Pharmacology Flashcards
Name four different types of Aminoglycosides ?
Amikacin
Streptomycin
Gentamicin
Neomycin (topical)
The drug of choice against severe aerobic gram (-ve) infections
Answer = B or D
All are natural products or semi synthetic derivatives of compounds
Mycin = derived from Streptomycess species
micin = derived from micromonospora species
Describe the spectrum of Aminoglycosides ?
The spectrum
The drug of choice against severe aerobic gram -ve infections
- moderate to low activity against gram +ve aerobes (penicillianse Staph)
- Pseudomonas, Aeruginosa, E.Coli and Klebsiella etc
Aerobic - The penetration into cells is O2 dependant across the cytoplasmic membrane Anerobes tend to be resistant, and these drugs are inactive in pus.
Answer = false
Effective against aerobic bacteria only
What is the mechanism of action for Aminoglycosides ?
MOA Aminoglycosides
The MOA is the irreversible inhibition of protein synthesis by irreversibly binding to the 30s ribosomal unit.
- blocks initiation of protein synthesis
- induce misreading of the mRNA template
- persistent suppression of bacterial growth even after the drug is below MIC - possibly due to the irreversible binding
Answer = A
Describe the pharmacokinetic (administration, distribution, regulations) properties of Aminoglycosides ?
Pharmacokinetic
Tier 2
Not approved for use in food animals in Australia
Concentration dependant - one large dose daily
- inter-individual variation is large
- narrow therapeutic range aerobic gram -ve
- oral absorption is poor
- administer parenterally (not digestive)
- good for intramammary use
- distribution complete following IV admin
- highly hydrophilic
- very poor CNS and / or eye penetration
- highly concentrated renal cortex, endolymph and perilymph of the inner ear
- bactericidal action may be enhanced within an alkaline medium
Most aminoglycoside antibiotics are eliminated non-metabolised primarily by glomerular filtration
Describe the regulations governing the use of Aminoglycosides ?
Regulations
Tier two drug - requires empirical evidence
Concentration dependant - one large dose daily
Not approved for use in food animals in Australia
Describe the regulations governing the use of Aminoglycosides ?
Regulations
Tier two drug
Concentration dependant - one large dose daily
Not approved for use in food animals in Australia
Answer = A
Describe the toxicity of Aminoglycosides ?
Aminoglycosides
Drug accumulates in these organs due to the high levels of phospholipids (anionic) and may persist in the kidney for years.
Ototoxicity (vestibular and cochlear)
- This is irreversible and may lead to impaired hearing and balance
- cats are more susceptible
Nephrotoxicity (renal cortex)
- reversable
- proteinuria, azotaemia (build up of nitrogen), serum creatine
Neuromuscular toxicity
- block pre-synaptic ACH at neuromuscular junctions by blocking Ca2+
- may lead to severe CVS and respiration
Name four commonly used potentiated Sulfonamides in Veterinary practice ?
Intermediate acting;
Sulfamethoxine
Sulfamethazine
Sulfamethoxazole
Sulfadiazine
Name two drugs we commonly use to potentiate sulfonamides with - for synergistic bacteriocidal properties ?
Trimethoprim
Ormetoprim
Answer = A, C and D
What is the mechanism of action for potentiated sulfonamides ?
Mechanism of action Sulfonamides
PABA
dihydropteroate
folic acid
- PABA is essential for the synthesis of folic acid in many microbes
- sulfonamides bind to the active site of dihydropteroate synthetase in the place of PABA thus inhibiting folic acid synthesis (Antimetabolite)
- bacteriocidal
Note folic acid is essential for mammalian cell function - which contributes to its toxicity.
Why is there sulfonamide resistance common, how did bacteria become resistant ?
Microbial resistance is widespread in Sulfonamides. This is in part due to the large extensive use of this drug within farming systems (feed and water additive)
Microbes achieve resistance through three primary mechanisms
- alteration of the dihydropteroate synthase pathway
- increase availability of freely available PABA
- impaired drug penetration into the cell
Provide the clinical indications for potentiated sulfonamides ?
