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68 Cards in this Set
- Front
- Back
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3 main types of antidepressant
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Monoamine uptake inhibitors.
Monoamine receptor antagonists. Monoamine oxidase inhibitors. |
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Tranylcypromine
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MAO-I
Non-reversible and non-selective |
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Toxic effects of Tranylcypromine
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Cheeses reaction.
Tyramine metabolised by MAO, if inhibited can cause hypertension, headache. |
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MOCLOBEMIDE
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MAO-I
Reversible and MAOA selective. |
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Toxic effects of MOCLOBEMIDE
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Less toxic than other MAO-I
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AMITRYPTILINE
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Tricyclic.
Competes with amine transporter - uptake 1, thereby blocking reuptake. |
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Toxic effects of AMITRYPTILINE
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Antimuscarinic.
Antihistaminergic. Antiadrenergic. Potentiate alcohol. Cardiac arrhythmia and seizures in overdose. |
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FLUOXETINE
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SSRI.
Selectively blocks serotonin reuptake pump at neronal membrane. |
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Toxic effects of FLUOXETINE
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Nausia, diarrhoea, agitation, anorgasmia.
With MAO-I causes serotonin syndrome - tremor, hyperthermia, CV collapse |
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MIANSERIN
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Monoamine receptor antagonist.
a2-adrenoceptor selective. REMEMBER: 5-HT release also controlled by inhibitory action on a2 adrenoceptors on serotonergic nerve terminals. |
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Use of a2-adrenoceptor antagonist.
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Block of α2 adrenoceptors on serotonergic neurons removes presynaptic inhibition and thus 5-HT release is enhanced
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Toxicity of MIANSERIN
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Drowsiness hypotension, cardia arrhythmia.
May cause bone marrow depression. |
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Replacement od MIANSERIN
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MIRTAZAPINE
Antagonist at a2, 5-HT2 and 5-HT3. Less side effects |
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NEFAZODONE
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Monoamine receptor antagonist.
5HT-1A selective. Inhibits 5-HT2 post synaptic receptors and pre-synaptic 5-HT reuptake. |
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Toxicity of NEFAZODONE
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Sedation, hypotension, cardiac arrhythmia. Minor risk of liver damage.
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Name SSRI
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FLUOEXETINE
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PINDOLOL
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B-blocker with affinity for 5-HT1A, can initiate early desensitisation. Given with MOA-I will produce faster results in mood improvement.
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3 possible future drug targets relating to ion channels in depression
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Nicotinic receptors - agonists, partial agonists and antagonists have shown antidepressant properties.
NDMA antagonists - KETAMINE shown to rapidly alleviate depression and last for several days. AMPAkines - drugs that potentiate response at AMPA receptor are effective in animal models. |
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Non-selective MAO-I
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TRANYLCYPROMINE
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Reversible MAO-I
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MOCLOBEMIDE
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Tricyclic drug for depression
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AMITRYPTILINE
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SSRI
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FLUOXETINE
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a2-adrenceptor antagonist in depression treatment
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MIANSERIN
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5-HT1A antagonist in depression treatment
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NEAZODONE
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B-blocker with 5-HT affinity in depression treatment
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PINDOLOL
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5 points FOR the monoamine theory
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1. Post mortem MOPEG/5-HIAA.
2. Proven drugs increase MA levels. 3. MA-I induce depression (Resperine, methyldopa) 4. ECT improves mood (increase MA response?). 5. Manic depressive urine levels of MOPEG. |
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4 points AGAINST the monoamine theory
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1. Amph/cocaine ineffective.
2. Time delay. 3. B-blockers not implicated. 4. Implication of other factors (separate question) |
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Extra factors in the monoamine theory
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1. CRH hyperfunction.
2. Reduced BDNF/malfunction of TrKB. 3. NMDA-r antagonists effective. 4. Neuronal loss. Neurogenesis via 5-HT1A and a2-adrenoceptors. 5. Andrew's review - relapse proportional to MA enhancement. All extra points to be added to discussion. |
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5-HT
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5-hydroxytryptamine
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Cheese reaction
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Tyramine is metabolised by MAO, if inhibited it may cause hypertension and headache.
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Antimuscarinic effects
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Dry mouth, constipation, blurred vision, urinary retention.
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Antiadrenergic effects
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Postural hypotension
Seizures Impotence |
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5-HT
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5-hydroxytryptamine
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Cheese reaction
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Tyramine is metabolised by MAO, if inhibited it may cause hypertension and headache.
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Antimuscarinic effects
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Dry mouth, constipation, blurred vision, urinary retention.
