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Clin Pharm > Exam 3 > Flashcards

Exam 3 Flashcards

1
Q

Mitosis; How long? Drugs that Target

A

o 1-7hrs
o Small % of cell cycle

Drugs
* Vinca alkaloids
* Taxols

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2
Q

G1 - 1st Gap Phase; What happens? Drugs that Target

A

o 7-170hrs
o RNA transcription
o Protein synthesis

Drugs
* L-Aspariginase (Elspar)

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3
Q

S-Phase; What happens? Drugs that Target

A

o 8-30hrs
o DNA synthesis in preparation for chromosomal duplication
o High metabolic rate

o High energy requirements

o Neoplastic cells have large nuclei

Drugs
* Antimetabolites

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4
Q

G2 - 2nd Gap Phase; What happens? Drugs that Target

A

o 1-4hrs
o pause prior to mitosis
o “checklist”
Drugs
* none

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5
Q

G0; What happens? Cells Involved

A

o Cells that are not actively cycling (replicating)
o Neurons, muscle cells do not re-enter cell cycle
o Hepatocytes normally do not re-enter cell cycle after maturity, but can

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6
Q

Fraction Cell Kill

A

o Chemo only kills fraction of cells not number of cells
o Very hard to completely eliminate (fraction of a fraction of a fraction)

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7
Q

Reasons for Chemo Failure

A

Dose limited by toxicity to patient

Drug resistance
* Failure to reach target
* Inactivation of drug
* Altered target
* Failure to undergo apoptosis

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8
Q

Response to Chemo

A

Complete
* Resolution of clinically apparent disease for at least 1mo

Partial
* Reduction of measurable tumor dimensions by at least 50% for 1 mo

Stable
* No change
* OR
* < 50% reduction in tumor dimensions

Progressive
* Growth of lesion
* OR
* appearance of new lesions

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9
Q

Resistance Criteria Based on 1 Dimension

A

Complete response:
o tumor no longer detectable,

Partial response:
o greater than 30% decrease in longest dimension of all target lesions

Stable disease:
o less than 30% decrease in the longest dimension of all target lesions, or less than 20% of tumor growth.

Progressive disease:
o greater than 20% increase in longest dimension was observed.

Biological response
o complete responders + Partial response + Stable disease

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10
Q

Chemo Dosing Based on Body Surface Area Vs Weight

A

Body Surface Area correlates w/
* Cardiac output

* Glomerular filtration rate

* Basal metabolic rate

Weight
* better for bone marrow stem cell turnover

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11
Q

Common Toxicities from Chemo Drugs

A

o BAGI

Bone marrow
* RBCs ->
* Neutrophils ->
* platelets

Alopecia
* Less common

GI
* Anorexia, nausea, V/D
* Premed w/ cisplatin to avoid nausea
* Lomustine at bed to allow sleep
* Doxorubicin for colitis associated nausea

Infertility
* Congenital malformations

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12
Q

Chemo Dosing & “cure” rate

A

o 20% dose reduction -> 50% reduction in cure rate

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13
Q

Chemo Safety Considerations

A

o Pregnant women should avoid
o Avoid contact w/ urine & feces 3 days post chemo
o PPE when prepping

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14
Q

Alkylating Agents for Chemo; MOA, Drugs, Use

A

MOA
* Interfere w/ DNA replication
* Form cross-bridges
* Mispairing

Drugs
* Cyclophosphamide
* Lomustine (can penetrate CNS)
* Chlorambucil
* Melphalan

Use
* Part of lymphoma treatment
* Mast cell tumors (lomustine)
* Histiocytic sarcoma (lomustine)
* Metronomic chemo

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15
Q

Cyclophosphamide, Lomustine, Chlorambucil Toxicities

A

Cyclophosphamide Toxicity
* BAG (worst at 7-14d)
* Sterile hemorrhagic cystitis

Lomustine Toxicity
* BAG
* Chronic neutropenia or thrombocytopenia
* Long-term hepatic, renal, & lung tox

