Pharmacology Flashcards
What are the main ion for 1) axonal transmission 2) pre-synaptic terminal
1) Na+ and K+
2) Ca2+
Ca release is triggered by Na+ and K+ wave of depolarisation
What are three ways of inactivating neurotransmitter
neuronal uptake (main), metabolism by glial cells and extraneuronal uptake
What is the function of cocaine
blocks neuronal uptake of NA, DA, 5HT
What is the different dose response of cocaine (high&low dose)
low dose: slow absorption, relief from fatigue, hunger, altitude sickness, some psychological dependence
high dose: rapid absorption, intense euphoria, severe psychological and physical dependence
What is the main cause of death from using cocaine
cardiac collapse
What is the main effect of amphetamine
it displaces NA from storage vesicle, so more NA can diffuse to synaptic cleft via non-exocytotic release. It can work under low concentration of NA
What is NA associated with in the brain?
stimulant effects, mood, appetite, cardiovascular control
Tyrosine is converted to L-DOPA via?
tyrosine hydroxylase
L-DOPA is converted to dopamine by?
dopa decarboxylase
dopamine is converted to NA by?
dopamine B-hydroxylase
NA is converted to adrenaline by?
PNMT
Dopamine rich area in the brain is associated with which function?
motor
What is the drug treatment of Parkinson’s disease?
L-DOPA + peripheral DDC inhibitor (block peripheral dopamine conversion)
What is Huntington’s disease? What is the drug treatment of Hungtinton’s disease?
GABA deficiency, lack of neuronal inibition
Treatment: Baclofen, GABA agonist, or Chlorpromazine, dopamine antagonist
T/F Neurotransmitters can be excitatory or inhibitory, and it determines whether a synapse is excitatory or inhibitory
False, first statement is correct, but the nature of the synapse also depends on the neurotransmitter receptor
What are the targets of analgesic drugs
pain and sensory pathways at all levels including periphery, spinal and the brain
What is the main difference in target between local and general anaesthetic
local: regionalised inhibition of pain and sensory pathways
General: depresses cortical processing of pain signals, with loss of consciousness
Describe the neural pathway of pain
peripheral nerve picks up the signal. Signal is relayed to spinal cord to secondary neuron. Secondary neuron carries information for processing in the thalamus, then finally to tertiary neuron that relays to the cortex
What is the significance of adding lime to cocaine
drug formation affects pharmacokinetics. A basic environment deprotonates the drug, making it more lipid soluble
Cocaine is not only a CNS stimulant, it is also a _________
local anaesthetic (first)
Define “local anaesthetic agents”
drugs that reversibly block conduction of nerve impulses at the axonal membrane
local anaesthetics are often ______ with different onset, duration and _______. They serve to block _______ Channels
weak bases
toxicity
Na+
Give an example of an aminoester
why is it short acting (45mins)?
procaine, it is short acting because it can be rapidly hydrolysed by esterases (like AchE)
Lignocaine is a _________ , which is a stabilised form of _________ and is no longer affected by _________ . However, it requires ________ of the liver, so the effect of drug varies between individuals
aminoamide
aminoester
esterases
conjugation
What are some examples of lethal toxins that lie on the same pathway as local anaesthetics?
tetrodotoxins
saxitoxin
immobilise preys or serve a protective function
Give three properties of local anaesthetic that make it a clinically useful drug
1) selective binding to Na channels (except for cocaine)
2) reversible binding without damaging nerves
3) will affect all nerves and excitable tissues, so local application is crucial for limiting systemic distribution
What are some other excitable tissues affected by local anaesthetics?
1) peripheral motor neurons (paralysis)
2) ANS nerves (hypotension, CNS convulsion, coma)
3) heart (anti-dysrhythmic to cardiac arrest)
With an epidural injection, we can block 100% and only lose ________% of motor neuron function
less than 50
if injected correctly
Which part of the Na channel does the local anaesthetic bind to? How is that different to toxins?
intracellular domain (S6, to be specific) toxins bind extracellular domains, so the effect does not dependent on channels being active
Why does benzocaine belong to a different class of anaesthetic
it is hydrophobic and therefore fast acting and not use-dependent (does not dependent on Na channel being open and active)
Why does lignocaine act slower than benzocaine
it is hydrophilic, so gets across the membrane slower than benzocaine.
Note that lignocaine is 65% protonated at pH 7.4, so does not diffuse well
There are two gates on a Na channel, what are they?
M gate extracellularly which opens during depolarisation
N gate intracellularly, which closes during hyperpolarisation
What is the effect of local anaesthetics blocking Na channels?
the neuron is unable to reach threshold potential, and action potential is therefore prevented
Does local anaesthetic affect resting membrane potentials?
No, the drugs can also stabilise axonal membrane
why are small fibres more sensitive to local anaesthetic
thinner membrane, quicker drug diffusion
Why does lignocaine cause cardiovascular symptoms like myocardial depression, vasomotor centre in brainstem, and hypotension?
Because it blocks Na channels on all excitable tissues, so there is direct blocking of myocardial fibres and vasomotor centres, and there is hypotension because of SNS block
Why does cocaine cause hypertension instead of hypotension?
it does block the sympathetic nerves, but it also blocks the reuptake of NA, hence increase cardiac output
The CNS and CV side effects of lignocaine are proportional to blood drug concentration. Which side-effect is not proportional?
hypersensitivity / allergic response
In a dental wound, why does a dentist need to clean it up as much as possible before using anaesthetic?
Inflamed areas tend to be acidic, and local anaesthetics are more in the charged, protonated form in acid. Cleaning up the wound lower the dose required
Describe the four stages of general anaesthesia
I) amnesia/euphoria, pre-excitement stage
II) excitement (last about 20 seconds)
III) surgical anaesthesia, unconsciousness but regular breathing
IV) medullary depression, one you want to avoid as there is CV/Resp arrest
All general anaesthetic increase likelihood of respiratory and CV side effects. What is often given in conjunction in order to prevent obstruction of airways
anti-muscarinics to block secretions, as secretions are retained
What should we consider if general anaesthetic is applied to a patient undergoing surgery sitting up?
must monitor CV function, as there is sometimes inadequate response to fall in BP and CO
What is Meyer-Overton Lipid Theory? What makes this theory plausible?
anaesthesia is caused by volume expansion of membrane lipids, impinging on the normal protein function. This is possible because drug effect can be reversed by pressure
What do anaesthetics do to the effects of neurotransmitters?
enhance inhibitory receptors (GABA) and inhibit excitatory (glutamate) receptors