Indications of potentiated sulfonamides
This antibiotic can be used in all animal species against a wide range of bacterial infections
- gram + and gram -ve bacteria broad spectrum
- respiratory tract infections
- urinary tract infections
- wound infections and foot rot
- soft tissue infections eg pyodermas
Answer = D
Answer = C.
Describe the pharmacokinetics for sulfonamides, what are the two exceptions ?
Pharmacokinetics Sulfonamides
- varied PKa values, and abilities to bind plasma proteins
- generally more soluble in alkaline PH ( crystallization may occur due to low urine PH or dehydrated animal)
- good oral absorption, parental and topical use
- widely distributed among tissues including CNS, CSF , prostate and pleura
Horses and ruminants are the exception
- variable oral absorption
- Trimethoprim is trapped in the ruminoreticulum and degraded
Answer = A
What are the potential adverse affects of using sulfonamides (7)?
Adverse effects of sulfonamides
Crystalluria
- renal tubular blockage and haematuria (blood in urine)
Keratoconjunctivitis (dry eye)
- check tear duct regularly
Hypersensitivity type three
- glomerulopathy, polymyositis, skin rashes and fever
Hematopoietic toxicity
- aplastic anaemia, hypoprothrombinemia
Thyroid metabolism disorders
- decreasing T4 levels
Diarrhoea in horses following oral administration
Carcinogenesis - lab rodents
Describe the indications and regulation of Metronidazole
Metronidazole
Indications
Metronidazole is used widely for anaerobic infections, inflammatory bowel disease and enteric infections
- used commonly in therapeutic regimes with other antibacterial eg fluoroquinolones, aminoglycosides and B-lactams
Regulation
- prohibited for use in food animals
- tier 2 / second line defence
What is the mechanism of action for Metronidazole ?
MOA Metronidazole
Diffuses into the cell where it is reduced to a free radical under anaerobic conditions (redox reactions)
The free radicals interfer with organism DNA causing breakage destabilisation and death.
- bacteriocidal
- Entamoeba and Giardia
- may also be effective against Trichomoniasis and Pentatrichomonas
- much less effective against aerobes
Describe the adverse effects of Metronidazole ?
Adverse effects of Metronidazole
Another unclean drug
- can cause GI upset
- stomatitis (gum inflammation
- important imunomodulatory effects
- after 7-10 days of full dose treatment may see neurological toxicity; ataxia, nystagmaus, head tilt and rolling over and over
Describe the pharmakinetic properties of Metronidazole ?
Pharmacokinetic properties Metronidazole
- formulated as an injectable and tablets
- less than <20% plasma protein bound
- moderately lipophilic
Metabolised in the liver (oxidation) and excreted in the urine.
Answer = B and D
Answer = A
Answer = A true
Answer = B false
Metronidazole is prohibited for use in food animals within Australia
Name 6 drug examples of Macrolides
Macrolides drug examples
Erythromycin
Clarithromycin
Tylosin and Tilmicosin
Spiramycin (is also anti protozoal)
Tulathromycin - improved G- activity
Azithromycin
Oleandomycin
What is the mechanism of action for macrolides ?
MOA Macrolides
Macrolides are bacteriostatic but are bactericidal in high enough concentrations
Inhibits bacterial protein synthesis
- binds reversibly to 50s subunit of the bacterial ribosome
- inhibiting translocation of peptidyl TRNA
- interferes with chloramphenicol binding
- competitive antagonism
Macrolides tend to accumulate within leukocytes and are transported into the site of infection
Describe the spectrum of activity in macrolides ?
Spectrum macrolides
Gram +ve and tier 2 drugs
- pneumococci, streptococci and staphylococci
- chlamydophilia
- campylobacter
- pasteurella
- rickettsia ( foal lungs)
- mycoplasm
- cornybacterium
- rhodococcus
- bacteroides
Most other gram -ve anerobes and enterobacteriaceae are resistant
Describe macrolides and their general indications ?
