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Pharmacology - Cardiac (Positive *Inotropic Agents Digoxin Milrinone …

- - - - Clinical Cases
        
        Digoxin Toxicity case
        
        Notes:
        
        note that elderly patients have declining renal systems
        
        they also have lower muscle mass, which is where creatinine is produced
        
        so you don't get a high creatinine with elderly patients like you do with younger people with renal failure
        
        Clinical Case
        
        Digoxin BE TOXIN case
        
        Clinical Case
        
        Notes:
        
        note that
        
        DIGOXIN B-E TOXIN your BE and Heart, BE MINE!!
        
        major S/E of digoxin toxin is BE
        
        brain and EYES
        
        BRAIN = confusion and lethargy
        
        EYES = colour vision changes
        --> seein gyellow usually
        
        HYPERKALEMIA = Digoxin inhibits the Na/ K+ pump
        --> stops K+ pumping in and collects outside
        
        not listed here but Digoxin is part of K BANK for hyperkalemia
        
        Life-threatening Arrhythmias = Digoxin inhibits the Na/ K+ pump
    - - SVTs - Digoxin, Adenosine, CCBs, Beta Blockers
        
        Digoxin 2 effects from blocking Na/K pump
        --> since Digoxin uses the ATPase pump as a workaround to increasing Ca+ levels, it has effects on contractility and slowed AV rate
        
        increase parasympathetic Ach release
        --> slows AV conduction ONLY (not SA)
        
        increased Ca++ = increased CONTRACTILITY of ventricle downstream of the A
        --> regardless of A Fib)
      - Digoxin MOA
        
        Digoxin HELP YOU DIG MORE... it DIGS calcium, HATES Na+/K pump
        
        goal is to raise intracellular Ca++ for more contraction
        --> does this through "back door ATPase pump"
        
        Na+/ K+ ATPase Blocker
        
        stops this ATPase pump to stop the Na+ / Ca+ exchange
        --> stops Ca++ going out
        --> increases heart contractility
      - Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        Digoxin and CHF case
        
        Clinical Case
        
        Notes:
        
        note that
  - - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
      - MOA
- - - - Warfarin Overdose vs Heparin Overdose
        
        note that rat poison has high dose warfarin derivative
        
        same as warfarin overdose
        
        signs of internal bleeding
        --> ecchymoses = bruising
        
        Warfarin OD Tx
        --> acute = FFFP = fresh frozen plasma (contains all clotting factors)
        --> long term = Vitamin K (takes days to take effect)
        
        Heparin OD Tx = protamine
        
        ecchymoses = bruising
      - Notes:
        
        note that warfarin works on both extrinsic and intrinsic
        --> factors 2,7,9,10
        
        Heparin works on factor 10a
      - Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        Warfarin case 1
        
        Clinical Case
        
        Notes:
        
        note that you can measure warfarin in 2 ways
        
        INR
        
        prothrombin time
        
        recall that the extrinsic and intrinsic pathway both converge on factor 10 to activate it into 10a,
        --> which activates factor 2 = prothrombin to become 2a = thrombin
        
        warfarin is a vitamin K reductase inhibitor
        --> reduces activity of factors 2,7,9,10
        
        works on factor 7 the most though
        INR = ratio of the patient's prothrombin time / control of general population
        --> note the target = 2-3 since they don't need to lower it as low as 1 = regular population
        INR = 0 is the extreme and means you can't form clots
    - - CYP Inducers:
        
        "Barb's Funny MOM refuses greasy carb shakes!!"
        (when Barb introduces you to her funny mom)
        
        Barb's = barbituates (phenobarbitol) (AED)
        
        Funny = phenytoin
        
        Mom = modafinil (narcolepsy tx)
        
        Refuses = rifampicin (Tb Abx --> note only inducer Abx)
        
        Greasy = griseofulvin (note only exception for antifungals)
        
        Carb = carbamazapine
        
        Shakes = St. John's wort
        
        also CHRONIC alcohol
        
        CYP Inhibitors:
        
        "SICK FACES.COM inhibit CYPing tea"
        (Abx, antifungals, grapefruit juice + amiodarone)
        
        S = sodium valproate (exception = ONLY AED inhibitor)
        
        I = Isoniazid (Abx)
        
        C = cimetidine (ant-acid H2 antagonist)
        
        K = Ketoconazole (antifungal)
        
        F = fluconazol
        
        A = alcohol (acute inhibits your CYP, alcohols get good at metabolizing)
        
        C = chloramphenicol (50s Abx)
        
        E = erythromycin (Mac Abx)
        
        S = sulfonamides (trimeth, etc. Abx)
        
        C = ciprofloxacin (quinalones Abx)
        
        O = Omeprazole (PPI)
        
        M = metronidazole (DNA inhibitor Abx)
        
        NOTES:
        
        the exceptions to the rules are at the beginning of both mnemoincs
        
        note that generally AEDs are CYP inducers (Barb's funny...)
        --> exception is sodium valproate (Sick) is an inhibitor
        
        generally Abx and antifungals are CYP inhibitors
        --> Abx exception is rifampicin (Barb's funny mom REFUSES)
        --> antifungal exception is griseofulvin
      - CYP inducers and Inhibitors
        
