Pharmacology Flashcards
pharmacokinetics
what a body does to a drug
pharmacodynamics
what a drug does to the body
ADME
Administration, Distributions, Metabolism, Elimination
Administration
Enteral - sublingual, swallowing, rectal
Parenteral - topical, intradermal, subcut, IM, IV, inhalation
IV - accurate control of concentration, used for drugs with narrow safety margins
Inhalation - rapid effect, may cough out, dependent on particle size and tidal volume
Distribution
reaches circulation - needs to penetrate tissues
active transport/carrier mediated
passive transport/diffusion
through membrane as pair with ion
can go into fat
must be neutral to cross
cross more rapidly if - neutral, high lipid.water partition in non-ionised compounds, low molecular weight, biological affinity with transporters, small size particles
effect of pH
Metabolism
2 phase - catabolic and anabolic - becomes drug derivative and the a water soluble drug
sometimes only 1 phase
Biotransformation
non lipid soluble drugs –> oxidised by cytochrome P450 enzymes –> either water soluble product or next phase –> broken down to transferase (water soluble)
liver metabolism
broken down by enzymes in the SER of hepatocytes
detoxification
forms inactive metabolites - sometimes metabolites produce similar effects to the drug itself
also can break down toxic metabolites
cats & paracetamol - no UTGs so causes methemoglobinuria
Cytochrome P450s (CYP450s)
enzymes
mosrtly formed in liver but some in intestinal walls
metabolise drugs
need iron - problem if anaemic
Excretion
major routes - renal, biliary, pulmonary
minor routes - mammary, salivary
Drug-drug interactions
levels of one drug altered by another
absorption - affected by pH, bacterial flora, decreased gastric emptying
excretion - urine pH and reduced renal excretion
inhibition or induction of enzymes
CYP450s affected by lots of drugs
Therapeutic window
concentration where we know there is an effect
TMax
maximum effect time
CMax
maximum concentration - needs to be below level of toxicity
Rate vs time graphs
zero order - flat horizontal line - IV infusion
first order - diagonal up - IM, Subcut, oral - absorption rate proportional to amount of drug
elimination rate
amount of drug eliminated per unit time
Initial volume of distribution (Vi)
volume of blood + interstitial fluid
Volume of distribution (Vd)
volume into which a drug appears to be distributed (litres/kg)
low Vd - mainly accumulated in extracellular fluid
high Vd - drug accumulating in another site (Eg. fat)
total body clearance
volume of blood/plasma cleared of parent drug per unit time
bioavailability
% of administered dose that reaches the plasma
compartment models
one compartment - spreads equally around the body
two compartments - vessel rich groups first then other tissues
vessel rich group –> muscle –> fat
loading dose
initial larger dose, followed by constant rate infusion
potency
amount of drug needed to produce 50% of maximum effect
efficacy
maximum therapeutic effwct/how well the drug activated receptors
affinity
tendency of drug to bind a particular receptor
Agonist
produces an effect at a receptor
full agonist - 100% activation
partial agonist - any less than 100% activation
Anatagonist
binds but doesn’t produce an effect
competitive - competes with agonists at binding sites - curve shifts to right
non-competitive - binds to a different site downstream of receptor (ketamine) - curve flattens and moves downward
irreversible - dissociates from receptor very slowly or destroys it
Inverse agonist
acts on receptor that usually fires on its own to reduce activation
therapeutic index
toxic dose/effective dose
EC50 - effective concentration - dose needed to reach 50% maximal effect
ED50 - effective dose - dose that will produce therapeutic effects in 50% of population
receptor types
ion channel cell surface transmembrane receptor
ligand regulated enzymes
g-protein coupled receptors
protein synthesis regulating receptor
tachyphylaxis
reduction in tolerance that develops of short period of time - becomes less effective with repeated doses
causes of loss of target sensitivity (6)
change in receptors - become resistant to stimulation
loss of receptors
exhaustion of mediators
increased metabolic degradation of drug
physiological adaption
