Pharmacology Concepts/ Definitions Flashcards
Grand mal
Intra cranial causes include: Encephalitis, hydrocephalus, trauma, epilepsy
Extracranial causes include Hepatoecephalopathy, toxicity (lead, paraldehyde), hypoglycemia & hypocalcemia.
Typically 4 phases:
- Prodromal: mild behavior change
- Aura: pronounced change in behavior prior to seizure
- Fit/ seizure
- Post ictal: associated with disorientation (these are characterised from human experience)
Petit mal
Partial Seizure:
- Characterized by a short period of unconsciousness
- May not be common in animals
- Sometimes classed as a partial seizure or focal seizure
Jacksonian seizure: slow-moving tonic spasm in appendage
Psychomotor: unusual behaviors
NB: In all cases seizures are a result of overstimulation and excessive electrical activity
Phenothiazines
Dopamine antagonist + anticholinergic, anti-histamine, and adrenergic (α) blocker
- Antiemetic
- Not useful for seizures or storms/fireworks
- No analgesia!
- Hypotensive
Examples: Acepromazine, Chlorpromazine, Promazine.
S.L.U.D.G.E - symptoms of Organophosphate poisoning
- Salivation
- Lacrimation
- Urination
- Defecation
- Gastrointestinal problems
- Emesis
a1 Receptor
- Activation causes the release of intracellular Ca2+ stores excitatory effects
- Found mainly on smooth muscle (contraction)
- Decreased smooth m. motility (GIT)
- Mydrisis (pupil dilation)
- Sphincter contraction (Bladder)
- Increased glycogenolysis (Liver)
a2 Receptor
- Activation causes inhibitory effects
- Located pre-synaptically (pre-synaptic inhibition of NA release)
- Decreased smooth m. motility (GIT)
- GIT sphincter constriction
B1 Receptor
- Activation causes increased Ca2+ conductance
- Located mainly on cardiac muscle (increased HR and contractility)
- Receptor on the heart that causes it beat faster and stronger
B2 Receptor
- Activation causes phosphorylation of intracellular proteins
- Located mainly on smooth muscle (relaxation)
- Dilates (causes bronchodilation, vasodilation)
- Decreased smooth muscle motility (GIT)
- Smooth m. relaxation (bladder)
- increased gluconeogenesis
B3 Receptor
- Found mainly on adipose tissue (lipolysis & thermogenesis)
- Mainly associated with hibernation of animals
Tricyclic Antidepressants
Three main effects of these drugs:
- Block reuptake of amines
- Anticholinergic (muscarinic)
- (also H1 and α1 adrenergic antagonist)
- Sedative
- Required twice a day
Dogs: Anxiety, some aggression, separation anxiety, noise phobias, OCD
Cats: Anxiety, spraying, over-grooming
Example Drugs:
Amitriptyline: Used in small animals, takes 10-14+ days
Nortriptyline: Has active secondary metabolites
Doxepin: Has anti histamine effects, Useful for anxious pruritus
Clomipramine: 200X serotonin > norepinephrine, generally for OCD, takes 6-8 weeks to take effect, can permanently affect neuroreceptor (withdraw use)
Side Effects:
- Sedation
- Anti cholinergic = dry mouth, increased thirst, urinary retention, constipation
- Tachycardia
- Ataxia
SSRI’s (Selective Serotonin Reuptake Inhibitors)
Cats: anxiety, spraying, OCD
Dogs: Anxiety, some aggression, separation anxiety, noise phobias, OCD
- Require 6-8 weeks to effect
- Only need once a day
Side effects:
- Hepatic/ Liver dysfunction
- GIT (lots of serotonin receptors), diarrhoea
- Increased anxiety
Example drugs:
Fluoxetine, Fluvoxamine, Paroxetine, Sertraline
Monoamine oxidase inhibitors (MAOI’s)
Monoamine oxidase inhibitors (MAOI’s)
- Selegiline Fears, phobias and age-related problems esp. canine cognitive dysfunction
Side effects:
- GI effects, restlessness or lethargy, anorexia
- Hyperactivity
- Depression
Contraindication:
- Do not combine with SSRIs, ephedrine, opioids, phenylpropanolamine
Glucocorticosteroids
- Corticosteroids stabilise cell membranes and prevent release of arachidonic acid (and histamine), which disrupts the inflammatory mediator pathway
- Induce gluconeogenesis in the liver
- Provide some control over allergies
- NOT analgesics
- Delay healing
- Increase susceptibility to infections (may activate latent infections)
- Antagonize insulin (beware diabetic patients)
- NOTE: Adverse side effects are dose and/or frequency related
USE:
- Control of immune mediated diseases
- Reduce inflammation and scarring
NSAIDs
- NSAIDs stop the release of COX-1 and COX-2, blocking pain (nociception).
