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VTS ECC 2024 > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Pharmokinetics

A

Study of Drugs:
Absorption
Distribution
Metabolism
Excretion

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2
Q

Pharmacokinetics

Cmax
Tmax
T1/2

A

Cmax; highest plasma concentration of a drug after its administration
Tmax: time to reach the highest plasma concentration after administration
T1/2: time required for the plasma concentration of a given drug to decrease to half of its original value

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3
Q

Absorption Definition

Examples

A

Movement of a drug to the circulatory system from site of administration
–First pass metabolism will effect absoprtion

Oral, Respiratory, transmucosal

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4
Q

Oral drug Absorption

A

–Oral drugs are disintergrated into a solution to be absorped by intentinal mucosa
–Formulation and Rate of dissolution can effect how the drugs absoprtion (liquid vs tablet)
–TM and rectal routes avoid 1st pass metabolism DT absoprtion in GI tract not drained by portal circulation

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5
Q

Repiratory Tract Absorption

A

–Highly effective absoprtion
–Alveoli are thin with excellent surface area and lined heavily with capillaries
–Allows drugs to rapidly and directly enter the systemic circulation

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6
Q

Factors that affect parenteral routes

A

Hypoperfusion
Vasoconstriction (during shock from RAAS)
Excessive SQ fat

IV perfered route

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7
Q

Distribution

What is it dependent on?

A

Process that determines how drug reaches site of action and what concentration it is
Dependent on:
–Physiochemical properties (lipid solubility etc)
–Concentration gradient between blood/site of action
–Ratio of blood flow to site of action
–Affinity of drug for tissue components (BBB)

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8
Q

MDR-1

Where is it located
What is it function?

A

Protein in GIT/Kidneys/Liver/BBB that can remove foreign substances (drugs) out of cells
–Mutation results in pts inability to remove a drug out of cells = increased drug sensitivty

Aussies/Collies/Whippets/Herding dogs

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9
Q

Protein Effx on Distribution

Ex of protiens

A

Drugs degree of binding to plasma protiens w/i blood
–Albumin/Alpha-1 Glycoprotein
–Drugs must be “unbound” for metabolism/elimination
–PLE/PLN/hypoalb → shift in level of unbound/active drug = greater drug efx

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10
Q

Metabolism

A

Biotransformation after clinical effect produced
–Liver mostly primarily responsible

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11
Q

First-Pass hepatic metabolism

Describe pathway

A

—drug reaches submucosal capillaries (stomach) → enters portal circulation → transported directly to liver
—significantly less drug available to reach systemic circulation = absorption markedly reduced
–Drugs not administered PO avoid potential first‐pass metabolism
–TM and Rectal routes avoid first‐pass metabolism → allow for absorption thru GIT segments not drained by portal circulation

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12
Q

Liver Metabolism pathways

#5

A

Oxidation (P450 system)
Reduction
Hydrolysis
Hydration
Conjuction

Divided into Phase I and II

further increase a drug’s water solubility and polarity, allowing for less tissue distribution and facilitating drug removal from the body

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13
Q

Phase I Liver metabolism reactions

x4

A

Oxidation (P450)
Reduction
Hydrolysis
Hydration

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14
Q

Phase II Liver metabolism reactions

4 examples

A

Conjugation

endogenous compounds such as glutathione, sulfate, glycine, or glucuronic acid

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15
Q

Feline Liver Metabolism

Example

which phase is affected?

A

–Decreased ability to perform phase II metabolism, specifically glucuronidation
–Cannot synthesize glucuronic acid to the extent needed to metabolize some drugs, resulting in toxicity (Acetaminophen)

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16
Q

Drugs that enhance P450

x3 examples

A

AKA Enzyme inducers
Results in ↑ drug metabolism
–phenobarbital, phenylbutazone, and St John’s wort

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17
Q

Enzyme Inhibitors

Examples

A

Drugs that derease metabolism of other drugs;
–cimetidine, chloramphenicol, erythromycin, fluconazole, grapefruit juice, ketoconazole, and omeprazole

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18
Q

Elimination

Main vs Other examples

x2 requirements for elimination

A

Drug removal from the body
Most eliminated via urine from kidneys
Others; bile/sweat/saliva/milk/tears/expiration

Need to be H2O soluable with smaller molecular wt and unbound to plasma proteins

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19
Q

Renal Excretion affected by:

A

Urine pH
UOP
Altered kidney blood flow (hypoperfusion)
CKD

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20
Q

Enterohepatic Recycling

Example

A

Drugs eliminated in bile can be reabsorbed later in GIT and enter systemic circulation

ex: NSAID toxicity → why activated charcoal/chloestyramine given

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21
Q

Context-sensitive Half life

A

Amount of time it takes for plasma concentration of drug to reduce by half after infusion has been stopped

i.e half life of time for elimination may be prolonged based on duration of CRI as compared to single dose

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22
Q

Pharmacodynamics

Ligand

A

Protein molecule receptor w/ cell membrane that recieves an endogenous chemical signal
–binds to receptor to produce cellular reponse with biological purpose
–can be activated by exogenous agents (drugs)

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23
Q

G-protein-coupled receptors (GPCR)

Examples x4

A

Most common/diverse group of cell membrane receptors
-Ligand binds to associated GPCR → causes GPCR to leave → replaced by GTP
– “active” state → GPCR activates 2nd pathways → results in cell fnx changes

