All of the drugs Flashcards
Furosemide: drug class
Diuretic
Loop diuretic
Furosemide: MOA
- Inhibit Na+/K+/2Cl- (ascending loop of Henle)
- ↓Na, K, Cl reabsorption → retained in tubule → presented to distal nephron → retain H2O (dilute urine)
- ↑ max fractional excretion of Na+ to 15-25% filtered load
Furosemide: other effects
- ↑intrarenal PGE2 synthesis → ↑ renal blood flow
- Initial ↓ renal vascular resistance w/o changing GFR
- Anti inflammatory
- ↑ thoracic duct lymph flow (high dose)
- Bonchodilation in Hu, Eq, Guinea pigs
- ↑ renin secretion
- Initial direct effect on macula densa
- 6h 2nd effect to ↓ volume and activation of ∑ system
Furosemide: 1/2 life
1.5-3h
Furosemide: bioavailability
variable
- Incomplete 40-50%
- Eq: almost no PO
Furosemide: IV, IM, PO onset, peak, duration
IV: onset 5min, peak 20-30min, duration 2h
IM: onset 10-15min, peak 30min, duration 4-8h
PO: onset 30-60min, peak 1-2h, duration 6-8h
Furosemide: pharmacoK
Protein bound: 86-91%
[Kidney to plasma] = 5:1
Furosemide: excretion
45% bile, 55% urine
Furosemide: indications
CHF
Edema
Congestion
Hyper Ca2+
HyperK+
Oliguric renal dz
Furosemide CI
Renal failure
- ↓ renal clearance to 15%
- 1/3 of diuretic effect
- 2x serum ½ life
- Constant rate of diuresis
HypoNa, hypoK, hypoCl, hypoMg
Metabolic acidosis
Hypovolemia
HF w/o fluid retention
Nonketotic hyperglycemic state
Ergogenic blood lipid changes
Ototoxicity
Nursing
Furosemide: drug interactions
Aminoglycoside
Amphotericine B → nephro/ ototoxicity
NSAIDs → can ↓ effect
Not mix with acidifying solution
Furosemide: MOA ototoxicity
Electrolyte disturbance in endolymphatic system
Furosemide: storage
Protect from light
Room Temp
Poorly soluble in water: can be used in dextrose 5% (D5W), saline 0.9%, LRS → stability 8h
Torsemide: drug class
Loop diuretic: high ceiling
Torsemide: MOA
Inhibit Na+/K+/2Cl- (ascending loop of Henle)
Torsemide: other effects
K+ sparing
Anti aldosterone/ mineralocorticoid effect
- Inhibit aldosterone R: bind cytoplasmic fraction of kidney
Antifibrotic effect
- Mineralocorticoid R blockade in
- ↓ lysyl oxidase & collagen cross linking → correlates w myocardial fibrosis and ventricular stiffness
Vasodilatory
Coronary protective
Torsemide: moelcule
Lipophilic anilinopyrimidine sulfonylurea derivative
Unique chemical structure → not related to furo
10x more potent vs furosemide
Torsemide 1/2 life dogs
120min
Torsemide bioav dogs
80-100%
Torsemide IV, PO peak, onset, duration dogs
IV: [peak] 2-5min, peak effect 20-25min, duration 90min
- Low urinary excretion rate
PO: onset 20min, peak 2h, duration 12h
Torsemide PO peak, onset, duration cats
PO: onset 20min, peak 4h, duration 12h
Torsemide 1/2 life eq
9h
Torsemide PO peak eq
3h
Torsemide: studies in Hu and rats
differences in myocardial fibrosis in torsemide patients (vs furo + spiro)
Spiro: drug class
K+ sparing diuretic
Aldosterone
antagonist
Spiro MOA
Competitive inhibition of aldosterone by binding to R
Interfere with Na+ reabsorption → ↑ max excretion of Na+ to 2%
Preserve K+ excretion
Spiro PO onset/peak
Slow onset
Peak 2-3days
Spiro: metabolism
Extensively/rapidly metabolized
- Metabolites active but less potent
Spiro: indications
CHF
Hepatic cirrhosis (inhibit ascites)
Spiro: CI
Steroid-like effect
Facial dermititis
Antiandrogenic effects (Hu): gynecomastia, hisurtism, impotence
Spiro: drug interaction
Caution with K+ supplementation and NSAIDs
Hydrochlorothiazide: drug class
Thiazide diuretic
Hydrochlorothiazide: MOA
Inhibit Na+ reabsorption in distal tubule
- ↓ diuretic effect compared to loop diuretic → most H2O already reabsorbed in distal tubule
Hydrochlorothiazide: other effects
Can lead to hypoK+
Can ↑ effect of other diuretic and anti-hypertensive agents
Will block region where hypertrophy occurs during long term use of loop diuretics
