L7 Flashcards
Drug receptor bonds covalent, electrostatic bond, hydrophobic bond
Covalent bond: strong and irreversible
Electrostatic bond: weaker but more specific
Hydrophobic bonds: can reach nucleus, affecting gene and function expression
Pharmacokinetic
Absorption
Bioavailability IV 100 Oral no 100
Distribution
Wall of intestine, into blood
CNS drug: blood brain barrier
Metabolism
Metabolise by liver
Metabolise turn prodrug to be active
React in liver:
Phase 1: reduction reaction
Phase 2: hydrolysis reaction (水解）
Inactivated drug-）activated drug✅✅
Excretion
By urine or feces
Drug deposition
Cardio:
delay drug to reach the target
Delay the drug to metabolise in liver
Hepatic:
Affect drug metabolise by liver enzymes
Renal:
Affect renal elimination
Drug in pregnancy affecting:
Teratogenic
Structural developmentment
Milk feeding contains diluted drug
Infant drug factors
Absorption:
slower gastric emptying time
Distribution:
water content of baby is 70%-) concentration
Metabolism:
Slower in baby
Elimination
Drug in elderly
Absorption: no change
Distribution: transporter decrease, slower
Metabolism: slower due to low metabolic rate
Elimination: slower due to weaker renal function
Drug interaction
Antacid: less acid in stomach
Alcohol: CNS depression
Anticoagulant: induce bleeding
Drug nutrients interaction
Grapefruit react with a lot of medicine
Side effects: no appetite, nausea
Affect nutrient production
Antibiotic kill microbiota-) vitamin k & b -
Increase secretion of ion:
Laxative, diuretic
Adverse drug reaction ABCDE
Augmented: expected
Bizarre: unexpected
Continuous: adverse reaction due to long term usage of drug
Delay: adverse reaction develop after using the drug
End of use: adverse reaction due to withdraw of the drug
Principle of drug selection
- Make specific diagnosis
- Select a specific therapeutic goal
- Select a drug to achieve the therapeutic goal
- Determine the appropriate dosage
- Plan for monitoring the drug action & determine an endpoint for therapy
- Plan for patient education
Pharmacodynamic
Drug+receptor= drug-receptor complex-) effector-) effect
Agonist
Activate the receptor which brings the effect
Antagonist
Prevent binding of other molecules
Allosteric
Not competing for the same binding site
Competitive:
Competing for the binding site
Type of drug target
Receptors
1. Intracellular
2. Cell surface receptor
Enzyme
Ion channels
Receptors
1. Intracellular receptors
For hydrophobic drugs
Bind to DNA
- Cell surface receptors
For hydrophilic drugs
Activate enzymatic changes
Enzyme:
Competitive binding / allosteric binding
Ion channels Nuclear/ transporter
Allow ion or other molecules to pass through in and out of cell
Epidermal growth factor receptor & treatment
Epidermal growth factor receptors-) uncontrol
-) uncontrolled cell growth & differentiation -) cancer
Treatment: molecular targeted therapy
Block the egf binding site
Egfr tyrosine kinase inhibitor
Prevent activation of signalling pathway
Receptors ( full / partial / inverse)
Agonist
1. Full agonist: activate to full extend
2. Partial arsonist: activated with increased response
Antagonist: prevent binding with other molecule
1. Inverse agonist: higher affinity, displace the original binding
Inert binding, no effect
E.g. plasma albumin, for transport only
Response
No drug cause only single effect ( therapeutic + adverse)
Therapeutic: beneficial
Adverse: toxicity
Maximum efficacy
No further response
A response reached system limit e.g. receptor all occupied
Potency
Effective dose ED50
REACHED 50% OF Emax
Toxic dose
Dosage produce toxic effect in 50% of animal (TD50)
therapeutic window
Range between minimum toxic dose and minimum therapeutic dose
Therapeutic index✅✅
TD50/ED50
larger TI = less likely to side effects = safe
