| Selective toxicity | Selective toxicity refers to the ability of a drug to target specific microorganisms or cancer cells without damaging the host's cells. |
| on what basis is selective toxicity achieved | Selective toxicity is based on differences between the biology of the target and the host, such as:
Unique structures (e.g., bacterial cell walls).
Specific metabolic pathways (e.g., folic acid synthesis in bacteria).
Genetic or molecular differences. |
| Examples of selective targets | Bacterial cell walls: Targeted by penicillins and cephalosporins.
Bacterial ribosomes: Targeted by tetracyclines and macrolides.
Viral enzymes: Targeted by reverse transcriptase inhibitors.
Cancer cell DNA replication: Targeted by antimetabolites like methotrexate. |
| How do selective drug targets work | Inhibition of cell wall synthesis (e.g., β-lactams).
Inhibition of protein synthesis (e.g., aminoglycosides bind to 30S ribosome).
Disruption of membranes (e.g., amphotericin B targets ergosterol in fungi).
Inhibition of nucleic acid synthesis (e.g., fluoroquinolones).
Metabolic antagonism (e.g., sulfonamides inhibit folate synthesis).
=S= SYNTHESIS |
| Therapeutic index = t for toxic | The therapeutic index is the ratio of a drug's toxic dose to its effective dose. A high therapeutic index indicates better selective toxicity. |
| : How do antibiotics achieve selective toxicity? | Antibiotics exploit unique bacterial features, such as:
Peptidoglycan in cell walls (e.g., penicillin).
Bacterial-specific DNA gyrase (e.g., ciprofloxacin).
Prokaryotic ribosome differences (e.g., erythromycin). |
| Why is ST harder in antiviral drugs - antiviral - more risk | Viruses use host cell machinery for replication, so targeting the virus often risks harming host cells. Selective toxicity is achieved by targeting:
Viral-specific enzymes (e.g., protease, reverse transcriptase).
Viral entry or uncoating mechanisms. |
| 4 challenges to selective toxicity - SRDS | Similarity between host and pathogen/cell.
Emergence of drug resistance.
Collateral damage to host microbiota.
Off-target effects leading to side effects. |
| Provide an example of selective toxicity in antimicrobials. | Penicillin targets bacterial cell wall synthesis, which is absent in human cells. |
| How do antifungals achieve selective toxicity? | Target unique fungal cell components, such as ergosterol in the cell membrane. |
| Why are some drugs more toxic than antimicrobials | such antifungals , fungi has similairites with humans cells |
| How do antivirals achieve selective toxicity? | Target viral proteins and processes essential for replication that are absent in host cells. |
| What is the basis of selective toxicity for anticancer drugs? | Exploit differences in the growth rate of cancer cells versus normal cells. |
| What are common targets for anticancer drugs?
Mum had cancer - M= Microtubule functions to be stablised | DNA synthesis: Methotrexate inhibits dihydrofolate reductase.
Microtubule function: Paclitaxel stabilizes microtubules.
Topoisomerase: Doxorubicin inhibits topoisomerase II. |
| Why do anticancer drugs often have significant side effects? | Normal rapidly dividing cells (e.g., in the GI tract, hair follicles) are also affected. |
| What is pharmacogenetics? | The study of genetic variations that influence individual responses to drugs. |
| What is the clinical relevance of pharmacogenetics? | Optimizes drug dosing.
Minimizes adverse drug reactions.
Improves therapeutic efficacy. |
| What are the two divisions of the peripheral nervous system (PNS)? | Somatic Nervous System: Controls voluntary muscles.
Autonomic Nervous System (ANS): Regulates involuntary functions (divided into sympathetic and parasympathetic). |
| What neurotransmitters are primarily involved in the PNS? | Acetylcholine (ACh) and noradrenaline
(NA). |
| What are the two types of cholinergic receptors? | Nicotinic receptors: Ionotropic, found in ganglia and skeletal muscles.
Muscarinic receptors: G-protein-coupled, found in parasympathetic target organs. |
| what activates cholinergic receptors - agonists activate receptors | Cholinomimetics, e.g., bethanechol (muscarinic agonist), nicotine (nicotinic agonist). |
| What are the two main types of adrenergic receptors? Think a= alpha | Alpha receptors: α1 (vascular smooth muscle), α2 (presynaptic terminals).
