Drugs Flashcards
Cyclosporine
- Calcineurin inhibitor–> suppresses cytokine expression –> decreased T helper cell function –> inhibits IL-2
- Effective in 3-7 days
- Activates platelets
- Requires blood monitoring
Side Effects: GI signs, Gingival hyperplasia, hepatotoxins, secondary infectinos
Cholinomimetic Drugs
Ranitidine & Nizatidine –> inhibit AchE –> promotes gastric emptying
Bethanechol –> binds muscarinic receptors –> effect motility throughout the GIT
Proton Pump Inhibitors
Irreversibly inhibit H-K ATPase on luminal side of the parietal cell
V Tach treatment
SPAM!
- Sotalol
- Procainamide
- Atenolol or Amioderone
- Mexilitine
Verapmil
Calcium channel blocker
(less effect on HR compared to diltiazam)
Metoclopramide
- Peripheral 5HT3 Antagonist –> block CRTZ
- Peripheral 5HT4 Agonist
- Central dopaminergic antagonist: crosses BBB–> blocks CRTZ (may have decreased effectiveness in cats)
- Increased doses promote gastrokinesis
light sensitive
Renal clearance–> if decreased clearance may see hallucinations, frenzied activity, hyperactivity
DDAVP
Desmopressin Acetate
Primary V2 receptor action
- Increased vWF release increased FVIII
- Increases tPA
- Increased ADH activity
*Ideal if vWD type I & hemophilia A (decreased FVIII)
- Helps in uremic coagulopathy and liver disease
IV only no PO bioavailability (nasal product SQ)
Cisapride
5HT4 Agonist –> most effective prokinetics
- increased gastric emptying & chronic constipation
- IncreSed LES pressure
**Doesnt cross BBB
**Ineffective against striated muscle–> not helpful for mega esophagus
**Macrolides may inhibit
-Metabolized by P450 enzymes
-Cardiac conduction issues in humans
NK1 Antagonist
Cerenia
- Blocks action of substance P in CNS & at peripheral NK1 receptors in GIT
-1st pass metabolism in liver –> increased bioavailability IV
Puppies<11 wks–> BM hypoplasia
Aspirin as antithrombotic
- Irreversible blockade of plt COX-1–> platelet cannot make new COX since no nucleus
- ATE risk
- 2-3 days before effective in dogs
**Not recommended in cats due to decreased efficacy
tPA
Tissue Plasminogen Activator–> primary activator in vivo
- Does not bind circulating plasminogen normally–> but can at high doses
**$$
Mycophenolate
- Inhibits inosine monophasic dehydrogenase –> suppresses B & T Cells
- Effective 3-7 days
- Hepatic conversion
Side Effects: GI signs, lymphopenia, secondary infections
Volume of distribution
- Amount of abx in circulation & surrounding tissues ESP interstitial space
- High Vd = spread to many sites & [peak] at site of infection lower (except in UTIs with drug renal clearance)
- Hydrophillic drugs have increased Vd with critical illness (due to vascular dysfunction, fluid exvasiation)–> decreased abx at site of infection
Pharmacodynamics
Effect drug has on body and infecting pathogen
pharmokinetics
PK
- Effect body has on the drug
*extremely variable in critically ill patients
- affected by volume of distribution & drug clearance
Drug Clearance
Volume of plasma completely cleared of drug per unit time
- Lipophilic –> hepatic
- Hydrophilic –> renal
Motilin Receptor Agonist
Erythromycin –> stim motilin receptor–> increased LES pressure & peristalsis in large and small intestine
Calcitonin
Decreases Ca in 2-3 hours
**ER use
Zinc for liver
Decreased GI absorption of copper (binds in GIT)
N-Acetylcysteine
- Replenishes cellular cysteine and glutathione concentrations
- May stabilize RBC glutathione
** Good for toxicities & hepatic lipidosis
Post Synaptic alpha1 & presynaptic alpha2 agonist
Vasoconstriction
- Arterial vasoconstriction may increase afterload and impede tissue perfusion
- Venous vasoconstriction impedes VR if too increased