Hydrochlorothiazide: PO onset/peak/duration
PO:
- Onset 1-2
- Peak 4h
- Duration 12-24h
Hydrochlorothiazide: features
Low ceiling diuretic: max response reached at low dose
Hydrochlorothiazide: indications
CHF/edema
→ chronic use of diuretics
Antihyper-tensive
Ca2+ excretion (Ca2+ oxalate urolithes)
Hydrochlorothiazide: CI
Renal failure/azotemia: marked ↓ effect
HypoK+, hypoNa+
HyperCa2+
Ventricular arrhythmias: ↓K+, Mg2+
Proarrhythmic drugs
Pregnancy:
- ↓ circulating volume
- Cross placental barrier
Sulfonamide type IM side effects: hepatic jaundice, pancreatitis, blood dyscrasia, angiitis, pneumonitis, interstitial nephritis, photosensitive dermatitis
Diabetogenic effects: ↑ risk of new diabetes
Urate excretion and gout: ↓ urate excretion + ↑ blood uric acid
Atherogenic changes in blood lipids: ↑ LDL cholesterol and triglycerides
Hydrochlorothiazide: drug interactions
Steroids: salt retention → ↓ effect
Indomethacin/ NSAIDs → interfere w PG → ↓ effect
Antiarrhythmics: class IA or III → prolong QT
Nephrotoxic ATB
Probenecid (gout tx) → block effect
Enalapril: drug class
ACEi
Enalapril: MOA
Block conversion of AngI → Ang II by binding AngI site on ACE
Effects of decr Ang II
- ↓ vasopressor effect
- ↓ H20/Na+ retention
o ↓ aldosterone release from adrenal gland
o ↓vasopressin (ADH) release from posterior pituitary - ↓ central/peripheral ∑ tone
- ↓ GFR preservation when ↓ blood flow
- ↓ myocardial hypertrophy/remodel
o ↓AngII
o ↑ [bradykinin] - ↓ myocardial collagen synthesis and ↑ degradation → prevent fibrosis from AngII/aldosterone
Enalapril: other effects
Mild vasodilator (arterial + venous)
- ↓SVR by 25-30% (↓afterload) → ↑SV and CO
- ↓venous tone: ↑ peripheral circulation, ↓PCWP, LV, LAP
Enalapril: affinity
ACEi > AngI
- 200 000x greater
Enalapril: 1/2 life
½ life = 7-8h initially, 11-19h additive
Enalapril: PO peak/duration
Peak 2-4h
Duration 12-24h
[Steady state] in 4days
Enalapril: bioav
Bioav. 60%
- Well absorbed by GI tract
Enalapril: metabolism
Metabolized in liver → become pharmacologically active
Secreted by kidneys
Enalapril: indications
Hypertension
CHF
Asympto patients w LV dysfct → can ↓ development of CHF (Hu)
Enalapril: CI
Pregnancy
RA stenosis
HyperK+
Renal dz
Angioedema
Hypotension
Enalapril: side effects
Damage to kidneys confined to proximal tubules
- Juxtamedullary region of cortex
- Necrosis of tubular cells
Regeneration possible
2 studies
- Lower incidence of azotemia in enalapril group
- Enalapril had no effect on [creatinine]
Effects on kidney thought to be mainly from ACEi 2nd hypotension → ↓ renal blood flow and GFR
Benazepril: drug class
ACEi
Benazepril: MOA
Same to enalapril
Benazepril: molecule
Non sulfhydryl ACEi
Benazepril: peak
1-3h
Benazepril: 1/2 life
22h
Benazepril: metabolism
Metabolism: liver → hydrolysed into benazeprilat to become active
Excretion: bile and urine
- Less dependent on kidneys
Benazepril: indications
Same enalapril
Nitroprusside: drug class
Vasodilator
Nitroprusside: MOA
NO formation → stimulate guanylate cyclase → ↑cGMP → vascular SM relaxation
Nitroprusside: Other effects
Arteriole: ↓SVR → ↑SV and CO
Venous: ↓PVR, ↑peripheral flow, ↓ cardiac volume, ↓ venous P
May ↑ LV compliance
↓LVP diastolic and end diastolic
↓LAP, LAD and LV diameter
Nitroprusside: molecule
NO compound w/o ester bound
- Release NO when non enzymatically metabolized
Nitroprusside: onset/duration IV
Rapid onset (almost immediate)
Duration: min
Nitroprusside: absorption
well GI
Nitroprusside: metabolism
Metabolism: hepatic → rapidly by nitrate reductase to <10%
- Rarely used PO
Nitroprusside: indications
Acute CHF
Hypertension
Nitroprusside: CI
Hypotension
Cyanide toxicity
Venous hyperO2
Lactic acidosis
Dyspnea
Nitroprusside: storage
*protect from light
Expensive!
