REVIEW RAMBLINGS Flashcards
What is the predominant tone of the eyes?
Iris radial muscle = sympathetic (a1)
Iris circular muscle = parasympathetic (m3)
Ciliary muscle = parasympathetic (m3)
(But ß also relaxes it)
What is the predominant tone of the heart?
Main tone comes from SA node = parasympathetic (m2) slows it down
(But ß1/ß2 accelerate it)
Predominant tone of the blood vessels
Predominant are the skin, splanchnic vessels = sympathetic (alpha contracts them)
Skeletal muscle vessels relax by ß2
Endothelium by NO release
Predominant tone of the bronchiolar smooth muscle
Parasympathetic (m3) —> contracts
Also relaxes by ß2 but no innervation
What is the predominant tone of the GI tract?
Parasympathetic (M3)
What is the predominant tone of the GU smooth muscle?
Parasympathetic (M3)
What is the predominant tone of the skin?
Sympathetic
Pilomotor smooth muscles and apocrine sweat glands are alpha, but eccrine is M (even though its sympathetic)
Describe presynaptic receptor regulation
IT’S A BIG KRIS-KROSS (see pic on slide 9)
Sympathetic fibers release NE, which can bind to its own a2 receptor and inhibit further release of NE
Parasympathetic fibers can also act upon sympathetic fibers by releasing ACh on M2 receptors —> inhibit NE release
Parasympathetic fibers release ACh which can act upon its own M2 receptors to inhibit further release of ACh
Sympathetic fibers can also act upon parasympathetic fibers by releasing NE on a2 receptors —> inhibit ACh release
How is postsynaptic regulation achieved?
Up-regulation of receptors (or denervation)
Down-regulation or desensitization of receptors (from excessive stimulation)
Other modulators regulating membrane potentials such as IPSP M2 or EPSP peptides
What are the steps of the baroreflex?
- Baroreceptor in carotid sinus senses arterial BP
- Signal to inhibitory interneurons in nucleus of the tractus solitarius
- Inhibitory interneuron signals vasomotor center
- Signal goes to autonomic ganglion —> motor fibers to sympathetic nerve ending —> a or ß receptor
See the animation on slide 13
General rules rules regarding drug effects
Any decrease in BP —> reflex tachycardia (immediate)
Any decrease in BP —> increased renin release —> increased Na+ and H2O retention (long term effect)
Name all the Carbonic Anhydrase Inhibitors
ACETAZOLAMIDE (Diamox)
Dorzolamide (Trusopt)
Brinzolamide (Azopt)
The last two are eye drops
What is the MOA for CA Inhibitors?
Inhibits CA enzyme —> blocks H2CO3 production —> Reduces H+ for exchange with Na+, resulting in INCREASED SODIUM (and H2O) LOSS
DOC for acute mountain sickness
Acetazolamide (Diamox)
How long does Acetazolamide last?
Diuretic effectiveness decreases in several days (why it’s not used as a regular diuretic)
What’s the main adverse effect of CA inhibitors?
HYPERCHLOREMIC metabolic acidosis
Develops b/c the Na+ loss is in the form of NaHCO3 and not NaCl
What is the prototype Loop Diuretic
Furosemide (Lasix)
MOA for Loop diuretic
Blocks the 1 Na+ 1 K+ 2 Cl- cotransporter
—> increased Na+ in the lumen —> diuresis
Most important indication for Furosemide
PULMONARY EDEMA - relieves pulmonary congestion by increasing systemic venous capacitance
HF - moves large volumes of water
Hypercalcemia - loops reduce reabsorption of Mg2+ and Ca2+ by reducing the K+ gradient
Most important adverse effect of Loops
HYPOKALEMIC METABOLIC ALKALOSIS - induces K+ and H+ loss at the DCT
Others: Hypocalcemia Hypomagnesemia Hyperuricemia Irreversible ototoxicity
Why makes Ethacrynic Acid a special Loop?