Chlorambucil Toxicity
* BAG
* Used for pts that don’t tolerate Cyclophosphamide
* Rare animal still develops GI signs

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16
Q

Mitotic Inhibitors; Where from? MOA, Drugs, Use

A

o Initially from nature

MOA
* Bind microtubules ->
* interfere w/ cell division by interrupting the mitotic spindle

Drugs
* Vinca alkaloids (tubules don’t form): Vincristine (Oncovin®)
or Vinblastine
* Taxanes (tubules don’t break down): Paclitaxel

Use
* Component of lymphoma protocols (Vincristine)
* Vincristine alone: TVT

* Vinblastine-canine mast cell tumor, lymphoma
* Vinorelbine- concentrates in lung
* Injectable only

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17
Q

Vinca Alkaloids & Paclitaxel Toxicity

A

Vinca Alkaloids Toxicity
* BAG
* Peripheral neuropathy
* Dose must be reduced in MDR1 mutants

Paclitaxel Toxicity
* BAG

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18
Q

Antibiotics for Cancer; MOA, Drugs, Use

A

MOA
* Most from plants
* Many
* Interfere w/ DNA & RNA synthesis
* Intercalation into DNA
* Inhibition of topoisomerase

Drugs
* Doxorubicin (Adriamycin®)
* Mitoxantrone

* Bleomycin

Use
* Doxorubicin has high activity against a variety of tumors
* Newer analogues (Mitoxantrone) with less cardiotoxicity don’t seem to have same efficacy as doxorubicin
* Bleomycin is used for electrochemotherapy

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19
Q

Antibiotics for Cancer; Toxicity, Specific tox for Doxorubicin

A
  • BAG
  • Colitis

Doxorubicin
* Cumulative cardiac tox
* Possible renal damage in cats
* Severe tissue reaction if extravasated
* MDR1 substrate

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20
Q

Platinum Compounds; MOA, Drugs, Use

A

MOA
* Lab created
* Intra-strand cross-link DNA ->
* Interferes w/ RNA synthesis & DNA replication

Drugs
* Cisplatin
* Carboplatin

Use
* Osteosarcoma (Cisplatin is agent of choice but replaced by Carboplatin due decreased)
* Carcinomas- anal sac tumors, squamous cell carcinomas, nasal carcinomas
* Intralesional in equine sarcoids

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21
Q

Platinum Compounds; Toxicity, Specific Tox for Cisplatin

A
  • BAG
  • Carboplatin much safer in cats than Cisplatin

Cisplatin Toxicity
* Emetogenic
* Nephrotoxic
* Ototoxic
* Fatal pulmonary edema in cats

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22
Q

Antimetabolites for Cancer; MOA, Drugs, Use

A

MOA
* Man made
* Interfere with purine and pyrimidine synthesis and incorporation into DNA

Drugs & Use
* Methotrexate - older UW-Madison protocol for lymphoma
* 5-fluorouracil – carcinomas
* Azathioprine – immune mediated dz
* Cytosine arabinoside - Canine non-infectious encephalitis, Acute leukemia, Lymphoma in horses

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23
Q

Antimetabolites for Cancer; Specific Drug Toxicities

A

Methotrexate
* BAG
* Drug interactions due to protein bound

5-fluorouacil
* BAG
* Central neurotoxicity

Azathioprine
* BAG
* Myelosuppression in cats

Cytosine arabinoside
* BAG

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24
Q

L-asparaginase Enzyme; MOA, Toxicity, Use

A

MOA
* Inhibits protein synthesis

Toxicity
* Allergic reactions
* Pancreatitis
* Vomiting

Use
* Lymphoma
* Tumors in CNS
* NO IV

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25
Q

NSAIDs for Cancer; MOA, Drugs, Toxicity, Use

A

MOA
* COX-2 overexpressed in many tumors
* Enhance apoptosis
* Decrease tumor invasiveness

* Block angiogenesis

* Increase immune response by suppressing T-regulatory cells

Drugs
* Piroxicam

Toxicity
* GI ulceration (can add misoprostol)
* Renal (keep patients hydrated)

