1
Q
Pyriprole
- application
A
- fleas and ticks only for dogs
- resistance has not yet been observed
- much more effective, but slow absorption (50%)
- can lead to stronger systemic effect thats why it should be avoided in cats and rabbits
- no bathing for 48hr
- never give to cats and rabbits
- dogs needs 3-10x overdose for it to be toxic
2
Q
Organophosphates
- Antidotes
A
Competitive antagonism
- SLUDGE <-> Atropine
Enzyme reactivation (pralidoxime, obidoxime)
3
Q
Amitraz (formamidine)
- mechanism of action
A
MAO-inhibitors
- responsible for the re-uptake of the catecholamines from the synaptic cleft
- if we inhibit these enzymes then the catecholamines will stay in the synaptic area and will cause further activation.
- Catecholamines found here: dopamine, adrenaline, nor-adrenaline
- in the parasites we hae Octopamin, which also is a neurotransmitter and catecholamine
- due to the inhibition of reuptake of catecholamines, excitation can happen in the host animal.
- It is more selective to the parasites Octopamin, but it can have an effect of the host animal too
a-2 Agnonist:
- sedatohypnotics. Xylazine, metomidine etc.
- SE: sedation, vomitting, bradycardia, hypothermia
4
Q
Fipronil
- mechanism of action
A
(frontline)
- GABA antagonist –> exicitation
- relatively slow effect (8hr 40-60%)
- good distribution in the skin (sweat gland and sebaceous glands) –> good residual activity
- Bathing: not for min. 2 days
- minimal systemic effect (very safe)
- shedded hair > 2 weeks (dermatophagoides farinae)
5
Q
A
6
Q
Macrocyclic lactones
- substances
A
- Avermectins and Milbemycins
7
Q
Macrocyclic lactones
- spectrum
A
mostly nemtodes (roundworms(
- fleas (selamectin!! pharynx paralysis) –> stronghold
- mange mites
- demodex spp.
- moxidectin (1xweek)
- milbemycin (1xday) for 4-6 weeks
- myiasis
- ticks (slow killing, not repellents
8
Q
Isoxazolines
- substances
A
- Fluralaner (bravecto)
- Afoxolaner (Nexgard)
- Sarolaner (Simparica)
- Lotilaner (Credelio)
9
Q
Neonicotinoid insecticides
- toxicity
A
- fastest acting group:
- kills 100% of the fleas within hr.
- effective against FAD
- environmental toxicity
10
Q
Organophosphates
- Pharmacokinetics
A
- Good absorption (oral 35% > dermal 2-14%)
- LD50 po vs LD50 dermal (200-800 vs 2000 mg/kg)
- Excellent distribution (special barriers, BBB)
- Metabolism (partial activation)
- diazinon (t1/2 hours) à diazoxon (t1/2 days)
- (80% urine metabolites, 20% feces)
- long t1/2 + biological accumulation!
- cat: increased sensitivity
11
Q
Carbametes
- substances, pharmacokinetics, applicaton
A
- Agent: Propxour
- Toxicity: much safer (<-> Atropine)
- pharmacokinetics: less lipophilic, oral vs dermal
- fleas and ticks
- collars, aerosol sprays, shampoos
12
Q
Isoxazolines
- efficacy
A
- fleas + ticks
- fleas within 8 hr
- ticks within 12 hr (lyme, babesia) (ehrlichia needs repellent!)
- mange mites (NOT sheep and cattle)
- demodex spp (1st. choice)
- poultry: Dermanyssus gallinae (fluralaner)
- oral water based drug mixed into the drinking water
13
Q
Isoxazolines
- toxicity
A
- large differences between LD50 and therapeutic doses
- Sarolaner: can be the most toxic, but only due to overdose
- 1x, 3x, 5x, overdose in 8 week old puppies
- 3x overdose: tremors, ataxia
- 5x overdose: seizures, tremors, ataxia
- –>GABA-antagonism: resolved within 24 hr
- can be given to MDR1 mutant dog breeds
- Fluralaner can be given to lactating and pregnant animals
14
Q
Insect growth regulators (IGRS)
- juvenile hormone analogues: mechanism of action
A
- no adulticide effect
- Pyriproxyfen has a long duration of action: 48 days
- inhibition of larval development (through eggs, pupas and also with digested blood)
- the larvae of the flea will eat the feces of the adult, and then the larvae will be harmed if they eat the feces.