Nitroprusside: other effects
*Tolerance does not develop
- Reflex ↑∑ drive can occur
Nitroglycerine: drug class
Vasodilator
Nitroglycerine: MOA
NO formation → stimulate guanylate cyclase → ↑cGMP → vascular SM cell relaxation
Nitroglycerine: other effects
Blood volume redistribution: central → peripheral
↓intraventricular pressure → ↓ edema
↓SVR → ↑ SV, ↓LAP, ↓edema
Nitroglycerine: molecule
Ester of NO
- Parent compound: 10-14x more potent
Nitroglycerine: 1/2 life
1-4min
Nitroglycerine: absorption
well GI
Nitroglycerine: metabolism
Metabolism: hepatic → rapidly by nitrate reductase to <10%
Rarely used PO
Nitroglycerine: indications
CHF
PH
Angina pectoris (Hu)
Laminitis (Eq) → ↑ blood flow to feet
Nitroglycerine: CI
Hypotension
MetHb
Tolerance
Dobutamine: drug class
inotrope +
Dobutamine: MOA
β1 = β2 > α1 agonist
Bind D-1R in kidneys → vasodilation
Dobutamine: molecule
Biosynthetic precursor of NE → stimulates NE release
Dobutamine: effect depends on
Low doses: inotropic effect + ↓ SVR
High doses: ↑SVR as action on lower affinity αR
Dobutamine: 1/2 life
½ life = 1-2min
- Rapid clearance
Dobutamine: pharmacoK
Plateau [CRI] achieved in 8min
Dobutamine: w/ tachycardia
*Inotropic effects w/o tachycardia
Dobutamine: indications
Acute CHF
Cardiogenic shock
Acute renal failure
Dobutamine: CI
Arrhythmias
Hydralazine: drug class
Vasodilator
Hydralazine: MOA
↑ [prostacyclin] → direct arteriolar SMcells
Hydralazine: other effects
↑ Ao compliance
↓ SVR by 40% and in vascular beds:
- Renal
- Coronary
- Cerebral
- Mesenteric
> skeletal
No effect on systemic venous tone
↑ contractility: reflex from NE release → histamine release
Hydralazine: metabolism
Metabolism: hepatic 1st pass → acetylation
Hydralazine: onset/peak/stability
Onset: 30min-1h
Peak 3h
Stability 8-10h
Hydralazine: When used for systemic hypertension w/o heart dz
- Reflex ↑∑ tone → ↑ contractility and HR → ↑CO → stable BP
- Addition of β-blocker blocks reflex
Not seen with CHF: ↓ response to ∑ tone
Hydralazine: indications
Systemic hypertension
Cases refractory to ACEi
Regurgitation/ shunt refractory to tx
Hydralazine: CI
Renal failure: affect hepatic metabolism →↑ [plasma]
Hypotension
Anorexia
Vomiting
Diarrhea
Systemic lupus erythematosus
Fever
Peripheral neuropathy
Hydralazine: drug interactions
Can ↑ furo delivery to nephron → ↑ GFR
Procainamide: drug class
Anti arrhythmic class 1A
Procainamide: MOA
Na+ channel blocker
- ↓ upstroke velocity of phase 0
Procainamide: other effects
May slow conduction or induce bidirectional block in re-entrant circuit
Procainamide: action depend on
extracell [K+]: if ↑ → ↓ resting membrane potential → ↑ effect
- ↓ tissue excitability
- ↑ duration of repolarization and effective refractory period
Procainamide: 1/2 life
3h
Procainamide: metabolism
Metabolism: liver
