MOA Flashcards
1
Q
Cabergoline
A
Dopamine agonist
Decreases prolactin
Causes luteolysis and decreases progesterone
Can stop lactation
2
Q
PGF2a
A
Luteolytic - causes decline in progesterone
Causes uterine contractions
Opens cervix and increases glandular secretions
(Do not give if cervix is closed)
3
Q
Oxytocin
A
Peptide hormone released by posterior pituitary
Mobilizes intracellular Ca and causes influx of Ca. (Gs GPCR)
Alters transmembrane ion currents and increases Na permeability of myometrium
Causes sustained uterine contractions
Also stimulates milk ejection and is involved in luteolysis
4
Q
Pentoxyphylline
A
Non-selective PDE inhibitor
Increases RBC deformability, reduces blood viscosity, decreases potential for PLT aggregation and clot formation
5
Q
Diphenhydramine
A
H1 receptor antagonist
6
Q
Diazoxide
A
Hyperglycemic: Inhibits insulin secretion(by opening K ATP channels which lets K leave, hyperpolarizes cell, no Ca entry which inhibits insulin), stimulates hepatic gluconeogenesis and glycogenolysis, stimulates epinephrine release, inhibits tissue use of glucose
Also has direct vasodilator effect on peripheral arterioles
7
Q
Allopurinol
A
Xanthine oxidase inhibitor
Used for acute tumor lysis syndrome (XO converts purines to uric acid)
8
Q
Vinca Alkaloids
A
Vincristine, vinblastine, vinorelbine
Binds to tubulin and prevents formation of mitotic spindle
Causes metaphase arrest
Vincristine can cause peripheral neuropathies
9
Q
Alkylating Agents
A
Cyclophosphamide, chlorambucil, lomustine(CCNU), melphalan
Bind alkyl groups to DNA creating cross links
Inhibits DNA uncoiling and replication
Toxicity: alopecia, BM,GI. Cyclophosphamide causes sterile hemorrhagic cystitis
Chlorambucil causes neurotoxicity, hepatotox with CCNU
10
Q
Platinum Agents
A
Cisplatin, carboplatinum
Bind platinum groups to DNA creating cross links
Inhibits DNA uncoiling and replication
cortical blindness (cisplatin), nephrotoxic in dogs (cisplat), fatal pulmonary edema in cats (cisplat)
11
Q
Anthracycline Antibiotics
A
Doxorubicin, mitoxantrone
Multiple MOAs, halts cell division and stimulates apoptosis
Topoisomerase II inhibition
DNA intercalation
Generation of free radicals
Doxo causes DCM after 6 doses, hemorrhagic colitis
Extravasation is bad (give dexrazoxane)
12
Q
L-asparaginase
A
Converts asparagine to aspartate and ammonia - depletes asparagine
Normal cells can synthesize asparagine but LSA cells lack asparagine synthetase
Without asparagine, protein synthesis is halted
13
Q
Antimetabolites
A
5-FU, cytosar (cytosine arabinoside), methotrexate, hydroxyurea
Analogues of normal cell metabolism compounds or nucleic acid bases
Inhibit use of cell metabolites in growth and division
Incorporated into DNA or RNA to prevent replication
5-FU cases fatal neurotoxicity in cats.
hydroxyurea specifically inhibits DNA synthesis by blocking the action of ribonucleoside diphosphate reductase
14
Q
Palladia (toceranib)
A
Tyrosine kinase inhibitor
Can cause PLN in dogs, nephrotoxicity in cats
15
Q
Metoclopramide
A
D2 antagonist: antiemetic. (central so has extrapyramidal effects)
5-HT4 agonist: prokinetic
5-HT3 antagonist: antiemetic (peripheral)
increases LES tone
16
Q
Domperidone
A
D2 antagonist. peripheral and central? antiemetic in CRTZ and increases ACh release in GI tract to promotes motility. but doesnt cross BBB…
Alpha 2 and beta 2 antagonism to GIT
minimal effects on LES
17
Q
Cisapride
A
Parasympathomimetic
5-HT4 and 5-HT2 agonist: prokinetic
5-HT3 and 5-HT1 antagonist
does not cross BBB so no extrapyramidal effects. increases LES tone.
18
Q
Ondansetron
A
5HT3 antagonist
Anti-emetic
19
Q
Erythromycin/Azythromycin
(for prokinetic effects)
A
Motilin receptor agonist
may decrease LES tone
20
Q
Ranitidine
A
H2 receptor antagonist (suppresses gastric acid)
Inhibits acetylcholinesterase in GIT (stimulates motility)
21
Q
Omeprazole
A
Protein pump inhibitor
Decreases gastric acid production by inhibiting H+/K+ ATPase in parietal cells
22
Q
Famotidine
A
H2 receptor antagonist
23
Q
Maropitant
A
NK1 receptor antagonist
Inhibits binding of substance P
24
Q
Misoprostol
A
PGE1 analog
decreases cAMP
Inhibits gastric acid secretion
Increases gastric mucus and bicarbonate
Increases turnover of mucosal cells and enhances mucosal blood flow
enhances tight junctions among epithelial cells
25
Prochlorperazine/Chlorpromazine
Anti-emetic
Dopamine antagonist
H1 antagonist
Alpha 2 antagonist
Muscarinic antagonist. also 5Ht2 antag.
