Pharmacology in Anaesthesia Flashcards
Name selective beta-1 antagonists
atenolol
metoprolol
bisoprolol
betaxolol
esmolol
Which drugs are safe to use in acute porphyrias
propofol
all neuromuscular blockers
all volatiles
opioids
local anaesthetics
?etomidate
Why do some anaesthetists avoid regional anaesthesia acute porphyrias?
In order to avoid confusion if neurological changes occur
Name dopamine antagonists
droperidol
promethazine
thiethylperazine
metoclopramide
Which disease causes increased resistance to depolarising neuromuscular blockers
myasthenia gravis
What is diazepam mixed with, and what is the result
Propylene glycol
Painful IV injection
What are the safe submucosal adrenaline doses for patients under anaesthesia
Anaesthesia with halothane: <2mcg/kg.
Arrhythmias occur in 50% of patients at doses >2.1mcg/kg
Anaesthesia with sevo/iso up to 1.2 MAC: 5mcg/kg
Arrhythmias occur in 33% of patients at doses 5-15mcg/kg
Side effects of propranolol
[propranolol is a non-selective B-blocker]
- blunted response to hypoglycaemia
- suppressed insulin secretion
- bronchoconstriction
- fatigue
- excessive myocardial suppression
- AV block
- rebound tachycardia after discontinuation
- accentuated response to potassium infusions
Effects of atropine
- reduced gastric acid secretion
- inhibition of salivary secretions
- tachycardia
- mydriasis
- decreased lower oesophageal sphincter tone
Which anticholinesterases can, and cannot, cross the blood brain barrier
Cannot cross:
neostigmine
pyridostigmine
edrophonium
Can cross:
physostigmine
Tell me about meperidine:
What is it,
What is important about its structure,
Metabolite,
Side effects
Opioid receptor agonist;
structurally similar to atropine;
metabolite normeperidine is renally excreted, causes delirium and seizures especially in patients with renal failure;
has local anaesthetic-like properties,
can impair myocardial contractility
Neuromuscular blockers that can cause histamine releast
- atracurium
- d-tubocurarine
- succinylcholine
Metoclopramide effects
- decreased secretions
- raised lower oesophageal tone
- increased gastric motility
- increased upper intestinal motility
- sedation
- dysphoria/agitation
- EPSEs
Causes of reduced sensitivity to non-depolarising neuromuscular blockers
hypercalcaemia
hyperparathyroidism
Drugs that enhance the effect of non-depolarising neuromuscular blockers
- aminoglycosides
- IV lignocaine
- magnesium
- volatiles
- dantrolene
- lithium
- furosemide
- calcium channel blockers
Laudanosine:
what is it,
how is it excreted,
what is its structure,
effect on CNS
Metabolite of atracurium and cisatracurium due to the effect of plasma cholinesterases;
renal and hepatic excretion;
tertiary amine;
crosses BBB and stimulates CNS
What are possible mechanisms for the cardiovascular effects of neuromuscular blockers
a. histamine release
b. effect on cardiac muscarinic receptors
c. effect on autonomic ganglia nicotinic receptors
Pre-curarisation attenuates which effects of succinylcholine
raised intraoccular pressure,
raised intracranial pressure,
myalgia,
bradycardia
What is the pH of thiopental and what is the relevance thereof
10.5
Highly alkaline, so high risk of tissue damage if injected arterial or subcutaneously;
bacteriostasis - stays sterile for 6 days at 22C;
is incompatible with most opioids, catecholamines, and neuromuscular blockers
Conditions where succinylcholine causes severe hyperkalaemia (only after a few days)
- severe burns
- severe abdominal infections
- stroke
- spinal cord transection
- myopathies
- muscular atrophy due to disease or disuse
Flumazenil:
what is it,
what are its side effects
specific antagonist to benzodiazepines;
nausea and vomiting
dizziness
tremors
hypertension
Triggers of acute intermittent porphyrias
- starvation
- dehydration
- stress
- sepsis
- certain drugs
Drugs that may trigger acute intermittent porphyrias
barbiturates
ketorolac
pentazocine
diazepam
phenytoin
Drugs that increase CSF production
enflurane
desflurane (only in setting of hypocapnoea)
