Pharmacology Flashcards
Define pharmacodynamics?
- what the drug does to the body
Define pharmacokinetics?
- what the body dooes to the drug
What is a drug?
- any substance that can be used in the treatment, diagnosis and prevention of disease
What does selectivity mean?
- the ability of a drug to distinguish between different molecular targets
What are receptors?
- protein macromolecules
What is an agonist?
- binds to a receptor to produce a cellular response
What is an antagonist?
- binds to a receptor to block the effect of an agonist
Define affinity?
- the strength of association between a ligand and its receptor
Define efficacy?
- the ability of an agonist to evoke a cellular response
Antagonists ____ affinity and _____efficacy
- possess
- lack
Agonists _____ affinity and _____ efficacy
- possess
- possess
What is EC50?
- the concentration of agonist required to produce a half maximal effect
What relationship is the graph between agonist concentration and effect when agonist conc is in log?
- sigmoidal relationship
How can competitive antagonism be overcome?
- increasing the concentration of agonist
What effect does competitive antagonism have on the graph?
- parallel shift to the right
What effect does non-competitve antagonism have on the graph?
- depression in the slope
- no parallel shift
What are receptors?
- protein macromolecules
- sensing elements
What are autocrine signals?
- the same cell that produces a signal responds to its own signal
What are paracrine signals?
- signalling over a short distance, doesnt require the signalling molecule to enter the circulatory system
What are endocrine signals?
- signalling over a larger distance, requires the signalling molecule to enter the blood stream
- much slower
Where are ligand gated ion channels located? what signalling molecule binds to them? and are they fast or slow?
- located in plasma membrane
- hydrophillic signals
- fast signalling
Where are GPCRs located? what signalling molceule binds? are they fast or slow?
- located in plasma membrane
- hydrophillic signals
- slow signaling
Where are kinase linked receptors located? what signalling molecule binds? are they fast or slow?
- plasma membrane
- hydrophillic
- work on a hours time scale
where are nuclear recpetors located? what signalling molecule binds to them? are they fast or slow?
- cytoplasm or nucleus
- hydrophobic
- very slow
How might ion channels be gated?
- ligand gated
- voltage gated
- physical stimuli gated
Example of a ligand gated ion channel?
- nicotinic acetylcholine receptor
Explain how a GPCR works?
- GPCR on plasma membrane, agonist binds, causes a confirmational change
- G protein bound to GDP –> GDP dissociates to GTP and beta and gamma subunit dissociate
- a bound to GTP can act as an modulator
How is the G protein made inactive?
- a subunit bound to GTP acts as an enzyme to hydrolyse GTP–> GDP + Pi
- this then makes it go to inactive form
Example of a kinase receptor?
- insulin
How do kinase receptors work?
- autophosphorylation
What are nuclear receptors?
- transcription factors
- responsible for sensing steroid and thyroid hormones
3 Main ways of drug movement?
- bulk flow
- diffusion
- soubility
Explain passive diffusion
- no transporter needed, drug simply passes through lipid membrane
Explain facilitated diffusion
- transporter needed
- no energy required
- down concentration gradient
Explain active transport
- transporter needed
- energy required
- against concentration gradient
Explain endocytosis
- invagination of drug, and released into a cell
Definition of pKa
- pH at which 50% of drug is ionised and 50% unionised
How do u calculate pKa for an acid?
pKa= pH + log (AH/A-)
Weak acids accumulate in areas of ____ pH
- high
Weak bases accumulate in areas of _____ pH
- low
Weak acids are absorbed in areas of _____ pH
- low
Weak bases are absorbed in areas of ___ pH
- high
What is the apparent volume of distribution?
- the extent to which a drug partions between the plasma and the tissue
How do you calculate apparent volume of distribution?
Vd= Dose/ [Drug] plasma
Low Vd suggests_____
high drug plasma concentration
high plasma protein
High Vd suggests____
low drug plasma concentration
low plasma protein binding
Main protein associated with plasma protein binding?
- albumin
Define drug metabolism
- enzymatic conversion of the drug to another chemical enitity
What organ is the main organ involved in the metabolism of drugs?
-liver
hepatic drug metabolising enzymes are located in the _____________ of the liver hepatocytes
smooth endoplasmic reticulum
non-polar drugs pass through the plasma membrane more easily to be metabolised.
true/false
true
Explain what occurs during phase 1 metabolsim
- oxidation, hydrolysis or reduction
- oxidation - cytochrome p450
- addition of a hydroxyl group
- makes the drug more polar
- RHS of liver
What is cytochrome p450?
- envymes that are haem proteins
- oxidises drugs during phase 1 metabolism
Explain what occurs during phase 2 metabolism?