Indication of macrolides
Gram +ve bacteria
- Camplylobacteriosis - rarely a first choice
- pneumonia and other respiratory infections (BRD)
- footrot
- mastitis - Oleandomycin
Describe the pharmacokinetic and metabolism of Macrolides ?
Pharmacokinetic features of macrolides
Most macrolides distribute well into most tissues except the CSF, and tend to concentrate in certain cells notably the lungs (accumulate leukocytes)
- -erythromycin destroyed stomache acid
- Azithromycin and Clarithromycin better absorbed longer half life
Metabolism
- primarily hepatic followed by biliary secretion
- erythromycin excreted in urine
Name two Lincosamides ?
Lincomycin
Clindamycin
Describe the mechanism of action for Lincosamides ?
These act by reversibly binding to the 50s ribosomal subunit
at the 23s portion inhibiting bacterial protein
biosynthesis
What are the clinical indications and spectrum for Lincosamides ?
Spectrum
- gram +ve anaerobic bacteria
Indications Lincosamides
2/3 tier drugs
- good bone penetration
- dose not penetrate into the eye or CNS
- useful against resistant penicillin staphlococcus and streptococcus sp.
- bone infections
- periodontal disease
- upper respiratory tract infections
- skin
What are the adverse affects of macrolides
Adverse affects of Macrolides
- muscle paralysis
- erythromycin known to cause GI upset
- non fatal diarrhoea in horses and small ruminants
- altered temperature / homeostasis
- cardiac effects
- IM injections are very painful
What is the spectrum and indications for Chloramphenicol ?
Chloramphenicol
Spectrum
- gram + and -ve
- aerobic and anaerobic
Indications
- Rickettsia
- Chlamydia
- Typhoid fever
- Brucellosis
- Bacterial meningitis
- Corneal infections
Answer = D
Answer = A
Answer = B
Answer = C
Answer = A
Answer = A
macrolide with rifampin
Answer = A
Describe the mechanism of action for Chloramphenicol ?
Chloramphenicol
Chloramphenicol penetrates bacterial cells by facilitated diffusion and then inhibits protein synthesis.
The drug binds reversibly to the 50s ribosomal subunit
- this prevents the binding of the amino acid containing aminoacyl tDNA to the acceptor site on the 50s roibosomal subunit.
Describe the mechanism of action for Chloramphenicol ?
Chloramphenicol
Chloramphenicol penetrates bacterial cells by facilitated diffusion and then inhibits protein synthesis.
The drug binds reversibly to the 50s ribosomal subunit
- this prevents the binding of the amino acid containing aminoacyl tDNA to the acceptor site on the 50s roibosomal subunit.
Answer = A
What features define general anaesthesia in clinical applications ?
Features with define general anaesthesia
We want to achieve four things
1 Loss of consciousness
2 Analgesia
3 Muscle relaxation
4 Amnesia
There is no single drug which can achieve all four features (without patient death), so combinations of drugs are most commonly administered
Answer = A true
Why is it crucial to induce anaesthesia rapidly ?
To avoid stages one and two of general anaesthesia
Stage one = general analgesia with voluntary excitement, with or without amnesia
Stage two = delirium and involuntary excitement
- salivation, urination, defaecation
- cardiovascular tachycardia
- bronchospasm
- laryngospasm
Identify six commonly used anaesthetic agents ?
Isoflurane
Sevoflurane
Methoxyflurane
Desflurane
Halothane
Nitrous oxide
What is the mechanism of action for inhalation anaesthetics ?
Inhalation anaesthetics
Poorly understood for inhalation anaesthetics
Most likely
- inhibition of glutamate receptors
- increased GABA activity
- many different theories proposed
What possible factors could affect the # inhalation anaesthetics ?
(effectiveness, potency, onset and duration of action).
Factors to determine the effectiveness of a given quantity of drug
Inhalation anaesthetics are delivered straight to the lungs for absorption and distribution.
Cardiac out put and ventilation ratio
- inspired concentration of anaesthetic
- alveolar ventilation and respiration
- solubility in blood and other tissues (blood : gas portion)
- more soluble anaesthetics tend to show a slower induction
- cardiac out put + diffusion ratio
- tissue perfusion and solubility in lipid (oil; gas partition coefficient)
- intrinsic activity within the CNS
Ventilation perfusion ratio is critical
If an inhalation anaesthetic had a higher solubility what would that affect ?