Augments ectopic pacemaker activity
**May increased BG and lactate (decreased insulin secretion and glycogenolysis)
Bethanechol
Parasympathetic agent–> stimulates cholinergic/muscarinic receptors for treatment of detrusor atony
*Urinary bladder contraction increased by PNS inpute
Leflunomide
- Inhibits dihydronotate dehydrogenase–> effects B & T cellls
*Inhibits S phase
Side effects: GI signs and myelosuppression
Grehlin & MOtilin
Grehlin (entyce) & motilin migrating motility complete in stomach –> stimulate GI motility, increase gastric emptying & gastric hunger
**Erythrimycin motili receptor agonist at microbial ineffective dose
Protamine
Reverse anticoagulent effects of heparin
Adverse reactions: systemic hypotension & anaphylaxis with repeat administration esp
Platelets on protamine insulin –> severe pulmonary hypertension
Yunnan Baiyo
Main active ingredient: Pseudoinseng root
dose dependent effect on platelet activation
No adverse effects reported but no quality control
Cabergoline
Dopamine antagonist
May be used with PGF2alpha analogs for pyometra
Causes luteolysis by reducing prolactin
Vitamin K antagonists
And monitoring
Ex: warfarin, coumarin, coumadin
- Inhibits vitamin K epoxide reductase –> FII, F VII, IX, & X + prostin s-c
**Procoagulant phase dose adjusted based off PT or INR2-3
Factor Xa Inhibitor
Rivaroxaban or Apixapan
Phenobarbital
- Prolongs opening of GABAa receptor–> increased Cl movement
- Inhibit glutamate & Ca Channels
- metabolized inthe liver
- 25% renal excretion
**Hepatotoxicity: Risk increased with serum concentration >40 mcg/ml
Bisphosphanates
Inhibits osteoclast function and promotes apoptosis
Inhibiys normal and abnormal bone reabsorbs
ie pamidronate, zoledronate –> takes a few days to work
Ketamine
NMDA noncompetitive antagonist–> NMDA receptor is excitatory receptor in N cells of dorsal root of spinal cord and thalamus
- Neuroprotective after reperfusion of ischemic tissues
Side Effects hallucinations, light headedness, inebriation
V1B Receptor
Located in Pituitary
ACTH release
Benzodiazepines
MOA: Primarily facilitates increase in GABA’s inhibition effects
Secondary MOA is antagonize serotonin and turnover ACH in CNS
*Diazepam: not water soluble –> IN, IV
- Absorbs plastic
*Midazolam: water soluble –> IM & IV
- Shorter half life
Side effects: dysphonia/excitatory signs, delayed awakening, seizures from acute benzo withdrawal
Keppra
MOA: Binds to the synaptic vesicle protein (SV2A) –> decrease neurotransmitter release from preganglion
- Urine excretion
Side Effects: salivation IV doses >1200mg/kg/day
Potassium Bromide
MOA: hyperpolarization of neuron by Br ions intracellularly through Cl channels
Excreted unchanged in urine
Reabsorbed via Cl channel in renal tubules–> diet changes may effect clearance
** Not recommended in cats: FATAL PNEUMONITIS
**Side effects: neuro deficits, PU/PD, vomiting, pancreatitis, upper and lower motor neuron deficits with increase in [Br-]
Where is V1A receptor
On vascular smooth muscle of kidney, pancreas, hepatocytes, thyroid, bladder, spleen, skeletal M & platelets
-At high doses: Cause vasoconstriction
- At low doses: vasodilation in cerebral, renal, pulmonary and mesenteric vessels
MOA V1a Receptor
Gq protein activation of phospholipase C & phosphoinositide pathways –> activate voltage gated Ca channels
- Also inactivates K-ATP channels –> opens voltage gated Ca channels –> increased cytosolic Ca2+
- Reduced blood flow to the inner renal medulla –> limits AVP there –> selective efferent arteriolar contraction–> increase GFR
V2 receptors
ON renal collecting duct, endothelial cells, platelets and vascular endothelium
