Chapter 12 - Antiparasitics Flashcards
What type of products do the FDA control?
Products that are administered internally (oral/injectable) or drugs absorbed to significantly into the body when applied topically
What type of products do the EPA control?
Products that are applied topically and not absorbed to any great extent systemically (considered to be pesticides)
Parasiticide
Kills parasites
Nonproprietary name
Active ingredient
Selective toxicity
Antiparasitic compound is highly toxic to the parasite, but has little or no adverse effect on the hosts tissue or to the person applying/administering the product
What are the 5 ideal characteristics in the perfect parasiticide?
1) Selective toxicity
2) Economical
3) Effective against all parasitic stages with one application
4) Safe for old, very you, pregnant, or debilitated animals
5) Does not induce resistance in the target parasite
What are some of the less important but still ideal characteristics of the perfect parasiticide?
Fragrant odor
Lack of offensive odor
Environmental safety
Selective Pressure
External agents which affect an organism’s ability to survive in a given environment
Endectocides
Ability to kill some internally living parasites and some externally living parasites
Endoparasites
Internally living parasites
Ectoparasites
Externally living parasites
Anthelmintic
General term - used to describe compounds that kill various types of helminths, or internal parasitic worms.
They may also be described as vermicide or as vermifuge
Helminth
Parasitic worm
Vermicide
Kills the worm
Vermifuge
Paralyzes the worm - often results in passage of live worms in the feces
Antinematodal
Anthelmintics used to treat infections of nematodes, or roundworms
True or False
All nematodes are technically roundworms
TRUE
whether or not they fit into the subset, when cut in cross section, they are round in appearance
Anticestodals / Cestocides / Taeniacides
Treat infections of cestodes which are tapeworms or segmented flatworms
Antitrematodal
Compounds that treat infections of trematodes which are flukes or unsegmented flatworms
Antiprotozoal
Compounds that treat infections of protozoa which are single celled organisms
Coccidiostats
Antiprotozoal drugs that specifically inhibit the growth of coccidia
Macrolides / Macrocyclic Lactones
Avermectins/Milbemycins
Antiparasitic drug - Neurotoxins whose primary mechanism of action is primarily through stimulation of a receptor site for the neurotransmitter Glutamate
Neurotoxins
Target specific receptors on neurons to selectively enhance or inhibit the activity of specific neurons or to enhance of inhibit the effect of the neuron’s neurotransmitter
Glutamate neurotransmitter
Negatively charged chlorine ions have flooded the cell due to stimulation of glutamate receptors making the inside of the cell more negative than normal and the muscle cannot depolarize (paralysis of the muscle or no firing by the neuron)
Glutamate
Neurotransmitter
γ-aminobutyric acid (GABA)
Neurotransmitter (similar to glutamate) that causes opening of chloride channels, and subsequent inhibition of neurons in the CNS (primarily the brain)
True or False
Even though γ-aminobutyric acid (GABA) receptors are “safely” protected from exposure behind the blood-brain barrier - Lipophilic drugs can readily diffuse through the blood-brain barrier and potentially gain access?
TRUE.
Gaining access to the GABA receptors in mammalian brains produces toxicity - but not in all animals every time a Macrolide is administered
P-glycoprotein (P-gp) Protein Pump
Found in: Blood-brain barrier, Liver and cells lining the GI Tract
Component of the blood-brain barrier whose function is to move drugs from the brain side of the blood-brain barrier back into the blood
(even if lipophilic drugs cross the blood-brain barrier the P-gp pumps them back into the blood before they can combine with GABA receptors on neurons in the brain)
List the 2 ways an impaired P-gp allows Macrolides to accumulate within the brain and increasing the risk for toxicity
1) P-gp can be inhibited by other drugs
2) P-gp itself can be defective
MDR1 (Multiple Drug Resistance 1)
Gene (genetic defect) in Collies and related breeds that codes for their P-gp. Produces the P-gp found on the surface of cancer cells that pump out any antineoplastic drug that makes it into the cancer cell, making the cancer cell resistant to drugs
MDR1 has more recently been referred to as ABCB1 (ATP-binding Cassette type B1)
Same gene as MDR1 but named for the type of protein it produces
True or False
Only a small concentration of macrolides need to be present in the tissues or fluid compartments where the parasite lives to kill them?
True
Lipophilic nature explains why they readily penetrate tissues and persist at low but still effective concentrations for a long period of time
Signs of Macrolide toxicity include:
CNS depression -> Hypersalivate, vomit, ataxia, stagger, depression, unresponsiveness, bradycardia, mydriasis, loss of menace response and coma. Prolonged seizures have also been reported.
