Pharmacology Flashcards
pharmacokinetics
what the body does to the drug
pharmodynamics
what the drug does to the body
non cellular mechanisms by which drugs produce an effect
- physical effects: lacrilube applied to eyes
- chemical: ranitidine on gastric HCl
- physiochemical
- modification of body fluid composition
cellular mechanisms by which drugs produce an effect
- physicochemical/biophysical mechanisms
- cell membrane structure and function mods (insulin)
- enzyme inhibition
- receptor mediated effects (opioids)
molecular targets for drugs
receptors- transduce signal from drug
enzymes- activated or inhibited
transporters- carry molecules across membranes
ion channels- open or close
nucleic acid- affect gene transcription
ligand definition
forms a complex with a bio molecule
receptor
proteins interact with extracellular physiological signals and convert to intracellular effects
characteristics of 4 types of receptor
ligand gated ion channels- miliseconds, ACh
G-protein-coupled receptors- seconds, ACh
kinase-linked receptors- hours, cytokines
nuclear receptors- hours, oestrogen
full agonist definition and example
able to generate a maximal response after binding to a receptor, high affinity and high intrinsic activity
example: methadone
partial agonist definition and example
drug that has an intrinsic activity of less than 1, receptor occupancy produces a sub maximal effect
example: buprenorphine
inverse agonist definition and example
drug binds and inverses the effect to the endogenous agonist.
example: histamine
antagonist definition and example
no effect but blocks endogenous mediators.
example: naloxone
theraputic index
maximum non-toxic dose/minimum effective dose
LD50/ED50
- measure of drug safety
- effective dose can be variable
how do drugs cross membranes
- aqueous diffusion
- passive lipid diffusion
- facilitated diffusion
- pinocytosis (cell drinking)
- active transport
bioavailability definition
the fraction of a dose reaching the systemic circulation after administration compared to the same dose administered intravenously
principles of drug absorption
- drug molecules are usually small weak acids or bases
- ionisation determined by pKa of drug and pH of surrounding tissue
- ionised drug molecules cross by facilitated diffusion or pinocytosis
- tissue pH can change (infection)
- absorption influenced by route of administration and drug formulation
routes of administration and absorbance
- IV- fastest route
- IM- absorption variable
- SC- slower than IM, unpredictable
- oral- absorption in small intestine, low lipid solulbilty
- inhalational
- epidural/spinal
- transmucosal (oral and rectal)
- transepithelial (skin, cornea)
principles of drug distribution
- apparent volume of distribution= amount of drug administered/plasma conc
5 factors determining drug distribution
- protein binding
- tissue binding
- organ blood flow
- membrane permeability
- drug solubility
principles of drug metabolism
- termination of drug effects: primarily biotransformation then excretion
- most drugs are lipophilic and highly plasma protein bound
- kidney excrete polar water soluble compounds most easily
- liver is primary organ of metabolism
clearance definition
the volume of plasma from which drug is completely removed per unit time
half-life definition
the time taken for the plasma concentration to fall 50% of its initial value
rate constant K=clearance/vol of distribution
hepatic metabolism
- convert drug to more polar metabolite
- oxidative, hydrolytic or reductive reactions
- conjugation with substrates
- requires energy
- resultant more polar compound more readily excreted
- glucuronidation (not cats)
- acetylation (not dogs)
- methylation
principles of drug excretion
biliary excretion, lung excretion, GI tract, renal
- renal excretion most common
- active via tubular secretion or passive by glomerular filtration
- may need to alter dose in animals with renal comprimise
bacteriostatic vs bacteriocidal
bacteriostatic- arrest bacterial multiplication
bacteriocidal- act primarily by killing bacteria
mechanisms of action of bacteriocidals
cell wall- interferes with maintenance of bacterial cell wall leading to rupture due to osmotic pressures
cytoplasmic membrane- drugs that interfere with the structure of the plasma membrane
nucleic acid metabolism- drugs may interfere directly with microbial DNA or its replication or repair
principles of antimicrobial therapy
- make diagnosis
- remove barriers to cure
- decide whether chemotherapy is necessary
- select the best drug
- administer the drug in optimum dose and frequency and by optimum route
- test for cure
aims of premedication
- decrease stress and risk of injury to animal and staff
- produce balanced anaesthesia
- reduced dose of induction and maintenance agents
- provide analgesia
- reduce side effects of anaesthetics (lower dose)
5 classes of drugs used for premedication
- phenothiazines
- alpha 2 agonists (analgesic)
- benzodiazepines
- butyrophenones
- opioids (analgesic)
mode of action of phenothiazines
dopamine receptor antagonist in CNS
mode of action of alpha 2 agonists
alpha 2 adrenergic receptor agonist in CNS
mode of action of benzodiazepines
enhance effect of GABA at GABA A receptor
mode of action of butyrophenones
dopamine receptor antagonist in CNS
mode of action of opioids
inhibits neurotransmitter release
phenothiazine licensing and example
- acepromazine (ACP)
- dogs and cats
alpha 2 agonist licensing and example
- dexmedotomidine
- dogs and cats
benzodiazepine licensing and examples
- diazepam (dogs and cats) and midazolam (horses)
butyrophenone licensing and example
- fluanisone (hypnorm)
- rabbit
opioid licensing and example
- methadone
- dogs and cats?
