Drugs Flashcards
Statins MoA and S/E
Statins work by inhibit HMG-CoA reductase (rate limiting step for cholesterol synthesis in liver)
Can cause liver function impairment, muscle aches
Test baseline liver function
Oral administration overnight cause liver most active at night
Sodium nitroprusside MoA and Tx
Release NO to increase cAMP/cGMP
But molecule has cyanide so only used in emergency hypertension
PDEI is suitable for what type of hypertension
Pulmonary
What drug can interact with nitrates
PDEI esp if poor vascular health and with angina
How does cardiac glycoside work
Block Na/K ATP to make cell more excitatble to increase calcium levels and facilitate binding of troponinC to ca -> increase contractility
Vasodilation drugs
Ca blockers - nifedipine (DHP) CGMP modulator - PDE I to prevent cGMP breakdown, GTN -> GC substrate spontaneous breakdown to NO Organic nitrates (amyl nitrates) K activators - (ATP sensitive channels), minoxidil
CTZ area include
DRG NTS postrema
Postrema is part of what and where is it
Part of CTZ that is outside the BBB
Antiemetics for general purposes
Aprepitant -NK1 antagonist Ondansetron - 5-HT3 antagonist Steroids (dexamethasone) Cannabinoids - nabilone Neuroleptics - dirty drugs - haloperidol, domperidone metaclopromide BDZ- diazepam, lorazepam
Vasodilators
K activators - amilodarone , minoxidil Ca blockers - nifedipine PDE3I or PDE5I Organic nitrate (amyl nitrate) GTN
Inotropics
Beta agonists (esp beta 1 - dobtamine)
Cardiac glycosides (digoxin) - block NaK/Katpase
PDE3I
Atropine (paraNS antagonist)
Antiarrhythmics
Class I-IV Na blockers - lidocaine (also block K) Beta blockers - metaprolol, atenolol K activator - amiodarone Ca L type blocker - verapamil
Motion sickness is due to
The activation of the LVC pathway
Labyrinthe-vestibular-cerebellum pathway (received from vestibular system in inner ears)
Tx for motion sickness
Antimuscurinics - mAChR blockers - scopolamine
Antihistamines -H1R antagonist - cinnarizine
Opioids acute OD Tx
Naloxone - IV over hrs (5 min halflife)
Mu receptor antagonist to prevent drug activity on GABA neurones
Opioid Tx long term
Methadone (mu receptor agonist)
- decrease dose overtime
- doesn’t get as much of a awarding effect
- help with withdrawal symptoms
- log halflife (1 day) - oral
Symptoms of opioid OD
Myosis - pinpoint pupil (activate paraNS)
Unconsciousness
Why do we vomit
To get rid of toxic substances and to prevent further ingestion thereby minimising toxin uptake
Define emesis
Emesis is a combination of vomiting and nausea. Of which the former is beneficial whilst the latter is not
3 levels of action in preventing toxin uptake
1) sight and smell - avoidance - prevent encountering with the substance
2) spit - slight ingestion but limited
3) vomit - empty gastric content to prevent further uptake of substance
Do rodents vomit?
No they feel nauseous but doesn’t vomit
Their body can digest the toxin and make use of t
Emesis associated with diseases
Uraemia - high urea in plasma alters metabolism
Infections
Gastroduodenal reflex - gut wall damages
Iatrogenic emesis types (CDMA)
Chemo drug induced - cisplatin induced
Dopamine induced
Morphine induced
Alcohol induced
How does cisplatin induced emesis occur?
Cisplatin target cells via creating interstrand or intrastrand cross link which makes it hard for cells to unwind DNA during replication thereby inducing apoptosis. However, cisplatin targets all dividing cells meaning more rapidly turnover cells are more susceptible. Hence cisplatin result in great nephro/GI/BM toxicity and the gut wall is so severely damaged that the patient can tip their oesophagus
Dopamine induced emesis is associated with what type of drug
L-DOPa given to Parkinson’s
Morphine is an emetic drug because
It acts on GABAa receptor to prevent the GABA neurone from firing. This disinhibits the break on dopaminetgic neurones therefore the increase in dopamine results in emesis
What drug is administrated in conjunction with morphine administration during first infusion
Anti emetic
- metaclopromide
Opiates example
Apomorphine
Morphine
Heroin
Alcohol induced emesis is due to what mechanism
Increase in plasma concentration will stimulate brain to provoke vomit reflex
Also alcohol prevent PG synthesis, which is a trophic factor for gut lining secretion and thus gut wall is damaged and 5-HT is released into the bloodstream and via the X afferent to the CTZ
Anticipatory emesis
Imitated due to past experience
Controlled by higher sensory centre of brain
Motion sickness emesis is due to
Activation of LVC pathway
Post operative emesis often due to
Stimulation of vagus nerve
General anaesthetics
Pregnancy emesis is due to
High hCG levels - indicate good pregnancy
In extreme cases dehydration can cause metabolite imbalances which result in vomiting
Where is the emetic centre
Medulla
Dorsal bit of the medulla consist of what structure that control vomit reflex
Reticular formation
CTZ consist of
Postrema, NTS, DRG which are anatomically close to each other
NTS is filled with (majority) what type of emetic receptors?