Ex: Adrenergic drugs/opioids/vasopressin/insulin

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24
Q

Ionotropic Receptors

3 categories

type of channel
x4 examples

A

Ligand-gate Ion Channels
–channel proteins that live w/i cell membrane
–ligand attach to receptor → activates receptor →allows ions (Na+/K+/Ca++/Cl-) to pass thru cell → produces biological response

Categories: cys-loop, ionotropic glutamate, ATP-gated channels
EX: acetycholine, serotonin, NMDA, GABA

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25
Q

Voltage-Gated Ion Channels

A

Class of protein receptors activated by changed in electrical membrane potential
–channels open or close to specific Ions (Na+/K+/Ca++/Cl-)

Ex: Local anesthetics working on Na+ channels

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26
Q

Chelation

Examples

A

Agents that bind directly to heavy metals in the body (lead/iron/copper)
Promote their elimination

Ex: deferoxamine/EDTA/dimercaprol

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27
Q

Agonist vs Antagonist

A

Agonist: bind to receptor to activate /mimic endogenous ligand
Antagonists: bind to receptor and blocks/dampens response
Agonists/Antagonists: compete for same binding site → effect determined by concentration of antagonist @ receptor

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28
Q

Theraputic Index

A

LD50/ED50
LD50 → lethal dose require to kill 1/2 population
ED50 →median effective/theraputic dose in 1/2 population

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29
Q

Pediatric patient considerations

#5

A

↑ TBW and ↓ fat stores
– prone to hypoglycemia d/t minimal glycogen stores and poor gluconeogenesis
–hypoproteinemia protein bound/hydrophilic drugs may have more profound efx
–Renal and hepatic system immature until 8wks old →prolong duration of effect/recovery
↑ BBB permeability = certain drugs have more profound CNS efx
–highly dependent on heart rate to maintain cardiac output and blood pressure.

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30
Q

Geriatric patient considerations

#4

A

↑ risk for concurrent dz states
–CKD/ hepatic dz/reduced mass/blood flow to organs
–decreased cardiac reserve → less able to compensate for CVS changes
–Reduced CO/contractility/lower BV/BP → delayed response to drug administration
–Hepatic biotransformation/clearance of drug w/o concurrent dz generally presevered w/ adequate amounts of P450

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31
Q

Apomorphine

Type, MOA, use

which receptor? why is not not as effective on cats?

A

–morphine derivitive
–Stimulates CRTZ to stimulate emesis
–non selective dopamine agonist
–less effective in cats (less dopamine receptors)

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32
Q

Xylazine

Type, MOA, use

A

Alpha-2 agonist
–also has Alpha-1 selectivity
–stimulates CRTZ
– emetic more effective in cats
–CNS depression (no excitment)

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33
Q

Dexmedetomidine

Type, MOA, metabolism type

A

Alpha-2 Agonist
–More selective for Alpha-2 receptors
–Causes emesis via central Alpha-2 stimulation
–CNS depression
–Emetic effect on CRTZ
–metabolized in liver via hydroxylation; dependent on hepatic blood flow
–elimintaed in urine/feces

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34
Q

Alpha-2 Agonists Mechanisms

MOA; sedation/analgesic location of effect

A

–Dose dependent effx
–Alpha-2 receptors in CNS/peripheral tissues
* medullary dorsal motor complex in the brain
–presynaptic α2-adrenoceptors ↓ norepinephrine release
–Sedation produced through inhibition of noradrenergic neurons in locus ceruleus (upper brainstem)
–Delayed central phase
– analgesia via the stimulation of receptors in the **dorsal horn of the spinal cord **and in the brainstem

Subtypes of Alpha -2 receptors → 2a, 2b, 2c

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35
Q

Alpha - 2a efx

A

supraspinal analgesia
sympatholytic efx (adrenergic blocker)
sedation primarily in CNS

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36
Q

Alpha-2b efx

location of efx

A

Cause of initial vasoconstriction
located in spinal cord and vascular endothelium
–vascular smooth muscle of both arteries and veins.

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37
Q

Alpha-2c efx

A

responsible for mediating hypothermia

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38
Q

Alpha-2 efx with anesthesia

A

– decreases the requirements for anesthetic drugs via decrease in norepinephrine release in locus ceruleus
– analgesia via the stimulation of receptors in the dorsal horn of the spinal cord and in the brainstem

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39
Q

Neuroprotective mechanisms of Alpha-2s

what does it decrease/inhibit?

A

–2-adrenoceptor-mediated ↓ of norepinephrine or glutamate or the activation of imidazoline receptors
–inhibition of massive norepinephrine release following brain injury

high doses may worsen ischemic brain injury.

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40
Q

Alpha-2 Biphasic Cardiovascular response

A

DOSE DEPENDENT
1st: BP/SVR ↑and HR/CO ↓
2nd: Delayed central phase;↓ in arterial pressure; HR/CO remain lower than normal; SVR either stays elevated or N
–vasoconstriction =↑ arterial blood pressure → bradycardia via baroreceptor response in vascular smooth muscle arteries/veins.

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41
Q

Reflexive Bradycardia with Alpha-2s

#4

A

–central sympatholytic action of α2-agonist → vagal tone unopposed = increase in parasympathetic efferent neuronal activity
–presynaptically mediated reduction in norepinephrine located in cardiac sympathetic nerves
–CO ↓ with HR
–DOES NOT have negative inotropic efx

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42
Q

Anticholinergic efx with Alpha-2s

#3

A

– Significantly ↑ myocardial work and O2 demands
– result in large increases in arterial pressure → mean blood pressure approx. 200 mm Hg (in dogs in one study.)
–addition of glycopyrrolate to xylazine appeared detrimental to cardiovascular performance.