26
Sucralfate
Negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcers or erosion, forms a physical barrier that restricts further caustic damage
Inhibits back diffusion of H+ ions, inactivates pepsin, absorbs bile acids
Stimulates mucosal prostaglandin and bicarbonate secretion
27
Penicillamine
Chelates copper, lead, iron, and mercury
Anti-fibrotic (inhibits collagen cross linking)
28
Colchicine
Anti-fibrotic: stimulates collagenase activity
Inhibits cell division by interfering with mitotic spindle
Inhibits synthesis and secretion of serum amyloid A
29
Urosdiol
Increases bile flow by increasing expression of membrane transporters
Suppresses absorption, synthesis, and secretion of cholesterol
Immunomodulatory (decreases NFkB, IL-1, and IL-2)
Protects hepatocytes from bile acids
Stabilizes mitochondria to prevent apoptosis and increases glutathione
30
S-Adenosyl-Methionine (SAMe)
Glutathione precursor
Essential part of:
Transmethylation (methyl donor)
Transsulfuration
Aminopropylation (thiol donor)
31
Silymarin, Silibinin (Milk Thistle)
Free radical scavenger
Inhibits lipid peroxidation and beta-glucuronidase
Reduces hepatic collagen formation and increases glutathione content
Inhibits cytotoxic effects of TNF
32
N-acetylcysteine
Glutathione precursor
Thiol donor
Sulfur donor
Free radical scavenger
(NOT a methyl donor like SAMe)
Improves hepatic blood flow via increased NO production
Mucolytic: reduces disulfide bonds in mucoproteins
33
Vitamin E
Antioxidant
Prevents action of peroxidase on cell membranes
(Competes with Vit K - do not use in coagulopathic patients)
34
Lactulose
Nonabsorbable disaccharide that gets digested to volatile FA and reduces colonic pH
Converts NH3 to NH4+ which gets trapped in the gut and excreted
Inhibits colonic bacterial production of ammonia and increases ammonia incorporation into colonic bacteria
Osmotic agent - increases colonic transit speed
35
L-Ornithine L-aspartate (LOLA)
L-ornithine is substrate of urea cycle
L-aspartate is substrate in conversion of NH3 to glutamine
May be beneficial in ammonia detox pathways
36
Cholestyramine
Binds to bile acids in GIT to prevent enterohepatic recycling
37
Benzodiazepines
Midazolam, Diazepam
Binds to GABA receptor and increases its affinity for GABA
Results in increased Cl influx and hyperpolarization of the postsynaptic cell membrane
Other possible mechanisms: antagonism of serotonin, increased release of GABA, and diminished release or turnover of Ach in the CNS
38
Phenobarbital
Barbiturate
Interacts with GABA receptor and prolongs opening of Cl channels resulting in hyperpolarization of the neuron
Also inhibits glutamate receptors and voltage-gated Ca channels. SE: hepatotoxicity, blood dyscrasia (immune mediated), superficial necrolytic dermatitis
39
Potassium Bromide
Causes hyperpolarization of the neuron via movement of bromide ions intracellularly through chloride channels
Can cause fatal pneumonitis in cats; pancreatitis in dogs
40
Zonisamide
Sulfonamide drug with multiple MOAs
Inhibition of voltage-gated Na channels
Inhibition of T-type Ca channels
Modulation of dopaminergic activity
Enhancement of GABA activity in the CNS
Inhibition of carbonic anhydrase activity
41
Levetiracetam
Binds to synaptic vesicle protein SV2A which results in decreased neurotransmitter release
42
Propofol
Potentiates effects of GABA
Decreases the rate of dissociation of GABA from its receptors
May also potentiate activity at glycine receptor and antagonize activity at NMDA receptors. Hepatic metab mostly except cats where lungs help out (although can induce oxidative heinz body anemia in cats). Reduces ICP and CMRO2 but also CePP.
43
Inhalant Anesthetics
Gaba-A agonist (maybe?)
44
Mannitol
Osmotic diuretic
Rheologic mechanism most important for reduction in ICP (immediate)
-Draws water out of other body tissues much more readily than brain
-Results in immediate plasma expansion and decreased blood viscosity -> decreased cerebral vascular resistance and transient increase in CBF
-Cerebral vasoconstriction causes CBF to return to normal
-Total cerebral blood volume is decreased leading to decreased ICP while maintaining CBF
Osmotic effect to reduce brain water is delayed 15-30 minutes
Also has free radical scavenging properties.
45
Gabapentin and Pregabalin
Bind to alpha-2-delta subunit of neuronal voltage-gated Ca channels and reduces Ca influx into neurons
Leads to inhibition of release of excitatory neurotransmitters
46
Baclofen
GABA-B agonist
Opens K channels and hyperpolarizes cells —> inhibits release of excitatory neurotransmitters in the spinal cord
47
General Opioid MOA
Opioid receptor is Gi protein
Binding results in inhibition of AC and reduced cAMP in cells
Also interacts with ion channels producing an activation of K conductance (post synap) and inhibition of Ca conductance (presynapt)
Net effects: reduced intracellular cAMP, hyperpolarization of cell, reduced neurotransmitter release.