Increased solubility
Rate of onset in inversely correlated with solubility in blood.
Blood serves as a ‘sink’ for soluble agents
Describe the effects of increasing the lipophilic character of a inhalation anaesthetic ?
Increased potency of inhalation anaesthetics
More lipophilic anaesthetics have a higher potency - because of the gradual accumulation in body fat the “hang over” effect.
Answer = F all of the above
Define MAC ?
Mac = minimum alveolar concentration at 1atm producing immobility in 50% of patients exposed to a painful stimulus
Factors determining the alveolar concentration toward the inspired concentration (FA/F1) will determine the minimum alveolar concentration
Describe four factors which could cause the MAC to increase ?
Describe seven factors which could cause MAC to decrease ?
Describe the Pharmacological features and systemic effects of Isoflurane
Isoflurane
- moderate potency (MAC 1.2 -1.7)
- pungent
- minimal hepatic metabolism
Systemic effects
- depresses respiratory drive and ventilation
- myocardial depressant, sensitises myocardium to catecholamines
inhibits sympathetic baroreflex responses and may cause a reduction in systemic vascular resistance (mean arterial flow)
- good muscle relaxant propertes
- anticonvulsant activity
- potentiates non - depolarising neuromuscular blockers
Answer = A
Describe Halothane and its systemic effects ?
Halothane
may induce convulsions
~ 30% metabolised to trifluroacetic acid in the liver and repeated usage can lead to hepatitis
Systemic effects
- dose dependant depression of the CNS, causes muscle relaxation (Minimal analgesia)
reduce cardiac output through contractility
- sensitizes myocardium to exogenous catecholamines
- decrease baroreflex response
- central depression of respiratory rate
- tachycardia
- acidosis and hyperkalemia
- disseminated intravascular clot (DIC)
Answer = B
Answer = B no analgesic properties
Answer = D
Describe the contraindications of using Halothane ?
Contraindications of Halothane
- causes of increased intracranial pressure eg tumour
- cardiac or severe respiratory dysfunction
- patients with hepatic or kidney disease
- animals that have suffered a malignant hypothermia
- halothane will interfere with hepatic metabolism and clearance of co admin drugs
- avoid Ca2+ and beta blockers
- potentiates the effects of non - depolarising neuromuscular blockers
Discuss the properties of sevoflurane ?
Discuss the pharmacological features and any contraindications of Nitrous oxide ?
Nitrous oxide (laughing gas)
Has a low potency so often used in combination
- has analgesic properties via NMDA receptors
- minimal cardiovascular and respiratory effects
Prolonged use inhibits methionine synthatase, causing folate deficiency and bone marrow defects
Contraindications
- cases of intracranial pressure eg brain tumours
- pneumothorax, gastric dilation or volvulus (not used in ruminants for this reason)
- severe respiratory disease
anaemic patients
What are the advantages and disadvantages of injectable anaesthetic drugs ?
Provide the classification of generally injectable anaesthetics ?
Provide the mechanism of action for barbituates (such as Thiopental), Propofol (Etomidate), Alphaxalone
MOA injectable anaesthetics
All act by enhancing the efficiency of GABA at different sites of GABA receptors.
What is the mechanism of action of Ketamine ?
Mechanism of action Ketamine
- glutamate antagonist
- binds non competitively to the NMDA receptor to inhibit excitory effects of glutamate
- ketamine has a weak action on GABA receptors
Answer = A true
What factors affect the speed, duration effect and recovery after a injectable anaesthetic ?
Describe the distribution - redistribution phenomenon of injectable anaesthetic drugs ?
Initial unequal distribution
The brain is well perfused initially. The CNS concentration quickly equilibrates with blood levels. Equilibrium in muscle and fat is slow.
- rapid vessel rich organs and CNS
- slow distribution in poorly vascularised organs
- metabolism contributes to lowering of plasma blood concentrations
The anaesthetic then redistributes out of the brain to restablish equilibrium with plasma. All these factors contribute to decreasing CNS effects
Which patient is most at risk ?