Effects: increase water permeability, increase vWF release, stimulate aggregation, vasodilation
MOA V2 receptors
Located at basolateral membrane of distal tubule & principle cells of cortical and medullary collecting ducts
-Coupling Gs signalling pathway –> increased intracellular cAMP –> fusion of aquaporin-2 vesicles –> increased free water reabsorption
- Increased release of vWF & FVIII from endothelial cells
- DDAVP is V2R agonist
Recombinant FVIIa
For hemophilia A (FVIII deficiency) & B (IX deficiency)
- HemoA patients may also have impairment of extrinsic pathway (TF + FVII)
HIgh doses (10x normal) can compensate for lack of F VIII & IX
** hypersensitivity reactions and $$ inhibit use
Dantrolene sodium
Binds ryanodine receptor to depress excitation-contrqaction coupling in skeletal m
*specific treatment for malignant hyperthermia
LMW heparin
Ex: enoxaparin, dalteparin
- BTW 25-30% molecules can bind BOTH antithrombin and FIIa
- Exert primary effect on FXa–> decreased hemorrhagic events compared to UFH
- Not protein bound –> dont bind endothelial cells
** excreted by kidney
- Protamine sulfate only partially reversed
Tranexamic Acid
Competitive inhibition of plasminogen activation (& noncompetitive of plasmin at high doses)
Competitive inhibitor activation of trypsinogen and enterokinase
6-10x more potent that aminocaproic acid
**Excreted unchanged in urine
Adverse Effects: GI & hypotension if given fast
Epsilon aminocaproic acid
Competitively inhibits plasminohen activation & at high doses inhibits plasmin directly
Renal excretion
Adverse Effects: GI & hypotension if given fast
Aminopentamide
Anticholinergic with some anti-emetic effects
Unclear if MOA due to cholinergic receptors in vomiting center or upper GI (Vagus N)
**not as effective as other 5HT2 or antihistamines
Trientine
Chelates Copper –> seems to chelate serum stores greater than tissue stores
Vitamin E
Antioxidant activity by protecting phospholipids from oxidative injury by scavenging ROS
Liver Dz
D-penicillimine
Chelates heavy metals and allows urinary excretion
May lead Cu deficiency –> microcytic hypochromic anemia
Antifibrotic and immunomodulatory properties
B1 agonists
Augment HR, contractility & ectopic pacemaker activity
May increase BG by increasing glucagon and ACTH secretion and lipolysis
5HT3 Antagonists
Ondansetron, Granistron, Dolesteron
Block serotonin 5HT3 receptor in CRTZ and MVC AND peripherally (intestinal vagal afferent)
Hepatic metabolism, eliminated in bile and renal
H2RA receptor antagonist
Block H2RA on gastric parietal cell –> decreases histamine
Ex cimetidine, ranitidine & famotidine
Cimetidine decreases P450
Omeprazole
PPI
Susceptible to gastric acid –> give as coated granule –> acts in duodenum
GIve 1 hr before meal on empty stomach
takes 2-5 days to work
Inhibits P450 –> consider if on clopidogrel
Thienopyridines
Ex: Clopidogrel, pasugrel
Irreversibly bind platelet P2Y12 receptor–> decreased ADP platelet aggregation
required hepatic biotransformation
Promazine Derivatives
Antidopaminergic & antihistamine –> CTZ
HIgher doses medulla vomiting center
Antispasmotic, anticholinergic, & alpha adrenergic blocking effects
Hepatic metabolism
Ex: chlorpromazine, acepromazine, or prochoraz
Doxapram
MOA stimulates respiratory via peripheral chemoreceptors
High dose: stim medullary center –> increase tidal volume and RR
Side effects: systemic catecholamine release, CNS stimulation and increased work of breathing
Heparins
- Reversed with protamine sulfate
- VTE
- LMWH»_space; UFH on Curative due to efficacy and safety
Dose adjusted by aPTT monitoring to 1.5-2x normal/baseline (more conservative is 1.2-1.5x)