Also inhibit GI transit by reducting ACh release via M2R centrally and peripherally
48
Butorphanol
Opioid agonist-antagonist
Kappa agonist
Mu antagonist
49
Buprenorphine
Opioid - partial mu agonist
Very high affinity for mu receptor but only produces partial response
50
Methadone
Opioid - full mu agonist
Presynaptically: closes Ca channels - reduced NT release
Postsynaptically: opens K channels - hyperpolarization
NMDA antagonist
Reduces reuptake of norepinephrine
51
Fentanyl
Opioid - full mu agonist
Short acting
80-100x more potent than morphine
52
Tramadol
Opioid - mu receptor agonist
Inhibits reuptake of norepinephrine and serotonin
NMDA antagonist
In humans, analgesia is dependent on metabolism to the M1 metabolite (O-demethyltramadol) but this does not occur in dogs. Does occur in cats
53
Etomidate
GABA-A agonist
Increases Cl conductance leading to hyperpolarization
Cardiovascularly sparing
Decreases ICP (if high) while maintaining CPP
Can cause adrenocortical suppression
Hyperosmolar - can cause hemolysis
54
Alfaxalone
GABA-A agonist
At low concentrations, modulates ion currents through GABA receptor
At high concentrations, direct GABA agonist
Dose dependent respiratory depression; also CV depression, but generally insignificant at clinical doses. decreases ICP and CBF and CMRO2
55
Flumazenil
Competitive antagonist of benzodiazepines at benzodiazepine receptors on GABA-A receptor
56
Ketamine
Dissociative anesthetic
Non-competitive NMDA antagonist - prevents glutamate from binding
Causes dissociation of the limbic and thalamocortical systems
Also acts at mu, delta, and kappa opioid receptors
Acts at monoaminergic receptors (antinociception)
Antagonistic activity at muscarinic receptors (anticholinergic effects)
Increases sympathetic tone and inhibits reuptake of norepinephrine
Increases ICP, negative inotropic effect. decreases BP but with more norepi, usually fine, unless patients exhausted catecholamine stores (eg critical illness).
57
Amantadine
NMDA antagonist
58
Atropine
Anticholinergic (parasymp antagonist)
Competitively antagonizes Ach at postganglionic muscarinic cholinergic receptors in PNS
Effects on heart mediated by pre and postsynaptic M2 receptors in SA and AV nodes and atrial myocardium —> increase in sinus rate, acceleration of AV nodal conduction, increased atrial contractility
Paradoxical worsening of bradycardia after administration due to more rapid blockade of presynaptic M1 receptors which inhibits negative feedback. Causes transient increase in Ach release and slowing of heart rate
Bronchodilation and reduced airway secretions via M2 and M3
Ophtho: Mydriasis, relaxes pupillary sphincter muscle
decreased tear production, decreased saliva production, ileus
59
Glycopyrrolate
Anticholinergic
Competitively antagonizes Ach at postganglionic muscarinic cholinergic receptors in PNS
4x more potent than atropine, slower onset of action, longer duration
60
Dantrolene
Ryanodine receptor antagonist
Peripherally acting muscle relaxant
Reduces Ca release from SR
Used for malignant hyperthermia and rhabdomyolysis
61
Methocarbamol
Centrally acting muscle relaxant
Selectively inhibits spinal and supraspinal polysynaptic reflexes through its interactions with interneurons
No direct effects on skeletal muscle
62
Succincylcholine
Depolarizing NMBA
Binds to and activate nicotinic receptor
Not susceptible to acetylcholinesterase
Ion channel remains open and repolarization does not occur
Initial uncoordinated muscle contractions and then flaccid paralysis. Can see Hyperkalemia (bc Na/Ca/K channels open for a long time - especially problematic in chronic injuries where there are many extrajunctional ACh R), increased ICP/IOP/intragastric pressure, muscle soreness
63
Pancuronium
Non-depolarizing NMBA
Also blocks cardiac muscarinic receptors —> tachycardia
64
Atracurium, Cisatracurium
Non-depolarizing NMBA; short-acting
Binds to but does not activate postsynaptic nicotinic receptor at NMJ
Degraded by Hofmann elimination and ester hydrolysis
Decomposes to laudanosine, a CNS stimulant that can cause seizures
Can cause histamine release
Can occasionally act on muscarinic or nicotinic receptors in ANS causing cardiovascular effects (tachycardia)
Cisatracurium is 4x as potent as atracurium (lower doses = less laudanosine = lower chance of CNS effects); less potential for histamine release
65
Vecuronium, Rocuronium
Non-depolarizing NMBAs
No cardiovascular effects
No histamine release
Rocuronium has faster onset of action, but less potent than vecuronium
Hepatic metabolism, bile and renal clearance
66
Edrophonium
Acetylcholinesterase inhibitor
Reversible inhibition
Brief duration of action
Not specific for NMJ - can see muscarinic signs (bradycardia, bronchospasm, meiosis, ileus, salivation) - treat with atropine or glycopyrrolate
67
Neostigmine, Pyridostigmine
Acetylcholinesterase inhibitors
Irreversible binding
Prevents breakdown of Ach (not specific for NMJ; can cause muscarinic signs)
Neostigmine works faster, pyridostigmine lasts longer
68
Local Anesthetics
Lidocaine, proparacaine, bupivacaine, mepivacaine
Inhibit Na channels and decrease AP propagation
Also inhibit K and Ca channels at level of spinal cord - may contribute to antinociception by blocking sensory pathways
Also inhibit tachykinins (e.g. substance P) and glutamate transmission leading to less depolarization of NMDA and NK receptors
69
Dexmedetomidine
Alpha 2 agonist
Presynaptic activation of alpha 2 receptor inhibits NE release
Postsynaptic activation inhibits sympathetic activity
Activation of inwardly rectifying K channels results in hyperpolarization and decreases firing rate of excitable CNS cells
Reduces Ca conductance into cells, inhibiting NT release; involves direct action on N-type voltage gated Ca channels (independent of cAMP)
Locus coeruleus has highest density of alpha 2 receptors; important for vigilance and nociceptive neurotransmission
Also works on alpha 2 receptors in spinal cord
70
Apomorphine
D2 receptor agonist in CRTZ
71
Acepromazine
Phenothiazine tranquilizer
Block postsynaptic dopamine receptors in CNS
Alpha-1 antagonist
72
Methimazole
Inhibits thyroid peroxidase
73
Potassium Iodide
Used for treatment of thyroid storm.
