Pharmacology Flashcards
1
Q
What is phenobarbital?
A
First line anti-epileptic. Promotes GABA- inhibitory mechanism. Metabolised in the liver. Side effects- sedation, PD, PP, hepatotoxicity. Time to effect 10-15d
2
Q
What are the side effects of phenobarbital?
A
TT4 and fT4 reduction
Effect on liver- ALP elevation
Rare but severe- behaviour alterations, immune mediated neutropaenia, thrombocytopaenia, anaemia. Superficial necrolytic dermatitis. Idiosynchratic hepatotoxic reactions.
3
Q
When is potassium bromide used in epilepsy?
A
As an add on- to reduce side effects or as 1st line. Time to effect 100-200d. However, may be preferable in a young animal as long term hepatotoxicity risk w/ phenobarbital. Excreted renally.
4
Q
What are the side effects of potassium bromide?
A
Sedation, weakness, PU, PD, GI irritation, (pancreatitis)
5
Q
What drugs can be used as add-ons for refractory seziures?
A
Gabapentin Pregabalin Levetiracetam Zonisamide Felbamate
6
Q
What is the first line choice for AED in cats?
A
Phenobarbitol 2-3mg/kg PO SID/BID. Side effects- PP, BM suppression, cutaneous hypersensitivities
7
Q
What is the second line choice for AED in cats?
A
Diazepam. Side effects- (acute) hepatotoxicosis, evaluation of liver enzymes 5-7d after inititiation
8
Q
What are the stages in stabilizing the epileptic patient?
A
ABC
Place IV catheter
Bloods- PCV, TP, glucose, electrolytes
IVFT
Antiepileptic drug- diazepam, phenobarbitone
Minimise complications- treat hypotension and hypoxameia, minimise hyperthermis and renal impairment
9
Q
What are the options for maintenance therapy of epilepsy?
A
Phenobarbitone, Potassium bromide
2nd line- diazepam, midazolam, propofol, levetiracetam, ketamin
10
Q
In most cases behavioural modification is enough to resolve an anxiety/ fear problem so what is the role of drugs?
A
When fear/ anxiety is great- risk of disinhibition, unavoidable conditions, suffering from chronic anxiety/ repeated fearful experiences
When px likely improved- longstanding/ severe so less likely to respond to behaviour modification, where distraction is difficult, if speed of recovery critical
11
Q
What are the two specific psychoactive drugs licensed for used in companion animals?
A
Clomipramine
Selegiline
12
Q
What is the mechanism of action of clomipramine?
A
Depression due to few occupied receptors. Blocks serotonin reuptake. Initially leads to incr serotonin in synapse (poss incr anxiety) and then long term leads to down regulation of Rs- clinical effects. Elevate mood, reduce anxiety, block development of panic
13
Q
What is the cause for the side effects of clomipramine?
A
H1-R antagonism- weight gain, sedation
ACh M1-R- constipation, dry mouth
a-adrenoceptor- hypotension, sedation
14
Q
What are the features of benzodiazepines as psychogenic drugs?
A
Not licensed. Only class consistently succeeds in all models, may have dangerous disinhibitory effect on aggression. Eliminate avoidant responses, inhibit memory formation
15
Q
What condition is clomipramine licensed for and what other conditions can it be used for?
A
Licensed- separation anxiety
Unlicensed- anxiety related problems (esp panic), stereotypy/ compulsive disorders, aggression where anxious apprehension is an obstacle to tx, spraying where anxiety, esp chronic, is a factor
16
Q
What are the different serotonergic drug classes and their SRI:NRI?
A
TCA- amitriptyline 1:4 (strongly noradrenergic, can cause explosive emotional reactions in man)
SRI- clomipramine 5:1
SSRI- fluoxetine 15:1, sertraline 150:1
17
Q
What are the possible drug interactions for serotonergic drugs?
A
Amitraz
Opioids (resp depression)
MAOIs (selegiline- serotonine syndrome)
Phenothiazines
18
Q
What are the specific medical cautions for use of serotonergic drugs?
A
CVS dz (arrhythmias) DM- TCA/SRI drugs hyperglycaemic Thyroid dz (altered metabolism of TCAs) Epilepsy Narrow angle glaucoma
19
Q
What is serotonin syndrome?
A
If drug dose persistently high or combined w/ an MAOI:
GI distress, head pain, agitation, incr HR, body temp, RR, muscular rigidity, convulsions, coma, death
20
Q
What is the action of selegiline?
