Orange content for Mid-term 1 Flashcards
What aspect of Phase I metabolism is responsible for many drug-drug interactions?
Competition for Cytochrome P450 (CYP) enzymes.
What are common red flag drugs that are CYP enzyme inducers / inhibitors?
What is important to know about glucuronoidation in infants?
Infants are often deficient in glucuronides, so drugs may need to be given at lower doses to avoid toxicity.
What are cholinergic toxicity symptoms?
SLUDGE
MTWF
SLUDGE = muscarinic receptors
S - salivation
L - lacrimation
U - urination
D - defecation / increased motility (diarrhea)
G - GI cramping
MTWF = nicotinic receptors
M - muscles cramps
T - tachycardia
W - weakness
T - twitching
F - fasciculations (also muscle twitch)
What are the functions and common medications of adrenergic antagonists?
What is the vascular effect of minoxidil?
What is a notable SE?
What is its black box warning?
Effect: it dilates arterioles
Notable SE: hairgrowth (rogaine)
Black box warning: Pericardial effusion
- What is the effect of Sodium Nitroprusside (Nipride)?
- What is it used to treat?
- What is its route of administration?
- What are its two metabolites?
- Notable concerns?
- Notable SEs?
- Dilates both arterioles and veins
- Reduces PVR and venous return to decrease hypertension
- IV only
- NO and Cyanide are both metabolites
- long-term use can lead to cyanide poisoning.
- Delayed hypothyroidism
The major pharmacologic difference between the dihydropyridine Calcium Channel Blockers and Verapamil is
Verapamil is more cardioselective
Differences between sodium nitroprusside (nipride) and hydralazine & minoxidil include all of the following EXCEPT
- Nipride dilates both arteries and veins; hydralazine and minoxidil dilate only arterioles
- Nipride is exclusively available as an IV formulation
- Prolonged use of nipride can lead to cyanide poisoning
- Hydralazine and minoxidil have no significant adverse effects
Hydralazine and minoxidil have no significant adverse effects
What are Ace Inhibitors used to treat?
What are the concerns about ACE Inhibitors?
What is the black box warning?
What are potential effects on K? Why?
ACE-I’s are used to treat hypertension and stabilise CKD (stabilizing renal function and reducing proteinuria)
Benefits are that there is no reflex sympathetic response and no major effect on HR or CO
Negative effects of ACE inhibitors naturally follow from the blocking of Angiotensin-2 and the incresaing bradykinin.
ACE inhibitors can cause severe hypotension, in particular when combined with diuretics.
Bradykinin increase can lead to angioedema (rare but possibly fatal) and a cough (not harmful).
Black box warning: NOT FOR USE IN PREGNANCY, can cause fetal hypotension and renal damage
Orange: Risk of hyperkalemia. Careful when using with K+ supplements or potassium sparing diuretics
What are the four concerns about beta blockers?
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With Ca channel blockers, which ones have more smooth muscle activity and which ahve more cardiac activity?
Why is this important?
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With adrenergic blockers, what is the difference between alpha 1 and beta blockers?
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Among the sub-classes of beta blockers, which are cardio selective and which has alpha activity?
When might one be better than the other?
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What is the difference between vasodilators that dilate the aterioles, and those that dilate both arterioles and veins?
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Which of the following prescriptive choices is not advisable?
- Using an alpha one antagonist in an elderly man with BPH
- Using a calcium channel blocker in a patient with angina
- Using a beta-blocker in a patient with labile type I diabetes
Using a beta-blocker in a patient with labile type I diabetes.
The reason is that it can mask symptoms of hyperglycemia.
How to ACE-I’s benefit patients with HFrEF?
Are ACE-I’s and ARBs equally effective?
- ACE-I’s affects:
- After-load reduction
- decreases amount of retained fluid volumed
- reverses cardiac remodeling
- ACE-I’s have an advantage over ARBs due to their preservation of bradykinin, which helps reduce or reverse remodeling.
What is prolematic about the inhibition of neprilysin?
What class of anti-hypertensives is a neprilysin inhibitor paired with and why?
Neprilysin breaks down ANP and BNP, so inhibiting it preserves these and helps reduce cardiac load. However, neprolysin plays a larger role than just metabolizing ANP/BNP. It also metabolizes angiotensin-II and bradykinin
Neprilysin inhibition should be paired with an ARB to suppress angiotensin-II. It should not be paired with an ACE-I, because the double-blocking of bradykinin breakdown creates a high risk of angioedema.
What is Entresto (sacubitril/valsartan)?
What is advantageous about this combination?
Sacubitril is an angiotensin receptor neprilysin inhibitor (ARNI).