routes of admin for premedication
- IV
- IM
- SC
- OTM (oral transmucosal)
clinical effects of ACP (phenothiazine)
- sedation
- anxiolytic
- sedation improved when combined with opioid and when animal is left in quiet environment
- SC is non-irritant and efficacious
- peripheral vasodilation- can lead to temp drop
ACP (phenothiazine) pharmacokinetics
- onset of effect after IV admin- 10-15mins
- slower than alpha 2 agonists
- onset of action after IM admin- 30-40mins
- duration of action- 4-6hrs
- liver metabolised
clinical effects of alpha 2 agonists
- sedation, analgesia, muscle relaxation
- use body surface area rather than weight for accurate dose
- bradycardia, reduced CO
- individual varied respiratory effects
- can be emetic in dogs and cats
- can depress GI activity
- reduces secretion of insulin
- renal effects- ^urine production
alpha 2 agonist pharmacokinetics
- onset of action after IV admin- 5mins
- peak effect at 30mins
- reversable with atipamezole
- duration of action- 2-3hrs
- liver metabolised
clinical effects of benzodiazepines (BDZs)
- minor tranquillisers, muslce relaxant, anticonvulsant
- can be unreliable in healthy animals
- combine with opioid, alpha 2 agonist, ketamine to improve sedation
- minimal effects on CVS, resp system (mild depression)
BDZs pharmacokinetics
- admin via slow IV
- short plasma half life
- hepatic metabolism, metabolites are active (prolonged effect)
- bioavailable when given intranasally (unlicensed)
- rarely liver failure has been reported in cats
- reversed using= fulmazenil
clinical effects of butyrophenones
- fluanisone
- only available in comb product with opioid fentanyl hypnorm
- provides surgical anaesthesia for minor surgery
- poor muscle relaxation unless combined ith diazepam/midazolam
- moderate-severe resp depression
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possible complications for premedicated patients
- excitement/excessive sedation
- airway obstruction (vomit/anatomical)
- CVS effects
- patient cant compensate for existing/hidden condition
anaesthesia definition
the reversable production of a state of unconciousness required to preform surgery and diagnostic testing
general anaesthesia definition
a state of unconciousness produced by an anaesthetic agent with absence of pain sensatoin over the entire body
regional anaesthesia
insensibility caused by an interruption of sensory nerve conduction in any region of the body
local anaesthesia
lack of sensation in a localised part of the body
sedation definition
the allaying of irritability or excitement
premedication definition
a drug/combination of drugs given prior to the induction of general anaesthesia
sequence of events during induction phase
- IV catheter placement
- pre-oxygenation
- admin of premed if not already given
- admin of induction agent
- security of airway
concept of anaesthesia triad
3 points of triangle- analgesia, narcosis, muscle relaxation
balanced anaesthesia definition
anaesthesia produced by smaller doses of two or more agents is considered safer than usual large dose of a single agent
brachycephalic breed complications during anaesthesia
- airway block
- GOR
- ocular
boxer dog complications with acepromazine
bradycardia and hypotension
collies/sheepdogs and MDR1 gene
- multi drug resistance
- MDR gene responsible for removing some drugs from brain
- with MDR1 mutation present, drugs arent removed and cause a build up causing neuro problems
- do not use ivermectin, butorphanol, acepromazine
dobermann and von willebrand factor BMBT
- dilated cardiomyopathy in 50% of over 6yr olds
- asymptomatic
CAPSAF enquiry
- post op complications were looked at in first 48hr period
- 50% of deaths occured within 3hrs of recovery
- ET intubation has been associated with increased mortality in cats
legislation surrounding anaesthesia
- protection of animals (anaesthetic act)
- prevents castration, dehorning without anaesthesia
- misuse of drugs act and misuse of drugs regulations
list the injectable agents commonly used to produce anaesthesia
- propofol
- alfaxalone
- ketamine
- tiletamine/zolazepam
list the injectable agents commonly used for euthanasia
- pentobarbital
- secobarbital sodium + cincocaine hydrochloride= somulose
criteria of the ideal injectable anaesthetic agent
- rapid onset
- non irritant
- minimal cardiopulmonary effects
- rapidly metabolised and eliminated
- non-cumulative
- good analgesia
- good muscle relaxation
propofol pharmacokinetics and pharmacodynamics
- how it meets ideal injectable anaesthetic agent criteria
- GABA agonist
- rapid onset
- lipid soluble
- rapidly metabolised and eliminated
- non-cumulative
- highly plasma protein bound