Drugs that inhibit CSF production
halothane
furosemide
acetazolamide
(and hypothermia)
Drugs that can enhance conduction via accessory atrial pathways
(and are thus contraindicated in WPW syndrome)
pancuronium
ketamine
verapamil
meperidine
What does pseudocholinesterase metabolise
acetylcholine
succinylcholine
mivacurium
ester-type local anaesthetics
Ageing affects the recovery index of which non-depolarising muscle relaxants
- vecuronium
- d-tubocurarine
- pancuronium
- rocuronium
Side-effects of cyclosporine therapy
- limb parasthesias (50%)
- nephrotoxicity (25-38%)
- hypertension
- headache
- seizures
- somnolence/confusion
- elevated liver enzymes
- allergy
- gum hyperplasia
- hirsutism
- hyperglycaemia
Indications for cyclosporine therapy
- anti-rejection after organ transplant
- Crohn’s disease
- uveitis
- psoriasis
- rheumatoid arthritis
Side effects of dexmedetomidine
- hypertension initially, then hypotension after an hour
- bradycardia
- sinus arrest
- respiratory arrest
Tolerance develops eventually to which effects of morphine
- euphoria
- analgesia
- nausea
- respiratory depression
Tolerance DOES NOT develop to which effects of morphine
constipation
miosis
Cimetidine: side effects
- confusion/delayed emergence
- bradycardia
- elevated aminotransaminases
- CYP inhibition therefore impaired metabolism of:
diazepam, lignocaine, propranolol
Post anaesthetic shivering:
causes
- hypothermia
- pain
- anaesthetic
- transfusion reaction
Post-anaesthetic shivering: drug treatment
- narcotics
- tramadol
- meperidine
- propofol
- cimetidine
- magnesium sulphate
- physostigmine
- dexmedetomidine
- ketanserin (5HT2-antagonist, anti-hypertensive)
Treatment for accidental intra-arterial injection of thiopental
- blocks: stellate ganglion, brachial plexus
- antithrombotics: heparin, urokinase
- intra-arterial agents: lignocaine, papaverine
Chlorpromazine:
What is it;
What are its effects/side-effects
D2-antagonist;
anti-emetic and antipsychotic;
potentiates narcotics;
interacts with guanethidine;
ECG changes;
lowers seizure threshold and causes EPSEs;
cholestatic jaundice;
impotence;
photosensitivity
Chlorpromazine ECG changes
QT prolongation
PR prolongation
blunted T-waves
ST depression
PVCs
Torsades de pointes
Drugs used in beta-blocker overdose
- GLUCAGON
- atropine
- dobutamine
- isoprotenerol (non-selective B-agonist, analog of adrenaline)
- aminophylline
- calcium chloride
Signs and symptoms of opioid withdrawal
hyperthermia
raised blood pressure and heart rate
abdominal cramps
jerking legs
other signs of sympathetic stimulation
Minoxidil: effects
- reduced blood pressure
- stimulates hair growth
- pericardial effusion
- cardiac tamponade
- pulmonary hypertension
Thiocyanate:
what is it;
signs of toxicity
products of metabolism of sodium nitroprusside especially in renal failure;
tinnitus
abdominal pain
muscle weakness
confusion, seizures, coma
Signs of cyanide toxicity
metabolic acidosis
resistance to antihypertensive effects of sodium nitroprusside
raised mixed venous partial pressure of oxygen
Examples of monoamine neurotransmitters
- dopamine
- noradrenaline
- adrenaline
- histamine
- serotonin
- melatonin
Primary precursor proteins of opioids
pro-opiomelanocortin
pro-enkephalin
pro-dynorphin
Examples of
1. excitatory
2. inhibitory
amino acid neurotransmitters
- glutamate, aspartate
- glycine, GABA
Acid drugs bind to:
Basic drugs bind to:
- albumin
- a1 acid glycoprotein (AGP)
Examples of peptide neurotransmitters
- encephalins
- orexins
- substance P
Name the neurotransmitter groups
- peptides
- excitatory amino acids
- inhibitory amino acids
- cholinergics
- monoamines
- nitric oxide
Define: neurotransmitter
A substance that transmits
physiologic information
in the nervous system
Which major channels do opioids affect, and how
- Calcium channels: inhibition, therefore inhibits release of substance P and glutamate
- Potassium channels: opens postsynaptic channels, causing hyperpolarisation and inhibiting the post-synaptic response
Name locations of opioid receptors
