Drugs for Neurodegenerative Diseases Flashcards
Drugs that increase Dopamine levels
Levodopa Carbidopa Amantadine Selegiline Rasagiline Tolcapone Entacapone
Levodopa - MoA
Increase dopamine levels by increasing the synthesis.
It is converted to dopamine by LAAD and metabolized to 3OMD by COMT. A drug that inhibits LAAD or COMT increases the amount of levodopa that enters brain tissue.
In the brain levodopa is taken up by dopaminergic neurons in the striatum and converted to dopamine by LAAD. Levodopa thereby increases the amount of dopamine released by the neurons in patients with PD, and is serves as a form of replacement thrapy. As the diseases progresses and more dopaminergic neurons are lost, the conversion of levodopa to dopamine therefor declines.
Levodopa - Indication
Idiopathic PD
Postencephalitic parkinsonism
Parkisonian symptoms caused by carbon monoxide poisoning, manganese intoxication, or cerebral arteriosclerosis
Levodopa - Adverse effects
Nausea and vomiting (when used alone)
Orthostatic hypotension
Cardias dysrhythmias. Adverse effects are reduced with the use of Carbidopa.
Long term; involuntary movements or dyskinesias
Psychotic effects, including hallucination and disoriented thinking
Sedation, agitation, delirium, vivid dreams or nightmares, euphoria after drug adm.
Discoloration of urine, sweat and or saliva
Loss of appetite
Levodopa - Interactions
Anticholinergic drugs –> slow levodopa absorption
Nonselective MOAIs inhibit the breakdown of dopamine and sometimes cause hypertensive crisis in patients receiving levodopa
Antipsychotic drugs block dopamine receptors and can reduce the effectiveness of levodopa and exacerbate motor dysfunction
Drugs that promote gastric emptying (antacids) can increase levodopa bioavailibility
Ingestion of high-protein foods can decrease the effectiveness of levodopa because amino acids can reduce the transport of levodopa into the brain
LAAD requires Vitamin B6 (pyridoxine) as a cofactor. For this reason, vitamin B6 supplements may enhance the peripheral decarboxylation of levodopa and shoult not be coadministered with levodopa
Carbidopa - Group + MoA
Analoug of levodopa
Inhibits LAAD thereby reducing the conversion of levodopa to dopamine in peripheral tissues and so increases the amount of levodopa that enters the brain
Carbidopa - Indication + Adverse effects
PD
Reduces the cardiovascular and GI side effects of Levodopa.
Amantadine - Group + MoA
Antiviral drug
Increases dopamine release from nigrostriatal neurons, may also inhibit the reuptake of dopamine by these neurons.
Amantadine - Indication
Early or mild cases of Parkinson disease
Prevention and treatment of influenza
Amantadine - Adverse effects
Sedation Restlessness Vivid dreams Nausea Dry mouth Hypotension Livedo reticularis- reddish-blue mottling of the skin with edema CNS side effects are more common in elderly pat.
Selegiline - Group + MoA
Modified phenylethylamine compound
Increase dopamine by inhibiting the breakdown.
Inhibits Monoamine oxidase type B (MAO-B) and thereby prevents the oxidation of dopamine to dihydroxyphenylacetic acid and hydrogen peroxide. By this selegiline increases dopamine levels in the basal ganglia and decreases the formation of hydrogen peroxide. In the presence of iron, hydrogen peroxide is converted to hydroxyl and hydroxide free radicals that may participate in the degeneration of nigrostriatal neurons in patients with PD.
Selegiline - Indication
Early or mild PD
Adjunct with levodopa for advanced disease, reduces the dose of levodopa needed, and may improve motor function in patients who experience wearing-off and on-off difficulties.
Selegiline + Rasagiline - Adverse effects
Confusion Dyskinesia Hallucinations Hypotension Insomnia Nausea.
