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Pharmacology for anesthesia Flashcards

1
Q

What is the goal of clinical pharmacology?

A

To maximize drug effectiveness and limit adverse effects.

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2
Q

Define the relationship between Pharmacokinetics and pharmacodynamics?

A

REFER TO HANDOUT

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3
Q

Define Pharmacokinetics?

A

Defines the relationship between drug dose, concentration in bodily fluids and tissues, and time
Simply: what the body will do with a given drug

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4
Q

What are the 4 interrelated processes associated with pharmacokinetics?

A

1.absorption,
2.distribution,
3.metabolism,
4.excretion

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5
Q

What is Absoption?

A

The processes by which a drug moves from the site of administration to the bloodstream.

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6
Q

What are the possible routes of drug administration?(9)

A

Oral, sublingual, rectal, inhalational, transdermal, transmucosal, subcutaneous, intramuscular, and intravenous.

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7
Q

Describe factors that affect absorption?(3)

A

1.Physical Properties of a drug
2.Dose
3.Site/route

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8
Q

What physical properties of a drug affect absorption?

A

1.Solubility
2. Diluent
3. Binders
4. Formulations

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9
Q

What is a diluent?

A

It is a filler used to increase weight and improve content uniformity/there are used to alter the viscosity of a solution in order to meet specifications.

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10
Q

Describe the volume of Distribution?

A

Apparent volume into which a drug has mixed-distributed throughout the body.

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11
Q

What factors affect Volume of distribution?

A

1.Lipid solubility
2.Protein binding
3.Ion binding- electrical charge
4.Molecular weight- smaller easy to cross membrane

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12
Q

How is Volume of distribution calculated?

A

REFER TO HANDOUT

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13
Q

Define Central Volume?

A
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14
Q

Describe peripheral Volume?

A
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15
Q

Describe Bioavailability?

A

Fractional dose of drug that is actually able to reach the systemic circulation.

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16
Q

What is Phase 1 metabolism?

A
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17
Q

What is Phase 2 metabolism?

A
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18
Q

What is Hepatic clearance?

A

It is the volume of blood or plasma that completely cleared of drug by the liver per unit time.

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19
Q

What is the formula for Hepatic clearance?

A

Hepatic blood flow * Hepatic extraction ratio

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20
Q

What is terminal half life?

A

Time required for the plasma concentration to decrease by 50% during the terminal phase of decline

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21
Q

How is terminal half life calculated?

A

t ½ = k x VD/CL, where k is a constant (0.693), VD volume of Distribution, Cl clearance.

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22
Q

What is clearance?

A

-Represents the volume of blood or plasma from which the drug is completely eliminated in unit time (ml/min)
-The rate of drug elimination (mg/min) per unit of blood or plasma concentration (mg/ml)

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23
Q

What organs are primarily responsible for drug clearance?

A

Liver and Kidney

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24
Q

How is total body clearance calculated?

A

Total body clearance is the sum of different ways of drug elimination
CL = CLR + CLH + CLx

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25
Q

What is the pharmacokinetic modeling used for?

A

To analyze drug distribution and elimination as well as complex patient situations to describe and predict drug behavior

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26
Q

What does the one compartment model state?

A

The rate of drug elimination is assumed to be proportional to the amount of drug in the body (X) at any time (t), it decreases exponentially with time and is consistent with first-order kinetics
dX/dt = k X

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27
Q

What is a first order reaction?

A

The reaction in which the rate of reaction is directly proportional to the concentration of reaction.

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28
Q

What is pharmacodynamics?

A

-Relationship between a drug’s mechanism of action and the biochemical and physiologic response produced in the body.
-Simply put: What does the drug do to the body.

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29
Q

How do drugs exert their effects?

A

By interactions with receptors, or cellular macromolecules, located throughout the body

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30
Q

What are the does -response parameters?

A
  1. ED50;Effective Dose for 50% response.
  2. ED90;Effective Dose for 90% response.
  3. LD50; Lethal Dose for 50% population.
  4. Therapeutic Index(TI);Ratio of LD50 to ED50.
  5. Minimal Alveolar Concentration; MAC Value.The concentration at which 50% of subjects do not produce a reaction to a standard stimulus.
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31
Q

What is ED50/90?

A

ED50/90-Dose of a medication that produces the intended pharmacological effect in 50%/90% of the patient population studied during clinical trials.

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32
Q

What is LD50%?

A

LD50- it is the dose required to kill half the members of a tested population after a specified test duration.

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33
Q

What is a therapeutic Index ?

A

Therapeutic Index-a ratio that expresses the relationship between the dose expected to elicit some adverse effect (e.g., LD50, TD50, etc.)and the dose needed to elicit therapeutic effects

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34
Q

What is MAC?

A

MAC- he minimum alveolar concentration (MAC) isthe minimum concentration of an inhaled anesthetic at 1 atm of pressure that prevents skeletal muscle movement in response to a surgical incision in 50% of patients.

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35
Q

Define agonism?

