Pharmacology Flashcards
What is the cascade of events when using GA ?
Describe the major organ responses of β1 and β2 agonists
- What Class of Drug induces Vomiting?
- Give an example of these
- What Class of drug would stop vomiting? What must you do before administration?
- Give an example of these
- Emetics
- Apomorphine (dopamine agonist) tablet mixed with water and then give IV or SC. or tab in the conjunctival sac. NOT FOR USE IN CATS
- Xylazine (Alpha-2 agonist at the CTZ) For CATS
- Anti-Emetics - Rule out GIT obstruction
- Metoclopramide (Maxolon) 1. anti-emetic effect (central action) 2. weak upper GI prokinetic effect (peripheral action) IV, IM, PO. Short DOA >6hrs
- Prochlorperazine (Stemetil) Blocks the CTZ via antidopaminergic and antihistaminergic effects
- Ondansetron (Zofran) Blocks Serotonin (5-HT3)
- Maropitant (Cerenia) Highly efficacious neurokinin-1 blocker. Stings! Use cold!
Define and explain the process of protein binding ?
Vd is affected by protein binding.
Drug molecules can bind to plasma proteins (albumin) = bound drugs.
Only free drugs can leave the blood
Protein binding is ; reversible & dynamic
with bound and unbound drugs is equilibrium.
Whatdo we need to check before using Prednislone eyedrops?
Must check for the presence of a corneal ulcer. DO NOT USE, can cause ulcer to get worse and eye rupture.
Provide examples of drugs which may inhibit or induce HME’s ? Hepatic metabolising enzymes
- Induced by anti-convulsants
- Inhibited by ketoconazole (anti-fungal) , can inhibit an expensive drug (cyclosporin) that is used in itchy skin - reducing the cost by using less of the more expensive drug.
- NSAID’s MOA will reduce inflammation by inhibiting cyclo-oxygenase (COX). Which COX would we prefer to select for?
- Name some NSAID’s that Select (Inhibit) for this COX.
- What is a NSAID with no selectivity
- COX-2
- Cox 2 Selective
- Firocoxib - Horses, Dogs, Cats
- Carprofen - Not as Selective for Horses
- Meloxicam
- Ketoprofen
What is the clinical uses of Tropicamide
- What is a MIC?
- What is MBC
- What if MBC>>>MIC?
- What if MBC ~ MIC?
Minimun inhibitory concentration
= the lowest concentration that prevents visible growth after 24hours incubation
Calculated quantitatively by serial dilution techniques
A MIC is a unique number that refers to a specific concentration of an antibiotic that will inhibit the growth of a particular bacterium. This means that there is a MIC for every combination of antibiotic-bacterium
- Minimum Bactericidal concentration = The lowest concentration where 99.9% of a culture is killed after 24hrs incubation.
- If MBC >>> MIC = Bacteristatic (microorganism arrestor)
- If MBC ~ mic = Bactericidal (microorganism killer)
Corticosteroids
What is a :-
- Glucocorticoids
- Mineralocorticoids
- Glucocorticoid - specifically relating to the corticosteroids predominatly produced by the Zona fasciculata “zone” of the adrenal cortex eg cortisol
- Mineralocorticoid - specifically relating to the corticosteroids predominantly produced by the Zona glomerulosa “zone” of the adrenal cortex eg. aldosterone
How does the vaopur concentration affect anaesthesia ?
Why does this occur ?
The more lipid soluble the vaopur the slower the
* anaesthetic induction
* rate of change of depth
* rate of recovery
Why - because the more molecules need to solubilise in the blood for equilibrium to establish or re-establish itself.
Explain the difference between the pattern of drug distrubution and the volume of distribution?
The propensity that a drug has for leaving the blood and entering thte tissues is calculated by the pharmacokinetic term volume of distribution (Vd).
Vd does not inform on the pattern of distrubtion ( lots of drugs in the brain) just the propensity of the drug to leave the blood.
List the sympathetic adrenoceptor agonist drugs and their uses.
- Adrenaline - Anaphylaxis, added to improve other drugs efficacy, cardiac arrest
- Noradrenaline - Similar to Adr but less Beta2 effects
- Salbutamol, Salmeteral - Beta2 agonists for rapid relief of bronchiolar constriction
- Clenbuterol - Beta2 Agonist primary affect the respiratory system but can cause uterine relaxation. This is used to facilitate calvings.