- Hu: metabolized into n-acetyl procainamide → class III anti arrhythmic properties
- May need higher dose in dogs vs Hu
Procainamide: PO pharmacoK
- Dosing difficult since short ½ life
- Sustained release tablets: allow q8h
o ↓ peak serum
Procainamide: indications
Ventricular tachy-arrhythmias
Preexcitation
SVT
Procainamide: CI
Hypotension and peripheral vasodilation
↓ inotropy
→ SLOW IV administration
Pro arrhythmic effect
Auto immune response → production of anti nuclear antibodies
Lidocaine: drug class
Anti arrhythmic class 1B
Lidocaine: MOA
Inhibit impulse/nerve conduction via Na+ channel block
- ↓ phase 0 depolarization
- W/o affecting conduction
- Little effect on atrial conduction and refractoriness
Lidocaine: other effects
Abolishes automatic/re-entrant ventricular tachyarrhythmias
- ↑ or ↓ conduction velocity w/I circuit
- Prolong refractory period
Lidocaine: incr effects
Better effect on damaged cells
- ↑ effect with ↑ extracell [K+]
- Hyperpolarization of partially depolarized cell → improve conduction in damaged myocardium regions
Lidocaine: metabolism
Metabolism: into monoethyl-glycinexylidide (MEGX)
- Primary liver
- Critical factors:
- Liver flow (↓CHF, βB)
- Liver microsomal activity
Lidocaine: 1/2 life
40-100min
Variable clearance rate
Lidocaine: onset/duration/effective
Rapid onset
Short duration
Effective
Lidocaine: toxicity
withdraw +/- diazepam
Lidocaine: indications
Ventricular arrhythmias
Local anesthesia
Lidocaine: CI
SSS → slow rate of phase 4 depol. In Purkinje Fibers → slow ventricular escape beat
Toxic on CNS: drowsiness, emesis, nystagmus, muscle tremors, seizures
- Cats > common
Depress ventricular fct → myocardial failure
Can induce AVB if conduction system dz
Hypotension
Lidocaine: drug interaction
Cimetidine
Propanolol
Halotane
→↓ liver clearance
(↓ dose)
Hepatic enzyme inducers → ↑ clearance
(↑ dose)
Mexiletine: drug class
Anti arrhythmic class 1B
Mexiletine: MOA
Na+ channel blocker
- ↓ upstroke velocity of phase 0
Mexiletine: Other effects
Interrupt re-entry circuits:
- Slow conduction
- ↓ membrane responsiveness
Suppress abnormal automaticity
↓ DADs formation induced by digitalis
↑ fibrillation threshold in ventricles
Mexiletine: molecule
Analog of lidocaine
Mexiletine: metabolism
Metabolism: not extensive 1st pass by liver (10%)
- Well absorbed GI
Mexiletine: 1/2 life
3-4h
Mexiletine: excretion
urine 80%, feces
Mexiletine: indications
similar to lidocaine
Mexiletine: side effects
- Vomiting
- Disorientation
- Ataxia
Mexiletine: overdose
seizures/ neuro signs
Flecainide: drug class
Anti arrhythmic class 1C
Flecainide: MOA
Na+ channel blocker
- ↓ upstroke velocity of phase 0
Tips and tricks class 1 anti arrhythmics
Class IA: Double Quarter Pound
Class IB: Lettuce, Mayo, Pickles
Class IC: Fries Please!