- muscle relaxation
- non-irritant
propofol- how it doesn’t meet injectable amaesthetic agent criteria
- no analgesia
- pain on injection
- post-induction apnoea common
- hypotension (myocardial depression)
- heinz body anaemia (RBC break down faster than they can be replaced)
alfaxalone pharmacokinetics and pharmacodynamics
- how it meets ideal injectable anaesthetic agent criteria
- steroid anaesthetic
- high theraputic index (window between effective and toxic dose)
- non irritant
- 20% plasma protein bound
- rapid onset
- rapid metabolism and elimination
- non cumulative
- some resp depression
- preserves baroreceptor tone
ketamine pharmacokinetics and pharmacodynamics
- how it meets ideal injectable anaesthetic agent criteria
- dissociative anaesthetic- NMDA antagonist
- maintains CV/resp function
- analgesia/antihyperalgesia
- non-cumulative through active metabolite nor-ketamine
- 50% plasma protein bound
- can be used as TIVA in horses
ketamine- how it doesn’t meet injectable amaesthetic agent criteria
- slow onset
- poor muscle relaxation
thiopental pharmacokinetics and pharmacodynamics
- how it meets ideal injectable anaesthetic agent criteria
- barbituate
- alkaline
- irritant perivascularily
- rapid onset
- highly plasma protein bound
- moderate CV/resp depression
- predictable
factors that may affect the elimination of an intravenous anaesthetic agent and thus recovery
- drug factors including dose
- species, breed, age
- co-morbidities
- CVS function
- hepatic function
- renal function
- hypothermia
principles of TIVA
- reduces exposurre to inhalant anaesthetic agents
- can be used in the field
ideal properties of a TIVA agent
- rapid metabolism and elimination
- fast onset
- high theraputic index
- pharmacokinetics available
options for induction of anaesthesia
- injectable
- IV
-IM - inhalant
- face mask
- gas chamber
advantages for injectable induction
IV- quick, less stress for animal, reliable
IM- fairly quick, reliable
SC- easy to admin, less painful than IM
disadvantages of injectable induction
IV- relies on IV catheter
IM- painful, slower onset
SC- slow onset, lower efficacy
advantages and disadvantages of gas chamber induction
- great for smallies
- easy set up
- cheap
- no skill needed
- stressful for animal
- difficult to observe
- risk of exposure to staff
advantages and disadvantages of face mask induction
- easy to set up and use
- can give oxygen, VA quickly
- doesn’t protect airway
- increases dead space
- human exposure
- not always tolerated
why correct positioning is important?
- facilitates placement of tubes, catheters
- prevents injury to all
- avoids stiff joints/sores
- ventilation
- surgical access
options for airway management during anaesthesia
- face mask
- laryngeal mask (LMA)
- supraglottic device (V-gel)
- ET tube (ETT)
prinicples of laryngeal mask
- sits over larynx
- reduced complications compared to ETT
- not designed for veterinary use
principles of V-gel
- species + weight specific design
- training needed before use
- blocks oesophagus (prevents aspiration)
principles of ETT
- protects airway
- prevents atmospheric exposure
- cuff system
- murphy’s eye (if main hole is blocked, air can still pass through)
confirmation of correct placement of an ET tube
- gold standard= capnograph
- visualisation of tube between vocal folds
- condensation inside tube
- appreciation of air movement
- don’t press on thorax
ideal inhalational agent
- non irritant
- minimal effects on CVS and resp function
- non toxic
- rapid uptake and elimination
- easily vaporised
- good analgesia and muscle relaxation
MAC definition
minimum alveolar concentration
- conc required to prevent purposeful movement in response to supramaximal noxious stimulus in 50% of patients
- decreased by premed, hypothermia, pregnancy
- increased by hyperthermia, young, hyperthyroidism
MAC purpose
compares potency of agents
partition coefficient definition
ratio of concentration of a compound in two solvents at equilibrium
blood/gas partuition coefficient
describes the solubility of a volatile agent
oil/gas partuition coefficient
higher the coefficient, the more potent the anaesthetic agent
factors that affect uptake, distribution and elimination of inhalational agent
- conc in inspired air
- alveolar ventilation
- blood/gas solubility
- CO
- blood/tissue solubility
does isoflurane meet the requirements of an ideal anaesthetic agent?
- profound CNS and resp depression
- hypotension (from vasodilation)
- no analgesia
- rapid uptake and elimination
potential risk of volatile gases to vet staff
- haemopoetic and neurological abnormalities
- effective scavenging can solve this