It’s not a sulfonamide derivative
It has the highest risk of ototoxicity
MOA for Thiazide Diuretics
Inhibition of sodium resorption at the early distal tubule by INHIBITION of the Na+ Cl- co-transporter
Dependent on PG synthesis
Major beneficial effect of thiazides
Relaxation of smooth muscle cells —> VASODILATION
Major adverse effects of thiazides
Reduced insulin secretion—> HYPERGLYCEMIA***
HYPOKALEMIC metabolic alkalosis***
Hyperuricemia
Contraindications for Thiazide use
SULFONAMIDE hypersensitivity
Hypokalemia —> digitalis toxicity and hepatic coma in CIRRHOTIC patients
DIABETICS (reduced insulin secretion —> HYPERGLYCEMIA
People with gout (hyperuricemia)
Those on LITHIUM (clearance reduced —> toxicity
What makes Metolazone a special thiazide?
Able to produce diuresis in patients with a reduced GFR (loops can work at low GFRs but most thiazides can’t except this one)
What makes Indapamide a special thiazide?
Pronounced vasodilation
Does not increase plasma lipids
Is metabolized by the liver and kidney 50/50
What are the two classes of potassium sparing diuretics?
Aldosterone antagonists
Direct inhibitors of Na+ flux
What are the side effects of Spironolactone?
Edema
HYPERaldosteronism
HIRSUTISM in women***
GYNECOMASTIA in men***
Occasional HYPERKALEMIA (usually only in combo with other K+ sparing drugs)
What is the only serious toxicity of potassium sparing diuretics?
Hyperkalemia
Duh
How are Osmotic Diuretics administered?
IV only
What is the MOA for Osmotic Diuretics?
Keeps water in the tubules —> produces water diuresis
Adverse effects of osmotic diuretics
Diarrhea and other GI effects (dehydration symptoms)
Excessive administration —> extracellular volume expansion —> PULMONARY EDEMA IN HF (CONTRAINDICATED)
Which receptors are targeted by Desmopressin
Activates V2»_space; V1 ADH receptors
What is Desmopressin used to treat?
Central Diabetes Insipidus
What is the main side effect of the -vaptans (ADH antagonists)
Hypokalemia
What did Demeclocycline used to treat?
SIADH (used before vaptans were developed)
Most HF is due to __________ dysfunction
Left Ventricular
What happens to preload in HF patients?
Increased sympathetic and RAAS activity —> Increased venous return —> Increased blood volume and venous tone
THAT’S WHY YOU NEED VENODILATORS
What happens to Afterload in HF patients
Increased sympathetic and RAAS activity —> increased peripheral resistance via arterial constriction
THAT’S WHY YOU NEED ARTERIODILATOR DRUGS
What happens to myocardial contractility in HF patients?
Decreased contractility as the myocardial muscle fibers are stretched too far as ventricles become dilated
Beta-blockers can REDUCE contractility
Inotropic drugs can INCREASE contractility
MOA for Digoxin
Inhibition of membrane sodium pump (Na/K ATPase) leading to cardiac effects:
- Increased intracellular Na+
- Increased intracellular Ca2+ leads to increased SR Ca2+ stores
- Increased actin-myosin interaction by intracellular Ca2+
- Increased CONTRACTILITY (Positive Inotropy)
Earliest signs of digoxin toxicity?
GI effects - even at low doses
Disappear after discontinuation
Most common and dangerous side effect of Digoxin?
Arrhythmias: sinus bradycardia, ectopic ventricular beats, AV block, and BIGEMINY
Must stop and give K+ if bigeminy occurs
What else do you need to know about Digoxin
ALL OF IT. KNOW ALL OF IT.
GO BACK RIGHT NOW AND READ THOSE SLIDES AGAIN.
When do you use Milrinone?
IV only for acute HF or severe exacerbation
Basically PALLIATIVE ONLY
Dobutamine and Dopamine should not be given with…
Beta blockers
Which diuretics are most effective at reducing mortality in HF patients?
Spironolactone and eplerenone
Additional benefits over other diuretics by inhibiting aldosterone receptors
Main side effect that occurs with ACE inhibitors but not ARBs?
Dry cough
Seriously, if you don’t know this by now, we aren’t really friends
What is the most important role of the neprilysin inhibitor in the Sacubitril/Valsartan combo?