- Phenylpropanolamine - Alpha1 - Constriction of urethral smooth muscle retaining urine therefore used for urinary incontinence
- Xylazine - ALpha2 agonist - sedative
- Yohimbine - Alpha2 antagonist - Reverse sedative effects of Xylazine
- Phenoxybenzamine - Aplha1 antagonist - Relaxing the smooth muscle of the uretheral sphincter - helps clear urinary blockages
- Propranolol, Atenolol - Beta antagonist - Beta Blockers
Describe the factors and identify the rate limiting factors that affect drug absorption?
Disintegration
Dissolution
Absorption
Drug solubility
Surface area
First past metabolism ; exception of oral mucosa & rectum, all absorption from the ailmentary canal , goes directly into the portal vein an so drugs will be exposed to the metabolising enzymes in the liver prior to reaching the systemic circulation.
Vascularity / disease process; decreased blood supply to the site of admin will decrease absorption, decreased GIT motility , delayed gastric emptying leading to reduced exposure time to the small intestine.
Bupviacaine (LA) is beneficial for what applications ?
Why is this the case ? & when is it no appropriate to use ?
- Good for epidurals
- Long acting due to strong affinity with the sodium channels ,slow associatation and disassociation means its long lasting, but also slow to be effective
- when rapid desensitisation is required, due to the slow onset of action it takes a long time to become effective
Explain what ADT or EOD is?
What must you do when a patient is longer term steroids? and why?
Alternate Day Therapy
A method for achieving the lowest possible dose that is still therapeutic, eg Treating a patient with prenisolone for its atopy.
Cephalexin
Beta Lactam
1st Generation Cephalosporin
- Predominantly Gram +ve
- Well suited for Staph pyoderm
Define loading dose and maintenance dose rate ?
Loading dose - amount of drug given intially to obtain the desired plasma concentration asap, expressed in mg / kg.
Maintenance dose rate; rate at which drug needs to be administered to maintain a desireg plasma concentration , expressed in mg/kg/min.
Define the pharmacokinetic parameter of elimination half life T 1/2 .
Is defined as the time taken for the blood/plasma drug concentration to fall by 1/2 (50%).
The pharmacokinetic parameters that determine half - life , are Vd and clearance.
Tetracyclines
- What is the Spectrum of Activity for tetracyclines?
- List the specific diseases where these antibiotics are indicated.
- List the limitations, side-effects
- List teh Tetracyclines
Tetracyclines
- Broad Spectrum bacteriostatic - Gram +ves, Gram -ves (not Pseudomonas), Anaerobes (variable)
- Gold Standard against Chlamydia and good agains Mycoplasma and Rickettsia
- Common side effect is GIT upset with given orally. Some nephrotoxicity,
- Oxytetracycline, Doxycycline (upper respiratory tract small animals)
Name a phosphodiesterase inhibitor
Mode of Action
Contraindications
Pimobendan
Generalised vasodilation including pulmonary, artery less afterload.
Weak Vasodilator
Can I use Corticosteroids as an antimicriobial?
NO
Why are Second generation H1 antagonists (eg Cetirizine) often advitised as “non drowsy?
Histamine contributes to arousal (wakefulness) in the brain and therefore the antagonism of histamine can cause drowsiness. Because the 2nd generation H1 antihistamines do not cross the blood brain barrier significantly (unlike 1st Generation) this side effect reduced and these drugs can therefore be sold as being non drowsy
- What do Macrocylic Lactones kill
- What is their MOA
- Toxicity?
- Name some?
- Broad spectrum - nematondes and arthropods (not trematodes or cestodes).
- Equine -endo and ecto-parasites as oral
- Cattle endo amd ecto-parasites as topical pour-ons
- Sheep endoparasites as oral drenches
- Small animal Heartworm prevention and mite management
- MOA - agonist at glutamate R & GABA-Gated chloride ion channels
- Toxicity, Safe except in Collie breeds who MDR1 gene
- Ivermectin (heartguard plus), Moxidectin (Proheart), Selamectin, Milbemycin
What is the equipment needed for an IV or inhalant GA ?
What control and speed do you have for IV and inhalants for induction and maintenance ?
IV- minimal equip ; suitable for fieldwork, IM for wild animals.
Inhalant - substantial & costly, 02 supply, vaporiser, anaesthetic circuit.
Induction IV - easy, quick & smooth, Bolus doses can be dangerous. Maint -difficult to make even if using additional boluses doses. finer control if using IV CRI.
Induction Inhalant - difficult, slow , usually struggle but maintenance has fine control.
- What is the main side effect of NSAID use?
- What can we try and do to alleviate these side effects?
- What are the other NSAID Side Effects?