A
Selective MAOIb inhibitor (inhibits catabolism of DA and histamine), but does have v low level of MAOIa inhibition (inhibits catabolism of serotonin, Ad, NAd). Direct antidepressamt effect via incr DA. Main uses for tx of fears, phobias, cognitive decline. Incr exploratory and risk taking behaviour
21
Q
What are the adverse effects of selegiline?
A
Agitation, GI signs (nausea, D+), drowsiness, headache, abdominal pain, hallucinations
22
Q
What are the drug interactions of siligiline?
A
TCA/SSRI- serotonin syndrome
Benzodiazepines
ACP
23
Q
What is allodynia?
A
Non painful stimulus becomes painful due to inflammation, tissue damage etc causing peripheral sensitsation
24
Q
How is pain information transmitted and modulated in the SC?
A
1st order neurons synapse in dorsal horn. Myelinated A(delta) fibres carry 1st pain (quickly- sharp pain). Unmyelinated C fibres- 2nd pain, visceral pain (slower). Amplified or suppressed in the SC. Dorsal horn has interneurons and ascending neurons. Can have descending inhibitory control
25
What is peripheral and central sensitisation?
Peripheral- inflammation, tissue damage etc change receptors from high threshold nociceptor to low threshold
Central sensitisation- painful info from periphery constantly opens NMDA receptors to brain---> chronic pain
26
What are the descending pathways of DNIC (diffuse noxious inhibitory control)?
Originate in the brain (amygdala, hypothalamus) relayed via brain stem, rostral and ventral medulla to SC. Release of inhibitory NTs (seratonin, NEp, endogenous opiods). Help modulate pain.
27
What are the stages leading to perception of pain in the brain and what drugs can be used to target them?
Transduction (nociceptors)- local anaesthetics, opioids, NSAIDs
Transmission (peripheral nerves)- local anaesthetics
Modulation (SC grey matter)- opioids, a agonists, local anaesthetics, NSAIDs, ketamine
Projection (SC white matter)- ascending input and descending modulation
Perception (brain)- opioids, a2- agonists, anaesthetics, benzodiazepines, phenothiazines
28
What are the 4 different opioid receptors?
delta- spinal and supraspinal analgesia, reduced gastric motility
kappa- spinal analgesia, diuresis, dysphoria
mu- analgesia, sedation, bradycardia, resp depression
nociception- hyperalgesia and allodynia, supraspinal inhibition of opioid tone
29
What are the different types of opioids?
Full u agoists- morphine, methadone, pethidine
Partial u agonist- buprenorphine (same overall action but doesn't produce maximal effect)
Mixed agonist-antagonist- butorphanol (antagonist a u, agonist at k)
Antagonists- naloxone, diprenoprhine
30
What are the side effects of opioids?
Arousal- CNS depression in dogs, CNS stimulation in cats, horses and ruminants (distribution/ type differences of Rs)
Nausea and V+- direct stim CTZ
Variation in pupillary diameter- miosis (Ds), mydriasis (Cs- due to catecholamine release)
Thermoregulation- decr thermoregulatory set point so panting; cats, horses, swine, ruminants cause hyperthermia due to incr muscular activity
Resp depression- decr responsive to CO2
Bradycardia
31
What is the controlled drug legislation for opioids?
```
Pure agonists (controled drugs)- locked cupboard, records kept, special prescription requirements, disposal according to legislation
Partial agonists (buprenorphine)- kept in locked cupboard w/ pure agonists (schedule 2 drugs) but no record necc
Butrophanol- currently exempt
```
32
What is tramadol?
Weak u-opioid R agonist. Setonin reuptake-inhibiting. NEp reuptake- inhibiting. NMDA R antagonist. Low conc of metabolites so effect ?
33
What are the effects of NSAIDs?
Anti inflamm
Analgesic
Anti-pyretic
Acute and chronic use
34
What is the use of ketamine?
Adjuvant to pain management. Sub-anaesthetic doses, blocks NMDA receptors (memory formation)
Indications for skin sx, grafts, burns and neuropathic pain
35
What is the pharmacology of local anaesthetics?
Reversibly block the transmission of action potentials along an axon. Interfere w/ action of Na channels.
36
How does sensitivity to local anaesthetics differ amongst nerve types?
B fibres most sensitive (sympathetic)
A delta next (pain)
A beta and alpha least sensitive (motor and proprioceptive)
Sensitivity of C fibres (unmyelinated) overlaps
37
With nerve blocks what is the order in which sensations are lost?