Reduced sodium retention
Also helps reduce vasoconstriction and cardiac remodeling but for some reason I circled sodium retention
Main side effects of Sacubitril/Valsartan?
Hypotension
Hyperkalemia (from the ARB)
COUGH and ANGIOEDEMA)
What is the main contraindication for Sacubitril/Valsartan?
Preggos
When do we use beta blockers in HF patients
Effective only in early stages of HF - dangerous in severe, end-stage HF b/c of the NEGATIVE INOTROPIC effect
Drug that reduces mortality if used in early HF
Carvedilol - b/c it’s a negative inotropic beta blocker
Just don’t give it in severe/end-stage HF
How do the three different vasodilators differ?
Sodium nitroprusside - mostly effects the VEINS
Isosorbide dinitrate - precursor of nitric acid (not sure what this means but I wrote it down 🤷♀️)
Hydralazine - increases NO
Which drug blocks the funny current in the heart?
Ivabradine (Corlanor)
It decreases HR when beta blockers can’t/won’t
Why do we treat HTN?
B/c it leads to an increased incidence of renal failure, CAD, HF, and stroke
Not sure why I highlighted this but I did
Only ______% of HTN is due to a specific cause
10-15%
Examples: Renal artery constriction Coarctation of the aorta Pheochromocytoma Cushing’s disease Primary aldosteronism (Conn)
What do we mean by “essential” HTN?
Cause is not known - multifactorial
What is the main difference between Stage 1 and Stage 2 hypertension in terms of management?
Stage 1 (SBP 130-139 or DBP 80-89) only needs one drug
Stage 2 (SBP ≥140 or DBP ≥ 90) needs two drugs
What is the most common cause of HTN treatment failure?
Non-compliance
People don’t want to take their damn drugs
What’s the biggest benefit of Central Acting Sympatholytics (Clonidine, Methyldopa) in treatment of HTN?
No reflex tachycardia
They stimulate medullary a2 adrenergic receptors —> reduced peripheral sympathetic nerve activity
When is Methyldopa recommended?
In pregnancy
Main adverse effects of central acting sympatholytics (clonidine and Methyldopa)
Sedation and other CNS effects
Xerostomia
ED
Methyldopa: hemolytic anemia with a (+) Coombs test
HTN med beneficial in BPH
Prazosin and other a1 adrenergic antagonists
They also do not adversely effect plasma lipids. Didn’t feel like make that a separate card…
Major adverse effects of a1 adrenergic antagonists
“First dose phenomenon” - postural hypotension may be pronounced with the first dose
Reflex tachycardia
Which is the only ß-blocker that IS a vasodilator?
Nebivolol - b/c it also includes NO release
Which are the non-selective beta blockers
Propranolol
Nadolol
Timolol
Which are the selective ß1 blockers?
Metoprolol
Atenolol
Nebivolol
Acebutolol
What are the HIP drugs?
Hydralazine
Isoniazid
Procainamide
All are capable of inducing SLE in slow acetylators
When is Fenoldopam used?
For emergency hypertensive situations
IV only with short half-life
Major cardiac effects of CCBs
Decreased contractility —> NEGATIVE INOTROPIC
Decreased impulse generation in the SA node —> NEGATIVE CHRONOTROPIC
Decreased AV node conduction —> NEGATIVE DROMOTROPIC
Which CCB is most likely to produce reflex tachycardia
Nifedipine (highest vasodilation —> marked hypotension —> reflex tachycardia)
Myocardial ischemia results from an imbalance between…
O2 supply vs O2 demand
Any increase in HR or contractility will increase the need for O2
Coronary flow may be decreased by…
Shortening diastole when HR increases
Increased ventricular end-diastolic pressure
Reduced diastolic arterial pressure
How do Nitrates and Nitrites work for angina?
Vasodilation via NO —> cGMP
UNEVEN VASODILATION - large veins are markedly dilated —> increased venous capacitance and decreased afterload
DOC for any acute angina attack - by reducing myocardial O2 requirement
Why is nitro given sublingually?