* Platelet dysfunction, bleeding 


Use
* Transitional cell carcinoma
* Palliation of other tumors w/ metronomic chemotherapy

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26
Q

Tyrosine Kinase Inhibitors; MOA, Drugs, Adverse Effects, Uses

A

MOA
* Inhibit cell signaling

Drugs
* Toceranib Phosphate
* Masitinib (unavailable)

Adverse Effects
* Neutropenia
* GI ulceration (avoid NSAIDs)
* Protein-losing nephropathy

* Vasculitis

Uses
* Mast Cell tumors
* Neuroendocrine tumors

* Anything for which we have no treatment

27
Q

Canine Melenoma Vx; MOA, Drugs, Adverse Effects, Uses

A

MOA
* DNA Vx ->
* Human tyrosinase taken up & processed by host cells ->
* Immune response triggered against tyrosinase on melanoma cells

Drug
* Oncept

Use
* Stage II or III melanoma in conjunction with standard tx for local disease

Adverse Effects
* Injection site pain

* Fever

* Hypersensitivity (rare)
* Localized vitiligo

28
Q

Metronomic Chemo

A

o Low doses of a chemotherapy drug daily

o Tends to be alkylating agents because they can be given orally
o May have antiangiogenic effects
o May positively affect immune cells

29
Q

Managing Adverse Effects of Chemo

A

o Maropitant for nausea
o Metronidazole for bacterial overgrowth Ds
o Morphine for pain
o Metamucil in diet to help w/ Ds
o Famotidine & Omeprazol to prevent ulcers in mast cell patients

30
Q

Seizures; Most common cause, Pathophysiology, When to Treat

A

Most common Cause
* Idiopathic/genetic epilepsy

Pathophysiology
* Excesive hypersynchronous electrical activity in the thalamocortex -> sudden transient event
* Glutamate depolarizes -> excitation
* GABA hyperpolarizes -> inhibition

When to Treat
* >2 seizures in 6 months
* cluster seizures
* status epilepticus
* known structural brain dz
* prolonged/severe post-ictal period
* consider QOL of patient & owner

31
Q

Phenobarbitol; MOA, Pros, Cons

A

MOA
* Bonds GABA receptor ->
* Hyperpolarization / inhibition

Pros
* Best efficacy
* Works in MANY species
* Inexpensive
* High bioavailability

Cons
* hepatic metabolism
* Q12 timing matters
* Takes 2wks to reach steady state
* Sedation
* Ataxia
* PU/PD
* Over time need high & higher dose -> Hepatotoxicity
* Withdrawal seizures
* MANY side effects

32
Q

Potassium Bromide; MOA, Pros, Cons

A

MOA
* Mimics Cl ->
* Hyperpolarizes / inhibits

Pros
* Good efficacy
* Inexpensive
* SID dosing

Cons
* Need to monitor salt intake
* Very slow clearance
* Renal excretion
* Contraindicated in cats
* Sedation
* Ataxia
* PU/PD
* Polyphagia
* OTHER

33
Q

Levetiracetam (Keppra); MOA, Pros, Cons

A

MOA
* Binds synaptic vesicle protein ->
* Prevent neurotransmitter release

Pros
* Rapid oral absorption
* Little hepatic metabolism
* Fewer side effects

Cons
* Should use w/ other drugs
* Variable efficacy & tolerance
* Sedation
* Ataxia
* Behavior changes (aggression)

34
Q

Zonisamide; MOA, Pros, Cons

A

MOA
* Blocks voltage gated Na channels ->
* Hyperpolarizes

Pros
* Few

Cons
* Should use w/ other drugs
* Variable efficacy & tolerance
* Hepatic metabolism
* Sedation
* Ataxia
* VERY MANY
* Don’t use

35
Q

Method for Using Multiple Seizure Drugs

A

o Start with 1st line drug

o Slowly titrate to effect

o Once maxed out, THEN reach for 2nd drug
o Once maxed out, THEN reach for 3rd, etc
o If >1 anticonvulsant, consider referral
o Make sure to look up drug interactions

