Basic Concepts in Pharmacology Flashcards
1
Q
ANS - cholinergics
- describe the major steps in the synthesis, storage and release of acetylcholine
- explain the actions of drugs which interfere with these mechanisms
- differentiate the actions of cholinergic receptor agonists with respect to the subtype/s of receptor activated
- explain the actions of drugs which interfere with parasympathetic neurotransmission
A
- enters cell via choline carrier, CAT takes acetyl from acetyl-coA to make ACh, which is stored in a vesicle. Influx of Ca2+ causes exocytosis, ACh is removed by acetylcholinesterase.
- Acetylcholinesterase inhibitors etc.
- ACh affects nicotinic receptors (musculoskeletal junction), and muscarinic receptors (M1-5)
- Muscarinic antagonists = parasympathomimetics; muscarinic antagonists = decrease parasympathetic output
2
Q
Envenoming
- differentiate between venoms, poisons and toxins
- discuss the different roles of venoms and toxins
- describe the pathophysiological processes which occur after snake envenoming
- describe the mechanism of action of neurotoxins at the NMJ
- explain the role of antivenoms in the treatment of envenoming
- identify the appropriate treatment strategies for envenoming
A
- Poisons are* any* chemical substances that impact biological functions in other organisms; Toxins are biologically produced chemical substances that impact biological functions in other organisms; Toxicants are synthesized chemical substances that impact biological functions in other organisms; Poisonous organisms* secrete* chemical substances that impact biological functions in other organisms; Venomous creatures* inject *chemical substances that impact biological functions in other organisms.
- 2
- 3
- Presynaptic (beta neurotoxins; slow, irreversible, early antivenom response); or postsynaptic (alpha neurotoxins; rapid, reversible, respond to antivenom)
- purified antibodies obtained from animals (horses) immunised against the venom
- First aid: vinegar (Box jellyfish); ice packs (redback); pressure, immobilisation (funnel-web)
3
Q
Drugs and the neuromuscular junction
- describe the chain of events which occur after an action potential arrives at the neuromuscular junction that eventually produces contracture of the skeletal muscle
- explain the actions of non-depolarising drugs at the skeletal neuromuscular junction
- explain the actions of depolarising drugs at the skeletal neuromuscular junction
- describe the symptoms of anticholinesterase poisoning
- describe the strategies for treatment of myasthenia gravis
A
- action potential arriving at the NMJ initiates calcium influx, release of ACh from vesicles, ACh binds to N receptor, Na+ influx into muscle endplate, depolarisation spreads, Ca2+ release from SR, contraction, ACh breakdown.
- Non-depolarising: no stimulation, nicotinic competitive antagonists
- Depolarising: stimulate N receptors, nicotinic agonists, inactivate Na+ channels
- Enhancement of ACh activity: parasympathetic overactivity (hypotension, fasciculation then NM blockade), respiratory failure; treatment with atropine (M)
- reduced N receptors ar muscle end plate, give anticholinesterase, atropine, corticosteroids or immunosuppressants
4
Q
Antivirals
- discuss the general principles of the treatment of viral infections
- discuss the use, mechanisms of action, clinical uses and problems associated with the use of antiviral drugs
A
Antivirals
5
Q
Antibacterials
- discuss the general principles of the treatment of bacterial infections
- discuss the use, mechanisms of action, clinical uses and problems associated with the use of antibacterial drugs
A
Antibacterials
6
Q
Anti-infectives
- describe why selective toxicity is important in chemotherapy
- discuss the main principles of selective toxicity and problems associated with the use of antiinfective agents
- discuss the use, mechanisms of action, clinical uses and adverse effects of examples from each of the major classes of:
- antiviral drugs
- antibacterial drugs
- antifungal drugs
- antiprotozoal drugs
- anthelmintic drugs
A
Anti-infectives
7
Q
Pain and Inflammation
- list the different classes of medication used to relieve pain and inflammation
- describe the role of mediators in pain and inflammation (and as a condition characterised by pain and inflammation, rheumatoid arthritis)
- describe the mode of action of non-opioid analgesics /antiinflammatory agents (e.g. simple analgesics, NSAIDs and steroids)
- describe the mode of action of the DMARD’s (disease-modifying antirheumatic drugs)
