BB Pharmacology NEW Flashcards
Rasagiline
Selegiline
Dopaminergic Drugs
Type: Affects Dopamine Inactivation
Class: MOAb Inhibitors
Stop dopamine from being degraded in the pre-synaptic neurons (Conversion from dopamine to DOPAC) + protect residual dopamine vs oxidation
Entacapone
Tolcapone
Dopaminergic Drugs
Type: Affects Dopamine Inactivation
Class: COMT Inhibitors
Stop dopamine degradation from DOPAC to Homovanillic acid.
(!) May alleviate dystonias and motor fluctuations in long-term management of L-DOPA, as well as prolonging the effect on L-DOPA.
Benzhexol
Benztropine
Dopaminergic Drugs
Type: Affects Dopamine Inactivation
Class: Antimuscarinic Drugs
Antagonists of muscarinic acetylcholine receptors (mAchRs). They increase dopamine release, inhibit dopamine re-uptake, inhibit overactivity.
Side Effects: dry mouth, flushed (hot) skin, dilation of pupils, tachycardia etc…
Reserpine
Tetrabenazine
Dopaminergic Drugs
Class: Affecting Dopamine Storage
Drug: Decreasing Release
Inhibits the vesicular storage of dopamine by irreversibly inhibiting the vesicular monoamine transporter VMAT2 (used in Huntington’s).
Amantadine
Dopaminergic Drugs
Type: Affecting Dopamine Storage
Class: Increasing Release
Inhibition of amine uptake, inhibition of MOA activity, release of dopamine (and noradrenaline) from monoaminergic terminals.
Alpha methyl-p-tyrosine
Dopaminergic Drugs
Type: Affecting Dopamine Synthesis
Competitive inhibitor of dopamine: blocks dopamine synthesis by inhibiting tyrosine hydroxylase (rate-limiting step in synthesis of dopamine)
L-DOPA/Levadopa
Madopar (has PDCI* Benserazide)
carbidopa is another PDCI
Peripheral Decarboxylase Inhibitor
Dopaminergic Drugs
Type: Affecting Dopamine Synthesis
Dopaminergic nerve fibres take up L-DOPA. Converted by the enzyme DOPA decarboxylase to dopamine.
Contains peripheral decarboxylase inhibitor along with L-DOPA to prevent the conversion to dopamine to occur outside the BBB (causes nausea/vomiting due to stimulation of the chemoreceptor trigger zone).
Pergolide
Quinpirole
Dopaminergic Drugs
Type: Post Synaptic Dopamine Receptor Agonists
Show little selectivity between D1 and D2 families of receptors.
Bromocriptine
Dopaminergic Drugs
Type: Post Synaptic Dopamine Receptor Agonists
Much higher affinity for D1 than D2, also used for other types of infertility.
Apomorphine
Dopaminergic Drugs
Type: Post Synaptic Dopamine Receptor Agonists
Non-selective potent emetic: that can be given as infusion.
Rotigotine (!)
ropinirole, pramipexole
Dopaminergic Drugs
Type: Post Synaptic Dopamine Receptor Agonists
Non-selective: which has recently been introduced. It can be given as a transdermal patch (continuous administration over 24hrs)
Chlorpromazine Haloperidol Spiperone Sulpiride Clozapine
Dopaminergic Drugs
Type: Post Synaptic Dopamine Receptor Antagonists
Drugs are used to treat schizophrenia (higher affinities for D2 then D1).
Paracetamol
Class: Treatment of Pain (Non-Opioids)
Drug: Analgesic
Anti-pyretic (anti-fever) and analgesic but little anti-inflammatory effects.
• Prevents pain: stopping prostaglandin synthesis in the CNS = through decreasing prostaglandin E2-induced reduction of glycine inhibition of spinal cord cells endogenous spinal inhibitory mechanisms: normal.
o Decreased glycine.
• Inhibit reuptake of endogenous cannabinoids from synaptic cleft = increases effect on antinociception.
Nausea and GI Bleeding.
Ineffective as Anti-Inflammatory:
• Reduces the active oxidised form of COX-2, preventing it from forming pro-inflammatory stimuli (e.g. prostaglandins/thromboxanes).
• BUT: in the presence of peroxides (exist at sites of inflammation) mechanisms becomes inefficient (COX-2 oxidisation by peroxides).
Ibuprofen
Class: Treatment of Pain (Non-Opioids)
Drug: NSAIDs
MOA:
Mild to moderate pain.
Both analgesic and anti-inflammatory.
• Inhibits the activity of COX-1 and COX-2 enzymes.
• Decreases prostaglandin formation, recruitment of leucocytes.
• Reduces sensitisation by these inflammatory mediators.
• (!) Also travel across the BBB to have effects on the prostaglandin synthesis in the CNS.
Side Effects/Notes
Related to inhibition of COX-1.
• COX-1 regulates production of prostaglandins in the GI tract (protect the mucosa).
• Long-term use of NSAIDs can lead to peptic ulcers.