What is the antidote for Avermectin/Milbemycin Toxicosis?
The is no antidote - animal may need to be kept alive in a comatose state for days to weeks before the effects of the drug wear off
True of False
Collies with the MDR1 mutation and poorly functioning P-gp should be able to tolerate the drug Ivermectin
True
The dose of Ivermectin needed to prevent hwd in dogs is 0.006 mg/kg
Toxicity was reported at about 0.1mg/kg (16 times the dose needed) and death at 0.2mg/kg (32 times the preventative dose)
What is the most common cause of Ivermectin toxicity in dogs?
Accidental exposure to large animal products or extra-label use of large animal products in small animals
Ivermectin
First macrolide available for use in vet med
heartworm, intestinal parasites, external parasites + extra-label demodectic mange, ear mites, microfilariae
Selamectin
Avermectin type of macrolide
Broad spectrum endectocide for heartworm, and several GI tract worm parasites and external parasites
What percentages of Selamectin do dogs/cats absorb?
Dogs – 4 %
Cats – 74 %
Teratogenic effects
Birth defects
What mechanism does Pyrantel mimic?
Excessive release of Acetylcholine would have on nicotinic acetylcholine receptors (nicotinic receptors) on parasites muscle cells - Excessive nicotinic effect causes initial stimulation and spastic contraction of the parasite’s muscles, followed by paralysis and death
What drug class does Pyrantel belong to?
Antinematodal
Scolex
Head of the tapeworm
Proglottids
Segments of the tapeworm
True or False
Tapeworms cannot regenerate if only the segments are removed and the head remains intact
False
Tapeworms can regenerate if the anticestodal only removes the segments but the head remains
Taenia and Dipylidium are what type of parasite?
Tapeworms
Dirofilaria Immitis is what type of parasite?
Adult heartworms
Microfilariae
Microscopic young (larvae) of heartworms
Toxocara species are what type of parasite?
Nematodes/Roundworms
Echinococcus granulosus
Dog tapeworm
Intima
Inner lining of the vessels
Heartworm Infection
Presence of the Dirofilaria Immitis adult worms in the heart and pulmonary arteries
Heartworm Disease
Does not occur until the infection is significant enough to produce clinical signs
Wolbachia pipientis
Gram-negative, intracellular bacteria that infects heartworms and microfilariae young and contributes to the clinical disease associated with heartworm infections
What sort of relationship do Wolbachia and Dirofilaria have?
Symbiotic - each organism appears to benefit from the presence of the other and removal of one organism seems to decrease the viability of the other
What are the 2 mechanisms dead and dying heartworms produce severe clinical signs?
1) Release of inflammation and immune stimulating proteins
2) Blocking of the pulmonary arteries by chunks of dead, decaying worms passing from the heart or larger pulmonary arteries to the smaller arteries where Emboli can lodge and obstruct blood flow
Emboli
Any detached mass or object traveling within the blood vessels
HARD stands for what?
Heartworm Associated Respiratory Disease
What is HARD usually mistaken for?
Feline asthma
Thromboemboli
Emboli made of thrombocytes or platelet clots
True or False
Cats are a natural host of D. Immitis
False
True or False
Cats are treated for heartworm disease the same way that dogs are treated
False
Cats controlling of hwd is mainly allowing the heartworms to die on their own and controlling the subsequent inflammatory response and embolic effect from the dead worms
Microfilaricides
Drugs used to kill the circulating Microfilariae produced by the adult heartworms
Adulticide
Drug used to kill mature(adult) heartworms that live in the pulmonary vasculature and the right chambers of the heart
What stage of heartworm larvae infects animals when injected into them by mosquitos?
Infective third-stage larvae (L3)
What drugs kill infective L3 and L4 larvae?
Heartworm preventatives kill the L3 larvae so they do not mature into adults
How effective is the current Melarsomine 3 injection heartworm treatment?
Reduces worm burden by 98%
Under what circumstances would you NOT treat heartworm in a dog?
Caval syndrome (class 4 hwd) Worms must be removed surgically
Caval Syndrome
Pulmonary vasculature and heart are so physically full of worms that they extend back into the vena cavae
Baylisascaris procyonis
Racoon roundworms
What does RiskMAP stand for?
Risk Minimization Action Plan - surveillance program
What drug is used to treat Wolbachia?
Doxycycline - 28 day course
Why is exercise restriction such an essential part of heartworm treatment?
Increased velocity and turbulence of blood through the heart and vasculature when an animal exercises can “shake loose” larger pieces of the worm to form bigger emboli that obstruct major pulmonary arteries and producing a far greater inflammatory response
How do animals acquire Coccidia?
