen blocking effects (from Spironolactone only)

-Acute renal failure (when paired with an NSAID)

-can cause kidney stones

What are the drug/herb interactions for potassium sparing diuretics?

- potassium supps should be used with caution

-Triamterene with NSAIDs (cause renal failure)

-Licorice root contraindicated

-Dandelion leaf (high in K+)

What nutrient depletions would you expect with potassium sparing diuretics?

-Spironolactone has NONE

-Amiloride can affect folic acid and calcium

triamterene- folic acid, calcium and zinc

what conditions are ace inhibitors used for? (4)

-HTN

-CHF

-Post-MI

-Diabetics (to preserve kidney fnx)

what do ace inhibitors do?

inhibit the angiotensin converting enzyme, which blocks formation of the vasoconstrictor angiotensin II and blocks degradation of vasodilator badykinin

What is the effect of an ace inibitor?

lead to a decrease in BP

What are the adverse effects of ace inhibitors?

-cough

-taste change (due to zinc binding)

-Pregnancy problems (fetal death in 2/3 tri)

What are the main herb/drug interactions with ace inhibitors? TQ

- ALL anti-HTN meds/herbs (lead to hypotension)

-antacids (dec. [ace inhibitors]

-potassium sparing diuretics/high potassium diets (cause hyperkalemia)

-NSAIDS

-licorice root

-Dandelion leaf

what nutrient depletion can occur with the use of ace inhibitors

zinc

generic names for ace inhibitors typically end with what?

"-pril"

April!

lisinopril, captopril, analapril are all examples of which type of medication

ace inhibitors

Angiotensin receptor antagonists are more _________ since they work at the level of the ____________.

potent; receptor

what is another name for angiotensin receptor antagonists? TQ

angiotensin II receptor blockers (ARBs)

what is the function of angiotensin receptor antagonists (ARBS)? TQ

block angiotensin receptors in vascular smooth muscle and in the adrenal cortex...causing vasodilation and decrease in aldosterone secretion

which medication works by blocking angiotensin receptors in vascular smooth muscle and in the adrenal cortex...causing vasodilation and decrease in aldosterone secretion

ARBs

which is a stronger drug...ARBs or ace inhibitors?

ARBS because they completely inhibit angiotensin action COMPLETELY!

Which conditions would you prescribe angiotensin receptor antagonists (ARBs)?

-HTN

-CHF (first line terapy!)

-post-MI

What are the adverse affects of angiotensin receptor antagonists (ARBs)? TQ

Pregnancy problems!!

I don't have time to find the answers to this but I suspect she will as a questions saying which of the following medications are all contraindicated for pregnancy. I'd figure this out

...

What are the Drug and Herb interactions of ARBs?

-some CYP isozymes

the rest are the same as ACE-inhibitors

- ALL anti-HTN meds/herbs (lead to hypotension)

-antacids (dec. [ace inhibitors]

-potassium sparing diuretics/high potassium diets (cause hyperkalemia)

-NSAIDS

-licorice root

-Dandelion leaf

what nutrient depletion would you expect with someone taking ARBs?

zinc

the generic names for angiotensin receptor antagonists (ARBs) end in what?

-sartan

Losartan, valsartan, olmesartan, irbesartan are all generic names for which type of drug?

angiotensin receptor antagonists (ARBs)

which drug acts on relaxing smooth muscle of the arterioles and/or decrease myocardial contractility (dec work of heart)?

vasodilators

calcium channel blockers are a type of _______________ that work by inhibiting __________ flow into ___________ and ____________ muscle cells...thus decreasing BP

vasodilator

What conditions would be used clinically with calcium channel blockers?

-HTN

-angina

-arrhythmias

what are some adverse effects of calcium channel blockers (vasodilator) TQ

-suppress cardiac contractility too much

-hypOtension/syncope

-peripheral edema (bc dec in HR)

which condition are calcium channel blockers a contraindication for?

CHF

because of how significantly these drugs can decrease HR

generic names for calcium channel blockers typically end in what?

-pine

Amlodipine, felodipine, nifedipine are all generic forms of which drug?

calcium channel blockers (vasodilators)

which two calcium channel blockers are considered 'cardioselective' and are used primarily as antiarrhythmics, and sometimes used for angina? TQ

hint-tricky naming

verapamil and diltiazem

Which drug is NOT impacted by NSAIDS? 100% TQ

Calcium Channel Blockers (vasodilator)

What are the drug/herb interactions for calcium channel blockers (vasodilators)?

-any anti-HTN agent (lead to hypotension)

-melatonin (dec activity of Ca channel blocker)

-statins

-grapefruit juice

when calcium channels are taken with this, it can dangerously increase levels in the blood.

statins!!

Isosorbide, hydralazine and nitrates are other _______________ that are used in CHF and angina tx.

vasodilators

positive inotropes are used to treat _________ and _________________.

What is an example of this?

CHF and arrhythmias

digoxin

potassium channel blockers are used to treat which cardiovascular conditions?

CHF and arrythmias

what is the most famous and widely used cardiac glycoside-containing plant that is commonly used for CHF, but can build up in the body and cause toxicity?

Digitalis purpurea (DiGOXIN!)

What is the mechanism of action of digoxin for CHF treatment?

increases FORCE of heart contraction by inhibiting the Na/K ATPase pump, causing a positive inotropic effect

T/F: digoxin has a narrow therapeutic window, meaning it can easily reach toxic levels and is easy to OD on

TRUE

What are the symptoms of Digoxin toxicity?

Dizzy, vomiting, irregular heartbeat, delirium or hallucinations, seizure, diplopia and chromatopsia (yellowing)