drug transporters remove drug from target site
Opioids
opiates = natural
opioids = synthetic
mu receptor (kappa in birds) - receptors at point of pain stimulus
reduce pain stimulus, reduce signal transmission
more receptors at synapse - negative feedback on Ca2+ channels –> hyperpolarisation
effect dependent on dose, species, route, stimulus
side effects - CVS, pruritus, vomiting
Morphine
full agonist - mu, kappa, delta
CD2
not licensed in veterinary species (but used anyway)
Methadone
full agonist at mu
premed, sedation, recovery
CD2
Meperidine/pethidine
full agonist at mu
increased hr (unusual for opiates)
CD2
short duration of action
Fentanyl
full agonist at mu
short acting
lipid soluble
CRI
CD2
bradycardia and slowed respiration following bolus
buprenorphine
partial mu agonist
long lasting
butorphanol
kappa agonist (birds)
good sedative, limited analgesia
antitussive
Local anaesthetics
block sodium channels in nerve fibres
becomes active in ionised form (weak bases so ionised at physiological pH)
speed of onset related to degree of ionisation
potency related to lipid solubility
narrow safety margin
lidocaine, prilocaine, bupivicaine
NSAIDS
COX 1 and COX 2 inhibition - prevents prostaglandin production
GIT effects
meloxicam, carprofen, aspirin
Galliprant - piprant class NSAID - blocks prostaglandins at EP4 rather than COX - should be less side effects
contraindications - renal or hepatic failure, hypervolemia, congestive heart failure, pulmonary disease, hemorrhage, slotting problems, spinal injuries, gastric ulceration, steroid use, shock or trauma, pregnancy
Alpha-2 Adrenoreceptor Agonist
bind to pre-synaptic alpha 2 receptors - decreased release of neurotransmitters
decreased hr and rr
synergistic with local anaesthetics
medetomidine, dexmedetomidine, xylazine, detomidine, romifidine
antagonised by atimpanezole
side effects - hypotension followed by hypertension, decrease CO and HR, respiratory depression
NMDA antagonists
chronic pain
continuously excited NMDA receptor –> continuous pain
ketamine
local anaesthetic blocks
small animal
- splash blocks
- epidurals
- dental blocks
- limb nerve blocks
- intraoperative articular blocks
horses
- diagnostic
- epidural
- eye and dental
- intraoperative and intraarticular
farm
- cornual
- caudal epidural
- inverted L
- IVRA
- paravertebral
dental blocks
intraorbital
maxillary
ophthalmic
mental
mandibular
epidural
spinal column outside dura - post op analgesia, standing surgery or abdominal and hind quarter surgery under GA
caudal - between sacral and coccygeal bones - blocks tail and perineum
cranial - lumbosacral - all motor sensation to hind limbs
complications - accidental vascular injections, hematoma, subarachnoid injection, infection, hypotension, respiratory depression, nerve damage, pruritus, urinary retention, motor dysfunction, hypothermia
effects of pain (9)
catecholamine release
weight loss
wound breakdown
hyperglycemia and insulin resistance
neutrophilia
cytokine production
poor immune function
reduced appetite
post op complications
signs of pain (11)
tachycardia
tachypnea
hypertension/hypotension
cardiac arrhythmia
pale mm
hypersalivation
mydriasis
sweating
trembling
increased urination or defacation
poor condition
pain behaviours
prey species - little pain behaviour
abnormal posture, movement, gait, activity
reluctance to move
agression
Glasgow pain scale
canine
acute
6 behavioural categories - vocalisation, mobility, response to touch, demeanour, posture, activity
score - 0-3/4/5 for each
validated
cat pain scales
UNESP Botucatu multidimensional
Glasgow RCMPS-F
Chronic pain scales
none validated for cats or whole body
validated osteoarthritis scales for dogs-
liverpool osteoarthritis in dogs
canine brief pain inventory
helsinki chronic pain index
canine specific outcome measures
Vapours
Nitrous oxide
halothane
isoflurane
sevoflurane
desflurane
Kinetics of vapour
rate or rise in blood depends on -
concentration of agent
ventilation
cardiac input - inverse
solubility of agent in blood - inverse
^ blood:gas coefficient - higher=more soluble
Minimum Alveolar Concentration (MAC)
Alveolar concentration producing immobility in 50% of patients in response to a noxious stimulus (for healthy unmedicated patients)
MAC affected by:
age
nitrous
hypotension
hypoxia
anemia
opioids - reduce MAC