Diclofenac
Class: Treatment of Pain (Non-Opioids)
Drug: NSAIDs
MOA:
Moderate to Severe Pain
Inhibit the formation of prostaglandins.
(!) Longer acting vs ibuprofen.
• Analgesic efficacy comparable to low-dose opioids.
Due to additional activity of inhibiting phospholipase A2 and reductions in arachidonic acid (needed for synthesis of prostaglandins and leukotrienes).
Side Effects/Notes:
• Lower COX-1 selectivity: reduces the risk of GI complications.
• Higher risk of CV complications due to inhibition of endothelial prostacyclin but not thromboxane.
• Therefore, contraindicated in people with IHD and strokes.
Rofecoxib
Class: Treatment of Pain (Non-Opioids)
Drug: NSAIDs
MOA:
Selective for COX-2 Inhibitors.
Side Effects/Notes:
Nausea and GI bleeding.
Amitriptyline
Class: Treatment of Pain (Non-Opioids)
Drug: TCA
MOA:
Often described for neuropathic pain as depression and insomnia are common complications.
- Inhibit reuptake of amines.
- Mainly 5-HT vs noradrenaline (SNRI).
- Inhibits sodium channels, L-type Ca2+ channels and subtypes of K+ channels and acts on NMDA receptors.
- Has affinity for various other receptors e.g. H1, muscarinic alpha-1 and alpha-2 adrenoceptors (cause of side effects)
Side Effects/Notes: • Weight gain • Appetite changes. • Muscle stiffness, constipation, urinary retention, dry mouth (muscarinic effects). • Postural Hypotension (adrenergic) • Nausea nervousness, dizziness.
Side effects due to anticholinergic activity (inhibition of acetylcholine muscarinic receptors, acetylcholine adrenergic receptors etc…).
Pregabalin
Class: Treatment of Pain (Non-Opioids)
Drug: Anticonvulsants
MOA:
Beneficial after 1 week of treatment.
• Binding to alpha2 delta 1 subunit of N-type voltage gated calcium channels.
• reduction in Ca2+ entry = decreased release of neurotransmitters (glutamate, noradrenaline etc…).
(!) Alpha 2 delta 1 subunits increased in some neuropathic conditions.
Side Effects/Notes:
More Common.
• Drowsiness, dizziness and headaches
Less Common
• Peripheral oedema, visual problems, weight gain, confusion.
Tramadol
Class: Treatment of Pain (Opioids and Opioid-Like)
Drug: Atypical Opioids
MOA:
Moderate to severe pain.
Anti-nociceptive/antihyperalgesic.
- Acts on mu opioid receptors
- Interacts with monoaminergic systems (inhibits serotonin and noradrenaline uptake, but not as good as tricyclic antidepressants).
Vs. Opioids: improved side effect profile, reduced abuse potential, lack of tolerance and dependence.
Side Effects/Notes: • Nausea • Vomiting • Sweating • Itching • Constipation
Side effects due to anticholinergic activity (action on acetylcholine muscarinic receptors).
Morphine
Fentanyl
Type: Treatment of Pain (Opioids and Opioid-Like)
Class: Typical Opioids
MOA:
Stimulate Mu Opioid Receptors
• Decreased neuronal excitability (by increasing K+ conductance) and decreased release of neurotransmitters (decreases Ca2+ influx).
Descending Inhibitory pathways
• Stimulate the periaqueductal gray (decreases pain efferent pathways)
• Inhibit the substantia gelatinosa of the SC. (Lamina II: where interneurons are.
Limbic System
• Reduces the anxiety of pain.
Side Effects/Notes:
• Paradoxically increased sensitivity to pain.
• Constipation, nausea, respiratory, depression and sleepiness.
Phenytoin
Carbamazepine
Sodium Valproate
Type: Anti-Epileptic
Class: Sodium Channels
Bind to the inner pore of the sodium channel in its inactivated state (immediately after depolarization). (!) Zero order kinetics seen in phenytoin.
Leads to an increased refractory period (delay in time taken to return to resting state) (!) Carbamazepine: liver enzyme induction.
Ethosuximide (used in absence seizures) Zonasamide Carbamazepine (NOT ABSENCE SEIZURES) Phenytoin (NOT ABSENCE SEIZURES) Topiramate Lamotrigine
Type: Anti-Epileptic
Class: Calcium Channels
- T-type calcium channels: require less depolarization to be activated.
- L-type calcium channels: allow post-depolarization calcium influx and are slowly inactivated. Inhibiting these channels causes inhibition of calcium influx post-depolarization.
N and P/Q-type channels: expressed at presynaptically (buttons).
Mediate calcium entry for neurotransmitter release.
Topiramate (EXTRA)
Type: Anti-Epileptic
Class: Calcium Channels
also increases GABA transmission and inhibits glutamate and works on sodium channels
Lamotrigine (EXTRA)
Type: Anti-Epileptic
Class: Calcium Channels
inhibition of glutamate release as well as target in sodium channels (inner pore binding)