- What over the counter NSAID may kill a cat?
- Mostly related to inadvertent inhibition of Cox1 NSAIDS potentially cause Erosion, ulceration and haemorrhage of the GI tract.
- Use of anti-ulcer mediations
- Histamine type-2 blockers
- Proton-Pump inhibitors
- PGE1 analogues
- Barrier medications
- Effects - Related to the inadvertant inhibition of COX-1
- Altered Platelet Function
- irreversibly reduces platelet thromboxane (TXA2) and temporarily decrease endothelial PGI2 –> a net decrease in platelet aggregation used therapeutically as an antithrombic
- Kidney
- Potential for
- Water retention –> Hypertension
- Decreased renal blood flow leading to interstital papillary necrosis and nephritis
- Patients with heart disease are at greater risk of kidney related NSAID complications
- Potential for
- Altered Platelet Function
- 1/2 a 500mg paracetamol
Explain the difference between Efficacy and Potency
Efficacy - maximum effect that a drug can produce regardless of dose. Potency - amount of a drug that is needed to produce a given effect
Cefovecin (Convenia)
Beta Lactam
Very high protein binding (>99%) and decreases clearance rates in dogs and cats prolongs DOA to 2 weeks (will be more efficacious if given q7d)
Skin, Urinary and dental conditions
Difficult to pill animals and where compliance will be an issue, costs about the same as the equivalent oral course. But Beware of the colour change.
Drugs are scheduled depending on what 2 factors?
- The risk of harm to people when used appropriately and inappropriately
- The risk of addiction to people eg Heroin
What does a Insect Growth Regulator (IGR) do
- What is the downside?
- Name some
- IGR
- Insect Growth Hormone antagonists (they dont grow up, - eg Methoprene (the Plus in frontline)
- Inhibit the chitin synthesis pathways –> cannot develop, needed for exoskeleton and eggs
- Not an adulticidal, so must give one if adults are present
- Fipronnil, Imidacloprid, Spinosad, Indoxacarb (Activyl)
Beta-Lactams
- What is the MOA for Beta Lactams
- Define the Sub-Groups
Beta Lactams
- Penicillin tranverses Gram +ve cell wall and reaches cell membrane, Binds to Penicillin Binding Protien (PBP), Disrupts Cell wall synthesis, Bacteria lyse due ot impaired osmotic regulation. BetaLactams can only kill bacteria during thei replication phase. It is a Time Dependent Bactercidal
- SubGroups
- Penicillins,
- Cephalosporins,
- Carbapenems
Beta Lactams
Of the Carbapenem Sub Group what is the Spectrum of Action
- One of our Reserve Drug Classes
- extreamly efficacious
- Gram +ve and -ve aerobes and anaerobes
- highly resistant to beta-lactamases
- not effective agains vancomycin-resistant Enterococci (VRE) or Methicillin-Resistant Staphylococcus aureus (MSRA)
- Often used for severly ill immunocompromised people
- Imipenem, Meropenem
- What is a Prokinetics? And when are they used?
- What do you need to beware of when using?
- Name some
- Stimulating GIT motility, GIT motility often decreased after surgery
- Can make GIT obstructions worse
- Metoclopramine
- Cisapride Dose-Dependent increase in motility from Stomach –> LI
What Gram +ve Obligate Anaerobe is found in ruminants
Clostridum
Understand when a loading dose should be administered.
To quickly enter the therapuetic window of desired drug plasma concentration.
to “fill up “ the Vd. when it is necessary to achieve a high plasma concentration quickly
What are the central CNS effects of histamine?
- Maintains wakefulness
- emesis
- Pharmacokinetic variation
- within the H1 antagonists, lipophilicity can effect the ability to cross the BBB and cause drowsiness
Name an α2 antagonist and its Clinical Uses
Yohimbine
Used to reverse the sedative effects of xylazine
What is the purpose of an excipient?
Excipient is an inactive substance used to carry an active substance. It may make the drug work better or make the drug easier to work with.
Understand the factors of how loading doses are administered?
- Bolus
- Route
Without a LD, 3-5 half lives are required to reach a steady blood concentration.
With a LD , steady blood concentration is achieved straight away.
Name some of the local anaesthetic ?
What is the mode of action for LA?
- Lignocaine, Mepivacaine, Bupivacaine, Proxymetacine.
- Blocking conduction of nerve action potentials & binds to receptor site on neurons NA channel -sodium channel closes - no nerve conductions
What is a corticosteroid?
