Pharmacology Flashcards
What is pharmacodynamics?
Effect of a drug on the body
What is pharmacokinetics?
Effect of the body on a drug
What are the 4 physicochemical reactions?
- Adsorption
- Precipitation
- Chelation
- Neutralisation
What is summation?
If 2 half doses of drugs are given at the same time, can get a full dose as a result of the combination
What is synergy?
When a dose is more than expected when a combined dose is given
What is potentiation?
Drug A stays the same but causes drug B to have an increased effect
What are the patient risk factors for drug interactions?
- Polypharmacy
- Old age
- Genetics
- Hepatic disease
- Renal disease
What are the drug risk factors for drug interaction?
- Narrow therapeutic index
- Step dose/response curve
- Saturable metabolism
What are the mechanisms of pharmacokinetics?
- Absorption
- Distribution
- Metabolism
- Excretion (ADME)
What are the mechanisms of pharmacodynamics?
- Receptor based
- Signal transduction
- Physiological systems
Describe the absorption of IV drugs
Starts low then get quick increase in blood concentration of a drug, which exponentially goes down after it peaks
Describe the absorption of oral drugs
Low peak which is reached slowly but takes longer to get rid of as it is still being absorbed from the gut even as it is being excreted
What is bioavailability?
How much of a dose of a drug you get
What type of drug is given in ICU to increase feed of pt.?
Drugs to increase gut motility
What effect does changing the pH of a drug environment have?
Changes portion of ionised: non-ionised drug
What does it mean if there’s a big volume of distribution?
Most of the drug will not go to the effector site
What happens if there is a low volume of distribution?
The drug is fairly targeted to the effector site
What happens in enzyme induction?
Drug A increases the effect of CYP450 to make drug B more potent
What is enzyme inhibition?
Drug A reduces the effect of CYP450 to make drug B less potent
What is given to overcome aspirin overdose?
NaCO3 which causes excretion of aspirin to happen faster
What drugs cause AKI?
NSAIDs, furosemide
What is the effect of grapefruit juice?
Affects CYP3A4 to increase bioavailability
What are the routes of excretion?
Renal, biliary
What is a drug?
Medicine or other substance which has a physiological effect when ingested or otherwise introduced into body
What is druggability?
Ability of a protein target to bind small molecules with high affinity
What are the 4 common drug targets?
- Receptors
- Enzymes
- Transporters
- Ion channels
What is a receptor?
A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to ligands observed effects
What are the 4 common receptors?
- Ligand-gated ion channels
- G protein coupled receptors
- Kinase-linked receptors
- Cytosolic/nuclear receptors
What do the majority of GPCRs interact with?
PLC or adenylyl cyclase
What can change the way a receptor responds?
Polymorphisms
What happens when a ligand binds a kinase linked receptor?
Causes polymorphism of components which then recruit molecules which only interact with phosphorylated component of receptor to amplify signal on IC side
What is a receptor ligand?
A molecule that binds to another molecule
What is an agonist?
A compound that binds to a receptor and activates it
What is an antagonist?
A compound that reduces the effect of an agonist
What is potency?
EC50, concentration that gives half the maximal response
What is efficacy (Emax)?
Maximum response achievable from a dose
What is intrinsic activity?
Ability of a drug-receptor complex to produce a maximal functional response
How do you determine intrinsic activity (IA)?
IA = Emax of a partial agonist ÷ Emax of full agonist
What is competitive antagonism?
Directly competes for binding to receptor
What is non-competitive antagonism?
Binds to an allosteric site of receptor to prevent activation of receptor
What are the 2 categories of cholinergic receptor?
Nicotinic and muscarinic
What factors govern drug action?
- Affinity
- Efficacy
- Receptor number
- Signal amplification
What is affinity?
Describes how well a ligand binds to receptor
What is efficacy?
Describes how well a ligand activates a receptor
What is receptor reverse?
Where an agonist needs to activate only a small fraction of existing receptors to produce a maximal system response
What is a signal cascade?
Response following ligand binding a receptor by causing a number of amplification steps
What is allosteric modulation?
Where antagonist (or ligand) binds to a site which isn’t the active site of that receptor
What is inverse agonism?
When a drug binds to the same receptor as an agonists but induces a pharmacological response opposite to that of the agonist
What is tolerance?
Reduction in agonist effect over time
When does desensitisation occur?
When proteins are uncoupled, internalised or degraded
What is an enzyme inhibitor?
A molecule that binds to an enzyme and decreases its activity
How do enzyme inhibitors work?
Prevent substrate from entering enzyme’s active site and prevents it from catalysing its reaction
What are the types of enzyme inhibitor?
- Irreversible inhibitors
2. Reversible inhibitors
How do irreversible inhibitors bind?
Covalent bond
What are the symptoms of Parkinson’s?
Hypokinesia Tremor at rest Muscle rigidity, motor inertia Cognitive impairment Degenerative disease of basal ganglia
What is the pathway for Parkinson’s?
Early degeneration of dopaminergic in nigrostriatial pathway leading to autonomic dysfunction and dementia
What are the 3 main protein ports?
- Uniporter
- Symporter
- Antiporter
How do uniporters work?
Use energy from ATP to pull molecules in
How do symporters work?
Use movement in of one molecule to pull in another molecule against a concentration gradient
How do antiporters work?
One substance moves against its gradient, using energy from second substance moving down its gradient
What is the mechanism of action for furosemide?
Inhibits luminal NKCC co-transporter in thick ascending limb of loop of Henle to cause loss of Na, Cl and K in urine
What is ENaC?
An apical membrane-bound heterotrimeric ion channel selectively permeable to Na ions
What high affinity diuretic blocks ENaC?
Amiloride
Where are voltage gated Ca channels found?
Membrane of excitable cells
How do voltage gated Ca channels work?
Ca enters cell, resulting in activation of Ca-sensitive K channels, muscular contraction, excitation of neurons etc.
What is amlodipine?
An angioselective Ca channel blockers that inhibits the movement of Ca ions into vascular smooth muscle cells and cardiac muscle celsl
How does amlodipine work?
- Inhibits Ca ion influx across cell membranes with greater effect on vascular SMC.
- Causes vasodilation and a reduction in peripheral vascular resistance.
- Lowers BP and prevents excessive constriction in coronary arteries
What is the main inhibitory neurotransmitter in the CNS?
GABA
What drug inhibits Na/K ATPase?
Digoxin
What is a heterodimeric protein?
Where 2 distinct proteins come together and assemble in the membrane
What is H/K ATPase responsible for?
Acidification of the stomach, activation of the digestive enzyme pepsin
What is the ideal target for inhibiting acid secretion?
Proton pump
What are the symptoms of irreversible inhibition of muscarinic receptors?
Salivation Defecation Urination Bradycardia Hypotension
What are the symptoms of irreversible inhibition of nicotinic receptors?
Twitching
Severe weakness
Paralysis of diaphragm
What are the symptoms of irreversible inhibition of the CNS?
Confusion
Loss of reflexes
Convulsions
Coma