sedatives - reduce MAC
LAs - reduce MAC
pregnancy - reduce MAC
Vapour MACs
isoflurane = 1.3
haloflurane = 0.9
sevoflurane = 2.2
desflurane = 10.3
vapour negative effects
CVRS depression
formation of reactive species
possible negative effects on anaesthetist - bone marrow suppression and foetal abnormalities
nitrous oxide
minimal CVRS effects
high MAC
expensive
analgesic
greenhouse gas
halothane
can cause hepatic necrosis
isoflurane
lower solubility - good
safer than halothane
causes vasodilation - low blood pressure
sevoflurane
newer
quicker induction than isoflurane
less soluble
higher MAC but quicker recovery
TIVA/PIVA
environmentally friendly
additional analgesia
reduced MAC of vapour
reduced CV depression
less pollution and organ toxicity
lidocaine - reduces MAC by 25%
ketamine - reduces MAC by 30%
Alpha-2s
Opioids - up to 40% MAC reduction
Antibiotics
cell wall synthesis inhibition - penicillin, ampicillin,bacitracin, cephalosporin
protein synthesis inhibition - tetracycline, streptomycin
cell metabolism inhibition - sulfa drug
RNA synthesis inhibition - rifampicin
DNA synthesis inhibition - quinolones
Antibiotics - adverse effects
toxicity
drug interactions
reduction in gut flora
tissue site necrosis
reduced metabolism
residues in food producing animals
resistance
hypersensitivity
anaphylaxis
Antibiotics - factors influencing success
bacterial susceptability
type of tissue
local factors - abscess, foreign material, low pH or oxygen
wound cleaning and drainage
compliance
Antibiotic Adjuncts
probiotics
anti-tetanus toxin
cleaning wounds
treat side effects of infection
analgesia
Antifungals
Polyenes - forms channels in fungal cell membranes
Antibiotic - inhibits mitosis
Azoles - inhibits ergosterol biosynthesis
Allyamines - inhibits ergosterol biosynthesis
Thiocarbamates - inhibits ergosterol biosynthesis
Antimetabolites - inhibits RNA and DNA synthesis
Profens - direct damage to fungal cytoplasmic membranes
Ringworm (dermatophytosis)
ring shaped lesions
zoonotic
fungal spores long lived in the environment
prevention - cleaning and disinfection, carrier control (cats)
treatment - hair clipping, ketnoazole (dog), itraconazole (cat), topical treatment, treat animals in contact, biosecurity
self limiting but can last 4-9 months - danger to immunocomprised people
Aspergillosis
commensal in most domestic animals
different forms - pulmonary, mycotic abortion, guttural pouch mycosis, nasal and paranasal, asymptomatic
diagnosis - radiograph (turbinate destruction), rhinoscopy (fungal plaques), can’t just culture - commensal
treatment - topical clotrimazole (needs to stay in place on fungal plaques for an hour - anaesthetic), surgical exposure and curettage, topical potassium iodide applied with endoscope
viral replication stages (5)
cell entry
uncoating
control of host protein and nucleic acid synthesis to make viral components
assembly
release
Antivirals
narrow therapeutic margin
target viral function or cellular function that virus needs
only a few and not effective against many pathogens
potential for resistance in human pathogens
some virostatic - need adequate host immune response
virbagen omega - only one licensed in animals - FIV, feline leukemia and parvo - doesn’t go into cell, releases interferon to increase cell resistance
some used unlicensed
feline infectious peritonitis
feline coronavirus
usually asymptomatic
diarrhea in kittens
wet form - fluid accululation in abdomen
dry - inappetance, jaundice, diarrheoa, weight loss, ocular or neurological signs
raised bilirubin without raised liver enzymes
vaccine types
inactivated - more expensive, needs adjuvant, more stable, no chance of reversion
attenuated - cheaper, no adjuvant needed, less stable, can revert
MRNA - quick to produce, more expensive, can’t revert
horse vaccines
equine flu
tetanus
equine herpes
equine rotavirus
strangles
recorded in horse passport
cattle
BVD
Infectious bovine rhinotracheitis
calf enteric disease
pneumonia
mastitis
salmonella
bluetongue
dogs
core
- distemper
- parvo
- adenovirus/infectious canine hepatitis
- lepto
non-core
- kennel cough
- rabies
- leishmaniases
- canine herpes virus
cats
core
- enteritis
- calicivirus
- feline herpes virus
non-core
- FeLV
- chlamydia
- rabies
- bortadella bronchisepta
rabbits
myxo
rabbit viral haemorrhagic disease