Valsartan is an angiotensin receptor blocker (ARB)
The ARNI inhibits neprolysin from breaking down ANP/BNP, our natural antihypertensive. It is not paired with an ACE-I because neprolysin also breaks down bradykinin, and in this case the double blockade of bradykinin metabolism would increase the risk of angioedema. The ARB does not affect bradykinin and makes a better partner for the ARNI, which does.
What medication do you give to slow a patient’s heart rate (chronotropy) with no effect on inotropy (contractility) or other cardiac systems?
How does it work?
What is a major risk?
What are digoxin and digitoxin?
What is their purpose?
What are the major safety concerns?
Digoxin and digitoxin are cardiac glycosides. They directly increase myocardial contractility.
They have a narrow therapeutic range.
What are the red flag concerns about digoxin?
What symptoms indicate a problem?
What electrolyte imbalance makes digoxin dangerous and why?
What drugs can create this situation?
What drugs can increase digoxin concentration?
Note: adjust dosing in renal failure patients
Define lusitropy. What cardiac medication is unique for enhancing it?
What are the effects of milrinone?
What are its advantages as a medication?
What are risks?
What are the five functional zones of the nephrons and what does each do?
proximal convoluted tubule = reabsorption
descending loop of Henle = urine being concentrated
ascending loop of Henle = dilution of the urine
distal convoluted tubule = finetuning electrolytes Na+, CL-, Ca2++ (mostly reabsorption)
collecting tubule & duct = fine tuning (salts, volume, acid-base)
How do electrolytes move across membranes?
How does water move?
What is the mechanism of action of spiranolactone and eplerenone?
What is the action of K sparing diuretics?
Are they strong or weak diuretics? Why?
What does it treat?
What are major concerns?
What are off-label uses of spiranolactone?
- K Sparing DIuretics block Na+ reabsorption and prevent K+ secretion at the collecting duct.
- Weak because at this point in the nephron there is a limited amount of sodium to impact.
- It treats secondary hyperaldosteronism. It treats heart failure by preventing binding of aldosterone, helping to reverse remodeling of the heart. Treats ascites, which is mediated by hyperaldosteronism.
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Off-label uses of spiranolactone:
- Also blocks androgen receptors; useful for polycystic ovarian syndrome and male-to-female transgender hormonal therapy.
What effect do thiazide diuretics have on calcium and potassium?
Decreasesd calcium excretion and increase potassium excretion, potentially causing hypokalemia.
What are purposes and significant adverse effects of thiazide diuretics?
What happens to urine in the ascending loop of henle?
Can water cross its epithelium?
Urine is diluted in the ascending loop of henle.
Water cannot cross the epithelium of the ascending loop. This allos us to remove Na+ without water following it, elading to dilution. K+ and Cl- are also actively reabsorped.
What is the consequence of loop diuretics blocking the Na/Cl/K transporter in the ascending loop of henle?
There will be more Na/Cl/K and more Mg and Ca in the urine (more concentrated) when it reaches the DCT. Sodium and half of the extra cloride can be reabsorbed, as well as calcium. But Mg, K and half of the extra Cl go on to the collecting duct. There is no mechanism for Mg and K reabsorption in the collecting duct. This will be excreted, risking imbalance.
The extra solutes in the urine requrie water, meaning there will be less water reabsorbed.
What are therapeutic uses for loop diurectics?
What is the only non-sulfa loop diurectic?
What are key signs for sulfa reactions?
What is a potential adverse effect?
Sulfa reaction can be Steven Johnsons Syndrome
It has a higher risk of ototoxicity than other loop diurectics
What are adverse effects of loop diurectics?
What does acetazolamide (carbonic anhydrase inhibitor) waste?
What is significant about this?
By instagating the wasting of bicarb this alkalizes urine and retains Cl-. This is helpful when you have wasted Cloride with other diureticz, acetazolamide can be used to correct this by retaining Cl-.
What are adverse effects of acetazolamide (carbonic anhydrase inhibitor)?
What is the role of diuretics in HF treatment? Does it effect mortality?
Diuretics provide symptom relief related to fluid retention but does not modify mortality.
What is diastolic HF (HFpEF)
What medicines would be used?
- Treatment is limited, so we can target related problems such as high BP (use beta blockers, ARBs,, ACE-Is)
- We would aim to reduce HR so that it gives more time for filling in diastole.
- Loop diuretics can reduce BP, but if you over-diurese you can affect cardiac output.
- Milrinone does not seem to be helpful in the longrun
Review therapies and role in diastolic vs systolic HF
In pediatric HF, what is the most common underlying problem? What should we therefore pay attention to?
Children with HF have very high caloric needs. They often need nutritional supplements.
Know the mechanism of action, and purpose in L sided systolic HF, for each of these (especially orange, but really all of them)
- For diurectics, know where along the course of the nephron each of the diuretics work and mechanism of action.
- Understand different advantages / disadvantages of classes
- e.g. loops, osmotics, thiazides
- Know the special cases (orange) that made certain drugs different