Oral potassium iodide prevents peripheral conversion of T4 to T3
Have to give AFTER methimazole.
Also inhibits formation/release of the hormone
74
Octreotide
Somatostatin analogue
Inhibits synthesis and secretion of insulin, glucagon, secretin, GH, gastrin, and motilin
Canine insulinoma cells have a high affinity for octreotide
75
Trilostane
Inhibitor of 3-beta hydroxysteroid dehydrogenase
Reduces synthesis of cortisol, aldosterone, and adrenal androgens
Inhibition is reversible and dose-dependent
76
Mitotane
Causes selective adrenal necrosis of zona fasciculata and reticularis
Spares zona glomerulosa (although not entirely true)
Also inhibits several enzymes required for steroid synthesis
77
Selegiline
MAO-type B inhibitor
Normally MAO-B is responsible for reuptake of dopamine
Dopamine causes suppression of ACTH
Used to treat pituitary dependent Cushing's
78
Desoxycorticosterone Pivalate (DOCP)
Long-acting mineralocorticoid
No glucocorticoid action
79
Fludricortisone
Synthetic corticosteroid
High mineralocorticoid and moderate glucocorticoid activity
Addisonian patients often still need to take prednisone since would not get enough corticosteroid activity
80
Short Acting Insulins
Regular
Lispro
Aspart
Glulisine
81
Intermediate Acting Insulins
NPH (Humulin N, Novolin N)
Vetsulin/Lente
Prozinc/PZI
82
Long Acting Insulins
Glargine/Lantus
Detemir/Levemir
Tesiba/Degludec
83
Doxapram
Respiratory stimulant
Activates peripheral chemoreceptors within carotid bodies
At high doses, stimulates medullary respiratory center
84
Theophylline
Methylxanthine
PDE III (and IV) inhibitor —> increased levels of cAMP
Smooth muscle dilation in bronchi and pulmonary vasculature
Can cause central respiratory stimulation
Stimulates diaphragmatic contractility and prevents fatigue
85
Aminophylline
Methylxanthine
PDE III (and IV) inhibitor —> increased levels of cAMP
Smooth muscle dilation in bronchi and pulmonary vasculature
Can cause central respiratory stimulation
Stimulates diaphragmatic contractility and prevents fatigue
86
Rutin
Stimulates macrophage breakdown of protein in lymph, enhancing its reabsorption
Used for chylothorax
87
Beta-lactam antibiotics
Penicillins, cephalosporins, carbapenems
Inhibit peptidoglycan synthesis thus inhibiting cell wall synthesis
Bactericidal
Time-dependent
Generally good for gram +, gram -, and anaerobes
88
Fluoroquinolones
Enrofloxacin, marbofloxacin, ciprofloxacin, pradofloxacin
Inhibits DNA gyrase and topoisomerase IV - prevents uncoiling and separation of DNA strands —> inhibits DNA replication
Bactericidal
Concentration dependent
Good for gram -, limited gram + (staph), bad for anaerobes, works well for intracellular organisms (mycoplasma)
89
Aminoglycosides
Amikacin, gentamicin, streptomycin, tobramycin
Inhibits protein synthesis by inhibiting 30S ribosomal subunit
Bactericidal
Concentration dependent
Great for gram -, some gram +, no anaerobes
90
Chloramphenicol
Inhibits protein synthesis by inhibiting 50S ribosomal subunit
Mostly bacteriostatic (can be cidal at higher concentrations)
Time dependent
Broad spectrum (gram +, gram -, anaerobes; does not get pseudomonas)
91
Clindamycin
Lincosamide
Inhibits protein synthesis by inhibiting 50S ribosomal subunit
Bacteriostatic or cidal depending on concentration
Time dependent, concentration enhanced
Best for gram + and anaerobes, toxo/neospora, some mycoplasma
92
Erythromycin, Azithromycin (ABX MOA)
Macrolides
Inhibits protein synthesis via 50S ribosomal subunit
Mostly bacteriostatic (can be cidal at high conc)
Azithro=Concentration dependent
Erythro=Time dependent, concentration enhanced.