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43
Q

Arrhythmogenic efx of alpha-2s

#2

A

— Bradycardia may reveal foci normally inhibited by the impulses coming from SA node.
–sensitizes the heart to catecholamine-induced arrhythmias

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44
Q

Respiratory Efx of Alpha-2s

A

Minimal
Can potentiate the respiratory depression induced by opioids

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45
Q

Other efx of Alpha-2s

#4

A

–transient Hypoinsulinemia/Hyperglycemia resulting from effect on pancreatic beta-cells inhibiting insulin release
– Inhibit release of ADH @ renal tubules/collecting ducts = diuresis
–Emesis via CRTZ stimulation
–lowers plasma level of circulating catecholamines

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46
Q

Anti-emetics types

#5

A

Phenothiazine derivatives; acepromazine/chlorpromazine/prochlorperazine
Serotonin (5-HT3) Antagonists; Ondansetron/Dolasetron
Neurokinin-1 antagonist; maropitant
Prokinetic; metoclopramide
Motilin receptor agontists; Erythromycin/Azithromycin

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47
Q

Phenothiazine derivatives

what receptors does it act on?

MOA/metabolism

A

–Centrally acting
–Reduces emesis via blockade of dopamine receptor in CRTZ/emetic center
(anti-dopaminergic - D2 /anti-histaminic efx)
–produce alpha-1 antagonistic efx
–metabolized by liver

acepromazine/chlorpromazine/prochlorperazine

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48
Q

Phenothiazine derivative efx on CVS

CS x4, which receptor does it affect?

A

↑ CVP
–effx HR (brady or tachy)
–varying degrees of vasodilation/hypotension (dose dependent) via a-1 blockage

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49
Q

Phenothiazine derivative efx on liver

A

Can cause CNS signs in pts with hepatic insufficiency (ex: PSS)

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50
Q

Serotonin (5-HT3) Antagonists;

examples

Locations

A

found both peripherally;
* responsible for intestinal vagal afferent input
* many 5-HT3 receptors in the GI tract
Centrally; in the chemoreceptor trigger zone [CRTZ] and medullary vomiting center [MVC]

Ondansetron/Dolasetron

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51
Q

Serotonin (5-HT3) metabolism/excretion

A

Ondansetron; metabolized by the liver
Dolasetron; metabolized to active fraction (hydrodolasetron) and eliminated by hepatic P-450 enzymes
–ultimately eliminated in urine and bile

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52
Q

Neurokinin-1 antagonist

MOA/metabolism

A

–blocks action of substance P in CNS and @ peripheral NK-1 receptors in GI tract
–bone marrow suppression in dogs < 8wks
–undergoes extensive first-pass metabolism in the liver

maropitant

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53
Q

3

Metoclopramide

why less effective in cats?

MOA

A

–antidopaminergic (D2) activity
– ability to block 5-HT3 receptors → potent blocker of the CRTZ
–sensitizes upper GI smooth muscle to acetylcholine efx → stimulates motility of the upper GI tract w/o promoting gastric, pancreatic, or biliary secretions
–extrapyramidal/sedative efx have been seen with high doses

less effective in cats due to lower dopamine receptors

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54
Q

Metoclopramide metabolism/excretion

A

metabolized in liver
primarily eliminated in the urine as unchanged drug or metabolites

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55
Q

Motilin receptor agonists

where does it take affect?

A

–stimulates motilin receptors
–used to promote GI motility; possibly via activation of 5-HT3 receptors
–↑ lower esophageal sphincter pressure/lower bowel peristalsis

Azithromycin/Erythromycin

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56
Q

Opioids

where is the highest concentration of receptors located?

CNS locations

brain and spinal cord location

A

Act @ specific receptors in brain/spinal cord
–thalamus has highest concentration of receptors

–spinal cord locations → substantia geltinosa
(regulate information transmission from primary afferent pain sensors)

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57
Q

What parts of the brain are responsible for emotional pain response?

x4

A

–limbic system
amygdala
corpus striatum
hypothalamus

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58
Q

What do opioids block and where?

A

– opioids block substance P in dorsal horn of spinal cord

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59
Q

Opioid Receptors

A

Part of large receptor membrane group matched with G proteins
Kappa → spinal cord/peripheral tissues (k1a, k1b, k2, k3)
Mu → CNS/some periphery/GIT (m1, m2, m3)
Delta → typically associated with Mu receptors (d1, d2)

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60
Q

Opioid MOA

#3

A

–endogenous/exogenous ligands activate G proteins as second messengers → modulates adenylate cyclase activity→ alters transmembrane transport of effectors
–interfere presynaptically with release of neurotransmitters → interruption of pain messages to the brain
–do not alter the responsiveness of afferent nerve endings to noxious stimuli

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61
Q

Opioid CNS efx

#3

A

–Efx on cerebral cortex → CNS depression
–Efx on hypothalamus/indirect activation of dopaminergic receptors → excitatory behavioral activity
–Resets thermoregulatory center in brain (hypothalamus) → panting response (activel cool themselves)
OR decreased body temperature from thermoregulatory center in the hypothalamus is reset to a lower setting.