To avoid hepatic destruction due to high first pass metabolism
Rapid absorption
Immediate angina release - onset in 1-3 min and duration 10-30 min
What is “Monday Disease”?
Explosive manufacturers chronically exposed to nitrate would get headache and dizziness on Monday but it would go away by Friday b/c they became tolerant to exposure.
Why are CCBs good for chronic angina treatment but not for immediate relief?
B/c you need VENOdilation for acute relief
What’s one big contraindication for Sildenafil (Viagra)?
Administration to patients who are concurrently using organic nitrates or nitrites in any form, b/c vasodilation effects can lead to unconsciousness
MOA for HMG-CoA Reductase Inhibitors
Active forms are structural analogs of HMG-CoA reductase intermediate in mevalonate synthesis
Reduce plasma LDL by inhibiting the reductase to increase high-affinity LDL receptors
MOST EFFECTIVE DRUG at lowering LDL
Hallmark side effects of Statins
Increased serum aminotransferase (liver toxicity)
Myopathy and/or muscle pain (w/ increased serum creatine kinase)
Rarely - rhabdomyolysis/myoglobinuria —> renal shutdown
Contraindications for statins
Preggos
Hepatic disease
What will increase the plasma concentration of statins?
P450 inhibitors
GRAPEFRUIT JUICE, macrolide (esp erythromycin), cyclosporine, ketoconazole, verapamil, ritonovir
What will decrease the plasma concentration of statins?
P450 activators
Phenytoin, griseofulvin, barbiturates, rifampin
Gemfibrozil will inhibit their metabolism
MOA for bile acid binding resins (Cholestyramine, Colestipol, Colesevelam)
Binding to bile acids and preventing their intestinal reabsorption
Too bad they taste like shit
In whom do bile acid binding resins have no effect?
Homozygous familial hypercholesterolemia (b/c no functional LDL receptors)
Who SHOULD bile acid binding resins be used for?
Preggos
Main side effect of bile acid binding resins
Floaty poops
Niacin is best for …
Increasing HDL
Watch out for that flush tho, and hyperglycemia
Fibrates are good for …
Reducing triglycerides
Too bad they give you gallstones and inhibit statins
How does Zetia work?
Blocks intestinal absorption (zebra with diarrhea lol)
No decrease in CV endpoints (mortality)
Only used in combo
Why don’t more people use PCSK9 inhibitors?
They’re expensive, monthly SC injections
Ain’t nobody got time for that
MOA Class IA antiarrhythmics
Preferentially block open or activated Na+ channels —> lengthen the duration of action potential
Quinidine, Procainamide
MOA Class IB antiarrhythmics
Block INACTIVATED sodium channels —> shorten the duration of action potentials
Lidocaine
MOA Class IA antiarrhythmics
Bind to ALL sodium channels —> no effect on the duration of action potentials
Flecainide
MOA Class II antiarrhythmics
Reduce adrenergic activity on the heart
BETA BLOCKERS, duh
MOA Class III antiarrhythmics
K+ channel inhibitors
Amiodarone, Sotalol
MOA Class IV antiarrhythmics
Calcium channel blockers —> decrease HR, contractility
Verapamil, Diltiazem
What are the “Miscellaneous” antiarrhythmics
Adenosine, digoxin, Mg, K
What is the Secondary action of the Class IA antiarrhythmics?
Blocking K+ channels —> prolongs the action potential duration and the effective refractory period
DOC for Torsade de pointes
Magnesium
Adverse effects of Quinidine (Class IA)
Low therapeutic index
Cardiac toxicity
Blocks alpha receptors
Paradoxical tachycardia
***TORSADE DE POINTES (aka “Quinidine syncope” - transient and rare to catch on ECG)
What is the gene that leads to slow acetylation?
NAT2 gene
Watch out for the HIP drugs:
Hydralazine
Isoniazid
Procainamide
DOC for acute ventricular arrhythmias
Lidocaine (Class IB)
But watch out for CONVULSIONS (one of it’s bad side effects)
What is the main side effect to worry about with Flecainide (Class IC)?