- deformity of mature forms, if they survive
- light, residual activity, pyriproxyfen > methoprene
- Pyriproxyfen: much more stable in the environment
15
Q
Isoxazolines
- mechanism of action
A
- GABA-antagonist, GluCl-channal antagonist
–> depolarization -> excitation
16
Q
Organophosphates
- mechanism of action and side effects
A
Contact poisons
Irreversible inhibition of ACh-E
- muscarinic ACh receptors
- SLUDGE (salivation, lacrimation, urination, diarrhea, GI pain, emesis)
- Nicotinic ACh receptors
- muscle tremors, spasms
- Central nervous system
- seizures, coma, death
17
Q
Neonicotinoid insecticides
- substances
A
- 1st. gen:
- Imidacloprid (advantage family, foresto)
- Nitenpyram (capstar)
- 3rd. gen:
- Dinotefuran (Vectra)
18
Q
Macrocyclic lactones
- mechanism of action
A
Glutamate mediated Chloride channel and GABA agonist
- GluGl = hyperpolarization –> paralysis
- not found in mammals and birds
- only found in nematodes and ectoparasites
- GABA agonists
- found in mammals and birds
- is an inhibitory receptor and will lead to paralysis in the animals
- PS: P-glycoprotein!
19
Q
Pyriprole
- mechanism of action
A
- derivate of fipronil
- similar characteristics: GABA-antagonist
20
Q
Pyrethroids
- mechanism of action
A
- increase Na-channels
- leads to constant depolarization
= Knock down effect
- contact poison + repellent
21
Q
Neonicotinoid insecticides
- mechanism of action
A
- ACH agonists
–> 560x affinity to nACh-receptors of parasites
- selective toxicity bc. it has a higher affinity to the parasitic receptors.
- safe in host animals, dogs and cats
22
Q
Organophosphates
- substances
A
- Diazinon (=diampylate)
- Coumaphos
- Phoxim
- Fenthion
23
Q
Organophosphates
- application
A
Broad spectrum in most species (diazinon)
- fleas, ticks, lice, mites, myasis
- mostly for dipping
- cats are very sensitive
Varroosis of honeybees (coumaphos)
- Vaporizers and fumigant strips
24
Q
Indoxacarb
- mechanism of action
A
(Activyl, Activyl plus)
- sodium channel blocker –> hyperpolarization
- also used in agriculture –> resistance
- prodrug –> bioactive metabolites (selective toxicity) –> cleavage of methoxy group –> effective flea control (adult, larva, egg)
- feeding and oviposition stops within 0-4 hr
- death within 4-48 hr.
- Good against FAD
- safe usage, environmentally safe
25
Pyrethroids
- toxicity
- safe in warm blooded animals
- cat spot on: TOXIC
* tremors, seizures, excitation: bc of Na-channel opening
- fish are especially sensitive
- no antidote (can only be treated clinically, eg Diazepam)
- Intralipid 20% sequestration
* by the lipid molecules the pyrethroids can be excreted before they act in the nerve system
- favourable prognosis in most cases (within 24 hr)
- local irritation, allergic reactions
* small dog breeds especially
26
Amitraz
- toxicity, side effects
- Toxic.
* More toxic than Pyrethroids, but not as toxic as Organophosphates
- narrow therapeutic index:
* Horse (a-2 agonist will lead to paralytic ileus), chiachuahua and cats are more sensitive
- oral administration is more toxic
- storage: sensitve to light and air
- Antidote: **Atipamezole** 0.05 mg/kg, half life is very long, almost 24hr.
Side effects:
- Sedation, bradycardia, hypothermia, emesis, hyperglycaemia (do not give to DM patients)
27
Macrocyclic lactones
- side effects
Ivermectin: MDR1 mutant animals
- the dog breeds dont have the protective P-glycoprotein pump function in the BBB
- they are MDR1-mutant animals. This gene is responsible for the Pglycoprotein. and when this have a mutation it wont work in a normal way.