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62
Q

Opioid CVS efx

#3

A

–Hypotension 2nd to histamine release
–minimal efx on contractility
–Vagally mediated bradycardia

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63
Q

Opioid respiratory efx

#2

A

Depresses repsiratory center’s responsiveness (medulla) to CO2 levels → dose dependent
–Elevated paCO2 leads to ↓ MV from ↓RR/TV
–Bronchoconstriction may also occur → wooden chest

caution in pts with head trauma/brain dz → hypercarbia → increase in ICP

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64
Q

Opioid induced hyperalgesia

A

Worsening pain response with higher doses

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65
Q

Other Opioid efx

#2

A

GI → intial stimulation then decreases motility
Urinary →release ADH, urine retention from bladder atony

66
Q

Opioid metabolism/excretion

A

Hepatic conjugation
Urine excretion

exception is remifentanil= rapidly metabolized by nonspecific plasma esterases

67
Q

Epidural Opioid administration

A

Effective pain relief begins within approximately 30 minutes and persists for 12 to 24 hours

68
Q

Morphine

MOA/contraindications

When is this medication contraindicated?

A

–primary mu receptors, with some activity at delta and kappa receptors
–Hypotension and bronchoconstriction may occur from histamine release
–Morphine contraindicated in patients with mast cell tumors or other histamine-release abnormalities

69
Q

Methadone

MOA

which receptors does it effect?

A

–primarily µ-receptor agonist
–also noncompetitively inhibits NMDA receptors
–reduces reuptake of norepinephrine → may also contribute to its analgesic effects

70
Q

Hydromorphone

MOA

A

–primary µ receptors and some activity at delta receptors
–does not stimulate histamine release

71
Q

Remifentanil

MOA/metabolized

A

– mu-opioid agonist structurally related to fentanyl with a rapid onset of analgesic action, and has rapid recoveries
–Unlike other opioids, remifentanil is rapidly metabolized by hydrolysis (fentanyl is metabolized in liver via P-450)
– may be associated with the development of hyperalgesia

72
Q

Butorphanol

MOA

which receptors are involved?

A

mixed-acting agonist-antagonist opioid
agonist activity primarily at the kappa- and sigma-opioid receptor
–Less potential to increase ICP
– Less likely to cause respiratory depression

73
Q

Buprenorphine

MOA; metabolism; elimination

which receptor is agonized, which is antagonized?

A

–partial-agonist opioid; limited agonist activity at µ-receptors in CNS; kappa-receptor antagonist
–delayed onset of action and long-acting analgesic properties
–highly protein bound
–metabolized in the intestinal wall and liver
–eliminated by biliary excretion into the feces/urine

74
Q

Adrenergic receptors

A

Mediate SANS response
–GPCR
–Divided into Alpha and Beta
* Alpha 1, Alpha 2
* Beta 1, Beta 2, Beta 3

75
Q

Alpha-1 Receptors

Locations/Efx

Ex agonist/antagonist

A

Adrenergic Receptors → GPCR
PRO SANS
-Blood vessels → vasoconstriction
–smooth muscles → urogenital tract contraction (trigonal restriction)
– Gland secretions
– Mydriasis (a-1 radial muscle of iris)

Ex; Phenylephrine (agonist) Prazosin (antagonist)

76
Q

Alpha-2 Receptors

Locations/Efx #5

Ex; agonist/antagonist

A

Adrenergic receptors (GPCR)
–pre-snyaptic nerve endings
–Brain → ↓ sympathetic flow
–Pancreatic B cells → inhibit insulin release
–platelet aggregation
–Blood vessels → vasoconstriction

2a, 2b, 2c

Ex; Xylazine (agonist) Yohimbine (antagonist)

77
Q

Alpha-2 a/b/c

A

2a = supraspinal analgesia/sympatholytic efx/CNS sedative efx
2b = initial vasocontriction; located in spinal cord/vascular endothelium
2c = mediates hypothermia

78
Q

Beta -1 Receptors

Location/Efx #4

Agonist/Antagonist

A

1 HEART (B1)
SA node = increases rhythminicy (via ↓ action potential threshold) = ↑ HR
AV node = ↑ conduction velocity
Ventricular Myocytes = ↑ contractility
↑ SBP
Kidneys; Juxtaglomelular cells = ↑ Renin release

Ex: Dobutamine (agonist) Atenolol (antagonist)

79
Q

Beta -2 Receptors

Location/Efx #6

agonist/antagonist

A

2 LUNGS (B2)
–Bronchi = bronchodilation
–Blood vessels = vasodilation (skeletal muscle/liver)
–↓ DBP
–GIT/Bladder relaxation
–Pancreas = Glucagon secretion
–Eye = secretions

Ex; Terbutaline (selective agonist) Propanolol (antagonist)

80
Q

Beta-3

A

Adipose tissue
Bladder relaxation

81
Q

Benzodiazepines

MOA/Location/Metabolism/Excretion

efx on appetite

A

–increase affinity of GABA transmitter
–antagonist of serotonin
–acts on limbic, thalamic, and hypothalamic levels of the CNS
– Low doses stimulate appetite via binding to benzodiazepine receptors
–metabolized in the liver to active metabolites via conjugation
–excreted in the urine

82
Q

GI protectants

Proton Pump Inhibitors

MOA/Efx/Benefits

A

Inhibits Na+/K+ ATP pump activity
= controls proton deposites into gastric lumen/HCl acid secretion
–Chronic omperazole therapy used to redue canine cerebrospinal fluid production
–Beneficial for musocsal injury/ulceration/upper GI hemorrhage