Flecainide: 1/2 life
13-19h
Flecainide: excretion
Excretion: hepatic + renal
- Unchanged
Flecainide: indications
Paroxysmal
SVT
Sustained VT
Catecholamine polymorphic Vtach
→ block open RyR channels
Flecainide: CI
Pro arrhythmic effects
- Structural heart dz: non uniform slowing of conduction
- More common w ventricular ectopy
↓LV fct
CNS side effects
RBBB, LAFB, SSS
Flecainide: drug interaction
Amiodarone (kinetic)
↑ - inotrope: βB quinidine, disopyramide
↓AV cond: quinidine, procainamide
Atenolol: drug class
Anti arrhythmic class II
Atenolol: MOA
β blocker: selective β1 antagonist
Atenolol: pharmacoK
Water soluble
- ↓liver clearance
Atenolol: bioav
80-90%
Atenolol: 1/2 life
½ life = 5-6h dog, 3.5h cat
Atenolol: excretion
Excretion: urine
- Unchanged
Atenolol: features
Acute withdrawal may exacerbate original issue
Atenolol: indications
Afib → ↓HR
SV and ventricular arrhythmias
SAS: ↓ sudden death
HOCM: ↓SAM
Atenolol: CI
Exacerbation of:
- CHF
- SA node dysfct
- AV node dysfct
↓ rate of subsidiary PM
↑ lower airway resistance: not use if lower airway dz
Diabetes: ↓∑ compensation for hypoglycemia → ↓ insulin secretion
HyperK+ → ↓ K+ flux from intra to extra
Hypotension
Propanolol: drug class
Anti arrhythmic class II
Propanolol: MOA
β blocker: non selective β1 and β2 antagonist
Propanolol: other effects
- ↓ catecholamine dependent automatic rhythms: normal + abnormal
- Slow conduction in normal ventricular myocardium
AV node:
- ↑ refractory period
- Slow conduction velocity
↓ myocardial contractility → ↓ O2 consumption
Propanolol: pharmacoK
Lipophilic molecule
Propanolol: metabolism
Metabolism: liver
- Extensive 1st pass
- ↑ [blood] with ↓ liver blood flow
Propanolol: 1/2 life
- 1.5h (1st dose)
- 2h (2nd dose)
Propanolol: effects depend on
Dose dependent change in myocardial contractility and SVR
Propanolol: indications
Afib → ↓HR
SV and ventricular arrhythmias
Propanolol: CI
Similar to atenolol
Amiodarone: drug class
Anti arrhythmic class III mixed
Amiodarone: MOA
Block outward K+ channel
- ↓ slope of phase 4 → ↓ SA rate
- Prolong AP duration → delay myocardial repol
Amiodarone: other effects
Prolong refractory period of atrial/ ventricular myocytes + AV node
- W/o changing resting potential
Interrupt re-entry circuit
- Anti fibrillatory effect
Other effects:
- Block α and β R
- Ability to block slow Ca2+
- Ability to block fast Na+
Amiodarone: pharmacoK
Highly lipophilic
- Rely on liver
- Accumulates 300x [plasma] in adipose tissue
[Myocardial] = 15x plasma
Amiodarone: absorption
Absorption: slow GI → distribution in adipose tissue
- Fill peripheral tissue depot, then
- [Blood/cardiac]
- Slow onset
Amiodarone: metabolism
Metabolism: liver
→ Desethylamiodarone: block fast Na+ channels
Amiodarone: onset
slow onset
Amiodarone: 1/2 life
Long ½ life = 3.2 days
- Up to 6mo
- Withdrawal: ↓ [plasma] in 3-10days + slow ↓ of tissue store
Amiodarone: clearance
Clearance: rapid except adipose tissue
Amiodarone: indication
SVT →Afib/ flutter
Ventricular arrhythmias
OK with structural heart dz
Amiodarone: CI
GI disturbance
Neurologic problems
Corneal deposits → visual impairment
Dermatologic → pruritus when given IV