Magnesium in tetanus
Calcium antagonist –> decreases muscle contraction/increases relaxation, & decreased NT release (Ach)
Helps with autonomic dysfunction and NM excitability
Mg toxicity: loss of patellar reflex is early sign, monitor for heart block, asystole, coagulopathy and decreased respirations
Zonisamide
MOA: inhibiy voltage gated Na channels, inhibits T type Ca2+, dopaminergic modulation, enhanced CNS GABAnergic activity, inhibits carbonic anhydrase
Hepatic metabolism, renal excretion
Side Effects: Ataxia, sedation, GI signs
Dogs: KCS, decreased TT4, idiosyncratic hepatotoxicity
Gabapentin
MOA unsure
Thought to bind to Ca channelse on neurons –> inhibit Ca2+ influx therefore decreasing release of hyperesthetic NT
Ursodiol
UDCA
Hydrophilic bile acid with cholerectic effects, cytoprotective to hepatic necrosis and immunomodulatory (decreases IL-2)
Vasopressin Stimuli for release
MOst potents: increased plasma osmolality, decreased BP and decreased circulating blood volume
Other causes: pain, nausea, hyporexia, hypercarbia, pharyngeal stimuli, glycopenia, mechanical ventilation, Drugs (Ach, opiates at high doses, histamine, gluatmine)
Conjugated estrogens
Thought to increase vWF & FVII & FXII
Administer at least 4-5 days before elective surgery
** For pets with uremia
Should be used with DDAVP
Methylxanthine
EX: Aminophylline, theophylline & caffeine
MOA: central respiratory stimulation –> leads to increased ventilation (improves skeletal muscle contractrion
Metabolic homeostasis
- Maintenance therapy for allergic airway disease
Azothioprine
Purine antagonist–> suppresses T cell activity
- Takes weeks to months to work
- ** Dont use with mycophenolate
Side Effects: GI signs, myelosuppression, hepatotoxicity, pancreatitis
Beta2 agonist
Causes vasodilation and bronchodilation
- May cause an increase in BG by increasing glucagon, ACTH secretion & lipolysis
- May cause an increase in cellular potassium uptake (resulting in preipheral drop in K+)
ex: terbutaline
Terbutaline
Emergent care for allergic airway disease
MOA: Beta 2 agonist resulting in vasodilation & bronchodilation
Nucleoside Analogs
Ex: Cangrelor & Ticangrelor
Reversibly bind P2Y12 receptor (newer drug ideal because of its reversibility)
Fibrinogen Receptor Antagonists
Ex: Abciximab (Reapro) - noncompetitive
Eptifibatide (Intigrilin) - competitive
Tirofaban (aggrastat) - competitive
MOA: Inhibit GPIIb/IIIa receptor
Competitice inhibition = recovery og platelet function after 4 hours of ending infusion
Unfractionated Heparin
High molecular weight: inactivates FIIa & FXa (1:1)
Low moleculr weight: inactivates FXa»FIIa (4:1)
- UFH binds to antithrombin (ie requires it to work) –> inhibits FIXa, Xa, XIa,XIIa & IIa with greatest effect on X & II
- Causes release of TFPI from endothelial cells
- Protein bound
- Binds macrophages, platelets & endothelial cells which alters its bioavailability
Direct Thrombin Inhibitors
MOA: inhibit both fibrin bound and circulating thrombin
Drugs in class:
- Argatroban
- Ximelagatran (Exanta)
- Dabigatra (Paradaxa)
- Divalirubdin
Streptokinase
Combines with plasminogen to form plasmin –> degradation of fibrin, fibrinogen, plasminogen, coagulation factors & streptokinase
**Nonspecific activator of BOTH free and bound plasminogen
*May cause severe drop in fibrin & coag factors
*Produced by streptococci –> antigen stimulation possible
Urokinase
More fibrin specific than streptokinase
Alpha2 Agonists sedation moa
Alpha2s found in CNS and SNS–> normally act as negative feedback loop for norepi at nerve and muscle
-Drugs modulate nociceptive signals in dorsal horn of spinal cord and brain & directly activate GABA
