Drug set 3

Suxamethonium

- NMJ antagonist

- Anesthetic (paralysis)

- Shorter duration of action as it is susceptible to degradation by BuChE

Pilocarpine

- Treatment for glaucoma

- M2 and M3 agonist, causing contraction of suspensory ligament of the lens

Atropine

- M2 antagonist at NMJ

- Deadly nightshade

- Can antagonise the effect of AChE inhibitor poisoning

- Rapidly increases heartrate

Rivastigmine

- Medium-acting reversible AChE inhibitor

- Carbamylates AChE to increase time taken to hydrolyse ACh

- Can cross blood-brain barrier so sometimes treats Alzheimer's

L-DOPA

- Crosses blood-brain barrier

- Increases catecholamine production by bypassing TOH (is a dopamine precursor)

Dextroamphetamine

- Structurally related to NA

- Stimulates NA release from vesicles

- Used recreationally as activates reward and pleasure systems

- Can also treat ADHD

Fluoxetine

- SSRI

- Inhibits only SERT transporters from uptaking serotonin

Phenoxybenzamine

Non-selective alpha-adrenoreceptor antagonist

- Given before surgery of adrenal gland tumours where there is massive release of catecholamine

- Prevents rapid vasoconstriction

other

What do alpha1 adrenoreceptors control?

other

- Vasoconstriction

- Contraction of uterine smooth muscle

other

What do beta1 adrenoreceptors control?

other

- Increase heart rate

- Relaxation of GI smooth muscle

other

What do beta2 adrenoreceptors control?

other

- Relaxation of uterine smooth muscle

- Bronchodilation

Salbutamol

- Beta2-selective adrenoreceptor agonist

- Inhaled to control asthma

- Induces bronchodilation

Propanolol

- Non-selective beta-adrenoreceptor antagonist

- Anti-hypertensive

- Antagonizes increase in heart rate caused by beta1 receptors

- Cannot be given to asthmatics due to binding to beta2

Beta-lactam antibiotics

- Penicillins, cephalosporins, carbapenems

- Interfere with peptidoglycan synthesis by inhibiting transpeptidases from cross-linking strands

- Transpeptidase mistake them for unlinked chains, hydrolyse, ring opens and is unable to be hydrolysed further, blocking

- Used with clavulanate or avibactam to overcome resistance

Vancomycin

- Glycopeptide

- Binds to terminating D-Ala4-D-Ala5 so it is unavailable for transpeptidases, preventing cross linking of peptidoglycan

- Resistance overcome by isoniazid

Levanmisole

- Anti-helminth

- Nictotinic ACh receptor agonist

- causes spastic paralysis of the smooth muscle layer

- Selective base don how little dose is required to kill the whole helminth due to its size

Clostantel

- Anti-helminth

- Uncouples oxidative phosphorylation

- Low therapeutic index

- Selective accumulation in the plasma proteins that helminths consume

Enfurvitide

- Anti-HIV

- Inhibits fusion of viral and immune membranes, preventing uptake of virus

List the drugs used in anti-HIV therapy and what they target

- Enfuvirtide: prevents membrane fusion and entry

- AZT (NRTI) and nevirapine (NNRTI) RT inhibitors

- Ratelgravir: DNA integrase inhibitor

- Saquinavir: protease inhibitor, preventing formation and presentation of gag120

Methicillin and MRSA

- Introduced to treat gram-positive infections that had become resistant to pencillin

- MRSA incidence up to 20-40% in USA hospitals

- Acquired mecA gene that encodes a new transpeptidase that is completely insensitive to beta-lactams

- Acquired fem gene that modifies peptidoglycan strands so better substrate for cross linking by new MecA transpeptidase

Clavulanate

- Natural product from streptomyces species

- Inhibitor of beta-lactamases

- Used in combination with beta-lactams

Tamoxifen

- Hormone receptor positive breast cancer tehrapy

- Binds to oestrogen receptor alpha to prevent pro-survival signaling downstream

T-VEC

- Oncolytic virus anti-cancer immunotherapy

- E1B-deficient herpes simplex virus

- Currently only approved drug of its type

- Melanomas

Downstream effects of alpha-s

- Adenylyl cyclase activation

- ATP -> cAMP

Downstream effects of alpha-i

- Adenylyl cyclase inhibition

- Decreased AMP -> cAMP

Downstream effects of alpha-q

- Phospholipase Cbeta activation

- PIP2 -> IP3 + DAG

- IP3 opens ligand-gated Ca2+ channels on ER to increase intracellular Ca2+

- SAG activates PKC