Hepatotoxicity: ↑ liver enzyme
Pulmonary fibrosis → inhibit phospholipase A → phospholipidosis
Exacerbation of dz
Hyper/hypothyroidism → inhibit T4-T3 secretion
Bone marrow toxicity: neutropenia
Hypotension → vasodilation
Amiodarone: drug interaction
↑ [serum]
- Diltiazem
- Digoxin
- Quinidine
- Procainamide
- Phenytoin
- Warfarin
Sotalol: drug class
Anti arrhythmic class III/mixed
Sotalol: MOA
Potent/non selective
- β blocker: β1 and B2
o Similar to propranolol but 1/3 potency
Sotalol: other effect
Prolong AP duration
↑ effective refractory period of atrial/ ventricular myocardium
↑AV node refractory period
↑ fibrillation threshold
Sotalol: pharmacoK
L isomer
- 50% > β blocker activity
Sotalol: absorption/bioav
Absorption: rapid
Bioav. 85-90%
Sotalol: clearance
renal
Sotalol: indications
SVT
Ventricular arrhythmias
Sotalol: CI
Similar to propranolol/ atenolol
Use with caution:
- ↓ cardiac contractility
- Slow HR
Diltiazem: drug class
Anti arrhythmic class IV
Diltiazem: MOA
Slow voltage dependent Ca2+ channel blocker → block Ca2+ entry into cell
Diltiazem: other effects
PREDOMINANT ACTION
AV node: negative dromotrope
- Slow conduction
- Prolong refractory period
Negative chronotrope: ↓HR
Vasodilation
Minimal effect on cardiac contractility or vascular SM cell
Diltiazem: absorption
Absorption: rapid GI
- 30min
Diltiazem: 1/2 life
½ life = 2-4h
- Shorter in Eq
Diltiazem: indication
SVT
Hypertension: 2nd tx or combination
Diltiazem: CI
Hypotension
Myocardia depression
Bradycardia
AVB
Diltiazem: toxicity
- IV fluids
- Ca2+ gluconate/chloride
- Sympathomimetics
Digoxin: drug class
other/class 5 anti arrhythmics
Digoxin: MOA
Blocks Na+/K+ exchanger
- Competitive binding of K+ site
- ↓ Na+ efflux in diastole → ↑ intra¢ Na+ → activate Na+/Ca2+ exchanger to pump out Na+ in exchange for Ca2+ → ↑ intra¢ Ca2+
Digoxin: other effects
↑ myocardial contractility from ↑ [Ca2+] = positive inotrope
Diuretic effect: block Na+/K+ pump on renal tubular → ↑ Na+ and H2O excretion
Stimulate p∑ system and ↓ ∑ tone → ↑ activity of vagal nerve
- Slow SA node d/c rate = negative chronotrope
- ↓AV node conduction and prolong refractory period
Digoxin: follow up
Test blood levels 5-7 days after starting digoxin, then each 6 months
- 4-6h post administration
Narrow therapeutic range: 1-2.5ng/ml
- Block 30% oof pumps in heart
Digoxin: pharmacoK
Digitalis glycoside
- Poorly liposoluble
Digoxin: bioav
PO 60%
Digoxin: metabolism
Metabolism: small hepatic (15%)
Digoxin: 1/2 life
23-29h dog
Digoxin: PO/IV
PO: well absorbed by GI
IV: slowly over 15min
- Rapid can cause peripheral vasoconstriction → ↑ afterload
Digoxin: excretion
renal mostly
Digoxin: indications
SVT
Myocardial failure
Digoxin: CI
- Muscular atrophy: similar R to K+ in muscles → ↑ [serum]
- Dehydration
- HypoK+ → ↓ competition for binding sites
- HyperNa+/Ca2+: ↑ inotropic/toxic effects
- Hypoxia: ↑ sensitivity to toxicity
- HyperT4: ↑ myocardial effects
Pro arrhythmic: ↑Ca
Tachyarhythmias/VT
Neurologic signs: depression
GI signs: V+, D+ (vagally mediated)
Hypotension
Digoxin: toxicity
↑ intracell Ca2+
Digoxin: drug interaction
↑ [serum]
- Aminoglyco.
- Amiodarone
- Anticholinerg.