- Physiology - The steroids that are produced by the adrenal cortex eg cortisol, aldersterone
- Pharmacology - Symthetic steroids with corticosteroid like effect eg prednisolone, dexamethasone, methylprednisolone
What are Schedule 5 drugs?
Give some examples
Must have the word CAUTION on the lable, very low risk unlikely to cause harm.
- Glyphosate (roundup)
- Methiocarb (Baysol Snail Pellets)
- Petrol
- Ethylene glyco (Radiator Coolant)
- Warfarin (RatSack)
Name the Various Drug Administration Routes and list the advantages and disadvantages to each
There are 2 main routes of administration, Oral (PO = per oral or Per OS) and Parenteral (given by injection).
Oral ;drug absorption unreliable and slow through gi tract. safest, economical & convenient route.
Parenteral abreviations -; Most rapid route , high concentrations quickly in systemic circulation. injection injuries, celluitis, pain.
IV - Intravenous; immediate pharmalogical response direct into bloodstream
IM - Intramuscular; greater response than SC due to greater tissue blood flow
SC, SQ - Subcutaneous ; slow rate of absorption , sustained effect.
Intrathercal ; injected directed into the spinal subarachnoid space, bypasses blood brain barrier.
Epidural; injected into spinal canal on or outside the dura mater
Intraosseous; delivered into bone marrow
Intra- articular ; delivered into synovial cavity of a joint
Intraperitoneal; admin into peritoneal cavity
Intrapleural; admin into the pleura
What are the legal authorities who regulate drugs
WA Health Dept
Dept of Agriculture
Veterinary Surgeons Board
Of teh 3 Main Antibacterial targes which are Time depenent, Dose Dependent bactercidals or Bacteristatic?
Explain Placebo Controlled - (negative controlled)
A term used to describe a method of research in which an inactive substance (a placebo) is given to one group of participants, while the treatment (usually a drug or vaccine) being tested is given to another group
Which GA are considered barbituates ?
What is the mode of action for barbituates ?
What other applications suit this GA ?
- Thiopentone & pentobarbitone
- Barbituates decrease the CNS excitability via GABA agonism.
- injectable GA, anticonvulsant, humane euthanasia.
List the uses of Adrenaline and what adrenergic receptors it increases or decreases activity of.
What is the sequence of events that translate an idea into a registered and scheduled drug?
- Drug Development - Very expensive, long winded process undertaken by the drug company
- Drug Testing - Huge financial investment to get the drug to the market, testing is done under the supervision of the body who will register the drug.
- Registration - Australian Pesticides and Veterinary Medicines Authority (APVMA) registration legalises supply, sale and use of veterinary chemical. Therapeutic Goods Administration (TGA) registers the drugs for people often utilising independent scientific advice.
- Scheduling - TGA schedule all “poisons” via Standard for the Uniform Scheduling of Medicines and Poisons.
Of the following Drugs which will agonise which adrenergic receptors?
- Adrenaline (Adr)
- Noradrenaline (NAdr)
- Salbutamol (=Albuterol), Salmeterol, Clenbuterol
- Phenylpropanolamine
- Xylazine
In terms of Inhalant GA , what does MAC stand for?
What is MAC ? and how does this affect the vaopur setting.
Minimum Alveolar Concentration
Which is the partial pressure (concentration) if anaesthetic vapour required to anaesthetise
EG an anaesthetic vapour with a high MAC requires a lot of the vapour to be inhaled to achieve anaesthesia and so the vapour setting will be higher.
Procaine Penicillin
Beta Lactam
Large Animal Practices use this alot
Excellent anaerobic coverage (G+ and G-)
DOES NOT work against Beta lactamase producing bacteria
IM, SC NEVER IV
GA barbitaute Thiopentone is an ultra short acting anaesthetic and has a ___________ anaesthetic effect ?
How does this affect its useage ?
Other considerations ?
Thiopentone is a cumulative anaesthetic.
the culmative effect is most pronounced in lean dogs because there is less fat for the drug to redistribute to , leads to very long recoveries from post op sedation
Avoid thiopentone use in sighthounds, and it needs to be in a highly alkaline (ph11) solution to maintain solubility , dont use in liver failure or for caesareans.
List the things that the Sympathetic chain of the Autonomic Nervous System controls
Fight or Flight
What are Corticosteriod side effects?
