Pharmacology Flashcards
What is the mechanism of action of TCAs?
—Anti-cholinergic
—Competitive antagonism of histamine H1/H2 receptors
—Inhibits the reuptake of noradrenaline/serotonin/dopamine at the presynaptic nerve terminal
—Antagonises alpha-1-adrenergic receptors
—Antagonises fast Na channels in cardiac
—Blockade of the cardiac delayed rectifier K channel
How does magnesium work in pre-eclampsia?
Antagonist at Ca channels - reduces vasospasm
NMDA receptor antagonist - anticonvulsant
Increased production of endothelial prostacyclin - may restore the thromboxane/prostacyclin imbalance
Describe the pharmacokinetics of TCA drugs
Absorption: well absorbed; peak plasma levels 2-4 hours after ingestion
Distribution: Large Vd; highly plasma protein bound
Metabolism: liver; active metabolites
Excretion: low renal excretion
Why do TCAs cause arrhythmias?
Lengthen phase 0 of the cardiac cycle by inhibiting Na channels
Delay in propagation of depolarisation in AV node etc causes prolongation
What drugs can be used for hypotension?
Beta blockers - esmolol (selective beta-1); labetalol (alpha and beta 1:7)
Vasodilators - GTN (decreased intracellular Ca); SNP (arterial and venous dilatation); hydralazine
Alpha blockers - phentolamine
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Describe sodium nitroprusside
- Vasodilator
- Given via infusion
- Needs to be protected from light
- Produces NO -> vasodilatation
- Rapid onset and offset
- Will cause a reflex tachycardia
What drugs prolong QTc?
Which can cause Torsade?
Sotalol
Amiodarone
Haloperidol
Erythromycin
Oxycodone
Quinolones
Sotalol causes TdP in 2-4%
Amitriptyline (& other TCAs)
Ciprofloxacin
Citalopram (& other SSRIs)
Dexmedetomidine
Erythromycin (& other macrolides)
Fluconazole (& other triazoles)
Haloperidol (& other antipsychotics)
Metronidazole
Ondansetron
Trimethoprim/sulphamethoxazole
How do drugs prolong QTc?
Blockade of the ‘rapid’ K+ outward channel
Common causative agents are:
-Class Ia and III
E.g. Sotalol; quinidine
-Anti-psychotics
-Anti-depressants
-Antihistamines
-Antimicrobials
What kind of reactions are:
-Phase 1
-Phase 2
Phase 1 - endoplasmic reticulum of hepatocytes:
Entirely oxidative; makes it hydrophilic; carried out by CYP450
Reduction
Hydrolysis
Phase 2: increase solubility to aid renal excretion
Glucuronidation
Sulphation
Acetylation
Methylation
Glycination
What is the volume of distribution?
The theoretical volume the drug would occupy if the concentration throughout the body was the same as the concentration in the plasma
What antiplatelet agents do you know?
‘ ‘ ‘
Cyclooxygenase-1 COX-1 inhibitor - irreversible inhibition of COX-1 in platelets resulting in decreased thromboxane A2 production (req’d for platelet aggregation)
‘ ’ ’
P2Y12 receptor antagonists
-thienopyridine derivatives metabolites bind irreversibly bind the ADP P2Y12 receptor, preventing it from activating intracellular processes that should increase platelet aggregation
-clopidogrel -> prasugrel -> ticagrelor (reversible)
‘ ’ ’
Glycoprotein IIb/IIIa antagonists
-activation of the receptor by fibrinogen stimulates the final common pathway in platelet aggregation; blocking this results in powerful antiplatelet action
-tirofiban
‘ ’ ’
Phosphodiesterase inhibitors
-dipyridamole
What opioid has the largest volume of distribution?
Diamorphine - 5L/kg
Fentanyl - 4L/kg
Morphine - 3.5L/kg
Alfentanil - 0.6L/kg
Remifentanil - 0.3L/kg
What do you use to treat verapamil OD?
Calcium:
Because verapamil is a calcium channel blocker
Glucagon:
Increases calcium entry into myocytes
Insulin:
Counteracts hypoinsulinaemia from verapamil; improves glucose uptake and improves myocardial activity
Activated charcoal depending on time
Intralipid (highly lipid soluble drug)
What are the important factors for drug transfer across the blood-brain barrier?
Molecular weight = most important
Lipophilicity of drug = most important if molecular weight <600Da
How do substances cross the blood-brain barrier?
- Diffusion - small lipohilic molecules/gases (O2/CO2/volatile/ethanol/nicotine)
- Channels - small ions/water
- Carrier-mediated - Glucose/Lactate/Pyruvate/Creatine/Neurotransmitter precursors
- Receptor-mediated - insulin/leptin/IgG/TNFa