36
Q

Treating Seizures in Emergency; Drugs, MOA, Things to know, Adverse Effects

A

Benzodiazepines – Diazepam or Midazolam

MOA
* Binds to GABA receptor

Things to know
* Binds to plastic
* Light sensitive
* Intranasal faster than IV
* Rapid distribution to CNS
* Metabolized by liver
* Short half life -> need frequent bolus or CRI

Adverse Effects
* Sedation
* Paradoxical excitation (rare)

37
Q

Drugs to Use at Home in Emergency Seizure

A
  • Rectal diazepam
  • Intranasal midazolam
38
Q

Buspirone; MOA, Use Adverse Effects

A

MOA
* Partial serotonin agoinist

Use
* Stress-related urine marking in cats
* Generalized anxiety

Adverse Effects
* Increased affection
* +/- aggression
* hypotension when on diuretics

39
Q

Trazadone; MOA, Use Adverse Effects

A

MOA
* Serotonin antagonist and reuptake inhibitor

Use
* Anxiety/phobias
* Facilitate post-op confinement in dogs
* Facilitate transport & exam anxiety in cats
* Need less propofol
* Calming to horses

Adverse Effects
* Sedation
* Ataxia

* GI effects (nausea, V+/D+)
* Disinhibition (aggression, tachycardia, anxiety)
* Priapism
* Pupil dilation (careful w/ glaucoma)
* Can cause serotonin syndrome when given w/ other drugs

40
Q

Alprazolam; MOA, Use Adverse Effects

A

MOA
* Benzodiazepine -> GABA agonist

Use
* Acute anxiety induced by loud noise stimuli
* Preferred for storms, fireworks

* Fast acting; given 30-60min prior to trigger

Adverse Effects
* Don’t use w/ carbonic anhydrase inhibitors
* Antacids reduce PO absorption
* Sedation
* Increased appetite
* Decreased learning
* Paradoxical excitement

41
Q

Dexmedetomidine; MOA, Use Adverse Effects, Similar Drugs

A

MOA
* Oromucosal gel
* Alpha-2 agonist
* 30-60 mins prior to stimuli

Use
* Noise phobia

Adverse Effects
* GI
* Periorbital edema
* Sedation
* Bradycardia

Similar
* Clonidine off-label

42
Q

Clomipramine; MOA, Use Adverse Effects

A

MOA
* Blocks pumps involved in reuptake of serotonin (5-HT) and norepinephrine (NE) ->
* Increase Conc of 5-HT & NE in synapse

Use
* Separation anxiety in dogs
* Steryotopies
* Noise phobia
* Urine spraying in cats
* Feather picking in birds

Adverse Effects
* decreased PO bioavailability (improved when given with food )
* Urine/fecal retention
* Cats more sensitive to adverse effects
* Sedation 

* GI signs
* Increased Liver values 

* Anticholinergic effects (dry mouth, tachycardia, etc) 

* Testicular hypoplasia risk in breeding dogs (at high doses) 

* Can decrease total and free T4

* Overdose: mydriasis, seizures, arrhythmias, death 

* Metabolized by Cyp450

43
Q

Fluoxetine; MOA, Use Adverse Effects

A

MOA
* Blocks pumps involved in reuptake of serotonin (5-HT) ->
* Increase Conc of 5-HT in synapse

Use
* Separation anxiety on dogs (licensed)
* Aggression in dogs & cats
* Compulsive disorders in dogs & cats
* Inappropriate urination in dogs & cats
* Overgrooming in cats
* Movement disorders (Scotties)

Adverse Effects
* Lethargy 

* GI signs
* Restlessness/anxiety 

* Tremors (+/- seizures?) 