- All the NSAID side effect (COX inhibition)
- GIT Ulceration
- Degrease PGE and Decrease PGI2
- additional action here is that is unclear decrease mucosal blood flow
- Kidney failure, hypertension
- GIT Ulceration
- Metabolic
- iatrogenic hyperadrenocorticism during therapy
- Suppression of the hypothalmic-Pituitary-Adrenal axis (HPA axis)
- Sudden cessation of corticosteroids leads to hypoadrenocortical crisis
- Immune System
- Immunosuppression
- more prone to infections and those infections will be more severe.
- Immunosuppression
List the uses of Noradrenaline and what adrenergic receptors it increases or decreases activity of.
Similar to Adr but has considerably less β2
effects
What are the Parasympatholitic drugs and thir clinical uses
Fluroquinolones
- What is the Mode of Action.
- Is there resistance and where should we not use them?
Flouroquinolones
- MOA = Inhibits DNA gyrase action –> Cell Death as cannot cut, untangle and rejoin DNA
- Big probelms once widespread resistance emerges, DO NOT use in Australia for food producing animals.
- REnal degeneration in Cats if label dose exceeded (5mg/kg), Cartlage Deformities (Chelates magnesium) avoid in growing animals
What are Schedule 10 drugs?
Give some examples
Substance of such danger to health as to warrant prohibition of sale, supply and use
Illegal importation
Substances that are prohibited for the purpose listed in each poison.
- Very strong alkali for domestic uses eg pH>11.5 (food additives) or Ph>12.5 (dishwashing additives)
- Ethylene glycol at > 0.25% in toothpaste or mouthwash
- formaldehyde at >0.1% in oral hygine products
- Paints with >0.1% lead
Briefly crtitique the manufactruere claim that their insect growth regulator registered for use against sheep lice is a “rapig knockdown lousicide” ?
Insect grwoth regulators by inhibitinh insect growth hormone and chitin synthesis they are not adulticides. Because they do not directly kill the lice, it is misleading to refer to them as lousicides.
Another LA topical use lignocaine with phenylephrine is more commonly used for ?
Mode of action ?
Other uses ?
topical LA to spray onto larynx of a cat prior to intubation,
Desensitises (not paralysis) & prevents potentially fatal laryngospasm in the cat
Can also be used for removing nasal foreign bodies & nose bleeds.
After Staining Bacteria what colour do Gram Positive bacteria stain?
What colour do Gram negative bacteria stain?
Purple = Gram Positive
Red = Gram Negative
In inhalant GA high lipid solubility gives you ?
A slow and low repsonse.
List the Neurotransmitters and receptors for the sympathetic, parasympathetic, somatic and neuroendocrine systems
Discuss with specific examples, the range of sequale for drug metabolism ?
- Excretion of water soluble metabolite
- Conversion of pro-drugs, through the formation of active metabolites (ie tramadol & prednisone)
H1 antihistamine toxicity?
- CNS
- sedation (drowsiness)
- But at high doses of after rapid IV administration, seizures or CNS excitement
- DO NOT GIVE H1 antihistamines intravenously
- Some antimuscarinic effects (dry as a bone, mad as ahatter, red as a beet)
- dry mouth, mydriasis, tachycardia
Define the term pharmacokinetic parameter clearance (CL).
Clearance describes the ability of an individual organ or the body to eliminate a drug.
List 3 major types of Diuretics
Relate site of action
Loop - Frusemide - Ascending Loop of Henley
Potassium Sparing (Spironolactone) - Collecting ducts
Osmotic (mannitol) -Moves fluid from tissues into plasma
What two controls should a drug study consist of? Describe why these are important.
1) Positive Control, Negative/Placebo Control. 2) In a drug study, a positive control is a compound that is widely accepted to have efficacy for a desired effect. A negative control should not have any effect, so any effect seen should be a representation of the error inherent to the study. By testing a drug against both of these controls, its efficacy AND proven inefficacy. These same controls can be used to measure a compound’s safety
Name some injectable GA ?
Thiopentone , pentobarbitone, propofol, alfaxalone,
ketamine, teletamine-zolazepam.
List the effects of Sympathetic discharge (aganosim)
What is a Placebo?
A Placebo is a tablet, injection etc that does not contain the active ingredient. It should be identical in its taste, appearance etc except that it has no effect (therapeutic or adverse.
What is the mode of action of a Glucocorticoid?
It inhibits Phospholipase A2 therefor decreasing Arachidonic Acid which suppresses COX (1 & 2) and LOX synthesis. Therefore decreasing prostaglandins and leukotrienes
Describe what is meant by Drug Absorption?
Getting the drug from site of administration into the blood (systemic circulation). No absorption phase for IV injections.
Rate and extent the drug gets into the blood is calcuated by the pharmacokinetic term - bioavailability