Strong pro-arrhythmic effect
MOA for Amiodarone (Class III)
Main MOA: Blocks K+ channels
Other MOAs: Blocks Na+ channels Beta-blocker (like Class II) Some Ca2+ channel blocking effect Alpha blocker
When DO we use Amiodarone?
Effective against both supraventricular and ventricular arrhythmias
DOC for ventricular arrhythmias —> used in ACLS
Adverse effects of Amiodarone
Slows sinus rate, conduction and prolongs QT —> no Torsade de pointes
Bradycardia, heart block, HF
PULMONARY FIBROSIS***
Yellowish-brown cornea and grayish-blue skin***
Thyroid dysfunction***
Non-selective beta blocker that is also a class III antiarrhythmic
Sotalol (Betapace)
Used in ventricular and supraventricular arrhythmias
Main adverse effect of Sotalol
Torsade de pointes
As CCBs, Verapamil and Diltiazem are only effective in…
The atria
Used for Reentrant supraventricular tachycardia and PSVT, a fib/flutter, and has marked effect on the SA/AV nodes
What’s the order of treatment options for PSVT?
Acute:
Adenosine, then Esmolol, then CCBs (Class IV)
Chronic:
Beta blockers, then CCBs
Where do the intrinsic and extrinsic pathways meet in the coagulation cascade?
Factor Xa
How is unfractionated heparin administered?
Exclusively IV
IM —> hematoma
Onset of action is immediate
What’s the benefit of LMWH over UFH?
Can be injected subcutaneously
Can be used in pregnancy
Lower incidence of HIT
What’s the downside of LMWH?
Protamine sulfate does not completely reverse the LMW heparins
Which anticoagulant comes from leeches?
Bivalirudin
Do you have to monitor anticoagulation with Dabigatran (Pradaxa)?
No - predictable anticoagulant effects, not monitored by PTT (true of all new anticoagulants)
What is the antidote to Direct Inhibitors of Factor Xa (the XaBan’s)
Rivaroxaban, Apixaban, Edoxaban, Betrixaban
Antidote is Factor Xa decoy (Andexxa)
MOA of Warfarin
Inhibits reduction of vitamin K —> interferes with synthesis of II, VII, IX, and X, Protein C and S
Takes time to take effect but lasts 4-5 days after d/c
—> start in combo with heparin for first 5 days
Adverse effects of Warfarin
Reversal of action (w/ vitamin K) takes time - can use fresh frozen plasma for immediate effects
Quickly reduces levels of Protein C —> cutaneous necrosis/infarction (warfarin-induced thrombosis)
Contraindications for Warfarin
PREGGOS
LOTS of drug interactions: Vitamin K - abx Clotting factors - estrogen/oral bc Platelet aggregation/function - aspirin Displace from binding sites on plasma albumin Inhibit/induce liver microsomes enzymes
MOA for Fibrinolytic Agents
Convert plasminogen to plasminogen —> lyses thrombus from within
How are thrombolytics different from fibrinolytic agents?
(Alteplase [tPA] and Tenecteplase)
Higher activity for fibrin-bound plasminogen vs plasma plasminogen —> “clot-selective”
Tenecteplase is more fibrin specific and resistant to PAI-1 than standard tPA)
MOA for Aspirin as an anticoagulant
Irreversible inhibition of the COX enzyme —> reduced production of TXA2
No prostaglandin synthesis —> decreased platelet aggregation
Lasts the life of the platelet (7-10 days)
When is aspirin useful?
Secondary prevention of CV events in most patients with established CVD
MOA for Clopidigrel, Ticlopidine, and Prasugrel
Irreversibly blocks the ADP receptor on platelets —> decreased platelet aggregation
Used in patients who are allergic to aspirin and DOC to prevent thrombosis in patients undergoing placement of coronary stents
What are the inhibitors of the GPIIb/IIIa receptor and what do they do?
Abciximab, Eptifibatide, Tirofiban
Decrease platelet aggregation by inhibiting GP IIb/IIIa receptors from binding fibrinogen
Used in angioplasty, atherectomy, and stent placement
BUT given IV (not oral like clopidigrel)