Best for gram + and anaerobes, some mycoplasma-azithrosomegramnegtoo
93
Trimethoprim/Sulfamethoxazole
Potentiated sulfonamide
Interferes with folic acid synthesis by preventing addition of PABA into folic acid molecule; folic acid needed for synthesis of nucleic acid
Bactericidal
Time or concentration dependent (depending on pathogen)
Gram + and many gram -, some protozoa, not good for anaerobes
94
Metronidazole
Causes strand breaks in DNA - results in inhibition of protein synthesis and cell death
Bactericidal
Concentration dependent
Anaerobes and protozoa
95
Tetracyclines
Inhibits protein synthesis by inhibiting 30S ribosomal subunit
Bacteriostatic (may be cidal at high concentrations)
Time-dependent, concentration enhanced
Wide range of gram +, gram -, anaerobes, and atypical organisms (mycoplasma, chlamydiae, rickettsiae, protozoa)
96
Vancomycin
Glycopeptide
Binds to peptide precursors in cell wall and inhibits cell wall synthesis
Also affects bacterial RNA synthesis
Bactericidal (static for enterococci)
Time dependent
Gram + aer and anaer
97
Amphotericin B
Macrocyclic polyene antibiotic (antifungal medication)
Binds to ergosterol in cell membrane and increases membrane permeability (forms micelles with hydrophilic core, inserts into fungal cell membrane and creates transmembrane ion channel)
Usually fungicidal, has postfungal effect
Very broad spectrum (all common systemic mycoses)
Nephrotoxicity
98
Azole Antifungals
Inhibit lanosterol 14-alpha demethylase, a P450 enzyme responsible for ergosterol synthesis
Imidazoles (ketoconazole, miconazole, clotrimazole)
Triazoles (fluconazole, itraconazole, voriconazole, posaconazole)
May also inhibit mammalian P450 enzymes
Generally first line for most systemic mycoses (except cryptococcus)
(Usually itraconazole, unless CNS or ocular involvement, then fluconazole)
99
Mycophenolate
Inhibits purine synthesis by inhibiting inosine monophosphate dehydrogenase -->
Inhibits T/B cells and suppresses B cell formation of antibodies
SE: GI, ulcerative colitis
100
Cyclosporine
Binds to cyclophilin and inhibits calcineurin dependent T cell activation.
Blocks release of IL2 and IFNg from T helpers
SE: severe GI upset, gingival hyperplasia
101
Azathioprine
Antagonizes purine synthesis so inhibits proliferation of T and B cells.
SE: mild GI, hepatotox, myelosuppression
102
Leflunomide
Pyrimidine synthesis inhibitor so prevents DNA/RNA synth.
Inhibits T cell proliferation and autoantibody production by B cells
SE: elevated LES, myelosuppresion
103
Epinephrine
Alpha 1, alpha 2, beta 1, and beta 2 agonist (+++)
contract: +++
HR +++
CO ++
tone +++
BP +++
104
Norepinephrine
+++ alpha 1 and alpha 2
+ beta 1
contract: +
HR: variable
CO: variable
tone +++
BP +++
105
Dopamine
Endogenous precursor to norepinephrine
Also causes release of NE from sympathetic nerve terminals
Low dose (1-4 mcg/kg/min) = dopaminergic - inhibition of NE release, splanchnic vasodilation
Medium dose (5-10 mcg/kg/min) = beta 1 (++) and beta 2 (+) - increased contractility and HR
High dose (10-20 mcg/kg/min) = alpha 1 and alpha 2 (++) - increased SVR
Table results:
contract ++
HR ++
CO variable
Tone ++
BP ++
106
Dobutamine
Beta 1 agonist (++)
Also some beta 2 (+) and alpha 1 (+)
Contract ++
HR +
CO ++
tone -
BP variable
SE: Tachycardia, Arrhthymias, GI
107
Phenylephrine
Alpha 1 and 2 agonist (+++) —> increased SVR
No beta
contract: 0
HR: -
CO: -
tone: +++
BP: +++
108
Vasopressin
V1 (vascular smooth muscle): vasoconstriction (Gq pathway)-IP3 acts on IP3 sensitive Ca channel on the ER → release of Ca, forms Ca-calmodulin complex that activates the MLCK and with ATP, phosph MLC → vasoconstriction. DAG stays in the cell and stimulates the influx of Ca through a Ca channel which acts with CM but also on a JAK2 pathway to prevent smooth muscle relaxation by inhibiting MLCphosphatase. also acts on the K ATP sensitive channel, closing them so get depolarized and Ca can enter.
---causes NO release in some vascular beds (cerebral, renal, mesenteric, pulm) ---> dilation
--also platelets have V1 --> increased Ca and thrombosis
--also kidneys --> reduced blood flow to inner medulla, contraction of efferent arteriole to increased GFR
V2 (kidney): Gs --> increased cAMP. AQP2 inserted in distal nephron, water resorption
-- also stimulates release of plt from bone marrow and release of vWBF and F8 from endothelial cells
V3 (anterior pituitary): release of ACTH. Gq. also some insulin effects
TABLE:
contractility: 0
HR/CO: -
tone/BP: ++
109
Desmopressin (DDAVP)
Stimulates V2 receptors —> insertion of AQP2 channels —> water resorption
Causes release of vWF from endothelial cells and macrophages
Less vasopressor (V1) activity than arginine vasopressin
110
Ephedrine
Sympathomimetic amine
Alpha (+) and beta 1+2 agonist (+) and increases release of NE from sympathetic nerve endings
contract: +
HR: +
CO: +
tone: variable
BP: +
Bronchodilation
111
Nitroprusside
Oxidizes sulfhydrl groups in RBCs and cell membranes or reacts with Hb to produce metHb - these reactions produce NO (as well as 5 cyanide groups)
Causes vasodilation, reducing BP and afterload dilates arteries and veins, arteries more
NO-->cGMP → inhibition of Ca influx into smooth muscles → decreased Ca/calmod stimulation of MLCK → decreased contraction.