* Panting, hypersalivation 

* Behavior changes (esp cats) 

* increased blood glucose (caution in diabetes) 

* MANY drug interactions

44
Q

Selegiline MOA, Use Adverse Effects

A

MOA
* Selegiline inhibits MAO-B ->
* Inhibits dopamine reuptake & stimulates dopamine production

* Dopamine breakdown results in free radicals ->
* Selegiline reduces breakdown & free radicals

Use
* Canine cognitive dysfunction (licensed)
* Hyperadrenocorticism
* Chronic anxiety
* Social/noise phobia
* Feline cognitive dysfuntion

Adverse Effects
* Aggression
* GI signs
* Restlessness/disorientation
* Repetitive movements, tremors
* Lethargy

* Salivation

* Deafness

* Pruritus
* MANY drug interactions

45
Q

Serotonine Syndrome

A

o Excessive serotonin results in ->
o Hypertension

o Tremors/Seizures

o Ataxia

o Blindness, mydriasis

o Hyperesthesia (nonspecific vs abdominal)
o GI signs
o Hyperthermia

o Coma, death

46
Q

Urinary Retention; Causes, Drugs to relax sphincter, drugs for detrusor contraction

A

Causes
* UMN bladder (spinal cord injury)
* Obstruction (stones, flutd, etc)

Drugs to relax sphincter
* Prazosin/Tamsulosin preferred (selective a-antagonists)
* Acepromazine (non-selective)
* Diazepam

Drugs for Detrusor Contraction
* Bethanechol (muscarinic agonist)

47
Q

Urinary Incontinence; Causes, Drugs to constrict sphincter, drugs for detrusor relaxation

A

Causes
* LMN bladder (spinal cord or nerve injury)
* Urethal sphincter mechanism incompetence

Drugs to Constrict Sphincter
* Phenylpropanolamine (a-agonist)
* Estrogens (increase sensitivity of alpha receptors)

Drugs to Relax Detrusor
* Propantheline (muscarinic antagonist)

48
Q

Pyrimethamine; MOA, Use, Adverse Effects

A

MOA
* Inhibits dihydrofolate reductases ->
* Interferes w/ folic acid synthesis necessary fro DNA & RNA synthesis

Use
* Toxo in dogs & cats
* Neospora in dogs
* EPM in horses

Adverse Effects
* Bone marrow suppression

49
Q

Amprolium; MOA, Use, Adverse Effects

A

MOA
* Analog of thiamine ->
* Competes w/ thiamine uptake in protozoal organisms

Use
* Preventative for coccidian
* Used in drinking water for poultry & cows

Adverse Effects
* Thiamine deficiency ->
* Polioencephalomalacia or polyneuritis

50
Q

Clindamycin; MOA, Use, Adverse Effects

A

MOA
* Long‐term exposure to low concentrations of clindamycin reduces level of replication of T. gondii
* Affects the protein synthesis of free parasites
* Impairs the ability of tachyzoites to infect host cells

Use
* Treatment of choice for toxo

Adverse Effects
* Unexplained death in cats w/ pulmonary toxo
* Must use higher does than for anaerobic infections

51
Q

Metronidazole; MOA, Use, Adverse Effects

A

MOA
* Intermediate metabolites affect DNA

* Alter essential metabolic pathways critical for protozoa survival

Use
* first‐line agent for treating giardiasis
* Effective against trichomonas (banned in cows)

Adverse Effects
* Dose-dependent vestibular toxicity in cats

52
Q

Ponazuril & Diclazuril; MOA, Use, Adverse Effects

A

MOA
* May act on the apicoplast of protozoal organisms

Use
* FDA approved for EPM in horses (need longer than stated)

Adverse Effects
* Blisters on nose & mouth (uncommon)

53
Q

Benzimidazoles; Drugs, MOA, Use, Adverse Effects

A

Drugs
* Albendazole
* Fenbendazole
* thiabendazole (ineffective against cestodes and trematodes) 

* febantel (pro‐drug of fenbendazole) 


MOA
* Binds parasite free beta-tubulin ->
* Inhibits cell division, motility, transport
* Also decreases energy production