- Can have COX specific and dual inhibitor NSAIDs depending on the desired outcome.
COX-1
COX-1:
- Inhibition is often undesirable
- Homeostatic function
- Nociceptor sensitization (central & peripheral)
- Increased gastric mucus secretion
- Reduced acid secretion
- Increased bicarbonate secretion
- Increased gastric mucosal cell turnover
- Increased platelet aggregation (clotting)
COX-2
COX-2:
- Inhibition often is desirable
- Inflammation
- Nociceptor sensitization
- Vasodilation
- Inhibition of platelet aggregation
- Increased Na excretion (inhibited reabsorption)
- Altered renal blood flow
Antiarrhythmic Drugs
Class One (I):
- Membrane stabilisers that block voltage-gated sodium channels
- Increases the refractory period
- Class 1a, 1b, 1c
Class Two (II):
- B blockers that antagonize adrenergic receptors
- Slow AV conduction and reduce contractility
- Longer fill time (reduced HR)
- Decreased oxygen demand in the myocardium
- Propranolol (non-selective), atenolol (selective B1)
Class Three (III):
- K+ channel blockers
- Antifibrillatory
(e. g.) Amiodarone, Sotalol
Class Four (IV):
- Ca channel Blockers
- Decreased heart rate
- Decreased AV conduction and decreased contractility
(e. g.) Verapamil and Diltiazem
What concurrent findings accompany severe liver disease?
- Ascites/oedema/pulmonary oedema (from hypoproteinaemia)
- Polyuria (decreased urea synthesis)
- Anaemia
- Hypocalcaemia ( decrease in albumin bound Ca and decrease in Vitamin D conversion)
- Hypoglycaemia
- Hypothermia
- Blood clotting
- Jaundice
- Increase in blood ammonia, bile acids, acid base & electrolyte abnormalities
- Hepatic encephalopathy
- Autonomic dysfunction (esp. chronic liver disease) causes increased circulating vasodilators and decreased response to vasoconstrictors
Type A Adverse Drug Reactions
Type A (augmented) reactions:
- Expected but exaggerated pharmacological or toxic responses to a drug
- Primary response exaggeration of the intended response (absolute or relative overdose)
- Secondary response affecting an organ other than the target (side effects)
- The reaction is predictable, dose dependent and usually avoidable.
- Includes the normal side effects of the drug
(E.g.)
- Tachycardia with β2 adrenoceptor agonist bronchodilators (e.g. salbutamol, terbutaline)
- Hypotension with Acepromazine
Type B Adverse Drug Reactions
Type B (Bizarre) reactions:
- Not related to the drug’s expected pharmacological effects
- Unpredictable, dose independent, difficult to avoid
- High mortality
- Drug allergies or drug hypersensitivity reactions
(e. g.) Penicillin allergy - Idiosyncratic reactions
(e .g.) malignant hyperthermia - Anaphylactoid reactions
(e .g.) histamine release on first exposure to the drug as with Cremaphor in “Saffan” - Allergic or hypersensitivity reactions:
- Drugs may act as haptens or as antigens
- Can occur with the active or the excipient
- Require previous exposure
- Severity does not correspond to the dose given
- Cross sensitivity may be seen to drugs with a related structure
(e. g.) A dog allergic to Penicillin G may also be allergic to amoxycillin
Type C Adverse Drug Reactions
Type C (Chronic) Reactions:
- Related to the cumulative dose and duration of administration
(e. g.) Hypothalamic pituitary adrenal axis suppression with long term corticosteroid administration
(e. g.) gastric bleeding after administering naproxen to a dog for 10 days (elimination half life = 72 hours)
Type D Adverse drug reactions
Type D (delayed) reactions:
- Time-related
- Usually dose-related
- Becomes apparent sometime after the use of the drug
- Uncommon
(e. g.) Carcinogenesis
Type E Adverse Drug Reactions:
Type E (end of use) Reactions: - Occurs soon after the withdrawal of the drug
(e. g.) Opioid withdrawal
(e. g.) Hypoadrenocorticism after withdrawal of long term corticosteroids
Type F Adverse Drug Reactions:
Type F (failure) Reactions:
- Unexpected failure of therapy
- Dose-related
- May be caused by drug interactions
(e. g.) A drug that induces liver enzymes may result in the increased rate of elimination of a drug metabolized by those enzymes
Pharmacological Drug Interactions vs Pharmaceutical Drug Interactions
Pharmacological Interactions:
- Pharmacodynamic Interactions:
- One drug might increase or decrease the effects of another
- (e.g.) Co-administration of NSAIDs and glucocorticoids
Pharmaceutical interactions:
- May occur in the syringe or before absorption
- (e.g.) in a liquid dosage form one drug precipitates another (diazepam in IV fluids).
