Pharmacology

Doxycycline class

tetracycline

minocycline class

tetracycline

Tetracycline spectrum of action

Broad, all 4 categories

tetracycline time dependent or conc. dependent?

time dependent

tetracyclines bacteriostatic or bacteriocidal

-cidal

methacycline class

tetracycline

tetracycline mechanism of action

diffuse into porins of gram(-) but enter cytoplasm of gram(+) which is energy dependent and has a protein carrier

tetracycline ribosmal unit

bind to 30S and interfere with protein synthesis and prevent attachment oto aminoacyl-tRNAto the mRNA-ribosome complex.

Tetracycline resistance

enzymatic hydroxylation, ribosomal RNA mutations, increase transport of drug out of cell, p-gp, plasmid generated protein protect ribosomal binding site

tetracycline distribution

lipid soluble

minocycline and doxycycline can enter CNS

sulfonamides mechanism

inhibit bacterial dihydropteroate synthesis thus the bacteria cant synthesize folic acid and then no protein and nucleic acid synthesis

sulfonamide examples

sulfamethoxazole and sulfadiazine

mechanism of diaminopyrimidines

inhibit bacterial dihydrofolate reductase

diaminopyrimidines examples

trimethoprim and pyrimethamine

sulfonamides are …

bacteriostatic and time dependent and broad spectrum

sulfonamide resistance mechanisms

produce insensitive dihydropteroate enzyme

chromosomal and or plasmid resistance

what are sulfonamides ineffective against

obligate anaerobes

preferred sulfonamide for CNS infection (equine protozoal myeloencephalitis)

sulfadiazine

sulfonamide contraindications

dont use with anticoagulants or in hypothyroid animals

illegal ELDU in dairy cattle >20mo

dobermans

uses for sulfonamides

UTI, CNS, skin, respiratory, GI, nocardia and actinomyces, protozoal infections, joints

what are diaminopyrimidines

dihydrofolate reductase inhibitors

adverse effects of sulfonamides

dose-related

urinary tract disturbance, hypothyroidism, keratoconjunctivitis sicca, hypersensitivity reactions, hematopoietic disorders

examples of fluoroquinolones

Enrofloxacin, Ciprofloxacin, Marbofloxacin, Orbafloxacin, Pradofloxacin

fluoroquinolones are…

bacteriocidal, concentration dependent, PAE, not effective against anaerobes, best against aerobic gram (-) and intracellular pathogens

fluoroquinolone mechanism of action

inhibit bacterial DNA gyrase or topoisomerase thus inhibiting DNA replication and transcription

fluoroquinolone contraindications

dont use with antacids/ cations

dont use in pregnant/lactating animals or those with seizures

avoid in athletic animals

NOT first-line drug

no ELDU in food animals(only against Haemophilus or Pasteurella)

fluoroquinolone adverse effects

neurotoxicity (lower threshold for seizure)

phototoxicity

GI tract disturbances

retinal degeneration in cats

athropathy

decreases bone growth in juveniles

cartilage damage

fluoroquinolone uses

safe in herbivores

UTI, gram (-) aerobes and some gram (+) and intracellular pathogens

bacitracin mechanism

inhibit peptidoglycan synthesis

bacitracin is…

bactericidal, topical, peptide antibiotic, against gram (+)

vancomycin mechanism

inhibit peptidoglycan synthesis

vancomycin adverse effects

histamine release

nephrotoxicity

ototoxicity

vancomycin uses

MRSA in humans as last resort

NO ELDU in food animals

polymyxin B mechanism

surface active cationic detergents induce antimicrobial activity by interfering with bacterial cell membrane phospholipids and structure

polymyxin B is…

concentration dependent and bactericidal

bacitracin-neomycin-polymyxin= neosporin

polymyxin B uses

Gram (-) bacteria NOT gram (=) or anaerobic bacteria

bowl sterilization

protective against endotoxin from gram (-)

mostly topical or parenteral

polymyxin B adverse effects

decreased activity in the prescence of pus

nephrotoxicity

respiratory paralysis

CNS dysfunction

virginiamycin mechanism

inhibit protein synthesis by binding to separate sites on 50S and block translation (bactericidal in combo S and M)

against gram (+)

rifampin mechanism

Inhibits the activity of DNA-dependent RNA polymerase

bactericidal with PAE

against gram(+) and intracellular pathogens

induce p450

rifampin adverse effects

resistance if used alone

hepatotoxicity

red orange urine

accelerates metabolism of heart medications and corticosteroids

rifampin uses

gram (+)

combo with macrolide for Rhodococcus equi pneumonia and pyogranulomatous enteritis in foals