Can cause cyanide toxicity
SE: hypotension, nausea
112
Nitroglycerin
Converted to NO
Relaxes vascular smooth muscle, primarily of venous side
Leads to decreased preload
Also can have dose dependent reduction in afterload
SE: hypotension, syncope/headache
113
Isoproterenol
Beta 1 and 2 agonist (+++).
vasodilator, may augment forward flow but caution with BP
contract: +++
HR: +++
CO: +++
tone: - - -
BP: - - -
114
Amlodipine
Calcium channel blocker with preference for vascular smooth muscle (dihydropyridine)
Inhibits L-type Ca channel
Causes vasodilation
afferent art > efferent so can cause decreased GFR
SE: hypotension, lethargy, gingival hyperplasia
115
Nicardipine
Calcium channel blocker with preference for vascular smooth muscle (dihydropyridine)
Inhibits L-type Ca channel
Causes vasodilation
afferent art > efferent so can cause decreased GFR
SE: hypotension, nausea, weakness
116
Hydralazine
Direct arterial vasodilator
SSAO inhibitor - alters cellular Ca metabolism in smooth muscle. prevents oxidation of NO and inhibits IP3 induced Ca release from the SR.
SE: hypotension, weakness, leth
117
Phenoxybenzamine
Non-selective alpha antagonist
Relaxes internal urethral sphincter and lowers SVR (alpha 1)
Inhibition of presynaptic alpha 2 receptors results in more NE release - counteracts SVR effects of alpha 1 blockade.
takes a week to kick in.
118
Prazosin
Alpha 1 antagonist
relaxes the internal urethral sphincter - reduces pre and prostatic pressure but not post prostatic intraurethral pressure or penile urethra so questionable in UOs. SVR decreases with minimal effects on CO
119
Bethanechol
Parasympathomimetic
Directly stimulates muscarinic receptors
In bladder leads to contraction of detrusor muscle and expulsion of urine
Used to treat urinary retention, dysautonomia, and incontinence
120
Phenylpropanolamine
PPA, Proin
Partial alpha-1 agonist
Causes release of NE and inhibits its reuptake at synaptic junction
Causes increases urethral sphincter tone
121
Furosemide
-Inhibits Na-K-2Cl cotransporter in thick ascending limb of the loop of Henle
-When inhaled, acts at pulmonary venodilator and bronchodilator, relieves dyspnea
-mostly it is secreted by OAT in prox tubule so acidemia may prevent secretion of lasix
-Causes vasodilation and decreased peripheral vascular resistance, Lowers preload by diuresis and venodilation
-"Renal protective" - Reduces renal tubular O2 demand by preventing NA absorption
-Chronic administration →distal tubule hypertrophy and upreg of NKCC
-Adverse effects: hypoNa, hypoK, hypoCl, hypoMg, metabolic alk, hypotension and hypovolemia, ototoxicity, mucosal dehydration in trachea, panc, interferences with thyroid testing
122
Thiazides
Inhibits Na/Cl cotransporter in early DCT —> decreased Na reabsorption —> diuresis
In nephrogenic DI causes a decrease in UOP:
-Inhibits Na/Cl transport in early DCT and prevents dilution of urine in this segment - results in Na loss and ECF contraction and decreased GFR
-Over time this volume contraction leads to increased Na and water reabsorption in PCT —> less filtrate presented to distal nephron so less excreted as urine
SE: GI upset, Hypokalemia Hypochloremic alkalosis Hyponatremia Hypomagnesemia Hypercalcemia
123
Spironolactone
Potassium sparing diuretic
Aldosterone antagonist
-in principal cells of DCT/CD: Less ENaC, less ROMK, , less activity of Na/K ATPase
-in alpha intercalated cells of CD, less activity of H-ATPase
overall increased Na, Ca,and H2O excretion, less K+/H+ excretion
SE: GI disturbances, facial dermatitis in cats
124
Fenoldapam
D1 agonist
Produces more renal vasodilation and natriuresis than dopamine
Causes systemic hypotension (but maintains GFR)
125
Clopidogrel
Platelet Inhibitor
Binds to P2Y12 receptor on PLT membrane and inhibits ADP binding
Inhibits PLT activation, granule secretion, integrin activation, and thromboxane A2 production
Irreversible
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Aspirin
COX-1 inhibitor (and a little COX2)
Reduces prostaglandin and thromboxane A2 synthesis
TXA2 is a PLT agonist
Platelets unable to synthesize their own new COX
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Abciximab
Anti-platelet drug
GP IIb/IIIa receptor (alpha-IIb-beta-3) inhibitor
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Ticagrelor
Anti-platelet drug
P2Y12 receptor inhibitor (reversible)
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Warfarin
Vitamin K antagonist
Inhibits Vit K epoxide reductase therefore inhibiting the recycling of Vit K
Vit K normally carboxylates factors II, VII, IX, and X (activates them). vit K also needed for protein C and S so little bit of procoag activity.
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Unfractionated Heparin
Binds and potentiates AT: inhibits FIXa, FXa, FXIa, FXIIa, and FIIa (thrombin)
Most profound inhibitory effects on thrombin and FXa (1:1 ratio)
Also causes release of TFPI from endothelial surface (so direct anticoagulant)
(Inhibits activation of FXIII —> prevents formation of stable fibrin clot??)
Highly protein bound, less predictable bioavailability
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Low Molecular Weight Heparin
eg dalteparin/enoxaparin.