Beta receptors: β1 (heart), β2 (lungs, smooth muscle), β3 (adipose tissue). |
| What drugs stimulate adrenergic receptors? a= alpha receptors so adnergic receptors such as a.... | Adrenergic agonists, e.g., adrenaline, salbutamol (β2 agonist). |
| What is SAR in pharmacology? (structure activity relationship) | The relationship between the chemical structure of a drug and its biological activity. |
| What are the structural requirements for muscarinic agonists? | positively charged nitrogen (usually a quaternary ammonium group).
An ester or ether group to mimic acetylcholine.
Correct stereochemistry for receptor binding. |
| What are key SAR points for nicotinic agonists? | A positively charged nitrogen.
A proper distance between the nitrogen and the carbonyl group to fit the receptor |
| What are anticholinesterases? | Drugs that inhibit acetylcholinesterase, increasing ACh levels in the synapse. |
| What are the two main types of anticholinesterases?,think inhibitors | Reversible inhibitors: E.g., neostigmine, donepezil.
Irreversible inhibitors: E.g., organophosphates like sarin. |
| How do irreversible anticholinesterases bind? irrevirsible to permantly inactivates | Covalently bind to the serine residue in the enzyme's active site, permanently inactivating it. |
| What structural modifications affect potency and selectivity? | Alkyl groups increase lipophilicity and CNS penetration (e.g., physostigmine).
Larger substituents reduce enzyme degradation. |
| Who developed the idea of selective toxicity | Paul Ehrlich - from staning dyes - the term was magic bullet |
| What is chemotherapy | A chemical bonds to and kills a microbe or tumour cell |
| What are B-lactams | They target cell wall synthesis in bacteria used in antibiotics such as penicillin is a type of B-lactam |
| What is antimicrobial resistance | The inability to kill or inhibit the organism with clinically achievable drug concentrations - mutations or innate |
| Types of bacterial resistance | Intrinsic and acquired ( gene transfer) |
| Differences between fungi and bacteria | Fungi is eukaryotic , organelles , contain sterols , cell wall is chittin.
Bacteria is prokaryotic , no organelles , no sterols , cell wall is peptidoglycocans |
| What are viruses | Not living ,
No organelles
No cell wall or membrane
Dependent on the host |
| What is cancer | Unregulated cell growth |
| Differences between normal cells and cancer cells | Cancer cell nucleus has mutated genes and has high metabolic demands |
| Ways of treating cancer | Surgery
Radiation and immunotherapy |
| Cancer therapies | If the cancer is due to hormones then hormonal anti cancer agents would be used etc |
| What is immunotherapy | Activating the host immune response to target tumour cell antigens |
| What is personalised medicine | Tailored to that person based on genetics , life style and environment |
| priciples of personalised medicine | Individualisation
Targeted therapy
Predictive and preventive |
| Benefits of personalised medicine | Reduce side affects
And more drug efficacy |
| Function of the PNS | Sensory Input: Gathers information from the external and internal environment (via sensory receptors).
Example: Feeling heat on your skin.
Motor Output: Sends signals to muscles and glands for action.
Example: Moving your hand away from heat.
Homeostasis: Maintains balance in bodily functions through the ANS. |
| Muscarinic receptors have 2 types | excitatory and inhibitory |
| Drugs acting on the cholinergic system | Agonists (enhance cholinergic activity)
Antagonists (inhibit cholinergic activity)
Acetylcholinesterase Inhibitors (prolong ACh action) |
| analogy of the cholinergic system | ACh is the "mail."
Nicotinic and muscarinic receptors are "mailboxes."
Enzymes like AChE are the "cleanup crew" to clear old mail. |
| Antibiotics - | bactericidal - irrevirsable lethal action on bacteria
bacteriostatic - reversibly inhibit growth |
| Test the susceptibility of anttimicrobial | determine which pathogen the bacteria is susceptible to |
| Types of bacteria resistance | Intrinsic - gram negative bacteria harder to penetrate
Acquired - resistance by gene transfer |
| Antifungal exam answer | Explain selective T
example terbinafine makes hole in the cell membrane of the fungi , by breaking down ergosterol in the cell membrane it causes the fungi to lose its structural integrity, leading to leakage of essential cellular contents and ultimately causing the fungi to die. |
| Antiviral answer | Explain selective T
Remdesivir.
Remdesivir inhibits the activity of the RNA-dependent RNA polymerase which is a type of viral protein so INHIBITS VIRAL PROLIFERATION |
| Anticancer answer | Explain Selective T
Vinca alkoid - anti cancer drug - more effective as only targets rapidly dividing cells - via targeting microtubules leads to a disruption in the cell cycle so programmed cell death |
