Core drugs 202 Flashcards
What is Diazepam/valium?
Benzodiazepine Indirect GABA(A) agonist
How does diazepam work?
binds to alpha subunit of GABA(A)
increases affinity for GABA
increases frequency of channel opening
high density of binding sites in amygdala
What is Diazepam used for?
treats GAD and panic disorder
What are the effects of diazepam?
Reduces anxiety causes sedation reduces convulsions relaxes muscles can cause anterograde amnesia
What is chlorpromazine
Typical antipsychotic, used to treat schizophrenia, bipolar disorders and hyperkinetic disorders
first antipsychotic discovered
How does chlorpromazine work?
potently blocks dopamine D2 type receptors (D1,D2,D3,D4) and has anti-serotonergic and anti-histaminergic properties
What are the effects of chlorpromazine
Prevents positive symptoms of schizophrenia.
Side effects: sedation, Parkinsonism and other extra-pyramidal side effects, dyskinesia, hypotension, anticholinergic effects, weight gain
What is haloperidol
Typical antipsychotic
potent blocker of dopamine D2 receptors (pro and post synaptic)
more potent than chlorpromazine
What does haloperidol do?
potently blocks D2 receptors
increases dopamine turnover so autoreceptors lose inhibition
blockage of post synaptic receptors causes upregulation
What are haloperidol’s effects?
prevents positive symptoms of schizophrenia
side effects: weight gain, sedation, temperature dysregulation, anticholinergic side effects, neuroleptic malignant syndrome, hypotension, raised prolactin, extrapyramidal symptoms (Parkinsonism, tardive dyskinesia, dystonia) - system becomes supersensitive to dopamine due to chronic blockade
What is risperidone?
atypical antipsychotic
used in long term treatment of schizophrenia and bipolar disorder
Where does risperidone act?
D2 receptors and serotonin receptors
more potent at serotonin receptors
Effects of risperidone
rapid antimanic effects
Side effects: arrhythmia, raised prolactin (sexual dysfunction and osteoperosis), weight gain, long term effect of glucose regulation
may produce more extrapyramidal side effects than most other atypical antipsychotics
What is clozapine?
Atypical antipsychotic
What does clozapine do?
Reduces psychosis associated with schizophrenia
Selective dopamine D4 receptor antagonist (brain)
Also acts on 5-HT receptors (antagonist)
Effects of clozapine?
Has greatest efficacy in treatment-resistant cases of schizophrenia
Also used for treatment of hyperkinetic disorders
Can improve positive and negative symptoms - without extra-pyramidal side effects
Side effects: weight gain, sedation, hypersalivation, tachycardia, hypotension, neutropenia
What is lithium
Mood stabilising drug
used in treatment of bipolar disorder
decreases risk of suicide
How does lithium work?
Specific mechanism for mood stabilisation is unknown, but has many modes of action
Interacts with multiple neurotransmitters (5-HT, NA, DA), affects cellular signalling and neurotrophic factors
Side effects of lithium
Blood tests taken every 3 months for 1st year - risk of lithium toxicity
Adverse long term effects on kidney function
What is amitryptiline
tricyclic antidepressant
used to treat depression, anxiety, chronic pain
How/where does amytriptiline act?
Acts on serotonin transporter (SERT) and noradrenaline transporter to prevent reuptake
mechanism in chronic pain is unclear: acts on descending inhibitory pathways (inhibits sodium and calcium channels)
also acts as antihistaminergic and anticholinergic- produces sedative effect
Side effects of amytriptiline
constipation, orthostatic hypotension, dry mouth, drowsiness, cardiotoxicity in overdose
What is fluoxetine/prozac?
SSRI (antidepressant)
What does fluoxetine do?
increases serotonin function by preventing its reuptake
Increased serotonin availability triggers downstream pathways (long term modulatory effects, secondary messenger cascades, gene transcription)
what is fluoxetine used for?
treatment for depression, anxiety, OCD, panic disorder, PTSD
What are the effects of fluoxetine?
Can be initially anxiolytic - 2/3 weeks until effects are seen
low toxicity, safe in overdose
Side effects: GI, headache, irritability, reduction of libido
What is ibuprofen?