Selegiline + Rasagiline - Interactions
Severe reactions may result if taken with meperidine or with fluoxetine or other SSRIs
Rasagiline - MoA
MAO-B inhibitor
Rasagiline - Indication
Monotherapy or adjunct medication in the treatment of parkinsonism
Tolcapone and Entacapone - MoA
Enhances the effectiveness of levopoa by inhibiting COMT, the enzyme that metabolize levodopa to 3OMD. By this action, it produces twofold increase in the oral bioavailability and half-life of levodopa.
Tolcapone: inhibits COMT in glial cells and inhibits conversion of dopamine to 3-methoxytyramine
Tolcapone and Entacapone - Indication
PD
Tolcapone and Entacapone - Adverse effects
Both: Diarrhea Nausea Discoloration of urine, sweat, saliva Tolcapone: Rare: fatal hepatitis
Dopamine receptor agonists
Bromocriptine Pramipexole Ropinirole Rotigotine Apomorphine Benztropine Trihexyphenidyl
Dopamine receptor agonists - MoA
Directly activate dopamine receptors in the stratum. Because they do not require functional dopaminergic neuron to produce their effects, they are sometimes helpful in advanced cases of PD, in which few dopaminergic neurons remain. They work by primarily activating D2 receptors and this leads to inhibition of the indirect neuronal pathway from the striatum to the thalamus and increase thalamic stimulation of the motor area of the cortex.
Dopamine receptor agonists - Adverse effects
Nausea
Orthostatic hypotension
Mental disturbances
Daytime sleepiness
Bromocriptine - MoA
Is a D2 agonist and a D1 antagonist.
Bromocriptine - Indication
Adjunct to levodopa in patients who have advanced PD and experience wearing off effects and on-off motor fluctuations.
Diabetes type 2
Bromocriptine - Adverse effects
Decreased prolactin levels Pulmonary and cardiac fibrosis Orthostatic hypotension Dry mouth Nausea Dose-related CNS effects: confusion, dyskinesias, sedation, vivid dreams and hallucinations
Pramipexole and Rotigotine - MoA
Selective D2 agonists
Also activates D3
Pramipexole - Indication
PD
Delay the need of levodopa
Restless leg syndrome
Pramipexole and Ropinirole - Adverse effects
Dizziness Hallucinations Insomnia Nausea Vomiting Sedation
Pramipexole - Interaction
Cimetidine inhibits renal excretion and increases serum levels
Ropinirole - MoA
Selective D2 agonists
Ropinirole and Rotigotine - Indication
PD
Restless leg syndrome
Ropinirole - Interaction
Ciprofloxacin increases serum levels
Rotigotine - Adverse effects
Somnolence
Slight hypertension and tachycardia
Site irritation
Apomorphine - MoA
Does not bind to opioid receptors, but rather Dopamine agonist.
Apomorphine - Indication
Treatment of acute intermittent hypomobility (freezing) episodes associated with PD
Benztropine and Trihexyphenidyl - MoA
Antagonists at cholinergic muscarinic receptor and also exhibit antihistamine activity
Benztropine: may also inhibit the neuronal reuptake of dopamine and thereby prolong the action of dopamine
Benztropine and Trihexyphenidyl - Indication
May be helpful as adjunct therapy in combination with levodopa and other drugs that augment dopaminergic activity. They reduce tremor
Can also reduce parkinsonian symptoms caused by dopamine receptor antagonists, such as haloperidol
Benztropine and Trihexyphenidyl - Adverse effects
Agitation Confusion Constipation Delirium Dry mouth Memory loss Urinary retention Tachycardia
Benztropine and Trihexyphenidyl - Interactions
Additive anticholinergic effects with antihistamines and phenothiazines
Drugs for Alzheimer disease
Donepezil Rivastigmine Tacrine Galantamine Memantine Caprylidene Dextrometorphan Quinidine
Donepezil, Rivastigmine, Tacrine and Galantamine - MoA
Reversible acetylcholinesterase inhibitors.