```
Pain
Cold
Warmth
Touch
Deep pressure
```
38
What is the structure of anaesthetics and how are they classified?
Aromatic ring- lipophilic joined to amine- hydrophilic.
The 2 are linked. 2 types:
-ester link
-amide link
They are classified esters and amides accordingly
39
How does the pharmacology of esters differ from amides?
Esters- metabolsied by plasma pseudocholinesterases, allergenic e.g. procain, tetracaine
Amides- metabolised in liver by amidases, allergic reactions rare e.g. lidocaine, bupivacaine, ropivacaine
40
How does the chemical structure of anaesthetic affect pharmacology?
Lipid sol determines potency- low dose w/ lipophilic
Protein binding determines DOA- binding to R
pKa determines speed of onset- pH in which 50% charged- uncharged diffuses across axon sheath
41
Lidocaine- pKa 7.8, lipophilic 43, protein binding 64%
| Bupivacaine- pKa 8.2, lipophilic 346, protein binding 95.5%. Which has greatest potency, longest DOA and quickest onset?
Lidocaine pKa closer to pH of blood (7.3-7.4) therefore more uncharged so quicker onset
Bupivacaine is more lipophilic and has greater protein binding so is more potent and have greater DOA.
42
What is the local anaesthetic licensed for use in large animals?
Procaine- only one licensed for FPAs.
In horses not many licensed but have +ve list (not licensed but recognised as safe etc)- nearly all can be used (skin and SC swelling reported in lidocaine, mepivacaine mainly used)
43
What are the 2 factors which determine DOA of a local anaesthetic?
Degree of protein binding (greater= longer)
Speed of absorption- e.g. schiatic n not many BVs around, slower absorption; brachial plexus, loads of BVs, incr absorption, shorter DOA
44
How can you reduce systemic absorption of local anaesthetic?
Vasoconstriction (adrenaline)- reduces local BF and thus incr DOA.
E.g. lignol- lidocaine and adrenaline
45
What are the toxic doses of lignocaine, bupivacaine, ropicavaine?
```
Lignocaine 10-20mg/kg (normal dose- 5)
Bupivacaine 3.5-4.5 (normal dose 2)
Ropivacaine 5 (normal dose 1.5)
```
46
What are the signs of toxicity in use of local anaesthetics?
CNS- sedation, tremors, seizures
CVS- direct action on heart and peripheral vasc and indirect action by blocking autonomic n fibres. Worst w/ bupivacaine due to incr DOA
Miscellaneous- allergy, methaemoglobinaemia (esp prilocaine- EMLA cream)
47
What are the topical local anaesthetics used in practice?
Eye drops- proparacaine (proxymetacaine), tetracaine (amethocaine). Can slow corneal healing
EMLA cream- lidocaine and prilocaine, used for venous catheterisation, 30mins before
48
When is infiltrative anaesthesia used in practice?
Injection around surgical site. E.g. field blocks (line blocks, inverted L block)
49
When is the cornual nerve block used?
Used for dehorning.
| Cattle- cornual branch of lacrimal n (halfway between lateral canthus and horn bud)
50
What is the paravertebral nerve block?
Perineural injection of spinal n at point of IV foramen. Advantage over the inverted L block- acts upon the peritoneum and abdominal wall mm are relaxed
51
What forelimb nerve blocks are used?
```
Brachial plexus (elbow distally)
Cervical paravertebral (shoulder, brachium)
Radial, Ulnar, Median (elbow distally)
IVRA (Bier’s block)
(below tourniquet)
```
52
What hindlimb nerve blocks are used?
Epidural (suitable for hip also)
| Femoral/ sciatic (stifle distally)
53
What are the indications for brachial plexus block?
Analgesia for sx of elbow and distal forelimb
54
What are the indications for epidural analgesia?
At the lumbosacral space. Abdominal and hindquarter sx in SAs under light GA, standing sx in FAs and horses, postop analgesia for above sx or injuries.
LAs, opioids, a2 agonists, ketamine, NSAIDs
55
What are the contraindications for and complications of epidural analgesia?
CI: distorted anatomy, infection at inj site, coagulopathy, septicemia
Complications: n damage, pruritus, urinary retention, motor dysfunction, accidental vasc inj, haematoma formation, infection, hypotension, resp depression due to cranial spread
56
What is the IVRA?
Analgesia for sx of distal limb. Apply tourniquet. Inj 2-3ml 1% lidocaine into distal vein. Limit 2hr due to ischaemia of distal tissue. Lidocaine only! Don't use bupivacaine
57
What is the action of COX-1 cf COX-2?