28
Fibronil
- application, toxicity
- spot on, spray (not good enough for fleas and ticks)
- decreased susceptibility - now only 92%
- minimal toxicity (10x binding to GABA-receptors)
- but toxic in rabbits! --\> excitation. tremors, convulsions
- 0.1% dermal vs 50% per os
29
Insect growth regulators (IGRS)
- Subgroups and substances:
- Juvenile hormone analouges
* Methoprene (frontline combo)
* Pyriproxyfen (Douwin, Vectra 3D)
- Chitin synhtesis inhibitors
* Lufenuron (Program). not used in vet.med anymore.
* Novaluron
30
Imidacloprid
- combinations
+ permethrin (advantics) --\> ticks
+ flumethrin (foresto) --\> ticks
+ moxidectin (advocate)
31
Pyrethroids
- substances
- 1st gen:
* Tetramethrin (NeoStomosan)
- 2nd gen:
* Permethrin (Expot, advantix, vectra)
* Deltamethrin (scalibor)
* Flumethrin (Kiltix, Foresto)
32
Imidacloprid
- mechanism of action, application, toxicity
(advantage, advantix, advocate, foresto)
- one of the most effective against fleas, rapid action (within 6hr \> 95%), for 4 weeks
- good against FAD
- epithelial debris (good to manage allergy. when it goes to the environment it can also kill det dust mite)
- collar, spot on
- 5-20 x overdose is still safe
33
Isoxazolines
- pharmacokinetics
- oral absorption
- feeding
* Fluralaner with food = better absorption
* Sarolaner and Afoxolaner with food = no difference
- high plasma protein binding = delayed and long duration
- slow metabolism = long half life and long duration
- Enterohepatic circulation
* only Fluralaner
* means that when it is excreted into the bile from the GI tract, the fluralaner is reabsorbed and goes into the blood circulation. and this makes the duartion of fluralaner even longer
- Accumulation in adipose tissues
* increases the duraton of action
- half life: long, 10-15 days
Differences:
- Afoxolaner: also excreted by kidneys (+bile)
* should be avoided in kidney failure
- Fluralaner (0.01%), sarolaner: almost entirely via bile
- Duration of action:
* Fluranaler (acts for 3 months): enterohepatic circulation)
* Sarolaner and Afoxolaner: 1 month
34
Pyrethroids
- application and spectrum
Spectrum:
- Ticks: OK (some resistance against bron dog ticks)
- Fleas: resistance is common
* They are less sensitive, so you often use combinations
- poor efficacy against mange mites
- Good fly control --\> imp. in large animals
- moderate efficacy against Vorroa mites (resistance can develop)
- good against Mosquitos. bc of the repellent effect
35
Amitraz
- kinetics, spectrum, application
Kinetics:
- moderate absorption (PO 13% \> dermal very low)
- half life 23 hr in dogs
Spectrum:
- mange mites, demodex, ticks
Application:
- 0.0025% solution in large animals
- collar, impregnated strips
- dipping solution
36
Isoxazolines
- combinations
- Sarolaner + selamectin = stronghold plus
- Afoxolaner + milbemycin (Nexgard spectra)
37
Insect growth regulators (IGRS)
- mechanism of action
- only act on insect that develops with metamorphosis (so they wont kill e.g ticks, mites etc)
- only kills the egg, larva and pupa (not the adult!)
Pharmacology 2
flashcards
Decks in class (13)
# Cards
-
Inflammation32
-
Hormones, lab 514
-
Hormones, ppt46
-
1. chemotherapy basics13
-
2a/2b. Penicillins, Monob, Carb.20
-
3. Cephalosporins13
-
4. Aminoglycosides16
-
5. Tetracyclines, macrolides, lincosamines42
-
6. Miscallaenous antibiotics51
-
Doses to know55
-
Antihelminthics50
-
Ectoparasiticides37
-
Drug list to know78