Use
* Hookworms
* Whipworms
* Tapeworms
* Giardia
* Fungi
* Mites
* Large & small strongyles
* pinworms
Adverse Effects
* Very safe
* All may cause teratogenic effects (no pregnant animals!)
* Albendazole may cause:
* weightloss, neutropenia, mental dullness in cats
* bone marrow suppression & liver tox in dogs

54
Q

Levamisole; MOA, Use, Adverse Effects

A

MOA
* Agonist at nicotinic acetylcholine receptors on nematode muscle cells ->
* spastic paralysis

Use
* GI & lung NEMATODES

Adverse Effects
* MOST toxic antithelmintic
* Muscarinic & nicotinic effects
* No antidote
* “SLUD”,
* respiratory distress, asphyxia
* CNS depression
* bradycardia,

55
Q

Pyrantel & Morantel; MOA, Use, Adverse Effects

A

MOA
* Agonist at nicotinic acetylcholine receptors on nematode muscle cells ->
* spastic paralysis

Use
* GI nematodes
* Tapeworms in horses (at high dose)

Adverse Effects
* VERY safe
* Not recommended to use concurrently with other cholinergic agonists (levamisole, others) or antagonists (piperazine, others)

56
Q

Piperazine; MOA, Use, Adverse Effects

A

MOA
* GABA agonist
* Cholinergic antagonist ->
* Flaccid paralysis in some nematodes

Use
* Ascarids
* Used to be used for heartworm preventative

Adverse Effects
* VERY safe
* CNS depression

57
Q

Melarsomine; MOA, Use, Adverse Effects, Antidote

A

MOA
* May affect glycolysis

Use
* Adult & 4-mo old heartworms
* Regimen of 2 injections + 2 injections 4 months later

Adverse Effects
* Very low margin of safety
* Liver toxicity
* Nephrotoxicity
* Thromboembolic pneumonia
* Contraindicated in vena caval syndrome
* Not indicated for cats

Antidote
* Dimercapol

58
Q

Emodepside; MOA, Use, Adverse Effects

A

MOA
* Binds to latrophilin like receptor->
* releases an inhibitory neuropeptide (GABA) ->
* flaccid paralysis

Use
* Broad nematodal activity
* Tapeworms
* Spot-on for cats
* PO for dogs

Adverse Effects
* VERY safe
* Less safe for MDR1 mutants

59
Q

Praziquantel & Epsiprantel; MOA, Use, Adverse Effects

A

MOA
* Interfere w/ Ca homeostasis ->
* Damage tegument
* Cause muscular contraction & paralysis

Use
* Praziquantel – drug of choice for E. granulosus (can use in ag)
* Epsiprantel – tapeworms in dogs & cats

Adverse Effects
* Vomiting w/ high doses

60
Q

Clorsulon; MOA, Use, Adverse Effects

A

MOA
* disrupts glycolysis after ingested by fluke

Use
* Adult liver flukes in ag

Adverse Effects
* VERY safe

61
Q

Triclabendazole; MOA, Use, Adverse Effects

A

MOA
* May bind to tubulin at different site than Benzimidazoles

Use
* Adult & up to 1wk old liver flukes (migratory stages)
* Greatest activity against liver flukes of all meds

Adverse Effects
* VERY safe

62
Q

Macrocyclic Lactones; Drugs, Desirable Characteristics

A

Drugs
* Ivermectin
* Moxidectin
* Anything with –ectin
* Milbemycin

Desirable characteristics
* high potency
* high lipophilicity
* high therapeutic index
* prolonged persistence in tissues

63
Q

Macrocyclic Lactones; MOA, Use, Adverse Effects

A

MOA
* Interfere w/ glutamate-gate chloride channels ->
* Hyperpolarization of cell membranes ->
* Paralysis ->
* Alters nutrient ingestion & makes parasite remain at site of predilection

Use
* Insects
* Some lice
* Mites
* Some helminthes of horses
* All helminthes of cows
* Heartworm prevention
* Nematodes

Adverse effects
* Neurotoxicity
* Avermectin sensitive
* Tox from eating poo
* Contraindicated in animals <6wks old

Clin Pharm (8 decks)

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