COX-1: mucosal protection, RBF, haemostasis
| COX-2: inflamm, pain, fever
58
What is the therapeutic aim of NSAIDs?
>80% inhibition of COX-2
| COX-1 inhibition should be <10%
59
What are examples of non selective COX inhibitors?
Aspirin
Phenylbutazone
Ketoprofen
Tolfenamic acid
60
What are examples of preferential inhibitors of COX-2?
```
Meloxicam
Carprofen
Mavacoxib
Cimicoxib
at least 2x greater inhibition of COX-2, usually 10-40x
```
61
What are examples of selective inhibitors of COX-2?
Firocoxib
Robenocoxib
100x selective for COX-2
62
What are the features of carprofen?
D: COX-2 preferential
C: COX-2 preferential, significantly longer 1/2 life than D, therefore only licensed for one off use
H: non selective
63
What are the pharmacokinetics of NSAIDs?
Well absorbed from stomach, SI, after SC/ IM inj.
Weak acids so readily penetrate inflammed tissue
Highly protein bound- accumulation in protein rich inflamm exudate
64
How are NSAIDs metabolised?
Hepatic metabolism. Excreted at varying rates depending on metabolic pathway and extend of enterohepatic circulation. Elimination varies between sp and drugs
65
What is prostaglandins role in GIT?
PGI2 (prostacyclin) and PGE2 maintains the integrity of the protective barrier that prevents gastric mucosa from damage by gastric acid. They inhibit gastric acid secretion, maintain mucosal BF, involved in secretion and composition of healthy mucous, may also act as intercellular messengers for stimulus of mucosal cell turnover and migration
66
What causes the GIT effects of NSAIDs?
COX-1 inhibition is main mechanism by which GI ulceration occurs. However, both COX-1 and COX-2 need to be inhibited to generate mucosal injury in the absence of pre-existing injury. Many gut cells express COX-2. COX-2 rapidly expressed in response to GI injury and contributes significantly to mucosal defense and repair. DON'T use in confirmed/ presumed/ potential GI inflamm (incl pancreatitis)
67
What are the contraindications of NSAIDs due to increased ulcerogenic potential?
Concurrent corticosteroids
Dehydration
Hypovolaemic shock
Disruption to normal gut BF
68
How do prostaglandins affect renal function?
Normal kidney COX-1, COX-2. When renal perfusion reduced, renal PGs maintain renal BF via vasodilatory actions (COX1 and 2), also involved in naturiesis (COX2). If well hydrated and healthy, reduced renal PG production is of little consequence. But significant if volume depleted, avidly retained Na (CHF, hepatic cirrhosis), pre-existing renal insuffiency
69
What should be taken into account in relation to liver when using NSAIDs?
Undergo extensive hepatic metabolism. Avoid if poss. If use essential incr dosage interval rather than decr dose.
70
What drugs should you take care of concomitant use when considering NSAID use?
ACE inhibitors- when renal perfusion reduced (AT other prop to kidney when decr RBF)
A2 agonists- severe hypotension
High dose ACP- potent hypotension
Diuretics- involve PG use, NSAIDs will inhibit this (interfere w/ action)
71
When should NSAIDs be avoided?
Evidence/ suspicion of GIT inflamm
Gut BF reduced/ may be reduced- shock, dehydration, reduced CO
RBF reduced/ may be reduced
Pathological Na retention is present- nephrotic syndorme, cardiac failure, cirrhotic hepatic dz
72
What is a stem cell?
An unspecialised cell w/ ability to self-renew and the capability of differentiating into multiple cell types
73
What are the 2 categories of stem cells?
Embryonic stem cells- totipotent
| Adult (or somatic) stem cells- multipotent
74
What are embryonic stem cells?
Derived from ICM of blastocyst (v small no of cells). Gives rise to the epiblast and the hypoblast. The epiblast gives rise to all of the cells in the adult. ES cells must be amplified for use
75
How are ES cells amplified?
IV fertilisation. Allow it to grow through morula stage to blastocyst w/ ICM. FNA cells from ICM, place into undifferentiated fibroblast culture (remain undifferentiated but multiply). Then form embryoid body and induced to differentiate by various GFs.
76
What are the pros and cons of ES cells?
Pros- can generate vast no of cells w/ capacity to make any cell, cells are young (telomere length)
Cons- take a long time to grow, ethical concern about destroying an embryo and concerns that if implanted in a lesion may differentiate into incorrect tissue or form teratoma.
