PHARMACOLOGY - Anthelmintics Flashcards
What are the three anthelmintic treatment strategies?
Interval treatment
Targeted treatment
Stategic treatment
What is interval anthelmintic treatment?
Interval anthelmintic treatment involves administering anthelmintics at specific time intervals to maximise impact based on the knowledge of the lifecycle of the parasite and the peristence of the drug
What is targeted anthelmintic treatment?
Targeted anthelmintic treatment involves administering anthelmintic drugs based on confirmed diagnosis of the parasite
What is strategic anthelmintic treatment?
Strategic anthelmintic treatment involves administering anthelmintic drugs based on confirmed diagnosis of the parasite, as well as considering the parasite lifecycle, seasonality, and risk of transmission
What are the main routes of administration used for canine anthelmintic products?
Oral
Spot-on
What are the main routes of administration used for feline anthelmintic products?
Oral
Spot-on
What are the possible legal classifications of canine and feline anthelmintic products?
- Prescription-only Medicines - Veterinarian (POM-V) (most common)
- Non-Food Animal Medicines - Veterinarian, Pharmacist, Sutiable Qualified person (NFA-VPS)
- Authorised Veterinary Medicines - General Sales List (AVM-GSL)
The AVM-GSL usually aren’t very affective
What are the main routes of administration used for equine anthelmintic products?
Oral
What is the legal classification of equine anthelmintic products?
Non-Food Animal Medicines - Veterinarian, Pharmacist, Sutiable Qualified person (NFA-VPS)
What are the main anthelmintic drug classifications?
Benzimidazoles
Macrocyclic lactones
Tetrahydropyramidines
Praziquantel
Emodepside
What is the mechanism of action for benzimidazoles?
Benzimidazoles bind to helminth tubulin, preventing microtubule formation which prevents mitotic spindle formation as well as glucose uptake which result in starvation of the helminth
Describe the nature of selective toxicity of benzimidazoles
Benzimidazoles have a high affinity and irreversible binding to helminth tubulin, however they have low affinity and reversible binding to mammalian tubulin
Which parasites are targeted by benzimidazoles?
Nematodes
Cestodes
Trematodes
What is the route of administration for benzimidazoles?
Oral
Why can benzimidazoles only be administered orally?
Benzimidazoles have a limited solubility and thus form a suspension - described as a white drench - which can only be administered orally as it is not sufficiently dissolved to be administered via other routes
(T/F) Benzimidazoles are well absorbed into the plasma
FALSE. Benzimidazoles have limited absorption from the gastrointestinal tract into the plasma which is beneficial as this allows the drug to target the gastrointestinal parasites
Limited GI absorption means that it will not be as effective against larval stages
What can be done to increase the efficacy of benzimidazoles?
Slowing gut transit time by administering benzimidazoles with food increases the efficacy
What happens when benzimidazoles are absorbed into the plasma?
Benzimidalozes are very rapidly cleared from the plasma
How are benzimidazoles metabolised?
Benzimidazoles are metabolised by redox reactions - reactions where reduction and oxidation are both taking place
Which benzimidazole metabolites are produced via the reduction pathway?
Reduction reactions produce sulphoxides which can be further reduced into sulphides
Which benzimidazole metabolites are produced via the oxidation pathway?
Oxidation reactions produce sulphides which can be further oxidised into sulphoxides which can be further oxidised into sulphones
Which benzimidazole metabolites are active?
Sulphides
Sulphoxides
Which benzimidazole metabolite is inactive?
Sulphones
How are benzimidazoles primarily excreted?
Benzimidazoles are primarily excreted faecally
What are the contraindications to the use of benzomidazoles?
Benzimidazoles are teratogenic and thus are contraindicated in early pregnancy
Give two examples of benzimidazoles liscenced for use in companion animals in the UK
Fenbendazole
Menbendazole
What is the mechanism of action for macrocyclic lactones?
Macrocyclic lactones stimulate glutamate gates chloride channels in invertebrate nerve and muscle cells resulting in an influx of chloride and persistent hyperpolarisation, resulting in flaccid paralysis. There is also evidence that macrocyclic lactones can target GABA receptors
Describe the nature of selective toxicity of macrocyclic lactones
Macrocyclic lactones target glutamate-gated chloride channels which don’t exist in mammals
Which parasites are targeted by macrocyclic lactones?
Macrocyclic lactones are endectocides meaning they target both nematodes and ectoparasites
What are the possible routes of administration for macrocyclic lactones?
Subcutaenous
Oral
Topical (i.e. Spot-on)
Describe the pharmacokinetics of macrocyclic lactones
Macrocyclic lactones are well absorbed particularly when administered subcuteneously or orally - topical administration is more variable. Regardeless of the route of administration, due to their lipid solubility macrocyclic lactones have a high volume of distribution (Vd) and accumulate in adipose tissue
High Vd means that it will be effective against larval stages
Why does topical/spot-on administration of macrocyclic lactones have a longer half life than other routes of administration?