- presynaptic terminals
- primary afferent neurons
- post-synaptic second-order pain transmission neurons
Name the pain pathways
- Ascending
peripheral nerves
dorsal horn of spinal cord
thalamus - Descending
midbrain
periaqueductal grey matter
rostral ventromedial medulla
locus coeruleus
Main effects of Substance P
- pain
- nausea and vomiting
What is aprepitant,
and what does it act on
- antiemetic for chemotherapy and post-operative nausea and vomiting
- Neurokinin-1 receptor antagonist
NMDA receptor antagonists
- ketamine
- dextromethorphan
- magnesium
- nitrous oxide
- xenon
Receptors affected by ketamine
- NMDA
- AMPA
- opioid
- acetylcholine (nicotinic and muscarinic)
- GABA
- Monoaminergic
Receptors in the cys-loop family
- GABA-A
- Glycine
- 5-HT
- Acetylcholine: nicotinic
Agonists of GABA-A
- barbiturates
- etomidate
- propofol
- benzodiazepines
- volatile agents
For gabapentin/pregabalin:
1. effect site
2. uses
- voltage-dependent calcium channels;
post-synaptic dorsal horn - relieving allodynia and hyperalgesia
On what three segments of the kidney nephron do osmotic agents such as mannitol exert their diuretic effects?
proximal convoluted tubule
thin descending loop of Henle
collecting duct
On what segment of the kidney nephron do loop agents such as furosemide exert their diuretic effects?
Ascending limb of loop of Henle
On what segment of the kidney nephron do thiazides exert their diuretic effects?
distal convoluted tubule
On what segment of the kidney nephron do potassium-sparing agents exert their diuretic effects?
collecting tubule
On what segment of the kidney nephron do antidiuretic hormone antagonists exert their effects?
collecting duct
In the proximal convoluted tubule, the filtrate is _____ (hypotonic/isotonic/hypertonic) to blood plasma.
isotonic
In the thin descending limb of the loop of Henle, the filtrate is _____ (hypotonic/isotonic/hypertonic) to blood plasma.
hypertonic
In the thick ascending limb of the loop of Henle and the distal convoluted tubule, the filtrate is _____ (hypotonic/isotonic/hypertonic) to blood plasma.
hypotonic
On what segment of the kidney nephron does the diuretic acetazolamide exert its effects?
proximal convoluted tubule
What are the clinical uses of mannitol?
treating:
shock
drug overdose
raised ICP/IOP
What is the mechanism of action of mannitol?
osmotic diuretic
increasing osmolarity in the renal tubules;
producing increasing urine volume
What side-effects are associated with mannitol?
pulmonary oedema
dehydration
In what two conditions is mannitol contraindicated?
anuric renal failure
congestive cardiac failure
What four side-effects are associated with acetazolamide?
hyperchloraemic metabolic acidosis;
neuropathy;
ammonia toxicity;
sulpha-like allergic reactions
What is the mechanism of action of acetazolamide?
carbonic anhydrase inhibitor;
self-limited sodium bicarbonate diuresis;
reduction of total body bicarbonate stores
What are the four clinical uses of acetazolamide?
Treating:
glaucoma;
altitude sickness;
metabolic alkalosis;
urinary alkalisation
What are three (general) the clinical uses of furosemide?
Treating:
oedematous states;
hypertension;
hypercalcaemia
What is the mechanism of action of furosemide?
inhibits sodium-potassium-chloride co-transport in thick ascending limb of loop of Henle;
abolishes hypertonic environment of renal medulla;
prevents ability to concentrate urine.
What is the effect of the diuretic furosemide on calcium handling in the kidney nephron?
increases calcium excretion
(loops lose calcium)
Name six toxicities associated with use of loop diuretics
ototoxicity;
hypokalaemia;
dehydration;
allergy (sulpha-like);
nephritis (interstitial);
gout
(OH DANG!)
Ethacrynic acid has a mechanism of action similar to which other drug?
furosemide
Which loop diuretic is used to diurese patients who are allergic to sulfa drugs?
ethacrynic acid
Serum levels of which substances are increased as a result of the effects of hydrochlorothiazide?
hyperglycaemia;
hyperlipidaemia;
hyperuricaemia;
hypercalcaemia