Stages:
1. INcreased SVR –> drop in HR
2. Decreased arterial pressure + decreased HR = decreased CO
AchE Inhibitors
- Neostigmine: Peak effect 7-10 min; duration was 60-70 min + glycopyrollate
- Edrophonium: peak effect 1-2 min
Duration 1 hr + atropine
** do not give evidence of twitch (>10% minimum height)
*Accumulation Ach: salivation, lacrimation, urination, diarrhea, dyspnea (bronchial secretion) , decreased HR & BP
Labile clotting factors
FV & FVIII
**Not present in frozen/stored plasma
Cryoprecipitate
Concentrated source of vWF, fibrinogen (FI), FXIII, FVIII
Misoprostal
PGE1 analog –> stimulates secretion of mucus & HCO3 & gastric mucosal blood flow
- Short half life
- Diarrhea & uterine contraction adverse effect
Dopamine
B1 ++
B2 +
Alpha 1&2 ++
Cont ++
HR ++
CO varies
Vasomotor ++
BP ++
** norepi precursor & NE release from nerve endings
** D1 : post synaptic receptor –> vasodilation
**D2 PRE synaptic –> inhibit NE release from SNS endings–> decreased vasoconstriction
** Does not cross BBB
Dobutamine
B1++
B2+
Alpha1&2 +
Cont ++
HR +
CO ++
Vasotone -
BP: variable
** increased forward flow when baseline BP ok
5-20 mcg/kg/min
Dopexamine
B1 0
B2 ++
Alpha 1&2 0
HR +
CO ++
Vasotone –
BP –
** Primarily vasodilator
Isoproteronol
B1 +++
B2 +++
alpha 1&2 0
Contractility +++
HR +++
CO +++
Vasomotor tone —
BP —
- If carefully administered, may augment forward flow and tissue perfusion
Epinephrine
B1 +++
B2 +++
A1&2 +++
Contractility +++
HR +++
CO ++
Vasomotor +++
BP +++
**Ventricular ectopic pacemaker activity possible
Phenylephrine
B1 0
B2 0
A1&2 +++
Contractility 0
HR -
CO - or +
Vasomotor tone +++
BP +++
Norepinephrine
B1 +
B2 0
A1&2 +++ (arterial AND venous)
Contractility +
HR varies
CO varies
vasomotor tone +++
BP +++
0.1 - 2 mcg/kg/min
*Should increase HR & CO if euhydrated
Ephedrine
B1 +
B2 +
A1&2 +
Contractility +
HR +
CO +
Vasomotor variable
BP +
0.25-1 mg/kg
*increase NE at sympathetic N endings
- bronchodilator
- prolonged use may deplete NE stores & tachyphylaxis
Vasopressin
B1 0
B2 0
A1&2 0
Contractility 0
HR -
CO down or 0
Vasomotor ++
BP ++
0.5-5 mU/kg/min
** V1 receptor: increased intracellular calcium & increased vasomotor tone
** Baroreceptor decreases HR
** Not acetylcholametic
** internal stores used up within 30 minutes to hours
Angiotensin
B1 0
B2 0
A1&2 0
Contractility 0
HR 0
CO -
vasomotor ++
BP ++
- vasoconstriction & aldosterone release
- Less potent than vasopressin –> preserve venous return
Telamisartin
Angiotensine II receptor blocker
- Can cause AoCRD in dogs (not cats)–> will decrease GFR –> do not use in AKI
Sodium Bicarb
Only indicated if pH<7.1 OR compensatory resp alkalosis (inc RR/menute vent) detrimental
**Contraindicated in hypoventilation as bicarb bind H+ and forma carbonic acid –> CO2+ H2O so need an increased in vent to get rid of CO2 or will cause drop in pH
Dose (mmol): 0.3 x BW (kg) x base excess
- Give 50% dose
*Controversial if even helps
* Risk of increase lactate
Potential complications:
- volume overload (increased Na)
- Tetany (decreased Ca2+)
- Decreased O2 delivery (inc Hgb affinity for O2 –> shift Oxygen-Hg dissociation curve to L)
- Increased blood lactate
- Hypokalemia
- Paradoxical intracellular acidosis
- Hypercapnia
- Hyperosmolality
- Hypocalcemia
- Hypomagnasemia
- Phlebitis
Fenoldapam
- Peripheral dopamine-1 agonist
- Indicated in hypertensive crisis
Adverse effect:
- Reflex tachycardia
- increased IOP
Amlodipine
- Calcium channel blocker
- Arteriolar vasodilation
- Minimal effect on heart
- First choice in cats
Adverse Effects:
- Increased HR
- Nausea
- Constipated
- Weakness
- May increase renal perfusion pressure
ACE Inhibitors