- describe the major side effects associated with the use of non-opioid analgesics and DMARD’s
A
- Analgesics:
- simple: aspirin, paracetamol; SA: increased bleeding time, peptic ulcers, exacerbation of asthma; inhibits COX
- NSAIDs, ibuprofen; inhibits COX reversibly
- >>> aspirin and NSAIDs inhibit prostaglandin synthesis at the site of injury
- opioids,
- local anaesthetics
- steroids: wide range of action; SE: hyperglycaemia
- DMARDs
8
Q
Pain and Inflammation
- revise the antithrombotic effects of aspirin
- describe the mode of action of opioid analgesics
- describe the mechanism of action of the local anaesthetics
- describe the major side effects associated with the use of opioid analgesics and local anaesthetics
A
- prostaglandins cause platelet disaggregation
- Analgesia: morphine-like drugs with high affinity for µ-receptors (G-protein coupled to K+ channels producing membrane hyperpolarisation and inhibit voltage-gated Ca2+ channels, leads to reduced neuronal excitability and inhibition of neurotransmitter release. SE: respiratory depression, decreased GIT motility, pupil contriction, morphine causes histamine release >> opioids act on CNS to alter pain perception
- reversible blockade of nerve conduction, by blocking the inner part of the Na+ channel; depth of block increases with AP frequency; target Agamma and C fibres first, SE: restlessness, CNS depression/convulsions, respiratory depression, myocardial compression = pronounced fall in blood pressure and death due to ‘escape into systemic’, which is why adrenalin (vasoconstrictor) are added >>> local anaesthetics block transmission of the noxious stimulus
9
Q
Drugs for neurological disorders 1
- appreciate that drugs to treat neurological disorders can target neurotransmission at several sites
- explain the rationale used for targeting andtreating epilepsy
- benzodiazepines / use‐dependent Na+ channels
- describe the benefit of benzodiazepines in anxiety and insomnia
A
- GABA inhibits neurons (where glutamate excites neurons); there are two methods to target:
- too much neuronal excitation: block inward Na+ current (lamotrigine)
- too little neuronal inhibition: activate the inhibitory neurotransmission via GABA:
- GABA transaminase metabolises GABA (valproate blocks), there is also a reuptake transporter, GABAA receptor can also be activated (benzodiazepines and barbiturates).
- Can also block Ca2+ channels in absence seizures eg. ethosuximide (T-type)
- Anti-anxiety drugs: benzodiazepines (target GABAA receptor) - sedative or hypnotics
- induce sleep, reduce muscle tone and coordinated, anti-convulsant; anterograde amnesia, tolerance and dependence eg. diazepam
10
Q
Drugs for neurological disorders 2
- be able to describe the mechanisms of action of various anti‐depressants / anti‐manic drugs
- be able to compare and contrast between the different classes of antidepressants / anti‐manic drugs
- be able to given an example drug from each the different classes of antidepressants / anti‐manic drugs
A
Anti-depressants:
- TCAs: block reuptake of NA and 5HT; block muscarinic receptors (dry mouth, blurred vision, urinary retention, constipation), H1 receptors (sedation), alpha1 receptors (orthostatic hypotension). eg. desipramine
- SSRIs: block reuptake of 5HT, results in down-regulation of postsynaptic 5HT receptors; initial anxiety, No OT and anticholinergic effects. eg. fluoxetine
- MAOA (monoamine metabolising enzymes): increases cytoplasmic and released levels of NA and 5HT; produce insomnia and sexual dysfunction
- MAOB works on DA in Parkinson’s
Anti-Manics:
- Lithium: accumulates in tissues and blocks the release of NA and 5HT (we dont know); many side effects: tremour, nephrogenic diabetes insipidus
- Anti-convulsants. eg. valproate, carbazepine
11
Q
Drugs for neurological disorders 3
- be able to describe the mechanisms of action of various anti‐psychotic drugs
- be able to compare and contrast between the different classes of anti‐psychotic drugs
- be able to given an example drug from typical and atypical antipsychotic families
A
- All potent anti-psychotics are dopamine receptor antagonists (D2 receptor)
- Side effects: inhibition of dopamine in the nigrostriatal pathway - akinesia, rigidity (Parkinsonian)
Anti-psychotics:
- Classical (positive symptoms): D2 blockade, and maybe alpha, H1, Muscarinic, D1
- eg. halperidol or chlorpromazine
- Atypical: D2 and 5HT2 blockade (causes weight gain), and maybe alpha, H1, muscarinic, D1