A

Stimulation of a receptor

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36
Q

Define Antagonism

A

Inhibition of a receptor

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37
Q

Define Synergism

A

Enhanced effect

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38
Q

Define additivity?

A

It is a combined effect

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39
Q

What is Partial agonism?

A

Partial Stimulation

40
Q

What is inverse agonism?

A

Reversal of receptor activity

41
Q

What is the triad of anesthesia?

A

1.Hypnosis
2.Analgesia
3.Paralysis

42
Q

What are the properties of an ideal volatile anesthetic agent?

A
43
Q

Define Oil :Gas partition coeffcient?

A

This measures the solubility of an anesthetic drug

44
Q

Define blood gas coefficient?

A

The solubility of inhaled general anesthetics in the blood

45
Q

What type of general anesthesia drugs cause hypnosis?

A

IV anesthetics
Volatile drugs

46
Q

What type of general anesthesia have an analgesic effect?

A

PCM, NSAID and Opioids

47
Q

What type of general anesthesia drugs cause paralysis?

A

-Depolarizing agents
-Non -depolarizing agents

48
Q

Why is hypnosis beneficial?

A

Amnesia??
Confirm if that is what he said

49
Q

What are the characteristics of an intravenous anaesthetic?

A

1.Rapid onset + rapid recovery
2.Storability: Long shelf-life at room temperature
3.Pleasant effect during the induction phase
4.Safety following extravasation or inadvertent intra-arterial injection
5.Analgesic at sub-anaesthetic concentrations
6.Minimal cardiovascular and respiratory depression

50
Q

What are the characteristics that are not wanted in an intravenous anesthetic drug?

A

1.toxic effects
2.emetic effects
3.pain on injection
4.histamine release or 5.hypersensitivity reaction
6.interference with other drugs
7.stimulation of porphyria
8.unpleasant experiences in the 9.peri-operative phase

51
Q

What are the types of iv anesthetics ?Give examples of each.

A

1.Barbiturates (thiopental, methohexitone)
2.Non-barbiturates (propofol, ketamine, etomidate)

52
Q

What are the IV anesthetics most commonly used in Malawi?

A

1.Thiopental
2.Ketamine
3.Propofol

53
Q

What is the MOA of thiopentone?

A

Prolonged GABA dependant Cl- - channel opening

54
Q

What are the characteristics of thiopentone?

A

1.Rapid Onset(One-arm-brain -circulation time)
2.Short Duration of action
3.Long half -time with repeated administration or infusion.

55
Q

What is the pH of Thiopentone?

A

10.5

56
Q

What are the effects of Thiopentone?

A

Antiepileptic activity
Minor degree of muscle relaxation
Hypotension
Histamine release
Unsafe in porphyria

57
Q

What kind of drug is Ketamine? And what is its MOA?

A

-Phenycylidine derivative

-NMDA receptor antagonist (others phencyclidine& dextrometorphan)

58
Q

What effect does the liver have on ketamine?

A

Causes demethylation of the ketamine to an active metabolite by the P450 enzymes

59
Q

What is the active metabolite of ketamine called?

A

Norketamine

60
Q

How does ketamine affect the sympathetic system?

A

Produces sympathetic nervous system stimulation, increasing circulating levels of adrenaline and noradrenaline

61
Q

Describe the different doses, onset and duration for the different administration routes of ketamine.

A

iv: 1-2mg/kg onset 10-20sec / duration 10-30min
im: 4-10mg/kg onset 1-5min / duration 45-60 min
rectally: 5-10mg/kg onset 5-10min / duration 2-3 hours

62
Q

In which circumstance is ketamine given orally or as a gas?

A

When it is used for recreational use

63
Q

Describe the dissociative state of ketamine?

A

Detachment from one’s body & external world (depersonalization & derealization)

Mimics schizophrenia
Unaware of own identity
Sensation of floating, euphoria
Loss of time perception
In adults combined with benzodiazepines

63
Q

What is the analgesic dose of Ketamine?

A

0.2–0.5 mg/kg

63
Q

What are the effects of ketamine?

A

Analgesia (acute, chronic, Complex reginal pain syndrom)
Anaesthesia
Hallucinations
Increased blood pressure
Bronchodilatation
Dissociative anaesthesia
Antidepressive
Airway reflexes are maintained

64
Q

What is the chemical name for Propofol? What is its mechanism of action?

A

2,6-diisopropylphenol
GABA Chloride channels

65
Q

Describe the characteristics of Propofol.(Including ph and PKA)

A

Highly lipid soluble
Oil-in-water emulsion
pKa 11
10mg/ml
Additives: soybean oil, glycerol, egg lecithin
pH 7 – 8.5

66
Q

In which situations is Propofol used?

A

Induction & maintenance of general anaesthesia
Sedation in ICU
Sedation for other procedures
Narrow therapeutic range
Given only by persons trained in its use
Advanced Airway management needs to be readily available

67
Q

What are the effects(Good)of Propofol?

A

Rapid onset of anaesthesia (one arm-brain circulation time).
Rapid recovery.
Little accumulation
Reduces laryngeal reflexes (ideal for use with LMA)
Safe in porphyria
Safe in Malignant Hyperthermia

68
Q

What are the side effects of Propofol?