Examples: Benazaprile, enalaprile, lisinopril
Effect: Art/venous vasodilation
- Decreased preload
- Decreased afterload
Adverse Effects:
- Secondary hyperkalemia (aldosterone inhibition)
- Reversible increase in BUN & Crea
Hydralazine
Arteriolar vasodilation (improved forward flow)–> unknown MOA
Adverse Effect:
- Reflex sympathetic activity
- Lupus like signs
- Anorexia
- Nausea
- V/D
- Tremor
Silymarin
Antioxident –> scavenger of ROS & decreases lipid peroxidation
**May suppress TNFalpha, IL-1B & NK-KB
Local lidocaine
- Reversibly Bind voltage gated Na channels in nerves –> prevents action potential conduction in nerve fiber
- Selective central blockade of afferent activity at level of spinal cord
- Active endogenous opiate system
Doxorubicin
Interrups DNA transcription/replication
- If given fast, histamine release
- Dose dependent via a decline in mitochondrial oxidative phosphorylation & oxidative damage –> Reacts with iron and causes myocyte damage via myofibril loss & cytoplasmic vacuolation –> DCM
Procainamide
Class 1A antiarrhythmic
- Moderately slows conduction ( decrease fast Na channels)
- Increases action potential duration (moderate blockade of K+ channels)
- Can prolong QRS complex and QT interval
- Prolongs ERP –> Good for re-entry tachyarrhythmias
- Potent decrease conduction velocity –> may predispose to intra-myocardial re-entry
** Ventricular arrhythmias refractory to lidocaine (May be more helpful with hyperkalemia) –> may predispose to torsades
** $$
B1 blockers MOA
Bind Gs Protein–> activate adenyl cyclase –> forms cAMP from ATP –> cAMP activates cAMP dependent protein kinase A –> phosphorylates L-type calcium channel –> increased Ca re-entry into cell –> increased inotropy
- Gs protein also increases chronotropy
- PKA can phosphorylate myosin light chains –> increase inotropy
- Normal NE binding to B1-adrenergic receptors
Digoxin
- increased PSNS tone –> decreased AV conduction prolongs AV refractory period
- Inhibits Na-KATPase –> +inotropy (this causes increased intracellular Ca –> can be proarrhythmic –> ventricular arrhythmia even at normal therapeutic doses)
*Hypokalemia with toxicity
* 73 hr 1.2 life
*Takes 7 days to reach therapeutic levels
Amioderone
- Class III primarily, but properties from all 4 classes
- Prolongs refractory period in atria, ventricles and AV junction
- May cause cardio conversion with Afib
*Adverse Effects:
- Hepatotoxicity
- + Coombs
- Phlebitis
- Allergic reactions
Class I Antiarrhythmics
EX:
- Procainamide (1A): intermediate Na channel effects
- LIdocaine (1B): minimum Na Channel effects
- Mexilitine (1B): minimum Na Channel effects
MOA:
- decreased fast inward Na current –> decreased slope = decreased conduction velocity
- Stabilize membrane (slowed conduction, decreased excitability & automaticity)
- No effect on nodal tissue
- Negative dromotropy
- Different effects on ERP due to K+ repolarization effects
Lidocaine (antiarrhythmic)
Class 1B angtiarrhythmic
- decreased potential duration
- QRS complex & QT interval unchanged
- Decreased ERP
- 2 mg/kg IV boluses ( up to 8 in 10 minutes)
- 50-75 mcg/kg/min CRI
Class II Antiarrhythmics
Beta Adrenergic Blockade
- Reduces effects of sympathetic stimulation (on nodal, conducting system and contracting myocytes–> no direct myocardial effects)
- Indirectly decrease catecholamine release
- Both SVT & VT
**Atenolol - B1 selective antagonist
(treat with cats and dogs with SAS)
** Propanolol - nonselective B analog
- Good for ventricular arrhythmia from hyperthyroid or pheochromocytomas
Sotalol
Class II & III anti-arrhythmic
-Has K channel properties
- Should be effective in 2 hrs