NK1 which uses substance P
Fenestration can be see at which bjtnof the CTZ
Postraema
What part of CTZ is outside BBB and why
Postrema and to sense toxins before they get into brain. Toxins tends to be polar which mean they can’t cross BBB
What would happen if we have an universal antiemetic
It will also repress RE or CVS function due to the similarity in neuronal phenotype
S/E of antiemetics
Sometimes sedative
EPS (extrapyrimidal motor side effects) if block dopamine receptors
Depression
Cushings if give steroids
How do we get High off substances and how is it regulated
Accumulation of extra cellular DA in the nucleus accumbens (Mesolimbic pathway). The high the plasma is saturated, the greater the high/rush/reward
What are we tolerant against
The rewarding effect produced by drug
Can dependence and tolerance be treated?
Yes and no respectively
Hyperlipidaemia drugs classes
Statins Vibrates PCSK9 inhibitor Bike acid binding resin Ezetimib - NPC1L1 blocker Fish oil Nicotine is acid
What type of hyperlipidaemia drug is not suitable for type IIb patients
Fish oil
S/E of bile binding resins
GI side effects
Very uncomfortable
Increase TG but decrease bile and cholesterol levels
Lorsartan belongs to what class of drug
ATI inhibitor
ACEI example
Captopril
DHPS are used for
Ca blockers used for Hypertension to decrease vasoconstriction
NON DHPS used for (e.g verapamil, diltiazem
Cardiac arrhythmia
What is an atheroma
Build up of fatty deposits
Where does atheroma tends to form
At bifurcations
What other haemodynamic factors contribute to intima thickening
Shear stress impacting on EC making them cobblestone like and upregulate VCAM1 which recruits WBC
FIBRATES MoA
Activate nuclear receptor and increase LDLR and lipoprotein lipase
Esp prescribed for type IIb
Hyperglycaemic fasting glucose level
> 7 mM
HbA1c levels for hyperglycaemia patient and normal person
DM > 48 mmol/mol and < 38 for normal
Chylomicron consist of
Cholesterol/ TG and FA
Hormone sensitive lipase can be stimulated by what and induce what process
Glucagon
Induce lipolysis to increase FA into bloodstream (bound to albumin)
Where does lymphatic drain
L/R thoracic duct and enter bloodstream via subclavian veins
Apoproteins binds to what receptor
LDLR, part of outer chylomicron (polar structure)
What is cholesterol synthesised from
Acetyl co A
VLDL is
FA + chylomicron remnants - made in liver
What is endogenous cholesterol used for
Bile synthesis
LDLR stimulate uptake of what
Cholesterol
Why is LDL good indicator of disease
More likely to be taken up by hepatocytw
Increase HDL aids uptake of
LDL from plasma
What inhibits the Rate limiting step of cholesterol synthesis in liver
Statins
Fibrates activate what receptor
PPARa/RXR
Fibrate MoA
Activate PPARa receptor which increase transcription of lipoprotein lipase expression in PNS to remove TG from VLDL and chylomicron
Increase HDL thereby promote LDLuptake by increasing LDLR
Type IIb prescription esp needs
FIBRATES
Which hyperlipidaemia drug affects fat soluble vit D uptake
Bike acid binding resins
What can be substitute Rx for bike acid binding resins
Ezetemib
- inhibit NPC1L1 receptor which is more precise and inhibits cholesterol absorption in gut. Doesn’t affect fat bit uptake
PSCK9 inhibitor MoA
Normally they bind to LDLR and promote internalisation of receptor in hepatocytes and promote degradation
Inhibitor prevent this and hence more LDLR expressed to take up LDL
Problems with using thiazolidinedione
Water retention and weight gain
Thiazolidinedione MoA
Binds to PPAp gamma receptor which result in sensitisation of cells to insulin
Inhibiton of Angiogenesis, decrease TG and increase HDL to promote LDL uptake
What is the bainbridge reflex
Increase SNS activity to the heart when blood volume increase
Might be protective reflex to prevent volume overload
What is the mesolimbic pathway (where does it run)
Aka the motivated pathway (dopaminergic)
Runs via the medial forebrain bundle from the VTA (ventral segmental area) of the midbrain to nucleus accumbens and limbic region
Long acting insulin
Glargine, determir
Rapid acting insulin
Aspart, lispro, glulisine
Intermediate insulin
NPH