Ex; omperazole/pantoprazole

83
Q

GI protectants

H2 Histageneric Antagonists

MOA/location/Examples

A

H2 blockers
–Specific antihistamines that reduce histamine action at receptors on gastric parietal cells = reduces stomach acid production

ex; famotidine/ranitidine/cimetidine

84
Q

GI protectants

Sucralfate

MOA/efx

A

Sucrose/aluminium complex
–binds to injured gastrointestinal mucosa to create physical barrier
–prevents stomach acid from reaching site of injury breakdown of mucus
– promotes HCO3 production

85
Q

GI protectants

Misoprostal

MOA/efx/indications

A

Synthetic prostaglandin E1 analogue
–improves gastric blood flow
–decreases acid production
–increases mucus production/HCO3 secretion
–promotes cell turnover
– prevents NSAID induced GI injury/ulceration

86
Q

Anti-Arrhythmic Classes

A

I: Na+ blockers; lidocaine/procainamide/mexiletine
II: Beta-blockers; propanolol/esmolol/atenolol
III: K+ Blockers; Sotalol/Amiodarone
IV: Ca++ Blockers; Diltiazem
V: Misc; Digoxin/Adenosine/Mg++

87
Q

Class Ia Anti-Arrythmics

example/MOA

A

Procainamide
–fast/powerful Na+ blockers
–prolongs the refractory times in atria and ventricles
–decreases myocardial excitability
–potent depression of automaticity and conduction velocity

SVT and/or Ventricular arrhythmias

88
Q

Ib Anti-arrythmics

example/MOA

A

Lidocaine/mexiletine
–rapid rates of attachment/dissociation to sodium channels in ventricular conducting tissue
–shortens the myocardial cell action potential
–supresses automaticity/conduction velocity in ventricles

No efx on atrial myocytes

89
Q

Class II; Beta-blockers

examples/MOA

A

Antagonizes beta-adrenergic receptors = ↓ HR/
–slow SA nodal discharge/AV node conduction
–↓ myocardial O2 demand

SVT

Ex; propanolol/esmolol/atenolol

90
Q

Class III; K+ blockers

examples/MOA

A

Prolongs refractory period/myocardial repolarization
– Sotalol; nonselective beta-blocker/selective K+ channel blocker
* negative inotropic effx
– Amiodarone; primarily K+ channel blocker
* also blocks Na+/Ca++ channels and β-adrenergic receptors

Ex; Sotalol/Amiodarone

91
Q

Calss IV: Ca++ Blockers

Examples/MOA

A

Antagonizes Ca++ channels
–inhibit influx of extracellular calcium ions into cardiac and vascular smooth muscle cells
–Lowers SA/AV node conduction

SVT/A-fib/Atrial tachyarrhythmias

Ex; Diltiazem (benzothiazepines)

92
Q

AntiArrhythmics

Class V: Misc

Examples/MOA

A

Digoxin; + inotropic efx = ↑ cardiac output;
* ↑diuresis, reduces edema secondary to a decrease in sympathetic tone
* lowers AV node conduction velocity
* prolongs effective refractory period (ERP)
* hypothyroidism prediposed to digoxin toxicity

tx; SV arrhythmias

Adenosine/MgSO4

93
Q

ACE Inhibitors

Examples/MOA

efx on BP
why is this beneficial for PLN?

A

Angiotensin Converting Enzyme Inhibitors
–Blocks conversion of angiotensin I → II
= lower arteriolar resistance; ↑ natruresis; ↓ BP/ventricular remodeling/hypertrophy
–Reduces renal intraglomerular pressure →
* inhibits angio II efferent arteriolar vasocontriction = ↓ proteinuria (beneficial fo PLN)

Adverse efx; hyperK+/hypotension

Ex; Enalapril/Benazepril

94
Q

Loop Diuretics

Examples/MOA/Uses

x3 benefits

A

Bind/Inhibit Na+/K+/Cl symporter on ALOH
Na+/Cl- STAY in tublular lumen = H2O FOLLOWS
= Diuresis (↑ Na+/K+ excretion)
–↑ Ca++ excretion via passive transport = help treat hypercalcemia
– ↓ renal vascular resistance = ↑ renal blood flow (oliguric/anuric renal dz)
–venodilating efx = ↓ pulmonary hydrostatic pressure = shifts fluid balance to systemic vasculature (CHF tx)

Adverse efx; dehydration/hypovol/azotemia/metabolic alkalosis

Furosemide/Torsemide

95
Q

Osmotic Diuretics

Examples/MOA/Uses

A

Hyperosmolarity = fluid shift from intracellular/interstitial space → intravascular space
–freely filtered by kidneys
–does not undergo reabsorption = osmotic diuresis
–Cerebral edema/anuric renal dz

Containdicated for CHF

Mannitol

96
Q

K+ sparing Diuretics

Examples/MOA/Uses

What do they antagonize?
What are they used to tx?