Underweight and overweight patients at greatest risk
Overweight patient
- The bolus distributes primarily to well vascularised tissue (brain, muscle)
- muscle has been replaced by fat so that fraction of drug ends up in the brain (brain has a larger share).
- Double whammy - the drug then builds up in fat prolonging recovery for an overweight animal. Perfusion of drug out of fat is limited.
Underweight patient
- concerns liver function - metabolism of drug
- The animal has very little muscle so the fraction of drug usually distributed to the muscle, is redistributed to the brain (greater fraction of drug distributed to the brain)
1 = vessel rich group and blood
2 = fat adipose tissue
3 = vessel rich group
Describe the general pharmacological effects of injectable anaesthetics ?
General pharmacological effects
- reversible dose dependant depression of the CNS
- dose dependant cardiovascular depression
- dose dependant depression of respiration and apnea.
First order kinetics
Compare therapeutic indices of injectable anaesthetics ?
Discuss the general characteristic of Propofol ?
Propofol (Etomidate, Guaifenesin)
A substituted isopropylphenol
- insoluble in water
- rapid onset and duration of action
- myocardial depression and peripheral vasodilation
- baroreflex not suppressed (as much as thiopental)
- antiepileptic effects
- minimal nausea, vomiting and foetal depression
Recovery in cats is prolonged - lack glucuronidase
A = enhancing the efficiency of GABA at different sites of GABA receptors
B = rapid onset - reasonable risk of overdose
C= Short half life so requires continuous slow administration - high risk of overdose.
D = No Propofol has no analgesic properties
Discuss the pharmacokinetic properties of Alfaxalone ?
Alfaxalone
A water soluble anaesthetic
- no histamine release
- rapid induction agent
- very short duration of action
- upto 50% protein bound and undergoes rapid hepatic glucuronidation and clearance
Effects
- Decrease BP may increase HR with minimal effect on cardiac output
- depresses respiration
- muscle relaxation but no analgesia
- no accumulation, rapid recovery and has shown good results for C sections
Alfaxalone
A = analgesic properties
B = rapid induction with depressive effects on respiration and blood pressure
C = decreases blood pressure
D = incremental small doses over time - top ups
Identify three dissociative anaesthetics ?
What is the effect of dissociative anaesthetics ?
Dissociative anaesthetics
Patient is dissociated from or unaware of their environment during induction
These drugs interupt cerebral association pathways and are associated with
- dissociation from the environment
- amnesia
- immobility
- catalepsia ( muscle rigidity)
analgesia
What are the systemic effects of Ketamine ?
Ketamine systemic effects
- induction agent avoids stages 1 and 2 of anaesthesia
- can also be used as a sole induction agent
- stimulates the sympathetic nervous system (increase HR, BP and cardiac output)
- maintain laryngeal and pharyngeal reflexes and skeletal muscle tone (catelepsy)
- maintain protective reflexes ( cough, swallowing, pedal and corneal)
- stimulates salivation - making it a poor choice for endoscopy or oropharygeal surgery
Ketamine is often combined with
- Benzodiazepines
- alpha 2 agonist
- Phenothiazines
- general anaesthetics
Describe the metabolism and secretion of ketamine ?
Ketamine
Ketamine is rapidly distributed into body tissues
- 50% proetin bound undergoes hepatic N- demethylation and hydroxylation of the cyclohexanone ring
- followed by glucuronidation and elimination in the urine
What are the contraindications of ketamine ?
Contraindications of ketamine
- increased intracranial pressure
- pathological tachycardia
- elevated sympathetic tone (hyperthyroidism)
- hypertrophic cardiomyopathy
- malignant hyperthermia
What drug could be used as a muscle relaxant ?
What drug could be used as part of an anaesthetic plan to provide anxiolytic effects ?
Define a tranquiliser, sedative and neuroleptanalgesia ?
Provide the names of three drugs with tranquilisers or neuroleptic properties ?