Binds and potentiates AT
Binds FIIa and FXa —> preferentially inhibits FXa (more 4:1 for X:II)
Not big enough to bind both AT & thrombin (so less inhibition of thrombin)
Since most activity against FXa, little effect on aPTT at standard doses - anti10a levels best
Bioavailability more predictable bc less protein bound
Longer half-life
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Rivaroxaban
Factor Xa inhibitor
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Tranexamic acid, Aminocaproic acid
-Synthetic lysine analogues
-Bind to plasminogen (at fibrin's lysine binding site) and prevent conversion to plasmin
-Inhibits plasmin directly at higher doses
-TXA 10x more potent than ACA and longer half life
134
Streptokinase
Nonspecific plasminogen activator
Combines with plasminogen to form complex that converts plasminogen to plasmin (binds both circulating and fibrin-bound plasminogen)
Plasmin degrades fibrin, fibrinogen, plasminogen, coag factors, and streptokinase
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Urokinase
Plasminogen activator
Binds with increased affinity to the lysine-plasminogen form (as opposed to the glutamate) which differentially accumulates within thrombi - fibrin-specific
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Tissue Plasminogen Activator (tPA)
Primary activator of plasminogen in vivo
Does not readily bind circulating plasminogen - does not induce a systemic proteolytic state at physiologic levels
Has high affinity for fibrin in thrombi- results in relatively fibrin-specific conversion of plasminogen to plasmin.
At recommended high clinical doses, a systemic proteolytic state and bleeding can occur
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Procainamide (also quinidine)
Class 1A antiarrhythmic - inhibits fast Na channels (moderate)
Moderate reduction in slope of phase 0 and amplitude of AP
Decreases conduction velocity in non-nodal tissue
Also inhibits K delayed rectifiers: prolongs effective refractory period and action potential duration
Also has some anitcholinergic effects (mild)
indications: monomorphic VT mostly, also Afib, atrial flutter, SVTs
SE: bradycardia, hypotension
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Lidocaine
Class 1B antiarrhythmic - inhibits fast Na channels (weak)
Mild reduction in slope of phase 0 and amplitude of AP
Decreases conduction velocity in non-nodal tissue
Decreases effective refractory period and action potential duration
Local anesthetic: inhibits Na channels and decreases AP propagation
Systemic analgesic mechanisms not well understood, likely many including action at ion channels (Na, Ca, K) and NMDA receptors
Inhibits ROS formation and lipid peroxidation
enhanced activity with tachycardia, acidosis, hyperkalemia, and ischemic/diseased tissue
SE: GI/seizures
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Mexiletine
Class 1B antiarrhythmic - inhibits fast Na channels (weak)
Mild reduction in slope of phase 0 and amplitude of AP
Decreases conduction velocity in non-nodal tissue
Decreases effective refractory period and action potential duration
indication: ventric arrhytm
SE: nausea, vomiting, ataxia
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Flecainide, Propafenone
Class 1C Antiarrhythmics
Inhibit fast Na channels (strong)
Large reduction in slope of phase 0 and amplitude of AP
Decreases conduction velocity in non-nodal tissue
No change in effective refractory period or action potential duration
indication: ventric arrhythm, SVT, A-fib
SE: arrhythmias (ventricular tachycardia - induces moreso than other agents in this class),
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Propranolol
Beta blocker, non-selective (Class II antiarrhythmic)
Inhibits funny current (Na) and L-type Ca channels.
Decreases sinus rate and contractility, depresses conduction through AV node (specifically, by blocking B1, prevents phosphorylation of L-type Ca channels and phospholamban so SERCA inhibited)
Decreases myocardial oxygen demand
Can inhibit conversion of T4 to T3 (useful in thyroid storm)
High first-pass effect (IV dosages ~10% of oral dose)
indications: SVT (not as good as CCB), inappropriate sinus tach (slows SA), V-tach secondary to increased symp tone. beta agonist toxicity, thyroid storm.
Dont give with SA dysfn (block/arrest), AV node conduction disturbance, pulm dz, CHF, systolic dysfn
SE: bradycardia, bronchoconstriction
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Atenolol/Esmolol
same as propranolol
Beta-blocker, beta-1 selective (Class II antiarrhythmic)
Decreased sinus rate, slowed AV conduction
Decreases myocardial oxygen demand
esmolol super short acting.
esmolol: SVT --> SE RTA, metabolic acidosis
atenolol: SVT, pulm stenosis --> SE fatigue
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Sotalol
Class III antiarrhythmic - K channel blocker
Blocks K channels responsible for phase 3 repolarization
Causes increase in action potential duration and effective refractory period so predisposes to early after depolarization
Increases Q-T interval
works best at low HR
used for SV and ventricular arrhythmias esp ARVC
Also has class II activity (beta-blocker, nonselective)
144
Amiodarone
Class III antiarrhythmic - K channel blocker
Blocks K channels responsible for phase 3 repolarization
Causes increase in action potential duration and effective refractory period
Increases Q-T interval
Also has properties of Class I, II, and IV - less arrhythmogenic than sotalol and decreased early after depolarization risk
indications:Unstable V-tach, A fib, V fib.
SE: interstitial lung disease/hypersensitivity pneumonitis, peripheral neuropathy
145
Diltiazem
Class IV antiarrhythmic - Ca channel blocker
Blocks L-type Ca channels
Nondihydropyridine - acts primarily on nodal cells
Slows AV node conduction, prolongs rise and repolarization of AP, and prolongs effective refractory period, prolongs PR interval. may speed myocardial relaxation and dilate coronary arteries so improve diastolic fn by improving coronary perfusion
-slows ventric rate to atrial tachyarrhythmias and prolongs AV node so tachyarrhythmia can be terminated
indication: SVT (including a-fib, a flutter)
SE: hypotension, bradycardia, GI signs
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Verapamil
Class IV antiarrhythmic - Ca channel blocker
Blocks L-type Ca channels
Nondihydropyridine - acts primarily on nodal cells
Slows AV node conduction, prolongs effective refractory period, prolongs PR interval, negative inotrope
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Digoxin
Inhibits Na/K ATPase
Leads to increased intracellular Na —> inhibits Na/Ca exchanger —> less Ca pumped out of cells —> increased intracellular [Ca] —> positive inotropy
Also increases vagal tone to heart —> reduction in SA firing rate (decreased HR) and decreased conduction velocity through AV node
Hypokalemia can cause digoxin toxicity because K competes with digoxin for binding
indication: afib
SE: Arrhythmias, GI, CNS
148
Pimobendan
PDE3 inhibitor, inodilator
Sensitizes troponin C to calcium —> increased contractility
also PDE3 inhibition —> increased cAMP—> more pKA, and thus: (1) phosphorylation of phospholamban --> more SERCA reuptake of Ca++, (2) more phosphorylation of L-type Ca channels --> more Ca entry --> increased contractility. also get veno/arterial vasodilation.