Ingestion of food or water contaminated with oocysts or eating a rodent that is infected with coccidia
Oocysts
eggs
What are the most common protozoas treated in veterinary medicine?
Giardia, Coccidia, Toxoplasma and Sarcocystis neurona
What class of antibiotics are commonly used to treat protozoal infections?
Sulfonamides
What symptoms are critical to look for when an animal is being treated with Sulfas?
KCS
Crystalluria (should always have water available)
Giardiasis
Infection with Giardia
How does Metronidazole treat Giardia?
Protozoacidal by disrupting the helical structure of protozoan DNA and interfering with other key molecules needed by the protozoa
What side effects can occur with metronidazole?
CNS/Neurotoxicity signs - usually temporary and reverse over several days with no long-term after effects
How do horses contract Sarcocystis?
Drinking water, grass, or feed contaminated by cats, opossum, or other wildlife that can she the sporocysts of Sarcocystis
What does Sarcocystis cause in the horse?
EPM (Equine Protozoal Myeloencephalitis)
Protozoa causes damage to the spinal cord or brain and can produce almost any neurologic sign depending on which area of the spinal cord is affected
What are the 4 different actions the Ectoparasiticides typically do as their mechanism of action?
1) Inhibit a neurotransmitter (Acetylcholine)
2) Enhance a neurotransmitter (GABA)
3) Block a neurotransmitter’s receptor (Chloinergic receptor)
4) Enhance a neurotransmitters receptor (GABA receptor opens chloride channels, nicotinic cholinergic receptor for acetylcholine)
How are Organophosphates and Carbamates most seen in vet med today?
Toxicity from exposure to agricultural or garden pesticides
What does SLUDDE stand for?
Salivation, Lacrimation, Urination, Defecation, Dyspnea, Emesis
What do actions of Organophosphates and Carbamates do to produce toxicity in animals?
Over stimulation of the PNS associated with muscarinic receptor overstimulation
Over stimulation of Nicotinic cholinergic receptors by OPs and carbamates produce what signs?
NMJ clinical signs (muscle tremors that progress in severity until receptors stop responding to overstimulation and block axonal depolarization waves)
Tremors -> shaking -> ataxia -> paralysis
What does NMJ stand for?
Neuromuscular Junction - where nerve axons contact skeletal muscles
What ultimately is the reason most animals die from OP/carbamate toxicity?
Hypoxia from being unable to adequately ventilate because the diaphragm is a voluntary skeletal muscle and may become paralyzed
What is the treatment for OP/carbamate toxicity?
Removing any insecticide remaining in or on the animal
Atropine at 10 times its typical pre-anesthetic dose
*Atropine does NOT block nicotinic receptor sites!!!
Why is atropine the drug of choice for reversing SLUDDE clinical signs?
It is a muscarinic cholinergic receptor agonist (blocker) that decreases the effect of the excessive acetylcholine at the muscarinic receptor site
Type I Pyrethroids produce what response?
Hyperactivity response
Type II Pyrethroids produce what response?
Paralysis type of syndrome
Synergists
Compounds added to the pyrethrin products to enhance their insecticidal effect
What are the 2 most common synergists used with pyrethrins
1) Piperonyl Butoxide (PBO)
2) MGK 264
Repellent
Can keep insects from landing on animals
Insect Growth Regulators (IGRs)
Compounds that retard or stop the development of flea eggs or flea larvae without directly killing the flea
Amitraz
Legend drug - one of the first effective agents available for treatment of demodectic mange in dogs (as a dip)
Animals treated with Amitraz may show what signs for 24-72 hours after treatment?
CNS depression/sedation/hypothermia
Amitraz is an a2 agonist, so what drugs can reverse many of the toxic effects of Amitraz?
Yohimbine, Tolazoline and Atipamezole - multiple dosages may be required to maintain reversal effect
Sequestration
Taking up and holding
Insect Development Inhibitors (IDIs)
Work by interfering with the deposition of Chitin into the flea egg and exoskeleton of the larva within the egg - Larvae that do hatch will be smaller and less likely to survive
Juvenile Hormone Analogs (JHAs)
Work by mimicking the actions of natural juvenile hormones that retard development into adult insects - by delaying development the larvae will eventually die
Chitin
Compound found in the exoskeleton of insects, the egg-tooth of flea larvae, and in the cell wall of fungal elements
Ovicidal
Compound kills the eggs of the parasite
Beta-Tubulin
Polymerize into microtubules, a major component of the eukaryotic cytoskeleton and one of many essential cellular functions
Ionophores
Combine with and transport ions across biological membranes