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Antiadrenergic effects
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Postural hypotension
Seizures Impotence |
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Main types of hypoglycaemic drugs
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Biguanide (METFORMIN).
Sulphonylurea (TOLBUTAMIDE) Glitazones (ROGGLITAZONE) Others - ARCABOSE, EXANATIDE, GLIPTONS. |
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Possible future drug/targets in diabetes
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B3 agonists - control lipolysis in fat cells, useful for obese patients.
PKC inhibitors - limit vascular complications |
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5 key mechanisms of METFORMIN
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1. Reduce gluconeogenesis.
2. Reduce insulin resistance in skeletal muscle. 3. Reduce carb absorption. 4. Increase fatty acid oxidation. 5. Reduce LDL and VLDL. 1, 2 and 4 most important. |
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METFORMIN mode of action
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Activates AMPK:
- prevents gluconeogenesis in liver - promote GLUT 4 in skeletal muscle - stimulate fatty acid oxidation |
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Sequence of events leading to AMPK activation with METFORMIN use
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-METFORMIN inhibits mitochondrial complex 1 of respiratory chain
-increase in AMP:ATP ratio -activation of AMPK -reduce expression of glconeogenesis genes and promote GLUT 4 translocation |
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Side effects of METFORMIN
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Dose related GI problems.
Lactic acidosis (rare) |
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Contraindications in METFORMIN
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Hepatic/renal disease.
Heart disease. Hypoxic pulmonary disease. |
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Example of sulphonylurea in diabetes treatment.
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TOLBUTAMIDE
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Mode of action of sulphonylurea (TOLBUTAMIDE)
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-Inhibit K-ATP channels on B-cells of the pancreas
-causes depolarisation and calcium influx -calcium - calmodulin binding then inane activation -release of insulin from granules |
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Side effects of TOLBUTAMIDE
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Hypoglycaemia, short acting so unlikely.
Weight gain. Skin reaction. Rare bone marrow damage. |
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Example of a glitazone used in diabetes.
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ROSIGLITAZONE
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Mode of action go ROSIGLITAZONE
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-Binds to nuclear factor PPAR-gamma
-creates PPAR-RxR complex -binds to DNA and promotes synthesis of Insulin-signalling proteins eg. GLUT 4 Thereby improves insulin sensitivity |
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Side effects of ROSGLITAZONE.
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Weight gain and fluid retention.
Risk of heart failure |
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Contraindications in ROSGLITAZONE.
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Pregnancy or breast feeding.
Children. |
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Contraindications in TOLBUTAMIDE.
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Liver failure.
Pregnancy. |
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ACARBOSE mode of action
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Inhibits intestinal a-glucosidase (converts polysaccharide to glucose)
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EXENATIDE mode of action
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Mimics GLP-1, incretin.
Insulin secretion in presence of high glucose. |
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Mode of action of GLIPTINS.
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Inhibits DDP-4, which acts to break down incretins GLP-1 and GIP.
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Parkinsons is a result of a deficiency in _____ in _____ following degeneration of ______ ______.
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Dopamine
Striatum Substantia nigra |
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D1 receptors are _____.
D2 receptors are _____. |
D1 - excitatory
D2 - inhibitory |
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Name of misfolded protein in PD.
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a-synuclein
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Area of brain affected by PD
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Basal ganglia - caudate nucleus, putamen, globus pallidus
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3 most used ranges of drugs in PD
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Levadopa (with another to prevent breakdown)
DA (D2) agonist MAO-B inhibitors |
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3 drugs used in multi drug study in PD
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LEVADOPA
BENSERAZIDE SELEGILINE |
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Dopa decarboxylase inhibitor in PD
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BENSERAZIDE
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MAO-B inhibitor in PD (current and improved)
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SELEGILINE
RASAGILINE - less side effects. May retard disease progression (Olanow, 2009) |
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D2 agonists used in PD
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BROMOCRIPTINE
ROPINROLE - D2 selective |
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COMT inhibitor used in PD
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TOLCAPONE
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Other drugs used in treatment of PD
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AMANTADINE - promotes DA release in basal ganglia. Tolerance soon develops.
Ach antagonists |
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Side effects of levadopa
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Vivid dreams
Hallucinations Confusion Postural hypotension |
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Recommended medications for increasing severity in PD (3)
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1. MAO-B inhibitors
2. D2 agonist 3. Levadopa with DDC inhibitor (BENSERAZIDE) |
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Toxic effects of MAO-I (TRANYLCYPROMINE)
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Cheese reaction.
Anticholinergic. Weight gain. Hypotension. Insomnia. Overdose. |