Tranquilisers
Phenothiazines
Butyrophenones (Acepromazine)
Benzodiazepines (diazepam, midozalam and zolazepam)
Provide three examples of sedatives ?
Sedatives
Alpha adrenergic agonists
Xylazine, Detomidine, Medetomidine and Dexmedetomidine
Anticholinergic agents
Atropine, glycopyrrolate
Opioid analgesics
Other centrally acting muscle relaxants
Provide four examples of Phenothiazines ?
Phenothiazines
Tranquilisers relieve anxiety
Acepromazine
Promazine CL
Chlorpromazine
Thioridazine
What is the mechanism of action for Phenothiazines (#3) ?
Phenothiazines
Acepromazine Chlorpromazine
Derivatives block dopamine (DA2 receptors)
- this alters motor control
- inhibits stimulation of CRTZ (anti emetic effect)
- may have 5-HT2 histamine and alpha adrenergic blocking effects
Thus controlling mood wakefulness, feeding , behaviour and vomiting etc
- crucial preanaesthetic
Describe the pharmacological effects of Phenothiazines ?
Phenothiazines
- generally well absorbed from one IM injection
- duration of action is 4-6 hours and dose dependant
- lipophilic
- well distributed
- metabolised by hepatic enzymes and has renal excretion
What are the effects and contraindications of Phenotthiazines treatment ?
Phenothiazines effects
- Sedative
- anti histamine and anti cholinergic
- potentiates analgesia (only)
- dopamine controls muscle activity may cause tremors or restlessness
- modification of thermoregulatory centres
- may lower seizure threshold in dogs
Contraindications
- peripheral vasodilation and arterial hypotension
- hypovolemic and shock
- bradycardia (decrease heart rate)
- reduced GI motility
Describe why Epinephrine is contraindicated for use with Phenoxybenzamine ?
Phenoxybenzamine irreversible binds alpha one receptors
(Epinephrin usually predominately binds with alpha 1 receptors causing an increase in blood pressure)
As the alpha one receptors are blocked, epinephrine carries out its effect through the B 2 recetors
” due to epinephrine reversal”
This causes a fall in blood pressure
B2 receptor activation leads are inhibitory in vascular smooth muscle = vasodilation / hypotensions
Answer = C
Why would Acepromazine be contraindicated in breeding stallions ?
Provide examples and the MOA Butyrophenone derivatives ?
Provide three examples of Benzodiazepines, and discuss their pharmacological effects ?
Benzodiazepines = sedatives
Diazepam
Midazolam
Zolazepam
Pharmacological effects
- sedative and hypnotics
-anxiolytic
- anticonvulsants and muscle relaxant
Not very reliable as sedatives in healthy animals
Benzodiazepenes tend to potentiate effects of narcotic analgesics, barbituates and dissociative anaesthetics
No analgesic effects=
What drug could be used as an antagonist to Benzodiazepines ?
Flumazenil
What is the mechanism of action for Benzodiazepines ?
MOA Benzodiazepines
Activation of the GABA receptors - a ligand gated channel
Activation leads to hyperpolarisation
This leads to
- sedation
- hypnotics
- anticonvulsants and muscle relaxant
- variable effects in healthy animals
What affects dose diazepam have on respiration and CVS ?
Diazepam
Respiration
- mild but dose dependant depression of respiration
CVS
- higher doses reduce vascular resistance, vasodilation
- increases coronary blood flow by increasing cardiac output
What three drugs dose Benzodiazepines potentiate (3) ?
Benzodiazepines potentiation of
Mild sedation and muscle relaxation
- potentiates ketamine’s for muscle relaxation
- potentiates opioids for analgesia
- potentiates barbituates
What are the adverse effects of Diazapam ?
Adverse effects of Diazepam
- minimal respiratory and CVS effects (except overdose)
- hepatic failure seen with repeated doses in the cat
- foetal abnormalities / avoid in pregnancy
- may markedly enhance CNS effects of other drugs
Provide four examples of an alpha two adrenoreceptor agonists ?
