1.2 Flashcards
(34 cards)
What are the 4 types of receptors?
Ion channel
Enzyme associated
Nuclear receptor
G-protein coupled
How do ion channels work?
Allow ions into cell
What are G-protein receptors made up of?
7 transmembrane protein receptor which is associated with a G-protein intracellularly
The G-protein is made up of 3 subunits (alpha, beta, gamma)
How are G-protein receptors activated and inactivated?
Inactive - with GDP bound Activated - GTP - An agonist binds extracellularly - This leads to conformational change - Ligand (GTP) exchanged for GDP - The normally alpha subunit dissociates from beta-gamma subunits and goes on to perform effector functions - Alpha subunit has an intrinsic GTPase - GTPase cleaves GTP and then it re-associates with other subunits in it's inactive state
What are these examples of: adrenoceptors, muscarinic receptors.
G-protein coupled receptors
What are the 4 ways drugs are handled by the body?
ADME mnemonic
- Absorption
- Distribution
- Metabolism
- Elimination
What is bioavailability?
Percentage of total oral dose of a drug that reaches plasma
What affects absorption of a drug?
Lipid-water solubility
1st pass metabolism (hepatic degradation of portal blood)
What are high bioavailability drugs used for in general?
Treating systemic pathology (e.g. atherosclerosis)
What are low bioavailability drugs used for in general?
Treating GI infection (e.g. oral vancomycin)
What is the bioavailability of an IV drug?
100% because all of the drug ends up in the plasma
What is vancomycin?
An glycopeptide antibiotic
Very useful against gram positive bacteria (especially MRSA)
Side effects of vancomycin.
Ototoxicity
Renal toxicity
And when given intravenously as a bolus it causes red man syndrome (allergic response, massive rash)
List two characteristics of a high partition drug (one that passes epithelium easily).
Small, non-ionised
Drugs are weak acids or bases, what does their ionisation depend on?
pH
- Acid: more ionised in alkaline environment and less ionised in acidic environment
What does pKa describe?
Relative ionisation
Where along the GIT are weakly acidic drugs mainly absorbed?
The gastric mucosa (pH 3.5)
Because equilibrium shifts to favour the non-ionised HA rather than the ionised H+ and A= (dissociative state)
What is the 2 phases of drug metabolism?
Phase 1: oxidation and hydroxylation
Phase 2: glucuronate/sulphate conjugation
Which enzymes are involved in phase 1 drug metabolism (oxidation/hydroxylation)?
CYP450
Why are the byproducts of oxidation/hydroxylation important?
They can be toxic
E.g. paracetamol undergoes phase 1 hydroxylation and rearrangement. The product is NAPQI which can undergo toxic reactions with proteins and nucleic acids at high levels
What is the purpose of glucuronate and sulphate conjugation?
Stabilise and increase solubility
Some drugs can interact with the CYP450 mono-oxygenase system. This system is responsible for number of phase 1 drug metabolisms.
Which drugs are potent inducers of the CYP450 system?
There are many cytochrome P450 enzymes each affected by slightly different drugs.
Rifampin (antibiotic) and carbamazepine (anticonvulsant + analgesic) are a potent inducer of CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP3A5
Other potent inducers:
- Phenobarbital (epilepsy treatment)
- Phenytoin (anticonvulsant)
Hypericum perforatum (St. John’s wort)
Some drugs can interact with the CYP450 mono-oxygenase system. This system is responsible for number of phase 1 drug metabolisms.
Which drugs are potent inhibitors of the CYP450 system?
- Amiodarone
- Cimetidine
- Ciprofloxacin
- Fluvoxamine
- Trimethoprim
- Metronidazole
- Paroxetine
- Terbinafine
- Quinidine
- Fluoxetine
- Clarithromycin
Define elimination and excretion.
Elimination: removal of active drug from the body
Excretion: removal of drug from the body by loss