NSAID (analgesis)
useful for acute pain but not effective in chronic pain
How does ibuprofen work?
inhibits prostaglandin synthesis and reduces inflammatory response
inhibits COX enzymes to prevent prostaglandin synthesis
prevents decrease in Na+ channel threshold caused by prostaglandins
What is morphine?
opiate (analgesic)
most effective drug for pain relief
agonist of endogenous opioid system
effective in chronic pain
How does morphine act?
endogenous opioid receptors which are Gi coupled
Open K+ channels and close Ca2+ channels, causing an inhibitory effect
Where does morphine act?
multiple sites of action: brainstem (disinhibition), spinal cord, peripheral (inhibits channels on nociceptors)
Different receptor subtypes depending on location - Mu are responsible for most analgesic/rewarding properties
Side effects of morphine?
numerous
addiction
Paracetamol/acetominophen
Analgesic, not NSAID, exact mechanism of action unknown
not effective in chronic pain
What does paracetamol do?
inhibits COX enzymes but doesn’t reduce inflammation
Acts on descending serotonergic pathways
Pizotifen
Anti-migraine used in prevention of migraines
limited side effects: weight gain, drowsiness
may be used as an antidepressant
Carbamezapine
Anticonvulsant
used to treat seizure disorders, neuropathic pain and bipolar disorders
used for bipolar when unresponsive to lithium - most effective against manic relapse
How does carbamezapine work?
competitively inhibit voltage gated Na+ channels - binds its inactive state, prolonging periods between successive firings (lengthens refractory period?)
raises threshold for action potential, lowers excitability
Exact mechanism for pain relief is unclear - work in spinal cord to reduce excitability
sodium valporate
anticonvulsant
used to treat epilepsy and bipolar disorder
anti-manic - useful in prevention of mania
useful in combination with other drugs
not to be used in women of child-bearing age
Mechanism of sodium valporate?
exact mechanism unclear
Actions on GABA
intracellular sodium blockade
epigenetic modification implicated
Phenobarbitone
Barbiturate
used to treat epilepsy
How does phenobarbitone work?
indirect GABA(A) agonist binds to GABA receptors, increases duration of channel opening increases overall GABAergic activity Epileptic neural discharges are less likely to be transmitted
phenytoin
anticonvulsant
used to prevent epileptic seizures
How does phenytoin work?
frequency and use dependent suppression - blocks Na+ channels responsible for the action potential when neural discharges are of sustained high frequency
Obstructs positive feedback which causes maximal seizure activity
depressive action doesn’t have effect in normal brain state with lower neuronal firing rates
Levidopa
dopamine precursor
converted to dopamine by dopamine decarboxylase
used to treat parkinson’s disease: gold standard
available in several formulations (oral pills, duodenal infusion)
What does levidopa do?
dopamine precursor turned into dopamine by dopamine decarboxylase
increases available amount of dopamine in nigostriatal system
always combined with dopa decarboxylase inhibitor to prevent peripheral conversion to dopamine
Entacapone
COMT inhibitor
Administered with L-dopa for treating Parkinson’s disease (early stages)
inhibits catelchol-O-methyl transferase enzyme which causes dopamine inactivation, so stops dopamine being degraded and keeps it around for longer
reduces peripheral metabolism of L-dopa increasing duration of action
can make dyskinesia worse and cause diarrhoea
Selegiline
Type B MAO inhibitor (MAOi)
selective monoamine oxidase inhibitor for dopamine
treatment for early stage PD and dementia
prevents degradation of dopamine and causes more dopamine to be released on subsequent activations
Ropinirole
non-ergot dopamine agonist
used to treat Parkinson’s
bypasses degenerating nigostriatal systems to directly activate dopamine receptors
doesn’t need enzymatic conversion
Stable and long-acting treatment (strong n stable)
Donepezil
Acetylcholinesterase inhibitor
blocks Ach breakdown, increasing its activity
used to treat dementia/ Alzheimer’s disease
improves cognition and behaviour, eases symptoms
Lidocaine/lignocaine
local anaesthetic, applied topically to skin
raises threshold for AP generation, lowering excitability
Blocks Na+ channels in inactivated state
stops action potentials locally (stops nociceptive firing)
Propofol
General anaesthetic, used to induce anaesthesia
administered by injection/ IV infusion
solvent - minimal accumulation
short redistribution - half life (4 minutes)
painful to inject
can have CVS/RS effects
Naloxone
opiate antagonist
opiate receptor blocker (competitive antagonist)
used clinically in emergencies to reverse opiate intoxication
Suxamethonium
neuromuscular blocking drug
acts on postsynaptic membrane
mimics acetylcholine, but hydrolysis is slower, leading to a blockade
induces short term paralysis with rapid onset/offset (short half-life of 2 mins)
multiple side effects
