Pharmocology Flashcards
Pharmacodynamics
What the drug does to the body (biological effects and mechanism of action)
Pharmacokinetics
What the body does to the drug (absorption, distribution, metabolism, excretion)
Potency
If A can do the same effect as B at a lower concentration it has a higher potency
Efficacy
Measure of how good a substrate is at activating a receptor. Low efficacy = low V max (maximum velocity/rate the enzyme catalyzes a reaction)
Km
Concentration of a substrate which permits the enzyme to achieve half of Vmax.
An enzyme with a high Km has a low affinity for substrate so needs a high concentration to produce half of the maximum response (Vmax)
Agonists
Reversibly binds to a receptor eliciting a response. Has affinity and efficacy
Antagonists
Blood receptor preventing activation
Affinity but no efficacy
What is a competitive antagonist and how does it affect the concentration/response curve
Both the agonist and antagonist try to bind to the same active site
Right parallel shift in graph (need high concentration of agonist to produce Vmax)
Vmax is the same but Km is higher (greater concentration needed to achieve half Vmax)
What is a non-competitive inhibitor and how does is affect the concentration/response curve
Non-competitive antagonist binds to allosteric site
Vmax is decreased as active site changes shape and an’t bind to substrate
Km is the same
Absorption
Process by which drug enters the body from its site of administration
Distribution
Process by which a drug leaves the circulation and enters the tissues
Once within tissues further distribution can occur via carrier mediated transport or diffusion
Metabolism
Process by which tissue enzymes (in liver) catalyse the chemical conversion of a drug to a more polar form that is more easily excreted
Excretion
Process that removes the drug from the body
Principally in kidneys
Elimination
Metabolism and excretion
pKa
pH when 50% of the drug is ionized and 50% is unionized
Acidic drugs become less ionized in an acidic environment
Basic drugs become less ionized in a basic environment
Oral Availability
Fraction of drug that reaches the systemic circulation after oral ingestion
Systemic availability
fraction of drug that reaches circulation after absorption
Vd
drug dose/plasma concentration
Kel
rate of removal = clearance x plasma concentration
After 5 half loves most of the drug has left the body
Liver metabolism
Phase 1 and phase 2 aim to make molecules more polar so they are easily excreted
If a compound is polar it will skip phase 1
Phase 1 liver metabolism
Involve cytochrome P450s, make drugs more polar via oxidation, hydrolysis or reduction
Phase 2 liver metabolism
Adding an endogenous compound to increase polarity
Polar molecules are readily absorbed by kidneys so secreted in urine
Glomerular secretion
If drug binds to proteins then only unbound drug is filtered through glomerulus.
Equilibrium balances producing more unbound drug.
Tubular secretion
2 active transport systems actively sevrete drugs into proximal tubule
OAT transports acidic drugs (penecillins)
OCT transports basic drugs (morphines)
Sympathetic Nerve Fibres
Come off T1 to L2 vertebrae
AcH is preganglionic then NA is post ganglionic - cause ejaculation
Parasympathetic nerve fibres
Cranial nerves III, V, IX and X
Sacral
AcH is preganglionic and post ganglionic
Cause erection
What is the mechanism of Sympathetic nerve transmission
- Action potential generated in CNS
- AP travels to presynaptic terminal of preganglionic neuron
- ACh released which opens ligand gated ion channels in the post ganglionic neurons causing depolarization and generation of AP
- AP travels to presynaptic terminal of neuron stimulating NA release
- NA activated g-protein coupled adrenoreceptors in the target cell
What is the mechanism of parasympathetic nerve transmission
-Action potential generated in CNS
AP travels to presynaptic terminal of preganglionic neurom causing the release of ACh
-ACh opens ligand gated channels on the post synaptic neuron generating an AP
-AP stimulates the release of more ACh at the post synaptic neuron terminal
-ACh activated g-protein coupled muscarinic acetylcholine receptors in the target cell
Acetylcholinesterase
Breaks down acetylcholine into choline and acetate in preganglionic transmission and in parasympathetic post ganglionic transmission
Cholinergic transmission (at synapse)
Delpolarisation by nicotinic ACh channels causes voltage activated Na channels to open mediating AP
Amount of depolarization that occurs at synapse depends on the amount of ACh present
Much reach threshold for AP to be fired
Mechanism of parasymapthetic post ganglionic transmission
- depolarization of post ganglionic nerve
- Ca influx
- ACh release
- ACh exocytosis
- Activation of muscarinic receptors
- cellular response
- ACh broken down by acetylcholinesterase and reuptake occurs
M1 receptor
- Gq protein
- stimulation of phospholipase C
- Increased acid secretion in stomach
M2 receptor
- Gi protein
- inhibition of adenylyl cyclase
- opening of K channels
- decreased heart rate
M3 receptor
- Gq protein
- stimulation of phospholipase
- contraction of bronchial smooth muscle
- relaxation of vascular smooth muscle
Sympathetic post ganglionic mechanism
- depolarization
- Ca influx
- NA release
- NA exocytosis
- activation of alpha/beta adrenoreceptors on effector cell
- cellular response
- NA reuptake into post ganglionic neuron (U1) and effector cell (U2)
- Broken down by MAO in post ganglionic neuron and COMT in effector cell
B1 receptors
- heart
- Gs protein
- stimulates adenylyl cyclase
- increase rate and force of heart
B2 receptors
- lungs
- Gs protein
- stimulation of adenylyl cyclase
- relaxation of bronchial and vascular smooth muscle
A1 receptors
- Gq protein
- stimulation of phospholipase C
- contraction of vascular smooth muscle
A2 receptors
- Gq protein
- inhibition of adenylyl cyclase
- inhibition of NA release
Effects of Cocaine
- Blocks U1 in sympathetic post ganglionic reuptake (reuptake into post ganglionic neuron)
- little reuptake of NA = increased adrenoreceptor stimulation
- Causes Increased BP via A1 stimulation and arrhythmia via B1 stimulation
Effects of amphetamine
Displaces NA into the cytoplasm
Causes a build up of NA
-too much NA stimulates A1 receptors causing increased BP and B1 receptors causing arrhythmia
Effects of prazosin (alpha receptor blocker)
- selective competitive antagonist for A1
- Venodilator so can be used as antihypertensive
Effects of atenolol
- selective beta blocker for B1
- competitive antagonist
- decreases heart rate and fore so antianginal and antihypertensive
Presynaptic autoreceptors
- negative feedback
- act back on themselves to decrease amount of neurotransmitter released
Ligand gated ion channels conformations
unoccupied closed
occupied closed
occupied open
What do G protein couples receptors consist of
- integrat membrane protein receptor
- internal G protein made of beta and gamma subunits with guanine nucleotide binding site
What causes turning on of g-protein coupled receptors
- Agonist binds
- GDP dissociated and GTP binds to alpha unit
- Alpha unit splits off from betagamma unit and activated effector protein
What causes turning off of g-protein coupled receptors
- GTP is hydrolysed
- switches off signaling
- Apha unit rebinds with betagamma subunits