When macrocyclic lactones are administered topically/spot-on, they are absorbed into the subcutaenous fat where is accumulates and creates a reservoir, resulting in a longer half-life
How are macrocyclic lactones metabolised?
Macrocyclic lactones have very minimal metabolism and are mostly excreted unchanged
How are macrocyclic lactones excreted?
Macrocyclic lactones are mostly excreted unchanged in the faeces and small amounts are excreted in the urine
What contributes to the long plasma half life of macrocyclic lactones?
The high volume of distribution and slow excretion of macrocyclic lactones contributes to their long plasma half life
Give three examples of macrocyclic lactones
Ivermectin
Selamectin
Milbemycin oxime
Why is ivermectin no longer liscenced in small animals?
Lipophilic drugs can cross the blood brain barrier however they are pumped back out by p-glycoproteins. However, there are certain breeds (such as herding dogs) that have a genetic mutation in the ABCB1 gene which affects these p-glycoprotein, allowing the drug to accumulate in the brain. Though mammals do not have glutamate gated chloride channels, they do have GABA receptors which can be affected by ivermectin resulting in side effects
(T/F) Ivermectin is liscenced for use in horses in the UK
TRUE.
Which species’ is selamectin liscenced in?
Dogs
Cats
Why can selamectin be used safely in dogs and cats?
Selamectin is safe in breeds with ABCB1 gene mutations as it does not require p-glycoproteins to be removed from the blood brain barrier
What is the route of administration for selamectin?
Topical (Spot-on)
Which species’ is milbemycin oxime liscenced in?
Dogs
Cats
What is the route of administration for milbemyxin oxime?
Oral chewable tablets
Which pharmacokinetic property should be you be aware of when administering milbemyxin oxime?
Despite milbemyxin oximes high lipid solubility, it isn’t well absorbed from the gastrointestinal tract to is more for targeting gastrointestinal parasites
Limited GI absorption means that it will not be as effective against larval stages
What are the potential side effects of milbemyxin oxime?
Transient trembling and ataxia
This tends to only occur due to overdose
What is the mechanism of action of tetrahydropyramidines?
Tetrahydropyramidines stimulate the nicotinic acetylcholine receptors at the neuromuscular junction, resulting in persistent depolarisation and spastic paralysis
Describe the nature of selective toxicity of tetrahydropyramidines
Tetrahydropyramidines have a higher affinity for helminth nicotinic acetylcholine receptors than mammalian nicotinic acetylcholine receptors
What is the most significant example of a tetrahydropyramidine?
Pyrantel
Which species’ is pyrantel liscenced in?
Dogs
Cats
Horses
Which parasites are targeted by pyrantel?
Nematodes
Cestodes (in some equine products)
Which pharmacokinetic property should be you be aware of when administering pyrantel?
Despite the high lipid solubility of pyrantel, it is not well absorbed from the gastrointestinal tract and thus is used to target gastrointestinal parasites
Limited GI absorption means that it will not be as effective against larval stages
What can be done to increase the efficacy of pyrantel?
Slowing gut transit time by administering pyrantel with food increases the efficacy
How is pyrantel metabolised?
Approximately 50% of pyrantel is metabolised and the rest is excreted unchanged
What is the primary route of excretion of pyrantel?
Pyrental is primarily excreted in the faeces
What is the mechanism of action of praziquantel?
Praziquantel causes a rapid influx of calcium into the helminth resulting is tetanic contraction of the musculature as well as causes a ionic disturbance which draws water into the helminth resulting is vacuolisation of the syncytial tegument, allowing the host immune system to clear the helminth
Which parasites are targeted by praziquantel?
Cestodes (mainly)
Trematodes
What is the main route of administration for praziquantel?
Oral
Describe the pharmacokinetics of praziquantel
Praziquantel is rapidly absorbed and has a high volume of distribution due to its high lipid solubility
High Vd means that it will be effective against larval stages
Why does praziquantel have such a short duration or action?
Praziquantel has such a short duration of action as it undergoes first pass metabolsim and rapid elimination
What is the mechanism of action for emodepside?
Emodepside inhibits acetylcholine elicited muscle contraction through binding to latrophilin-like receptors at the neuromuscular junction, resulting in flaccid paralysis
What is the nature of selective toxicity for emodepside?
Latrophilin-like receptors are not present in mammalian species
Which species is emodepside liscenced in?
Cats
Which parasites are targeted by emodepside?
Nematodes
Describe the pharmacokinetics of emodepside?
Emodepside is rapidly absorbed and has a high lipid solubility resulting in a high volume of distribution (Vd). Emodepside is minimally metabolised and is rapidly excreted mostly unchanged in the bile
High Vd means that it will be effective against larval stages
What is profender?
Profender is a commercially available combination of emodepside and praziquantel