- eg. clozapine
Drugs take 2-3 weeks to take effect
12
Q
Drugs for neurological disorders 4
- be able to describe the neurochemical deficits and pathology in PD / HD
- be able to describe the mechanisms of action of various drugs used in the treatment of PD (and HD)
- be able to compare and contrast between the different classes of drugs used in the treatment of PD
A
- Loss of dopamine in striatum (nerve endings), loss of neurons in the substantia nigra (cell bodies); the nigrostriatal system collects/integrates signals from the cortex and prepares the motor system for the next movement in a given sequence of movements
- Targets:
- increase synaptic concentration of dopamine: levodopa (dopa) + dopa decarboxylase inhibitors (periphery); SE: dyskinesia
- Dopamine (D2) agonists. eg. bromocriptine; SE: nausea, vomiting, hypotension, delusions, anxiety
- Prevent dopamine metabolism: MAOB Inhibitors eg. selegiline; SE: insomnia, headache; COMT Inhibitors prolong the hald life of levadopa; SE: diarrhoea, nausea
- Alter efficacy of interacting neurotranmitters: dopamine neurons usually exert a tonic inhibitory effect on cholinergic neurons in the striatum, in PD the cholinergic system is intensified. So muscarinic antagonists can be used (eg. benzotropine)
- Huntingtons: loss of GABA neurons in striatum, causes Dopamine hyperactivity, causing motor hyperactivity. Treatments:
- Dopamine antagonists (chlorpromazine)
- GABA agonists
- Tetrabenazine, depleted dopamine in the brain
13
Q
Adrenergic Pharmacology
- Describe the process of adrenergic neurotransmission
- Identify the key transmitters and their actions
- Characterise the effects produced at sub‐types of adrenergic receptors
- Identify the key adrenergic drug groups and representative agents
- Discuss the mechanisms of action of important adrenergic drug groups and clinical considerations.
A
- NA is removed within the preganglionic nerve terminal by MAO, and is degraded by COMT extraneuronally
- NA and Dopamine both come from tyrosine and dopa
- alpha 1 - major blood vessels (NA>A)
- alpha 2 - systemically (NA>A)
- beta 1 - heart (A>NA)
- beta 2 - airways and blood vessels (A>NA)
- beta 3 (A>NA)
14
Q
Hypertension
- understand pathological changes occurring in CVS as a result of high BP
- discuss the non-pharmacological management of hypertension
- list the major classes of drugs used in the treatment of hypertension
- describe the mechanisms of action of antihypertensive drugs and possible adverse effects
A
- A - angiotensin concerting enzyme inhibitors and angiotensin antagonists: vasodilator and increase sodium and water excretion; SE: cough (bradykinin), headache, hyperkalaemia; Avoid in pregnancy
- B - beta blockers: decrease sympathetic drive to heart, inhibit renin release; Do not give to asthmatics, exacerbate and mask hypoglycemia
- C - calcium channel blockers: blockade of L-type (voltage) channels, reduced intracellular Ca2+, slow AV nodal cells (verapamil), cause vasodilation and reduce cardiac contractility; Avoid in heart failure or beta blockers; SE: cardiac depression, flushing, oedema, constipation
- D - diuretics: increase water and sodium excretion (Loop - Cl-; Thiazide - Na+ and Cl-; K sparing - Na+); SE: hypokalaemia, erectile dysfunction, digoxin increases toxicity
- E - extras
15
Q
Inotropic Agents
- Signs & causes of heart failure
- Pathophysiology of heart failure
- List major drug classes used in the treatment of heart failure
- Describe mechanisms of action of drugs used in treatment of heart failure & adverse effects
- Focus on inotropes- e.g. digoxin
A
- Decrease in cardiac output: unable to meet metabolic demands (tachycardia, short of breath, oedema), common and under-diagnoses. With many different causes: AMI, CHD, Arrythmias, Hypertension etc. (increase in EDV/Pressure = increase in CO)
- Syndrome arise mainly from reflex mechanisms attempting to maintain cardiac output, which often worsens the cardiac state
- Treatment
- Life-style changes
- Decrease cardiac workload: diuretics (loop SE: hearing loss, increase Mg, Ca excretion, hypovolemia; potassium sparing); RAS inhibition; beta-blockers (SE: heart failure!)
- Increase cardiac contractility: digoxin (inhibits Na/K ATPase and increases intracellular calcium; SE: narrow safety margin, excreted by kidneys, arrhythmia, increased GIT motility, stimulates vagal and vomiting centres, visual disturbances, bad with hypokalaemia), beta1 agonist (eg. dobutamine increases contractility and CO