Important considerations for drug dosing in the neonate
In the neonate there may be:
- More efficient absorption from the GI tract
- Increased permeability of the blood-brain barrier
- Decreased plasma protein binding (ppb) and increased volume of distribution (vd) and subsequent slower elimination
- This may be seen as increased drug efficacy or toxicity
- Oral administration of antibiotics may upset the colonization of the GI tract with bacteria
- Hepatic microsomal enzymes develop slowly and at different rates in different species (between 1-8 weeks of age).
- Renal excretion is poorly developed in neonates
Which of the following drugs may be administered via the intra-tracheal route during CPR?
ALADIN: A: Adrenaline L: Lignocaine A: Atropine D: Diazepam I: Isoprenaline N: Naloxone
Adverse events of vaccines
- General Malaise (lethargy, fever, inappetence)
- Discomfort or pain at the injection site
- Mild respiratory signs
- Anaphylaxis
- ‘Blue eye’ (antigen-antibody complex with CAV-1)
- Allergies
- Birth defects (live vaccines)
- Lameness
- Neoplastic changes (Injection site sarcomas)
- Autoimmune disease
Adverse effects of antihistamines
- Central nervous system depression
- Central nervous system excitation
- GI disturbances (vomiting, diarrhea)
- Cardiac arrhythmias
- Pain at injection site
Antibiotics of cattle
Procaine G Penicillin:
- Most common
- Bacteriocidal (kills bacteria)
- Disrupts cell-wall synthesis (effective against Gram-positive)
Oxytetracycline:
- Bacteriostatic (prevents the growth of bacteria)
- Broad spectrum
- Effective against Gram-positive, Gram-negative, and Mycoplasma
Cephalosporines:
- Bactericidal (kills bacteria)
- First to third generation
- The third generation is extremely important in AMR
- Should NOT be your first choice of treatment
- No milk withhold
Sulphonamides: (Sulfadimidine, sulfadiazine)
- Bacteriostatic
Trimethoprim + Sulphadiazine:
- Broader spectrum
- Bactericidal
- Anticoccidial activity
- Resistance to sulfonamide
- Renal excretion
Macrolides: (Erythromycin, Tylosin, Tulathromycin and Tilmicosin)
- Bacteriostatic
- Inhibit protein synthesis
- Bactericidal (in higher doses)
- Primarily Gram-positive bacteria and Mycoplasma
- No CNS distribution
Erythromycin:
- Alternative to penicillin
- Use for mastitis in cattle
Tylosin:
- Gram-positive and mycoplasma infection
- Useful for Mastitis, but is a narrow spectrum
- Used in feed as a growth promotant
Tulathromycin:
- Respiratory infections
- Single injection
- Not used in adult cattle producing milk.
- Not used in bobby calves
Tilmicosin / Micotil:
- Narrow Spectrum
- Concentrates and persists in tissue / especially the lungs
- Use in BRD and Calf pneumonia
- IV can cause death!
- Not used in milking cows.
- Can cause death in humans!
NSAID Toxicity
- GIT disturbances (Colic)
- Hypoproteinemia
- Renal toxicity (Nephrotoxicity)
- Bruxism (teeth grinding due to gastric ulceration)
- Inhibition of bone healing
Banned drugs in racing animals
- Erythropoiesis - stimulating agents, including but not limited to erythropoietin (EPO)
- Insulins
- Growth Hormones
- Insulin-like growth factor-1
- Schedule 8 and 9 substances
Some S8s are exempted - e.g. butorphanol, ketamine, methadone, morphine, and pethidine.
Other excluded substances:
- Antimicrobials (except procaine penicillin)
- Antiparasitics that are approved and registered for use in horses
- Ranitidine (ulcer)
- Omeprazole (ulcer)
- Ambroxol (mucolytic)
- Bromhexadine (mucolytic)
- Dembrexine (mucolytic)
- Registered vaccines (Hendra, TAT etc) (5 days clear required)
- Orally administered glucosamine, chondroitin sulphate
Treatment records for racing animals
- Name of Horse
- Date and Time
- Name of the treatment or medication
- Route of administration
- Amount of medication given
- The duration of treatment (if applicable)
Chemotherapy protocols
Multiagent protocol:
- CHOP protocol (B Cell), LOPP (T Cell)
- Use drugs with differing modes of action
- Survival times (12-15 months)
Single-agent protocol:
- Fewer drug doses
- Shorter survival time (6-8 months)
Metronomic chemotherapy:
- Fixed, low-dose continuous chemotherapy
- Administered daily/ weekly over prolonged periods (months to years)
- Minimal or no drug-free breaks
- Less side effects
- Improved consistency and duration of tx
Targeted Therapy:
