Pharmacology Flashcards
Describe amitriptyline; mechanism of action and side-effects?
Amitriptyline
Drug class: TCA
MA: Majority of the TCAs act primarily as SNRIs by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET) -> an elevation of the synaptic concentrations
SEs:
- Anticholinergic: dry mouth, blurry vision, urinary retention, constipation, sedation, orthostatic hypotension (alpha-adrenergic blockade), tachycardia, prolongation of QT interval, weight gain (antihistamine-1 effect)
- Highly anticholinergic, very sedating
- Falls risk in elderly patients
- Dangerous in overdose due to narrow therapeutic to toxic range, causing fatal cardiac arrhythmias.
Half-life: 20hrs
Describe fluoxetine; mechanism of action and side effects?
Fluoxetine (Prozac)
Drug class: SSRI
MA: SSRIs increase the extracellular level of the neurotransmitter serotonin by limiting its reabsorption (reuptake) into the presynaptic cell. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having strong affinity for the serotonin transporter and only weak affinity for the NE and DA transporters.
SEs: Agitation, akathisia, anxiety, panic, insomnia, diarrhoea, GI upset, headache, sexual dysfunction (delayed ejaculation, impotence, anorgasmia), increase risk of suicidal thoughts and behaviours
-To avoid fatal serotonin syndrome, no SSRI or SNRI should be combined with a MAOI. An SSRI should be discontinued at least 5 weeks before starting a MAOI.
Half life: 1-3 days
What is serotonin syndrome?
Serotonin syndrome:
Serotonin syndrome: life-threatening condition associated with increased serotonergic activity in the central nervous system (CNS). Triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities
- Mental status changes can include anxiety, restlessness, disorientation, and agitated delirium.
- Autonomic manifestations can include diaphoresis, tachycardia, hyperthermia, hypertension, vomiting, and diarrhoea
- Neuromuscular hyperactivity can manifest as tremor, myoclonus, hyperreflexia, and bilateral Babinski sign.
To avoid fatal serotonin syndrome, no SSRI or SNRI should be combined with a MAOI. An SSRI should be discontinued at least 5 weeks before starting a MAOI.
Describe Phenelzine; class, mechanism of action and side-effects?
Phenelzine
Drug class: MAOI
MA: Block the ability of the enzyme monoamine oxidase to inactivate monoamines (e.g. norepinephrine, dopamine, serotonin, acetylcholine, histamine) in the synaptic cleft. Thereby ensuring more monoamines bind to the post synaptic cleft.
SEs: Orthostatic hypotension, somnolence, weight gain
- “Cheese Crisis”: Eating tyramine whilst on a MAOI -> MAOI stops the MAO-A enzyme from destroying NE -> increased NE in synapse -> can increase BP to hypertensive crisis
–> Avoid: all cheese, fermented/ aged foods, wine, liver.
Interactions: Potential lethal interactions with MAOIs: SSRIs, SNRIs, TCAs, carbamazepine, methadone, tramadol
Half-life: 4-5hrs
Describe Nefazodone; indications, class, MA and SEs?
Nefazodone (Serzone)
Drug class: SARI
Serotonin-2 antagonist and reuptake inhibitor (SARI); combined actions as potent serotonin 5-HT2A receptor and 5-HT2C receptor antagonist and weak serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI)
Indication: antidepressant, anxiolytic and hypnotic
SEs: Sedation, hepatotoxicity, dry mouth, nausea, dizziness
- Less sexual dysfunction
Half-life: 2-4 hrs
Describe Mirtazapine; class, MA and SE?
Mirtazapine (Remeron)
Drug class: NaSSA
MA: Noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors.
- Has antihistamine, α2-blocker, and antiserotonergic activity.
SE: Weight gain, sedation, dry mouth, constipation, increased appetite
- No sexual dysfunction, no nausea or diarrhoea
Half-life: 20-40 hrs
Describe Trazodone; class, MA and SE?
Trazodone (Desyrel)
Drug class: SARI
MA: Serotonin-2 antagonist and serotonin reuptake inhibitor (SARI) via antagonism of 5-HT-2A receptor, H1 receptor, and alpha-1-adrenergic receptors -> reduces levels of neurotransmitters associated with arousal effects (serotonin, noradrenaline, dopamine, acetylcholine, and histamine)
SEs: Priapism (may lead to impotence), orthostatic hypotension, sedation
Half-life: 10-15 hrs
- Used to manage sleep issues (at lower doses).
- Should be avoided with MAOIs.
Describe Bupropion; MA and SE?
Bupropion (Wellbutrin)
MA: NE and DA reuptake inhibitor and nicotinic receptor antagonist
SE: GI (nausea, anorexia), dry mouth, nausea, constipation, anxiety, tremor, risk of seizures at higher doses (lowers threshold), hepatotoxicity
- Less sexual dysfunction than similar agents.
Indication: depression adjunct, smoking cessation
Contraindicated: eating or seizure disorders
Half life: 14hrs
Describe Lithium; mechanism of action and SEs?
Lithium
MA: It inhibits excitatory neurotransmitters such as dopamine and glutamate, and promotes inhibitory GABA-mediated neurotransmission.
- Dopamine: Chronic lithium -> alter the functionality of G-protein coupled receptors (GPCR) subunits responsible for post-synaptic activation of DA receptors -> DA neurotransmission inhibited
- Glutamate: Acutely stimulates NMDA receptor (glutamate receptor) -> increasing glutamate availability in postsynaptic neuron. After chronic administration -> lithium induces NMDA downregulation -> modulates glutamate neurotransmission (elevated in bipolar mania)
- GABA: At the presynaptic level, lithium facilitates GABA release. At the postsynaptic level it upregulates GABA-B receptors. GABA is an inhibitory neurotransmitter that modulates dopamine and glutamate neurotransmission (reduced in bipolar)
SEs: Mild GI symptoms, fine hand tremor, mild thirst, polyuria, metallic taste
- Lithium toxicity (>1.5mmol/L): blurred vision, worsening GI symptoms (anorexia, diarrhoea, vomiting), muscle weakness, drowsiness, ataxia, coarse tremor, muscle twitching
Severe toxicity (>2mmol/L): hyper-reflexia, disorientation, seizures, syncope, renal failure, nystagmus, circulatory failure, coma, death
Half-life: 24hrs
What interacts with Lithium?
Interactions: caffeine promotes excretion, NSAIDs interferes with excretion, HCT retains Li as salt, ACE-I retains Li as salt
Describe lithium monitoring?
Monitoring: WBC, UEC, TFTs, renal function (SG, BUN, Cr), fasting blood glucose, bHCG, ECG recommended prior to treatment and annually thereafter.
-> 6 monthly for TSH and Cr
Serum levels: Serum levels should be taken 10-14hrs post previous dose. Lithium levels: monitor 3 monthly once stable on med
- Therapeutic range: 0.4-1mmol/L
- Lithium toxicity: >1.5mmol/L (>2 is severe)
Describe sodium valproate; MA and SE?
Sodium valproate
MA: Unknown. Blockade of voltage-gated sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).
SE: Thrombocytopenia, pancreatitis, weight gain, hair loss, GI upset, cognitive dulling, teratogenic (neural tube defects), hepatotoxicity
Monitoring: FBC, LFT, pancreatic enzymes, bHCG in childbearing women.
Note: Valproate increases the plasma levels of lamotrigine and thus the titration schedule should be halved.
Half-life: 8hrs
Describe Carbamazepine; MA and SE?
Carbamazepine
MA: Reducing high-frequency repetitive firing of action potentials -> enhancement of sodium channel inactivation
SE: Nausea, vomiting, slurred speech, dizziness, drowsiness, low WBC count, high LFTs, cognitive slowing, teratogenic (craniofacial defects).
Monitoring: Nausea, vomiting, slurred speech, dizziness, drowsiness, low WBC count, high LFTs, cognitive slowing, teratogenic (craniofacial defects).
Half-life: 18-55 hrs