A

Reduces laryngeal reflexes
Dose dependent fall in SVR, no reflex tachycardia, slight fall in CO
Considerable fall in BP (cave hypovolaemia)
Pain on injection
Spontaneous excitatory movements (misinterpretation can happen)
Crosses placenta (not used in obstetrics)

69
Q

Give examples of inhalational Anesthetics?

A

Halothane
Isoflurane
(Enflurane)
Sevoflurane (standard in rich countries)
Desflurane
Xenon

70
Q

What are the oldest anesthetics used?

A

Inhaled anesthetics

71
Q

What is volatile substance?

A

Liquid at room temperature with low boiling point (e.g. Halothane 50oC)

72
Q

What is MAC a measure of? Describe the relationship?

A

Potency
The lower the MAC the greater the potency.

73
Q

Describe the relationship between MAC, potency and gas:oil coefficient?

A

The more lipid soluble the anaesthetic, the lower the MAC and the greater the potency

74
Q

What is the Meyer-Overton Hypothesis?

A

It is the theory of anaesthetic action which proposes that the potency of an anaesthetic agent is related to its lipid solubility

Hypothesis proposed that once a sufficient number of anaesthetic molecules were dissolved in the lipid membranes of cells within the central nervous system, anaesthesia would result by a mechanism of membrane disruption.

75
Q

Describe the gases according to the meyer-overton correlation?

A

REFER TO HANDOUT

76
Q

How is Blood :Gas coefficient related to Rapid onset

A

???

77
Q

What is most widely used inhaled anesthetic?

A

Halothane

78
Q

Describe the characteristics of Halothane?

A

Colorless liquid, pleasant smell & to breathe
Decomposed by light, thymol as preservative
20-25% metabolized in the liver (hepatotoxic)

79
Q

What are the effects of Halothane?

A

Cardiac dysrhythmias
Increased cerebral blood flow and ICP
Reduced myocardial contractility, HR, CO, BP
Reduced VT, increased RR & PaCO2, reduced laryngeal reflexes & airway resistance
Uterine relaxation (cave obstetrics)

80
Q

What is the chemical name of ISoflurane?

A

Halogenated methyl ethyl ether

81
Q

Describe the characteristics of ISoflurane?

A

Expensive(not widely used in Malawi)
Colourless volatile liquid but has an irritant smell
Lower blood gas solubility that Halothane and therefore provides rapid onset of and recovery from anasthesia
Low toxicity to liver and kidneys
`

82
Q

What are the side effects of Isoflurane?

A

Increases cerebral blood flow and ICP( less than Hal)
Does not cause arrhythmias(does not increase myocardial sensitivity to adrenaline)
Little effect on myocardial contractility.Dose dependent fall in blood pressure due to decrease in SVR
Reduced VT, increased RR

83
Q

What are the types of muscle relaxants? Give examples?

A

Depolarizing: Suxamethonium
Non-Depolarizing:
Steroids: Vecuronium ,Rocuronium, Pancorium
Ester: Atrcaurium

84
Q

What kind of drug is Suxamethonium? What is its MOA?

A

-2 molecules of Acetylcholine joined together
-Leads to persistent depolarization of the motor endplate

85
Q

What are the characteristics of Suxamethonium?

A

Rapid onset of action- 1 min
Short acting - 4-6 min after observable muscle fasciculation

86
Q

What are the effects of Suxamethonium?

A

1.Mild to severe muscle fasciculation which can lead to increased CO, BP, ICP
2.Myalgia
3.Hyperkalemia (burns, neurological conditions, peripheral nerve injuries, renal failure, acidosis) which can lead to cardiac arrest
4.Dual block
5.Increased intraocular pressure
6.Malignant hyperpyrexia
7.Parasympathetic effects

87
Q

What is the MOA of NDMRs?

A

Competitive reversible blockade of the Acetylcholine receptor without change of the membrane conductance or ionic permeability

88
Q

What is the most widely used NDMR?

A

Vecuronium.

89
Q

What are the characteristics of vecuronium?

A

1.Cheap
2.Little CVS effects
3.Rare Histamine release

90
Q

What is the onset of action and duration of action of vecuronium?

A

Moderately short onset of action – 2min
Moderate duration of action – 20min

91
Q

How is Atracurium metabolized?

A

By Hofmann degradation into Laudanosine and ester hydrolysis

92
Q

What is he difference between Vecuronium and Rocuronium?

A

1.Fast onset of action (60 sec) – similar to Suxamethonium
2.Longer duration of action than Vecuronium
3.Less potent but otherwise similar to Vecuronium
4.As the price has come down, it starts to replace Vecuronium

93
Q

When atracurium used?

A

Drug of choice in renal failure and hepatic failure

94
Q

Effects of atracurium

A

Can lead to severe Histamine release and profound hypotension

95
Q

Where is atracurium stored and where?

A

Fridge because it is unstable

Anesthesia (12 decks)

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