A

Antagonizes Aldosterone via binding @ receptor site in DCT/Collecting duct
= Na+/Ca++/H2O excretion WITHOUT K+ loss
–Hyperaldosteronism tx
–CHF tx → slows myocardial remodeling/fibrosis

Adverse efx; hypERK+

Spironolactone

97
Q

Phosphodiesterase III Inhibitor

Examples/MOA/uses

A

Inhibits PDE-III via ↑ intracelllular Ca++ sensitivity in cardiac conductile apparatus
= ↑ contractility
– + Inotropic efx
–Vasodilatory efx = ↓ pulmonary hypertension
–Slows < 3 dz progression
– DOES NOT ↑ myocaridal consumption or work
–CHF, DCM, Chronic valve Dz

Adverse efx; hypotension/plt aggregation inhibitor

Pimobendan

98
Q

Phosphodiestrerase V Inhibitor

Example/MOA/uses

A

Inhibits PDE-V
-found in smooth muscle of pulmonary vasculature
–causes vasodilation
–Inotrope and arteriolar dilator
–Tx Pul. hypertension

Sildenafil

99
Q

Parts of brain responsible for modulating emotional pain response

#4

A

limbic system
amygdala
corpus striatum
hypothalamus

100
Q

Role of Substantia Geltinosa with pain

A

Regulate information transmission from primary afferent pain sensors

101
Q

Alpha-2 analgesic efx

A

–analgesia via the stimulation of receptors in the dorsal horn of the spinal cord and in the brainstem

102
Q

What effect do opioids have on dorsal horn of spinal cord?

A

opioids block substance P in dorsal horn of spinal cord

103
Q

Propofol

Definition, MOA, adverse efx

A

Short-acting anesthetic that produces its hypnotic effect via potentiation of GABA-induced Cl- current via its interaction with the GABAA receptor
– as infusion, set be discarded every 12 hours or if contamination occurs
–myoclonus possible in umpremedicated dogs
– ↑ in context-sensitive half-time as the duration of administration increases
– causes dose-dependent vasodilation and myocardial depression resulting in hypotension

104
Q

Alfaxalone

Definition, MOA, adverse efx

A

Synthetic neuroactive steroid anesthetic that binds to the GABA receptor in CNS
– causes dose-dependent decreases in respiratory rate, minute volume, and BP
– Ataxia, muscular tremors, and opisthotonus-like posture can be observed
– cause transient increase intraocular pressure (IOP) typically self resovling after few minutes

105
Q

Ketamine

Definition, MOA

which recptors are involved?

A

Dissociative anesthetic, functioning on the NMDA, opioid, monoaminergic, and muscarinic receptors as well as voltage-gated calcium channels
– Antagonism at the NMDA receptor = dissociation @ limbic and thalamocortical systems,= not appear asleep but does not respond to external stimuli.
– sympathomimetic effects of ketamine resulted in fewer interventions for bradycardia or hypotension
– causes bronchodilation → beneficial for MV

106
Q

How is Ketamine metabolized/excreted?

A

– Dogs = Metabolized by the liver to inactive metabolites and renally excreted
– Cats = ketamine is metabolized in kidney to the active metabolite, norketamine, then excreted unchanged in the urine
– cats with renal disease → significant accumulation with prolonged anesthetic times possible

107
Q

Adverse effects of Ketamine

A

– sympathomimetic effects may lead to an increase in cerebral blood flow and intracranial pressure
– Respiratory depression has been noted with high doses
– Reports of ketamine causing acute congestive heart failure in cats with mild to moderate heart disease have been reported

108
Q

Etomidate

Definition, MOA, adverse efx

A

– Imidazole derivative that interacts with the GABA receptor to induce anesthesia
– choice for induction in patients with cardiovascular disease due to its minimal effects on cardiopulmonary variables
– not an ideal agent for maintenance of anesthesia for prolonged periods due to its adrenocortical suppression 4-6hours post injection

109
Q

Neuromuscular blocking agents

A
110
Q

inhaled β2-agonists

MOA, examples

A

Stimulation of the β2-receptor causes an increase in intracellular levels of adenylate cyclase, which decreases intracellular calcium levels and subsequently causes smooth muscle relaxation of the bronchial wall.

(albuterol, salmeterol)

111
Q

Capromorelin (Entyce)

A

ghrelin agonist
– interactions with the hypothalamus and vagus nerve
– regulate cardiac, gastric, and pancreatic function and may result in anxiety.

112
Q

Multidrug-resistant (MDR) organisms description

A

– are identified frequently from dogs and cats in veterinary ICUs with an association of isolating MDR organisms (MDROs) from patients after being hospitalized for more than 3 days in a teaching hospital
– measure of an antimicrobial agent’s decreased ability to kill or inhibit the growth of a microorganism

113
Q

MDR

Different types of resistance.

x3

A

–Intrinsic resistance is an inherent feature of a microorganism that results in lack of activity of an antimicrobial drug or class of drugs
– Circumstantial resistance is when an in vitro test predicts susceptibility, but in vivo the antimicrobial lacks clinical efficacy
– Acquired resistance can occur via many different mechanisms; exposure to prior antimicrobials in veterinary medicine

114
Q

Risk factors for multidrug-resistant organisms

A

previous antimicrobial use, admission to an ICU, infection control lapses, prolonged length of hospital stay, recent surgery or invasive procedures, mechanical ventilation, or colonization or exposure to a patient with colonization of a MDR organism.

115
Q

Methicillin-resistant staphylococcus

A

– most commonly Staphylococcus pseudintermedius
– primary mechanism of resistance is the acquisition of the mecA gene, which confers methicillin resistance
– encodes an altered penicillin-binding protein, making it resistant to all members of the β-lactam family

116
Q

MRS treatment

A

the antimicrobial typically used empirically would be vancomycin
– alternative to vancomycin for MRS in veterinary medicine is aminoglycosides
– MRS is identified that is also a vancomycin-resistant Staphylococcus sp. or oral therapy is needed, linezolid is used

117
Q

MDRO

Enterococcus

A

–Enterococcus faecalis and Enterococcus faecium
– Enterococci have a high level of intrinsic resistance to many antimicrobials, including all cephalosporins, clindamycin, and aminoglycosides at serum concentrations achievable without toxicity

118
Q

Treatment of MDR Enterococcus spp.