Combination with erythromycin can be used in the treatment of proliferative enteropathy

no use in food animal - carcinogenic

nitrofurans mechanism

inhibit bacterial carbohydrate synthesis (prevent convert to Acetyl CoA)

bacteriostatic

nitrofuran uses

not systemic uses due to toxicity

UTI

carbadox mechanism

inhibit bacteria by intercalating with DNA and causing mutations (carcinogenic)

novobiocin mechanism

inhibition of DNA gyrase through a different site to that of fluoroquinolones

novobiocin uses

gram (+) especially S. aureus and those resistant to penicillin

what class is metronidazole

nitroimidazole

nitroimidazole uses

bactericidal

protozoa that cause intestinal diseases

against obligate anaerobes

can penetrate CNS

metronidazole adverse effects/contraindications

not to be used in pregnant/lactating animals

not to be used in debilitated animals

dose related CNS toxicity

immunosuppressive drug

NOT in food animals (but can be used in pocket pets)

linezolid mechanism

Reversibly blocks protein synthesis by binding to 23S ribosomal RNA of 50S subunit

against aerobic and anaerobic gram (+) bacteria

inotropy

contractility

lusitropy

relaxation

what must you know when selecting a medication

indication, mechanism, safe dose range, adverse effects

preload

volume! prior to ventricular contraction

preload reducing drugs

diuretics

venodilators

frank starling relationship

increase preload stretches sarcomeres increases force of contraction and stroke volume

diuretic function

increase urine, sodium excretion, potassium excretion

loop diuretics

site of action: thick ascending loop of henle

Furosemide (lasix), torsemide

inhibit resorptive Na/K/Cl cotransporter

loop diuretic adverse effects

dehydration, electrolyte abnormalities, RAAS activation, azotemia

furosemide use

first choice for CHF (2mg/kg)

sequential nephron blockade

improve diuresis with diuretics that act at different points in the nephron to avoid resistance

thiazide diuretics

hydrochlorothiazide (HCTZ)

inhibit resorption of Na/Cl in distal convoluted tubule

mineralocorticoid receptor antagnonists

spironlactone

antagonizes action of aldosterone (block Na resorption, retain K)

better for anti-remodeling/ anti-fibrotic effect

positive inotropic agent

phosphodiesterase 3 inhibitors= pimobendan (vetmedin)

negative inotropic agents

calcium channel blockers

beta blockers

pimobendan

inhibit PDE3 - reduce cAMP breakdown

increase inotrophy and lusitropy

increase release and reuptake Ca = more sensitive

decrease preload and afterload

vetmedin uses

DCM

chronic degenerative valve disease

CHF

first line for heart failure

afterload

pressure! in LV to open aortic valve

pressure in ventricle must be > systemic/pulmonary pressure in order to open valve

Systemic afterload reducer

amlodipine

pulmonary afterload reducers

sildenafil

neurohormonal control of BP

Catecholamines inc. BP

RAAS inc. BP

ADH inc. BP

Natriuretic peptides dec. BP

epinephrine

increase myocyte contractility (beta 1)

increase vasodilation (beta 2)

norepinephrine

increase myocyte contractility (beta 1)

increase vasoconstriction (alpha)

calcium channel blocker

amlodipine

angiotensin II receptor blocker

telmisartan

ACE inhibitor

enalapril

benazepril

osmotic diuretics

mannitol

carbonic anhydrase inhibitors

acetazolamide

dichlorphenamide

loop diuretics

furosemide

torsemide

ethacrynic acid

thiazide type diuretics

hydrochlorothiazide

chlorothiazide

potassium sparing diuretics

Amiloride, Triamterene

Spironolactone, Eplerenone

Osmotic diuretics mechanism

Mannitol is filtered through the glomerulus but cannot be reabsorbed. Causes osmotic imbalance in proximal tubule, descending limb and in collecting ducts, drawing extra water towards it.Hypovolemia

Osmotic diuretics adverse effects

Hypovolemia

Osmotic diuretics ion changes

increase K/ HCO3/ Ca excretion

Carbonic Acid Inhibitors mechanism

Inhibition of proximal convoluted tubule sodium bicarbonate reabsorption by inhibition of carbonic anhydrase

Carbonic Acid Inhibitors adverse effects

Metabolic acidosis

Carbonic Acid Inhibitors ion changes

increase K/Ca excretion and increase HCO3 excretion by a lot

Loop diuretics mechanism

Inhibition of Na/K/2Cl (NKCC2) cotransporter in thick ascending loop of Henle

Loop diuretics adverse effects

Hypokalemia

Metabolic Alkalosis

Hypomagnesemia

Hypercalciuria

Loop diuretics ion changes

decrease HCO3 excretion

Thiazide diuretics mechanism

Inhibition of Na/Cl cotransporter in distal convoluted tubule

Thiazide diuretics adverse effects

Hypokalemia Metabolic Alkalosis Hypocalciuria

Thiazide diuretics ion changes

decrease HCO3 and Ca excretion

K+-sparing diuretic mechanism

Inhibition of aldosterone-responsive epithelial Na channel (ENaC) in distal nephron + collecting tubule

Inhibition of aldosterone receptors in distal nephron + collecting tubule, reducing Na channel and Na/K ATPase

K+-sparing diuretic adverse effects

Hyperkalemia

Acidosis

K+-sparing diuretic ion changes

decrease K excretion and no change to Ca

Quinidine

Ia Na channel blocker

atrial fibrillation in horses

speeds up AV conduction

Gi effects, worsen digoxin toxicity, horsie problems

procainamide

Ia Na channel blocker

slow conduction velocity and stop reentry

not first line

lidocaine

Ib Na channel blocker

ventricular tachycardia

not orally effective

2mg/kg in emergencies

slow conduction velocity and stop reentry

preferential for damaged tissues

mexiletine

Ib Na channel blocker

oral lidocaine