        CASE #2
        
        Case presentation:
        
        Notes:
        
        note that both antibiotics and antifungals inhibit the CYP 450 enzyme
        --> they stop warfarin from being metabolized and increase its effects
        
        thus anyone who is currently on warfarin and they are starting on antibiotics or antifungals
        --> their warfarin needs to be lowered during the course of Abx
        --> it then needs to be raised when they are done
      - Case presentation:
      - Notes:
        
        Solution = B
        
        Fluconazole is an anti-fungal and antifungals are CYP inhibitors
        --> meaning they reduce CYP --> reduce warfarin metabolism --> increase warfarin actions
        --> less clotting and higher prothrombin time
  - - - Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
- - - - Cases
        
        Angina Treatment
        
        Case Presentation:
        
        Notes:
        
        Solution = HR increased and End diastolic volume decreased
        
        GTN = glycerol trinitrate or nitroglycerine is 1st line treatment for angina
        
        it causes systemic venodilation, which lowers the venous return to the heart
        --> this lowers the end-diastolic ventricular volume
        --> the heart thus has to work less harder and requires less O2
        --> this gives relief from the pain and ischemia
        
        peripheral resistance also decreases due to venous dilation from GTN
        --> the afterload also decreases and there is also a drop in BP
        
        drop in BP from GTN causes reflex tachycardia
        
        Tetralogy case
        
        Clinical Case
        
        Notes:
        
        note that
    - - Oral Isosorbide dinitrate case
        
        Notes:
        
        note that
        
        Clinical Case
    - - Vasodilators / *Nitrates
        
        NO releasing drugs
        
        NO --> cGMP --> myosin light chain dephosphorylation
        --> inactivates them --> vasodilation of SM
        
        *Arteriole Specific VAsodilators
        
        "MINOR HYDRO effects"
        
        Minoxidil and Hydralazine
        
        they ONLY dilate arterioles and NOT the veins
        
        MOA
        
        note that vasodilators like Minoxidil and Hydralazine ONLY dilate arterioles and NOT the veins
        --> thus the Baroreceptors and Renal perfusion juxta cells notice pressure drop
        
        activation response of RAAAS system and increase sympathetic to to the heart replace alot of the effects of these drugs
        
        NOT effective long term,
        
        ONLY used as add on for other anti-hypertensives in resistant HTN or in HTN emergencies
        
        Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        Nitrates
        
        also Nitrate pathway drugs
        
        increased cGMP / PDE5 inhibitors
        
        Nitrates Side Effects
        
        flushing
        --> from too much vasodilation of the peripheries
        
        Headaches are common
        --> not due to the vasodilation (as previously thought, makes sense conceptually)
        --> more to do with inflammation from NO
        --> from increased CGRP
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        NO your ABCs ... easy as cGMP .. and PDE
        
        Guanylate Cyclase activators
        
        increase cGMP --> protein Kinase G
        
        ANP... easy as cGMP... BNP easy as cGMP... Viagra... easy as cGMP ... and PDE
        
        NO, ANP, BNP, sildenafil (PDE5),
        --> all act on the same cGMP pathway fro vasodilation
        
        ANP and BNP relation to Viagra = sildenafil MOA
        
        Guanylate Cyclase activators
        
        increase cGMP --> protein Kinase G
        
        ANP... easy as cGMP... BNP easy as cGMP... Viagra... easy as cGMP ... and PDE
        
        sildenafil inhibits PDE5, which breaks down cGMP
        --> thus same pathway as ANP and BNP to cause vasodilation
        
        MOA
        
        note that vasodilators like GTN or Isosorbide dinitrate cause vasodilation mainly on LARGER VEINS
        
        1 more item...
        
        PDE non-specific --> both PDE3 cAMP platelets / PDE 5 endothelial SM
        
        Cilostazole, dipyridimole
        
        In PAD, you want "CILO STAYZ oPenDE"
        
        2 more items...
        
        Nitrate Tolerance
        
        note that people build tolerance to nitrates very easily
        
        they need a nitrate free time every night
        --> when CO is the lowest
        
        tolerance builds to NO and more responsive to vasoconstrictive agents
- - - - MOA
        
        Clopidogrel irreversibly blocks the P2Y12 component of ADP receptors on the platelet surface and prevents platelet aggregation. Clopidogrel is as effective as aspirin in the prevention of cardiovascular events in patients with coronary heart disease
      - Clinical cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
- - - - Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
- - - - Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        Notes:
        
        for reduced EF, need to focus on the neurohormone system first
        --> to stop remodelling and dilation = volume overload
        
        2nd focus = get O2 to heart muscles and reduce O2 need
        --> use beta blockers
  - - - Body's own PRIL for ACE lysis:
        
        Neprilysin breaks down both peptide hormones of RAAS and ANP/BNP
        
        sacubitril is used to stop it along with an ACE since it stops the body from shutting down both pathways
        
        Secubitril / valsartin combo
        
        Neprilysin inhibitor / Arb
        
        Neprilysin breaks down both RAAS and ANP/BNP systems