- Diltiazem
- Esmolol
- Flecainide
- Quinidine
Drugs altering microsomal enzymes
Pimobendan: drug class
PDE3i
Pimobendan: MOA
Phosphodiesterase 3 inhibition
- inhibit PDE enzyme → ↓ cAMP breakdown → ↑ cAMP
- ↑ inotropy, chronotropy, dromotropy, vasodilation
Ca2+ sensitizer
- ↑ Troponin C sensitivity to Ca2+ → ↑ contractility
Pimobendan: other effects
Anti inflammatory
↑ sensitivity to baroR
↑ lusitropy
↓ platelet agreggation
Pimobendan: PO absorption
- Absorption: can change with food and stomach pH
- Onset 1h
- Persist 8-12h
- [Steady state] 2 days
Pimobendan: bioav
70%
Pimobendan: 1/2 life
30-120min
Pimobendan: metabolism
liver → more potent metabolite
Pimobendan: excretion
feces 90%
Pimobendan: indications
CHF
Preclinical CVD and DCM
+/- HCM
Pimobendan: CI
GI upset
Proarrhythmic: reported but not proven
SAS
Pimobendan: drug interaction
Ca2+ channel blockers
Β blockers
→ ↓ inotropic effect
Sildenafil: drug class
PDE5i
Sildenafil: MOA
Phosphodiesterase 5 inhibition
- Found in pulmonary vasculature
- Inhibit PDE enzyme → ↓ cGMP breakdown → ↑ cGMP → vasodilation
Sildenafil: absorption
GI 90%
Sildenafil: metabolism
extensive 1st pass (CYP450 → 3A4)
- N-demethylation: 40% potent
Sildenafil: bioav
PO 54%
Sildenafil: 1/2 life
3-5h
Sildenafil: peak PO
1-2h
Sildenafil: elimination
fecal 70%, urine 15%
Sildenafil: indications
PH
R to L shunting
Sildenafil: CI
Hypersensitivity possible
L sided heart dz: can ↑ venous return to L heart → CHF
Hypotension
Sildenafil: drug interaction
Ketoconazole
Erythromycin
Cimetidine
→ ↑ [drug]
Theophylline: drug class
Bronchodilator
Sympathomimetic
Theophylline: MOA
Non-selective phosphodiesterase inhibitor
Adenosine antagonist
Theophylline: absorption/bioav
well PO
>90%
Theophylline: 1/2 life
1-6h dogs,
14-18h cats,
12-15h Eq
Theophylline: indications
Inflammatory airway dz
SSS/SA node dysfct
AVB
Theophylline: side effects
- GI: V+, D+
- Tachycardia
- Excitement/ agitation
- Tremors
- Seizures
Theophylline: overdose
Overdose: hypoK+
Theophylline: drug interaction
Cimetidine
Erythromycin
Propanolol
→ ↑ [] by ↓ metabolism
Phenobarbital
Rifampin
→ opposite
Lomotil: drug class
Opiate agonist
Lomotil: MOA
Bind to mu-opiate R in intestines
- Stimulate SM segmentation in intestines
- ↓ peristaltis
- ↑ fluid/electrolyte absorption
Lomotil: indications
Opioid effect used to ↓ inflammation and coughing
Coughing (dogs)
Diarrhea
Lomotil: absorption
Absorption: PO
- Hu: rapid, peak after 2h
Lomotil: metabolism
liver
Lomotil: elimination
60% bile and feces
Lomotil: 1/2 life
12-14h
Lomotil: CI
D+ from toxins, parvovirus
Hypersensitivity
Atropinization: hyperT, tachycardia, urinary retention, dry MM
Caution:
- Addison
- ↑ cranial P
- HypoT4
- Liver dz
- Kidney failure
Lomotil: drug interaction
↑ ½ life of hepatic metabolized drugs
Hyoscyamine: drug class
anticholinergic
Hyoscyamine: MOA
Competitive antagonist of Ach effect on muscarinic R
- Parasympatholytic → ↑HR
Hyoscyamine: other effects
antiemetic
Hyoscyamine: absorption PO/IV, peak, duration, onset
Absorption: not affected by food
- Peak PO 30-60min, IV 15-30min
- Onset PO 20-30min, IV 2min
Duration 4h
Hyoscyamine: 1/2 life
3.5h
Hyoscyamine: elimination
Urine mostly unchanges
Hyoscyamine: indications
Bradycardia
AVB
SSS
Vomiting: associated w
- Motion sickness
- GI dz, ↓ motility/ secretions
Hyoscyamine: CI
Glaucoma
Intestinal ileus
Gastroparesis
Tachycardia
Hyoscyamine: drug interaction
Other anti muscarinics