Alpha two adrenoreceptor agonists
Xylazine
Detomidine
Medetomidine
Dexmedetomidine
Provide the mechanism of action and effects of an alpha 2 agonist ?
Alpha 2 agonist Detomidine
MOA
Stimulation of alpha 2 receptors triggers a G protein receptor signalling which decreases sympathetic outflow
- presynaptic alpha 2 receptor activation inhibits epinephrine (NE) release
Effects
- sedation (reversable)
- muscle relaxation
- mild to moderate analgesia
Alpha two receptors are widely expressed in the cardiovascular, respiratory, CNS and gastrointestinal systems.
Describe the pharmacokinetic properties of Alpha 2 agonists ?
Pharmacokinetic properties of Alpha two agonist
- short duration of action
- highly lipophilic
- well absorbed following IM or IV injection (oral administration not recommended)
- metabolism is primarily by hepatic oxidation, glucuronidation and urinary excretion
Some of these drugs are not to be used in animals for food production.
What are the adverse effects of alpha 2 agonist ?
Alpha two agonist, adverse effects
- transient vasoconstriction
- reflex bradycardia, hypotension and decreased cardiac output follows
(due to vagal and central alpha 2 stimulation)
This affect may be prevented through the use of Atropine.
Provide a summary of Phenothiazines ?
Phenothiazines
Provide a summary of Benzodiazepines ?
Provide a summary of alpha 2 agonist ?
Answer = A
Define the terms pain, acute pain and chronic pain ?
Pain = An unpleasant sensory and or emotional experience associated with actual or potential tissue damage
Acute/ adaptive pain =
May last 1-3 months and is commonly associated with tissue damage/injury. This pain can be nociceptive and inflammatory in origin and serves to sense and protect against actual or potential tissue damage
Chronic / maladaptive
Greater than three months and is often associated with some chronic disease eg neoplasia, degenerative joint disease and damage in neural tissues or plastic changes in pain processing (neuropathic).
Name five local anaesthetics ?
Procaine
Lidocaine
Rapivacaine
Mepivacaine
Bupivacaine
What is the mechanism of action for local anaesthetics ?
Local anaesthetics
Rapivacaine, Bupivacaine and Procains
Local anaesthetics bind to intracellular
VOLTAGE GATED ION CHANNELS
and this inactivates Na+ channels at specific sites with no loss of consciousness.
Axonal conduction is slowed by reversibly inhibiting Na+ influx and K+ efflux and the rate and magnitude of nerve depolarisation.
Nerve impulses generated downstream from the blocked nodes of Ranvier are not propagated to the ganglion
Ideally = reversable, no toxicity and a reasonable duration of action.
Describe the pharmacological features of local anaesthetics ?
Local anaesthetics
Aromatic esters or amides linked to side chains (weak bases)
- active in ionised form
- but must penetrate cell membranes in non ionic form
Procain and Chloroprocaine - hydrolysed cholinesterase a metabolite associated with allergic reactions
Lidocaine, Bupivacaine and Mepivacaine
Are more stable with longer half lives - metabolic inactivation occurs in the liver with minimal induction of allergies
Considerations
- PH
- exhibit use / frequency dependancy
- lipophilicity and protein binding
- tissue perfusion and vasodilatory activity
- preferential activity (neuron size)
Answer = A
Answer = A
Answer = B
Answer = E
Answer = C
Answers
- True
- True
- False
- True
Provide some examples for the use of local anaesthetics ?
Indications
- skin and subcutaneous tissue minor operations
- lumbosacral epidural
- topical use
- peripheral nerve block eg dental, brachial plexus
- postoperative ileus in horses
- malignant ventricular arrythmias
What are the adverse effects of local anaesthetics ?
Adverse effects of local anaesthetics
These effects are abserved due to excessive concentration in plasma of local anaesthetics
- restlessness, agigtation, generalised CNS depression
- followed by seizures and respiratory arrest
- decreased contractility and vasodilation
Treatment = barbituates
What is dose frequency dependence of LAs
Frequency dependence
Depth of block increases with AP frequency
- increased open probability of the channel
- a higher affinity for active channels than for resting channels
This is useful for the anticonvulsant effects of anaesthetics
What is preferential activity of LA ?