Donepezil and Rivastigmine: improves cholinergic neurotransmission
Donepezil - Adverse effects and Interactions
Bradycardia, diarrhea, GI bleeding, nausea, vomiting
Anticholinergic drugs inhibit effects
Rivastigmine and Galantamine - Indication
Delays global cognitive impairment and slows the progression of AD.
Rivastigmine and Galantamine - Advese effects
Risk of bradycardia and AV block
Nausea, vomiting, anorexia, weight loss
Rivastigmine and Galantamine - Interactions
Both
Anticholinergic drugs inhibit effects.
Rivastigmine: Nicotine increases oral clearance
Galantamine: Inhibitors of CYP2D6 increase serum levels
Tacrine - Adverse effects
Hepatotoxicity
Diarrhea, nausea, urinary incontinence
Memantine - MoA
Noncompetitive antagonist at NMDA receptor. Blocks glutamate neurotransmission at NMDA receptors.
Memantine - Indication
AD
Dementia
Memantine - Adverse effects
Confusion Dizziness Drowsiness Headache insomnia
Caprylidene - MoA
Medical food that is metabolized into ketone bodies which the brain can use for energy when the processing of glucose is impaired.
Caprylidene - Indication
Age associated memory impairment
AD
Dextromethorphan
Quinidine - MoA
Dexmetromethorphan: inhibits excitatory glutamate release by agonist action at sigma-1 receptors and blocks NMDA receptors –> Excitatory neurotransmission that underlies emotion lability is reduced
Dextromethorphan
Quinidine - Indication
Emotional lability (pseudobulbar effects). seen in pt w neurodegenerative diseases
Dextromethorphan
Quinidine - Interactions
Quinidine is an inhibitor of CYP2D6 and therefore increases the bioavailability of dextromethorphan
Drugs for Huntington Disease
Diazepam
Haloperidol
Tetrabenazine
Diazepam - MoA
Potentiate GABA
Diazepam - Adverse effects
Arrhytmias, CNS depression, drug dependence, hypotension, and mild respiratory depression
Diazepam - Interactions
Alcohol and other CNS depressants potentiate effects.
Cimetidine increases and rifampin decreases serum level
Haloperidol - MoA
Block dopamine receptors
Haloperidol - Adverse effects
Extrapyramidal side effects
Increased prolactin levels
Haloperidol - Interaction
Barbiturates and carbamazepine decrease and quinidine increases serum levels
Tetrabenazine - MoA
Reversibly inhibit the human vesicular monoamine transporter type 2 VMAT2, resulting in decreased uptake of monoamine into synaptic vesicles and depletion on monoamine stores (dopamine, norepinephrine, serotonin) leading to decrease neurotransmitter release from nerve terminals.
Tetrabenazine - Indication
Chorea in in HD
Drugs for Multiple sclerosis
Interferon beta-1b Interferon beta-1a Peginterferon beta-1a Natalizumab Daclizumab Alemtuzumab Mitoxantrone Glatiramer acetate Dalfampridine Fingolimod Teriflunomide Dimethyl fumarate Prednisone Baclofen
Interferon beta-1b - MoA
Increases the cytotoxicity of natural killer cells and increases the phagocytic activity of macrophages. In addition, it reduces the amount of interferon-gamma secreted by activated lymphocytes
Interferon beta-1b - Adverse effects and interactions
Chills, diarrhea, fever, headache, hypertension, myalgia, pain and vomiting
Increases serum levels of zidovudine
Natalizumab - MoA
Block the molecular pathway involving cell adhesion that draws lymphocytes into the CNS
Daclizumab - MoA
Monoclonal antibody to IL-2 receptor, block interleukin-mediated activation of lymphocytes
Alemtuzumab - MoA
CD52-directed cytolytic monoclonal antibody
Alemtuzumab - Adverse effects
Life-threatening adverse effects of autoimmune, infusion reactions, and increased malignancies
Mitoxantrone - MoA
Acts by suppressing the activity of T cells, B cells and macrophages that are thought to lead the attack on the myelin sheath. Antineoplastic drug
Glatiramer acetate - MoA
Synthetic protein that mimics the structure of the myelin basic protein, a component of the myelin nerve fibers. This drug blocks myelin-damaging T cells by acting as a myelin decoy.
