Anaesthetic Drugs Flashcards
What are the pKa values of the induction agents?
Thio: 7.6
Prop: 11
Etom: 4.2
Ket: 7.5
Are the different induction agents weak acids or bases?
Thio: Acid
Prop: Acid
Etom: Base
Ket: Base
How does Suggamadex work?
- Modified gamma-cyclodextrin
- Encapsulating agent
- Binds free NMB molecules
- Creates Conc gradient between IV compartment and NM junction
- Drug moves down Conc gradient away from NM junction terminating its effects
Give an example of short, medium & long-acting anticholinesterases
Short: Tensilon - used to diagnose myasthenia
Med: Neostigmine/ Pyridostigmine
Long: Echothiophate - used in Sarin/nerve gases, last weeks due to covalent bonding
What are the Sx of an anti cholinesterase overdose?
SLUDGE
S: Salivation
L: Lacrimation
U: Urination
D: Defecation
G: GI upset
E: Emesis
Death by paralysis & resp depression
Tx: Atropine/ Pralidoxime
How does Neostigmine work?
- Carbamylates active site of enzyme
- Once bonded hydrolyses ACh
- Inhibits action of plasma pseudocholinesterase so prolongs effects of Sux & Miva
- Reverses competitive NMB
What is Thiopentone made from?
-Sulphur analogue of pentobarbitone
- Formulated as sodium salt (yellow powder)
- Highly insoluble in neutral pH so need transforming from kept to enol form (alkaline)
- Stored in glass vials containing Nitrogen
What’s an absolute contraindication for Thiopentone?
Acute porphyria
How much Thiopentone is in the active form at normal pH?
-12%
-60% free drug = unionised
- Non-protein bound & unionised
- Rapid onset due to high lipid solubility
- Emergence due to rapid redistribution
What are the 2 types of local anaesthetic drug groups?
- Esters: Contain COO link, hydrolysed in plasma
- Amides: Contain NHCO link, hepatic metabolism
What are the types of LA esters?
- Amethocaine
- Cocaine
- Procaine
What are the types of LA amides?
- Bupivacaine
- Etidocaine
- Lignocaine
- Ropivacaine
- Prilocaine
In what way is systemic absorption of LA greater than epidural administration?
- Caudal injection
- Intercostal injection
What drugs bind to the b subunit on GABA?
Propofol
Volatiles
Etomidate
Barbituates
What are the uses of Thio?
- GA
- Status epilepticus - produces isoelectric EEG = max reduction of cerebral O2 requirements (may need inotropes)
What are the SE of Thio?
- Dose-dependent reduced CO/SV/SVR
- Resp: broncho/laryngospasm, resp depression
- Anaphylaxis
- Renal: Reduced UO due to inc ADH release
Why do acidotic patients require less Thio?
- Reduced plasma-protein binding
- Greater fraction of drug in unionised form
- Fewer plasma protein binding sites
Why does Thio infusion lead to linear metabolism?
Zero order: Saturation of hepatic enzymes (P450)
Is intra-arterial injection of Thio bad?
- More Keto formation than Enol
- Less water-soluble solution
- Precipitation of Thio crystals which wedge in small blood vessels
- Tx: Procaine, Papaverine, analgesia
What are the effects of Propofol?
- Reduced SVR/BP/contractility, Brady,
- Resp depression
- Antiemetic (Dopamine antagonist)
- Propofol syndrome
- CNS excitatory effects
What is Propofol bound to?
98% protein bound to Albumin
How is Propofol metabolised?
- Hepatic
- 40% Conjugation to glucuronide
- 60% metabolised to Quinol excreted as Sulfate & Glucuronide
What is Ketamine derived from?
Phencyclidine
How is Ketamine presented?
- Racemic mixture
or - Single S enantiomer (2-3 times as potent as R enantiomer)
What are the effects of Ketamine?
- Sympathetic NS stimulation
- Inc circulating NorA/adrenaline
- Inc HR/CO/BP/Myocardial O2 requirements
- Inc RR, preserved airway reflexes, BronchoD
- Dissociation
- Salivation
- Severe interstitial cystitis (high does)
- Inc cerebral blood flow/ICP/O2 consumption
Which type of Ketamine produces less cardiac depression?
S(+) Ketamine
Better for IHD (doesn’t block ATP sensitivity K+ channels)
What happens in Ketamine dissociation?
- Dissociation between thalamocrtical & limbic systems
- a rhythm replaced by 0 & d wave activity
- Takes 90secs rather than 1 arm-brain cycle to work
How do Ketamine levels fall?
- Conc falls in bi-exponential fashion
- Initial fall = lipid membrane distribution
- Slower fall = hepatic metabolism
How is Ketamine metabolised?
- Least protein bound of all GAs
- Demethylated to active metabolite norKetamine by P450
- Then metabolised to inactive glucuronide excreted in urine
What is Etomidate?
Imidazole derivative & ester
What are the effects of Etomidate?
- Fall in PVR
- Adrenocortical suppression
- Precipitate porphyric crisis
How does Etomidate cause adrenal suppression?
- Inhibits enzyme 11B-hydroxylase & 17a-hydroxylase
- Inhibits cortisol & aldosterone synthesis
What are the kinetics of Etomidate?
- 75% bound to Albumin
- Action determined by rapid distribution into tissues
- Elimination based on hepatic metabolism (hepatic esterase, plasma cholinesterase)
What are the effects of N2O?
- Fall in TV, inc in RR
- Inc sympathetic activity
- Mild cardiac depression
- Inc cerebral blood flow
How is Sux broken down?
Hydrolysed by plasma cholinesterase to choline & succinylmonocholine (weakly active)
What type of block does Sux produce?
Phase 1 block: Train of 4 >0.7
Repeated administration = phase 2 block like Non-depolarising NMB
What is the MOA of Sux?
Binds to nicotinic Ach receptors
Depolarises membrane
Lack of plasma cholinesterase at NMJ
Sux remains attached to receptor blocking its action