Preferential activity of LA depends upon neuron size
- high sensitivity for thin non myelinated nerves; pain touch and temperature
- medium sensitivity = thin myelinated nerves
for sympathetic nerves; visceromotor function - low sensitivity thick and myelinated nerves the somatic system and motor function
How dose a high PH affect the action of LA (in such a case as inflammation) ?
High PH and LA
High PH
- Charged cationic form of LA bind to receptor site, reducing its effectiveness
Low or neutral PH
- uncharged form is required to pass through the cell membrane
We can alter the efficiency of LA by altering the internal or external PH.
Describe the principles of MINDME ?
Answer = B
Answer = A
Poor distribution in lipophilic tissue
Answer = A
Ototoxicity =
This is irreversible and may lead to impaired hearing and balance (cats are more susceptible)
Nephrotoxicity
High levels of phospholipids thus attracting aminoglycosides
- inhibits lysosomal phospholipases and may persist in the kidneys for years.
Describe common examples of the Floroquinolones ?
Floroquinolones
Enrofloxacin (Baycox)
Pradofloxacin
Marbofloxacin
Orbifloxacin
The big guns finish in floxacin
Describe the mechanism of action for the Floroquinolones ?
Floroquinolones mechanism of action
Bactericidal
Quinolones bind bacteria DNA gyrase (topoisomerase 2 and 4) enzymes that controls the supercoiling of bacterial DNA by catalysing the cleavage / reunion of strands in the DNA molecule.
This leads to the stabilisation of the DNA complex; broken strands can no longer be released and
DNA replication is blocked
Answer = A
Answer = C
Describe the spectrum of activity and indications of the Fluroquinolones ?
Fluroquinolones
Mostly active against gram -ve aerobes
- some activity against gram +ve aerobes
- some hit chlamydiae, Mycoplasma, Bartonella, Brucella and some Mycobacterium
- has shown better activity against Pseudomonas the B lactams and gentamicin
Considered a big gun tier two drug, not suitable for routine non life threatening situations.
Indications
Examples for which fluroquinolones may be indicated
- recurrent UTIs pseudomonas, Kelbsiella
- bacterial prostatitis in a dog
- deep granulomatous pyoderma
- serious respiratory tract infection
- febrile, neutropenic patients with (G-) systemic infections
- extensively used against G(-ve) bacterial infections in small mammals, birds, reptiles and fish.
Good for stubborn gram negative aerobes + good penetration into poorly vascularised areas.
Answer = false
Describe the pharmacokinetic properties of Fluroquinolones ?
Pharmacokinetic properties of Fluroquinolones
- good oral absorption
- good distribution to most tissues / especially the prostate, kidney, liver, lungs, bones, skin and CSF.
- low protein binding
- low ionization
- highly lipophilic
However, food antacids and surfactant (di,tri valent cations) may lower absorption.
Concentrates in the genitourinary tract and respiratory secretions have higher conc than plasma
- extremely high levels within phagocytes (10* plasma).
Partially metabolised in the liver - with high GI or renal secretion
Describe the regulations surrounding the fluoroquinolones ?
Fluroquinolones
These are ‘concentration dependant drugs’ with a strong post antibiotic affect.
Recognised in Australia use of quinolones in food producing animals is prohibited
Answer = D and C
Define the MSW ?
The susceptible wild type population is readily killed after exposure to an antibiotic. Where as the nutant population may be amplified.
The hypothesis is that selection of resistant mutants occurs when the when drug conc are within the MSW (mutant selection window).
The MSW lies between MIC and mutant prevention concentration.
1.
Narrow spectrum efficient
- Answer = B
Describe the adverse affects of the fluroquinolones ?
Answer = A
Name commonly used potentiated Sulphonamides in Veterinary medicine ?
Potentiated Sulphonamides
Sulfamethoxine
Sulfamethoxazole
Sulfamethazine
Sulfadiazine
Frequently used as food and water additives on farms.
Potentiated commonly with Trimethoprim and Ormetoprim