A

two options: (1) the combination of ampicillin and gentamicin or (2) vancomycin.

119
Q

Pseudomonas aeruginosa

A

nonfermenting Gram-negative organism found widely in the health care environment
– very high level of intrinsic resistance
– resistant to the majority of β-lactam antimicrobial with the exception of ticarcillin, piperacillin, ceftazidime, and the carbapenems

120
Q

β-Lactamase-producing gram-negative bacteria

A

– one the most frequent mechanisms of acquired resistance in Gram-negative organisms

121
Q

β-lactamase

A

an enzyme that hydrolyzes and disrupts the β-lactam ring in the β-lactam group of antimicrobials
– confers resistance to penicillins, aminopenicillins, carboxypenicillins, and narrow-spectrum cephalosporins

122
Q

Thrombolytics

Clopidogrel MOA

A

– is a thienopyridine that selectively inhibits ADP-induced platelet aggregation but has no direct effects on arachidonic acid metabolism
– requires hepatic biotransformation to produce the active metabolite.
– antiplatelet medication

123
Q

Thrombolytics

Aspirin MOA

A

– antiplatelet medication
acts on the arachidonic acid pathway and irreversibly inhibits both cyclooxygenase pathways
– decreases prostacyclin (plt adhesion) AND thromboxane (fever/pain) synthesis

124
Q

Cyclooxygenase (COX)

A

rate-limiting enzyme that converts arachidonic acid to eicosanoids

125
Q

Antifibrinolytic drugs

A

– Aminocaproic acid and tranexamic acid
– competitively inhibiting the lysine-binding sites on plasminogen, which prevents the conversion of plasminogen to plasmin in addition to direct inhibition of plasmin action

126
Q

Drug-associated platelet dysfunction: Antimicrobials

x2 examples

A

Beta-lactams: Dose- and time-dependent effects on platelet function
Cephalosporins

127
Q

Drug-associated platelet dysfunction: Antithrombotics

where does it inhibit platelets?
x3 examples

A

Heparin
Factor X inhibitors:
Rivaroxaban
Apixaban
– synergistic inhibitions of tissue factor (fIII) -mediated platelet aggregation and platelet-dependent thrombin generation occur when given with antiplatelet drugs

128
Q

Drug-associated platelet dysfunction: Selective phosphodiesterase (PDE) inhibitors:

A

Pimobendan: vitro antiplatelet effects seen at 1000x fold higher than clinically achievable concentration
Sildenafil: Potentiation of platelet inhibition with concurrent use of nitric oxide donors

129
Q

Drug-associated platelet dysfunction: Nonsteroidal Antiinflammatory Drugs

A

Conflicting data in the literature. May exacerbate platelet dysfunction in animals with increased thrombopoiesis.

130
Q

low-molecular weight heparin (LMWH)

which factors does it effect?

A

– LMWH has reduced anti-IIa activity relative to anti-Xa activity and also has better predictable pharmacokinetic properties.
– standard doses has a minimal effect on aPTT
– benefits is its reduced affinity for binding to plasma proteins or cells compared with UFH, leading to a more predictable dose response relationship and longer half-life
– 100% bioavailability after subcutaneous administration

131
Q

Target value when using UFH

A

use the aPTT, with an accepted therapeutic target range of 1.5 to 2.5 times the normal control aPTT value.

132
Q

unfractionated heparin (UFH)

A

– pharmacokinetics of UFH are quite variable and depend on the proportion of heparin molecules large enough to bind thrombin
– therapy must be monitored closely and titrated to effect to avoid under treatment or bleeding complications

133
Q

Commonly used anticoagulants

A

warfarin,
unfractionated heparin (UFH),
low-molecular weight heparin (LMWH)

134
Q

Factor Xa inhibitors

A

– anticoagulants that have been approved for use in people for the prevention of venous thromboembolism
– do not require AntiThrombin for FXa-inhibitory activity.
– Rivaroxaban (Xarelto) is a direct inhibitor of factor Xa

135
Q

Indications for thrombolytic agents

A

–acute PTE
– deep vein thrombosis (DVT), acute myocardial infarction (AMI), and acute ischemic stroke (AIS) in people

136
Q

Thrombolytic agents

Streptokinase

A

– Streptokinase is considered a first-generation thrombolytic
– readily binds circulating plasminogen, potentially inducing a systemic lytic state Streptokinase has a longer half-life compared to t-PA
– extracellular protein produced by streptococci that binds plasminogen in a 1:1 complex promoting the conversion to plasmin

137
Q

tissue‐type plasminogen activator (t‐PA)

where is it produced?

A

produced by endothelial cells and is essential to intravascular fibrinolysis
– used as Thrombolytic agent, second generation agent

138
Q

NSAIDS

What is Arachidonic acid?

What releases it and where?
What inhibits it?
what promotes it? x4

A

– released following tissue injury by phospholipase A2
– Pro inflammatory mediator in lipid plasma membrane that lead to production of Prostaglandins and Leukotrines
– Steriods INHIBIT Arachidonic acid = anti-inflammatory
– Promoted by Thrombin, Angiotensin II, epineprhine, bradykinin

139
Q

How do steriod inhalants treat asthma?