- conjugation
- combination of the drug with polar molecules to form a water soluble metabolite
- terminates all biological activity
- LHS of liver
- can therefore be excreted in the kidneys
Define excretion
- dug/drug metabolites excreted in urine, faces or bile
What is the principal organ involved in excretion?
- kidneys
What occurs at the kidney tubules?
- water and most electrolytes reabsorbed into the blood stream
- drug metabolised rendered polar by phase II metabolism aren’t re absorbed and are excreted in the urine
What does Cmax mean?
- maximum drug plasma concentration
What does Tmax mean?
- the time at which Cmax occurs
Cmax = the maximum drug plasma conc
clearance is a ______ parameter
- flow parameter
What is the equation for drug clearance (CL)
CL = rate of elimination/[drug] plasma
Explain Vmax on a elimination drug graph
- saturation of elimination mechanisms
- maximum drug elminimation
what does first order kinetics refer to in drug elimination
- drug elimination increases as drug plasma conc increases
What does Km mean?
- drug plasma conc at which it is 1/2 Vmax
Equaion for elimination half-life
t1/2 = 0.693 x vd / cl
factors that effect Vd
- ageing
- obesity
- pathological fluid
factors that effect Cl
- cytochrome p450
- renal failure
- cardiac failure
MEC meaning?
- minimum effective concentration
MTC meaning?
- maximum therapeutic cncentration
Therapeutic ration?
TR = MTC/MEC
The higher the therapeutic ratio the _______ the drug
- safer
Rate of elimination =
wash out
= clearance x plasma conc
How many half-lifes are normally required in a wash out of infusions?
- 5 half lifes
Why would u give a leading dose?
- starting with a higher dosage and then decreasing
- employed to decrease the time taken to reach a steady state
Define depolarisation
membrane potential becomes less negative
Define hyperpolarisation
membrane potential becomes more negative
Na+ naturaly flows __________
inwardly
Ena is around_______mV
+60mV
K+ naturally flows_________
outwardly
Ek is around _________mV
-100mV
When ion channels are closed what happens?
- no influx or outflux of ions
what is resposible for the upstroke on a neuron action potenital?
- opening on Na+ channels
What is responsible for the downstroke on a neuron action potential?
- opening of K+ channels
What causes the upstroke of a neuron action potential?
- delayed closure of K+ channels
Na+ responds______
radiply/slowly?
- rapidly
Na+ is a self_________ channel
self-reinforcing
+ve feedback
K+ is a self__________channel
self-limiting
-ve feedback
Name the 3 states of Na+ channels and how the get to each state
- closed state
- (depolarisation) open state
- (maintained depolarisation) inactive state
- recquires repolarisation to closed state again
The inactive state of a Na+ channel is responsible for what?
- the refractory peroid
Define absolute refractory peroid?
- no stimulus no matter how strong will not elicit a 2nd action potential
Define relative refractory peroid?
- a stronger than normal stimulus may elicit a 2nd action potenital
Nerve cells may be described as ______ which means the action potenital will ________ far from origin
- leaky
- wont spread far
How might the spread of an action poteintial in a nerve cell be improved?
- increase diameter of axon
- insulate (myelin)
How do myelinated axons spread action potentials?
- saltatory conduction
- “jump” from raniver
ANS is made up of ________ neurons
efferent or afferent?
- efferont neurons
What does the ANS regulate?
- regulates functions that do not require conscious effort
Explain the length of axons in sympathetic and parasympathetic neurons
- sympathetic (short, long)
- parasympathetic (long, short)
Explain how action poteintials are spread
- action potential arrives
- increase in Ca2+ into cell
- causes release of Ach
- Ach binds to postganglionic receptors
- causes increase in Ca2+
- increase in Ach (parasympathetic) or NA (sympathetic)
In sympathetic neurons NA binds to what type of GPCR?
- Adrenoceptor
In parasympathetic neurons Ach binds to what type of GPC?
- Muscarinic
What is a nicotinic receptor
- 5 glycoprotein subunits
- central channel (Na+, K-, Ca2+)
What can reverisbly block a nicotinic receptor?
- hexamethonium
Parasympathetic effects what muscarinics?
- M1 –> Gq
- M2 –> Gi
- M3 –> Gq
M1 –> Gq causes?
- increased acid secretion
M2 –> Gi causes?
- decreased heart rated
M3 –> Gq causes?
- increased secretion
- resp constriction of smooth muscle
Sympathetic effects what receptors?
- a1 –> Gq
- a2 –> Gi
- b 1 –> Gs
- b2 –> Gs
a1 –> Gq causes?
- increased vascular contracility
a2 –> Gi causes?
- inhibition of NA release
b1 –> Gs causes?
- increased Heart rate
b2 –> Gs causes?
- resp relaxation of smooth muscle