77
What are adult stem cells?
Undifferentiated cells found amongst differentiated cells in many (poss all) adult tissues. Tend to be dormant in normal tissue. Induced upon injury. Don't have infinite capacity so if you grow them in culture there is a limited no you can generate.
78
What are the pros and cons of adult stem cells?
Pros- can harvest your own stem cells reducing rejection, more limited capacity means won't be forming teratomas
Cons- hard to get enough cells
79
What are induced pluripotent stem cells?
Take skin derived fibrobasts. Add genes in viral construct to tell cell to become embryonic. Can be selected by abx (viral construct has abx selection gene) and expand in culture.
80
What are the pros and cons of induced pluripotent stem cells?
Pros- easy to amplify, make all cell types, no ethical concerns. Cons- not identical to ES cells (gene expression) and have shorter telomere length
81
What are the conditions for which there are licensed use of stem cells in vet med?
Horse tendon/ ligament injury- mesenchymal stem cells from BM of sternum. Harvested, amplified and differentiated into tendenoblasts.
In USA- dervied from adipose tissue (less cells but easier to access) differentiated for bone/ catilage/ tendon repair
82
What can mesenchymal stem cells differentiate into?
Osteoblasts, chondroblasts, adipoblasts, tendenoblasts and myoblasts.
83
What questions do we need to ask when medicating pets?
What dz are we treating? What drugs would be effective and why? Potential side effects? Patient conditions/ signalment? Drug admin to maximise effect?
84
What does a drug need to be therapeutically effective?
Be absorbed into BS (unless treating locally), be transported to site of body where action required, have its action terminated once effect achieved, be eliminated from body safely
85
What are pharmacokinetics vs pharmacodynamics?
Pharmacokinetics: what body does to drug
Pharmacodynamics: what drug does to body
86
How is absorption of a drug influenced?
Ability to cross membranes, route of admin, chemical formulation (particle size, rate of dissolution of a tablet), vol of inj
87
How can a tablet be altered to aid absorption when given by oral route?
Coated to resist dissolution in stomach but allow dissolution by higher pH in SI- where drugs absorbed due to large SA/ villi etc
88
How does the bioavailability of a drug differ between IV/ oral admin and why?
IV bioavailability- 1
Oral <1 due to incomplete absorption, metabolism in gut, gut wall, 1st pass metabolism in liver, enterohepatic recycling and incomplete reabsorption after excretion in bile
89
What is the first pass effect?
Oral drugs must pass liver before reaching systemic circulation. May be metabolised in liver affecting how much enters circulation. If big difference between IV and oral dose indication that significant 1st pass metabolism- higher dose needed orally. Care re pathology!!
90
What is the effect of hepatic dysfunction on 1st pass metabolism?
Incr risk of toxicity for drugs w/ narrow therapeutic index, prolonged duration of drug effect
91
How is the vol of distribution of a drug calculated?
Total amount of drug/ plasma conc. V low- confined to plasma, low- confined to plasma and interstitial space, intermediate- drug enters total body water, v high- drug sequestered in tissue e.g. accumulates in fat
92
What are important factors with regards to distribution of drugs?
BF (shock, dehydration, cardiac failure, age, drugs- propanolol), protein binding (e.g. to alb, not available for diffusion/ interaction with Rs, care as young and geriatric have decreased plasma protein), membrane permeation (aqueous/ lipid/ facilitated diffusion, pinocytosis), tissue sol
93
Which body parts are better for aqueous diffusion of drugs?
Gut, cornea, bladder, most capillary bed.
| Few/ no pores (not good)- BBB, blood-eye, blood-milk, blood-prostate, blood-bronchus
94
If targetting a body part not susceptible to aqueous diffusion what type of drug is required?
Lipid soluble- so can cross lipid bilayer.
95
What does metabolism do to a drug and where does it occur?
Makes drugs more water sol, terminates drug action, activates some drugs, may create toxic metabolites. Mainly in liver, also gut, skin, kidney, lungs
96
What is phase 1 metabolism?
Occurs in ER. Involves oxidation, hydrolysis, reduction. If not water sol yet has to proceed to phase II
97
What is phase 2 metabolism?
Occurs in microsomes or cytosol. Involves conjugation of products of phase 1 with natural substances- glucuronic acid, glutathione, glycine, sulphate, acetyl coA. Involves specific transfer enzymes, usually causes detoxification, occasionally causes hepatotoxicity, enzymes may be induced--> tolerance. So differ markedly
98
What is phase 3 metabolism?