A

– by inhibiting Arachidonic acid which ultimately stops formation of LOX from turning into Leukotrienes
– Leukotrienes cause BRONCHOCONSTRICTION

140
Q

5‐lipoxygenase (LOX)

A

metabolizes arachidonic acid into various leukotrienes
–pro-inflamamtory mediators especially with allergic and autoimmune reactions

Blocked by steriods

141
Q

NSAIDS

cyclooxygenase (COX) enzymes

A

– metabolizes arachidonic acid into prostaglandins, prostayclin, and thromboxanes
– NSAIDS inhibit COX enzymes
– COX-1 COX-2 COX-3

142
Q

NSAIDS

COX-1

A

– COX-1 activity produces thromboxane A2 resulting in platelet aggregation and vasoconstriction
– produces prostaglandins generally involved in GI tract maintenance
* protect GIT mucosa from stomach acid and produce HCO3

143
Q

NSAIDS

COX-2

A

– COX-2 activity produces prostacyclin
– anticoagulant effects
– vasodilation
– plt aggregation inhibitor

144
Q

NSAIDS

Review of Prostaglandins

GI and renal benefits

A

normally produced via COX-1 activity
– involved with physiological housekeeping functions including gastroprotection via secretion of gastric mucus and production of bicarbonate,
– renal perfusion under hypotensive conditions
– vascular homeostasis via thromboxane and prostacyclin production.

145
Q

NSAIDS

Induced prostaglandins are produced by:

A

– COX-2 activity and overexpressed after tissue injury.
– involved in the production of inflammatory mediators such as endotoxins, cytokines, and growth factors responsible for sensitizing peripheral nociceptors

146
Q

NSAIDS

COX-3

where is if found?
effects of COX-3 inhibition

A

– subform of COX-1
– found in the canine and human cerebral cortex
– Inhibition of COX-3 decreases prostaglandin E2 synthesis suggesting central mechanisms of analgesia seen with acetaminophen and metamizole.

147
Q

metabolism of NSAIDs

Main enzyme and mechanisms

A

– primarily via cytochrome P-450 enzymes
– either via glucuronidation or oxidation into inactive or less active metabolites

148
Q

What is specific to Cats metablizing NSAID?

A

– Cats have deficient glucuronidation and may therefore be more susceptible to NSAID toxicity when given drugs that use this pathway for metabolism
– Therefore; acetaminophen is contraindicated in this species, and carprofen must be used carefully due to its slow elimination and longer half-life than in dogs.

149
Q

Adverse effects of NSAIDS

A

– GI signs
– GI ulceration (less common in cats)

150
Q

Upper GI adverse effects from NSAIDS

A

– NSAID induced COX-1 cytoprotective effects in the gastric mucosa results in decreased local blood flow and suppression of bicarbonate secretion and mucus production
– once damage has occurred in the GI mucosa, depression of COX-2 activity impairs tissue healing

151
Q

NSAIDS

Role of COX enzymes and prostaglandins with Renal effects

x3

A

– Both COX-1 and COX-2 are constitutively expressed in the kidneys
– Prostaglandins involved with kidney maturation in pediatric animals
– maintain renal perfusion and autoregulation, particularly in situations of hypoperfusion to the kidneys

152
Q

NSAIDS

What are the effects of PGE2 and PGI2

Prostaglandins

A

PGE2: promotes fEver, and Pain (Eww)
PGI2: Prostacyclin (cycling keeps it moving)
– promote vasodilation
– prevents platelet aggregation
– inhibition of Na+ reabsorption with a protective function of the kidneys.

ANTI-COAGULANT**

153
Q

NSAIDS

What are the effects of thromboxane A2?

A

Produced by COX-1
– modulates renin production and vasoconstriction
– promotes platelet aggregation
– results in thrombosis
– Bronchoconstriction

PRO-COAGULANT**

154
Q

NSAID Renal effects

A

– interfer with the autoregulation of renal perfusion pressure
– however not expected in normovolemic patients

155
Q

NSAID-induced lower GI toxicity

A

– not dependent on acid secretion.
– jejunal and ileal mucosal damage are mainly related to enterohepatic recycling and consequent prolonged and repeated exposure of the intestinal mucosa to the drug and its compounds.

156
Q

Hepatic effects of NSAIDS

A

increases in liver enzymes and acute liver toxicosis may be observed after the administration of NSAIDs in patients with preexisting liver disease.

157
Q

NSAIDS

Grapiprant

What receptor does it effect?
how does it prevent inflammation?

A

– Piprants are EP4 prostaglandin receptor antagonists
– EP4 receptor is involved in the PGE2-induced inflammation and sensitization of peripheral nociceptors

Galliprant

158
Q

NSAIDS

Acetaminophen (paracetamol)

Effects/MOA
Elimination

A

– analgesic and antipyretic effects but has weak antiinflammatory activity
– inhibit PGE2 synthesis in the central nervous system related to COX-3 activity
– relies on conjugation with glucuronide and sulfate by transferase enzymes cats lack glucuronidation

159
Q

How does Aspirin inhibit Platelet function?

A

Inhibits thromboxane A2 synthesis
along COX-1 pathway

160
Q

DDAVP to reduce bleeding

Where does it take effect and how?
Which pts benefit from this?

A

– can be given in animals with milder hemorrhage.
– most commonly used in bleeding patients to release von Willebrand factor and factor VIII from Weibel–Palade bodies in the endothelial cells
– enhances the density of platelet surface glycoprotein receptors, thereby increasing their adhesion potential

VTS ECC 2024 (17 decks)

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