Dalfampridine - MoA
Block potassium channels and enhance the conduction in damaged nerves
Fingolimod - MoA
Sphingosine-1-phosphate receptor modulator, block the egress of lymphocytes from lymph nodes, reducing the number of lymphocytes in blood.
Teriflunomide - MoA
Reduce the proliferation of overactive immune cells (including T- and B-cells) that attack and damage the nerve in the CNS by acting pyrimidine synthesis inhibitor.
Teriflunomide- Adverse effects
Hepatotoxicity
Dimethyl fumarate - MoA
Its main metabolite is monomethyl fumarate (MMF). MMF activates the Nuclear factor (erythroid-derived 2)-like 2 (Nfr2) pathway.
Prednisone - Indication
Acute exacerbations of MS
Prednisone - Adverse effects and Interactions
Aggrevation of: DM, GI-bleeding, mood changes, pancreatitis and seizures.
Barbiturates, Carbamazepine, phenytoin, rifampin decreases serum levels
Which drugs are used for relapsing MS?
Interferon beta-1a Alemtuzumab Fingolimod Teriflunomide Dimethyl fumarate
Drugs for Amyotrophic lateral sclerosis
Baclofen
Gabapentin
Roluzole
Baclofen - MoA + group
GABAb receptor agonist, when activated they reduce motor neuron excitability
Antispastic
Baclofen - Adverse effects
Dizziness, Fatigue, Weakness
Riluzole - MoA
Protect motor neurons from the neurotoxic effects of excitatory amino acids and prevent anoxia-related death of cortical neurons
May inhibit voltage-gates sodium channels that mediate the release of glutamate from neurons
Riluzole - Indication
ALS
Prolongs the time before patients require a tracheotomy and also to prolong life by approximately 3 months.
More effective in those with bulbar-onset disease than in those with limb-onset disease
Riluzole - Adverse effects and Interactions
Asthenia, diarrhea, dizziness, drowsiness, increased hepatic enzyme levels, nausea, vomiting, paresthesias, vertigo
Quinolones and Theophylline increases serum levels.
Omeprazole, rifampin and smoking decreases serum levels
Antispastic Agents
Baclofen Cyclobenzaprine Orphenadrine Methocarbamol Carisoprodol Tizanidine Dantrolene Botulinum Toxin A
Cyclobenzaprine
Orphenadrine - MoA and Indication
Centrally mediated effects on catecholamine reuptake, and antimuscarinic and antihistaminergic receptor actions
Muscle spasms by acute painful musculoskeletal conditions (short-term)-
Methocarbamol - MoA
General CNS depression
Carisoprodol - Indication
Muscle spasms caused by musculoskeletal conditions (short-term)
Tizanidine - MoA and Indication
Centrally acting alpha2 adrenoceptor agonist, blocks nerve impulses through presynaptic inhibition of motor neurons.
Spasticity of MS
Dantrolene - MoA
Block the release of calcium from the sarcoplasmic reticulum in muscle fibers, directly relaxes the muscle
Dantrolene - Indication
Life saving in malignant hyperthermia triggered by halogenated anesthetics
Neuroleptic malignant syndrome
Spasticity
Botulinum toxin A - MoA
Paralyses muscles by blocking the release of acetylcholine on the presynaptic side of the muscle endplate junction
Botulinum toxin A - Indication
Upper-limb spasticity in stroke patients Cervical dystonia Strabismus Blepharospasm Urinary incontinence resulting from detrusor overactivity in patients with spinal cord injury and MS
Gabapentin - Group and Indication
Antiepileptic
ALS
Slows decline in muscle strength
Gabapentin - Adverse effects and Interactions
Ataxia, dizziness, drowsiness, nystagmus, tremor
Antacids decreases serum levels