Active transport. Efflux reactions (p-gp) or influx transporters (organic anion transporters). Bodys defence mechanism
99
What factors affect metabolising enzymes?
Species, genetics, age, dz, hormonal status, environmental factors, drug-drug interactions, endogenous compounds
100
How do cats metabolise drugs differently from dogs/ humans)?
Often limited glucoronidation (phase II) but good acetylation and sulphation
101
How do dogs differ from others in their metabolism of drugs?
```
Limited acetylation (more prone to issues with sulphonamides).
Glucuronidation rel unaffected by hepatic dz
```
102
How do pigs differ from others in their metabolism of drugs?
No sulphate conjugation
103
How do herbivores differ from others in their metabolism of drugs?
V efficient metabolic capacity, DOA may be short. Goats metabolise faster than sheep- require diff doses
104
Why is paracetamol very toxic to Cs but not Ds?
Metabolised by 3 pathways in all spp- glucuronidation, sulphation, cytochrome-p450-mediated oxidation. Oxidation yields toxic metabolite. Glucuronidation is the major pathway in most sp, cats have v low conc glucuronyl transferase so metabolism via this pathway insignificant. Sulphation major metabolic pathway in cat but capacity limited so as dose incr greater capacity oxidised--> toxicity
105
How does age affect drug distribution/ metabolism/ elimination?
Distribution: greater vol distribution in paediatric, reduced lean body mass and total body water and lower plasma protein
Metabolism: reduce hepatic metabolism in neonates, reduced hepatic BF, mass and function in geriatric
Elimination: glomerular and tubular function reduced in neonates and geriatric
106
What is first order vs zero order (saturation) kinetics?
First order- rate of elimination directly proportional to drug conc
Zero order- rate of elimination is constant independent of plasma conc due to saturation of metabolising enzyme at rel low conc of drug
107
How do drugs affect hepatic enzymes?
Enzyme induction: usually incr metabolism thus potentially reduces drug effect, if has active metabolite can incr toxicity risk
Enzyme inhibition: reduce metabolism thus may incr drug activity and toxicity risk
108
What are the types of ADR?
```
A- augmented
B- bizarre
C- chronic
D- delayed
E- end of tx
F- failure of tx
*doesn't = overdose
```
109
What are type A ADRs?
Expected but exaggerated/ toxic response. Exaggeration of intended response, 2ry response affecting an organ other than target organ but predictable based on pharmacology (bioavailability, distribution, metabolism, elimination), toxic response. Dose dependant. Avoidable if enough known about drug and patient. Differences in drug disposition, higher free plasma conc
110
What are the factors influencing drug disposition?
```
Species
Body size- larger require less per kilo
Body composition
Age
Pathology (hepatic, renal, CVS dz)- affects bioavailability, distribution, metabolism, elimination
Genetics
Concomitant use of other drugs
```
111
How should you dose an animal with liver disease?
Use lower end of dose range. Increase dosing interval. Monitor closely
112
What are pharmacogenomics?
Study of effect of genetic and genomic differences between individuals on pharmacological behaviour of drugs
113
What is the importance of the P-glycoprotein or MDR-1 protein?
Important drug efflux transporter. Significant impact on GI absorption, distribution, metabolism, excretion and toxicity. In homozygous mutants ivermectin can pass to BBB and achieve toxic conc as P-gp not pumping it back out again.. Collie, Australian shepherd, border collie, shepherds/ sheepdogs
114
What drugs are the substrates for P-gp?
ACP, butorphanol, dexamethasone, digoxin, doramectin, doxorubicin, ivermectin, loperamide, moxidectin, selamectin, vincristine. Not all to same effect though.
115
What are type B ADRs?
Unexpected/ aberrant, unrelated to pharmacological effect, not dose dependent, unpredictable and idiosyncratic. Allergic reactions, direct toxic effects on organs associated with actions unrelated to desired therapeutic effect, aberrant responses in diff sp. Hypersens- type 1 (anaphylaxis), type II (cytotoxic Ab- haemolytic anaemia, thrombocytopenia), type III (Ag-Ab deposition in joints and skin), type IV (cell mediated- skin)
116
What are pseudoallergic drug reactions?
Resemble drug allergies but no immunologic basis. Anaphylactoid reactions. Don't require previous exposure. Most dz when given rapidly IV, may be due to non-specific release of mediators of hypersensitivity, can be due to direct effects of drug on tissues.