- Not effective as ventricular antiarrhythmic in <2 mg/kg (boxers require 80 mg)
- Lower dose is most effective beta blockade → decreased contractility effects
Sodium Nitroprusside
Titrate to SBP (no less than 90 mmHg) –> typically titrate to 10-15 mmHg from baseline
- Arteriolar + venous vasodilator
- May cause hypotension due to arteriolar dilation (caution if already hypotensive –> use inotrope too)
- May cause increased VQ mismatch as reduces hypoxic pulmonary vasoconstriction
- May see reflex tachycardia
** can cause cyanide toxicity
Class III Antiarrhythmic
- Active on non- nodal tissue
- Selectively prolongs the action potential duration and refractory period
- Anti-adrenergic effects
- QT interval prolonged –> helpful for re-entry arrhythmias
- Blocks K in phase III
Ex:
Sotalol: nonselective B effect, but fewer neg inotropic effects
Amioderone: may prolong refractory period in atria, ventricles and AV junction
MOA B2 blockers
Normal NE binding B2 adrenergic receptors
- Gs protein binding –> ATP to cAMP –> inhibition of myosin light chain kinase –> decrease contraction vascular smoothe muscle
** B2 blockers may cause mild vasoconstriction
Theophyilline
Methylxanthine
MOA: thought to be due to inhibition of phosphodiesterases types 3 and 4, resulting in increased intracellular concentrations of cAMP and/or antagonism of adenosine receptors
In resp tract, decreases the release of inflammatory mediators from mast cells and eos
Adenosine antagonism inhibits some of bronchoconstriction
**Controversial, but extended release compounded in at least one form has shown good bioavailability
**May cause agitation or vomiting
Nitroglycerin
- venodilator
- Minimal hypotension and tachycardia seen with drug
- May cause tachyphylaxis quickly and reduced efficacy after 24 hr
- transdermal paste
Propofol
Potentiates GABA induced chloride current via interaction with GABAA receptor
-If CRI - discard induction set q 12 hrs due to lipid emulsion
- Avoid in cats due to prolonged infusion of benzyl alcohol
- Dose dependent vasodilation and myocardial depression → hypotension ( improved stability if given with opiate)
** Propofol infusion Syndrome: metabolic acidosis, arrhythmias, rhabdomyolysis, and renal failure → seen in humans. On case report of happening in a dog
Alfaxalone
Neuroactive steroid anesthetic that binds to the GABA receptor in the CNS
- At induction or recovery may see agitation. Noise, hypersensitivity, excitement, head shaking, tremoring, paddling, twitching, apnea, cyanosis → monitoring while weaning off alfax CRIs
-Dose dependent decrease in RR and minute volume→ may be detrimental in weaning period
- Dose dependent decrease in BP
Dexazoxane
- Antidote for doxorubricin extravasation
- Remove IC cath as much drug as possible
- Administer 10x extgravasiated dose IV within 3 hrs of event then q 24 hrs x 3 days
- monitor site for 10 days
SID of IV fluids
- 0.9% NaCl = 0
- LRS = 28 mmol/L
- Plasmalye/Norm = 49 mmol/L
- NaHCO3 = 1000mmol/L
Crystalloid fluid compositions
- Osmolality, [Na], [K], [Cl], [Mg2+], [Ca2+], lactate, acetate, gluconate
For fluids: normal saline, LRS, PLyte 148, NOrm R, PLyte A, 3% NaCl, 7.5% NaCl, 23.4% NaCl
Hypotonic Fluids
- HAve effective osmolality lower than that of the patient
- Resul in redistribution of fluid into the INTRACELLULAR compartment
- Indications: maintenance fluid requirements, treatment of solute free water deficits and drug administration
**NEVER BOLUS: may result in cerebral edema and death (Na causes water shifts from ECF to ICF compartments)
Maintenance type crystalloids
[Na+] of 40-77 mEq/L
Replace sensible and insensible losses