Does NOT increase intracellular Ca concentration
SE: GI upset, may cause arrhythmias
149
Sildenafil
PDE5 inhibitor
Inhibits the breakdown of cGMP in pulmonary vasculature
Increased cGMP results in NO mediated vasodilation in pulmonary vasculature
150
Enalapril
ACE Inhibitor
Prevents conversion of Ang I to Ang II —> reduced aldosterone release, reduced peripheral vasoconstriction, reduced plasma volume.
also causes an increase in bradykinin → arterial and venous vasodilation.
151
Benazepril
ACE Inhibitor
Prevents conversion of Ang I to Ang II —> reduced aldosterone release, reduced peripheral vasoconstriction, reduced plasma volume
also causes an increase in bradykinin → arterial and venous vasodilation.
152
Telmisartan
Angiotensin II Receptor Blocker
Reduces aldosterone release, peripheral vasodilation (arterial and venous), and decreases plasma volume via excretion of Na
SE: GI upset, hypotension
153
Algepristone
Progesterone receptor antagonist
Converts closed to open cervix
Results in expulsion of material w/in 24hours
Not available in US
154
Latanoprost
Synthetic PG analog
increased aqueous outflow via uveoscleral outflow, causes miosis to allow more outflow of the normal iridocorneal angle
Do not use if anterior lens lux
Can cause uveitis
155
Dorzolamide
Carbonic anhydrase inhibitor
Decreases production of aqueous humor
156
Phenylephrine (ophtho)
Sympathomimetic
Selectively binds alpha 1 receptors leading to vessel constriction (hence why we use for hyphema)
157
Tacrolimus
inhibits both T-lymphocyte signal transduction and IL-2 transcription
158
Tropicamide
parasympathetic antagonist, allows sympathetic actions to dominate
acts on the pupillary sphincter muscle to cause its relaxation and thus dilation
Short acting
159
Hypertonic saline
-hyperosmotic resuscitation fluid. allows us to use a smaller volume of fluid to achieve a similar increase in pressure by drawing volume from their interstitial space rather than adding additional intravascular volume (3-4x increase in blood volume compared to the volume administered).
-may help reduce any cerebral edema
-improves CBF by dehydrating cerebrovascular endothelial cells and increasing vessel diameter
-decreases brain excitotoxicty by promoting reuptake of glutamate into intracellular space, and reducing adhesion of PMN cells to microvasculature, modulating the inflammatory response.
improves the rheology of circulating blood
-may have positive effects on myocardial function.
-Caution with hyponatremic patients. Can also aggravate pulmonary edema/contusions because of rapid volume expansion
-May be superior to mannitol in reducing (and sustaining it) ICP and improving CCP
160
Prednisone
-decreases phagocytosis of RBC (in IMHA)
-inhibits complement
-decreases cytokines (esp proinflam production via inhibition of NFkB)
-decrease circulating level of T-lymphs
-down regs expression of Fc receptors on macs
161
Mirtazapine
TCA that blocks presynaptic A2R, which blocks the normal feedback loop and results in increased norepi.
Also antagonizes: 5HT2, 5HT3, H1.
Can cause agitation, orthostatic hypotension in ppl, hyperactivity, mydriasis.
162
Capromorelin
Ghrelin R agonist, stimulates GH release and therefore IGF1 release.
SE: V/D, hypersalivation, nausea, hypotension
163
Cyproheptadine
serotonin R antagonist (5Ht2) and H1 R antagonist
appetite stimulant
may cause vocalization, aggression. also inhibits feline airways smooth muscle contraction
164
Terbutaline
beta-2 adrenergic receptor agonist
increases cAMP in bronchioles --> activating protein kinase A, inactivation of myosin light-chain kinase, activation of myosin light-chain phosphatase, and relaxing smooth muscle in the bronchiole.
may increase mucociliary clearance and decreased release of inflam mediators from mast cells
165
Milrinone
PDE3 inhibitor - prevents cAMP breakdown
↑ cAMP - ↑Ca++
↑ contractility
↑ CO
↑ SV
↑ Heart rate
↑ Ejection fraction
↓ preload & ↓ afterload
PDE3-i: cardiac inotropy, lusitropy, and peripheral vasodilatation
indication:CHF
SE: Ventricular arrhythmias Bronchospasm Hypokalemia
166
hIVIG
-binds Fc R on mononuclear cells preventing destruction of plts by inhibiting phagocytosis
-binds pathogenic AutoAB
-decreases cytokine release
-inhibits C3/C4 of complement
-inhibits Fas-Fas binding so get less apoptosis
SE: Anaphylaxis, fever, risk of thromboembolic events (increases conc of circulating thrombin/antithrombin complexes, possibly increases plt activation/number), renal failure, hypotension, fluid overload