- D5W - Become hypotonic as the Dextrose is metabolized leaving solute free water→ cannot give free water directly as will cause hemolysis and endothelial damage
- AKI: some argument that should be giving hypotonic fluids during stabilization phase as high Na content of isotonic fluids may be more likely to cause fluid creep→ fluid retention
Isotonic Fluids
- Havew effective osmolality like the patient (270-310 mOsm/L)
- Same [Na+] as extracellular fluid compartment → minimal effect on intracellular volume/ minimal fluid shifts between compartments
- Vary on concentration of electrolytes (Na, Cl, K, Mg, Ca)
- Typically contain organic anions (lactate, gluconate, acetate)
Electrolytes and organic anions contribute to strong ion difference can impact pH following metabolism of organic ions (except gluconate → renal excreted unchanged) - Up to 50% intravascular volume lost in 30 minutes in healthy individuals
Volume kinetics vary→ influenced by rate of infusion, patients physiology, degree dehydration, surgery, anesthesia - AKI: increasing evidence to avoid NaCl
Examples: Plyte 148, Norm R, LRS, PLyte A
***0.9% saline is isotonic UNbalanced solution → better for patients with metabolic alkalosis (pyloric obstruction) → if normal Cl when given this, patients may develop hyperchloremic metabolic acidosis
Balanced solutions
Balanced: considered balanced IF:
- Isotonic & iso-osmotic
- Maintains or normalizes acid-base balance through its strong ion difference
- Contains electrolytes similar in concentrations as patient’s plasma
Ex: plasmalyte 148, NOrmR & LRS
Indications: replenish ECF deficits & maintain ECF volume
Hypertonic fluids
Tonicity greater than the patient→ infusion increases osmolality of extracellular fluid → redistribution of water out of intracellular compartment into ECF compartment
Osmotic shifts occur immediately following administration
Repeated doses may lead to hemolysis and phelbitis if given in small peripheral veins
Hypertonic Saline
- 3-7.5% can be directly infused without dilution
- Osmolal Effects: increasing plasma osmolality & [Na+] & [Cl-]; endogenous release of vasopressin
- Cardiovasc effects (proven in humans): arteriolar vasodilation - decreased afterload, volume loading (increased preload), reduced endothelial swelling, weak + inotrope; coronary vasodilation
** Do not admin >1 ml/kg/min b/c may cause hypotension secondary to central vasomotor center inhibition or peripheral vasomotor effects mediated by acute hyperosmolarity (bradycardia and vasodilation
Improves CPP → increases MAP and decreases ICP - Immunomodulatory effects: suppression of neut respiratory burst & cytotoxic effects → may be particularly beneficial in trauma patients
** Can expand ECF by 3-5x - but only for 30 min before redistributed to interstitium → combined with synth colloid (CCM)
**Prep of stock solution of combining 23.7% hypertonic NaCl with 6% hetastarch or other starch in 1:2 ratio and dosed at 3-5 ml/kg slowly IV for hypovolemia
Desmopressin Acetate
- Synthetic vasopressin analog available in IN and inj. form (oral form poor bioavail)
- Binds V2Rs –> more potent antidiuretic and procoag avail & less pressor
- ## dose dependent increase in plasma levels of fVIII & plasminogen
Digoxin
inhibit Na-K ATPase→ less Na pumped out of cell→ Na gradient altered making Na Ca exchanger function change→ less Ca pumped out increasing intracellular Ca
Positive inotrope
Fox glove, cardiac glycosides
Allopurinol
Inhibits xanthine oxidase
- renal side effects
Not recommend in vet med for ATLS
Clopidogrel
- Bloacks P2Y12 receptor on platelets
- For ATE
- loading dose to reach efficacy more quickly
- Requires P450 –> do not use with omeprazole!!
