B2 Flashcards
Describe the therapeutic uses of pilocarpine & cevimeline
Directly acting cholinomimetic drugs which acts on M3 receptors
Pilocarpine ( natural alkaloids)
I) act as sialogoagues to treat xerostomia , Sjogren’s syndrome
II) treatment of glaucoma -> stimulate pupil contraction ( miosis) -> ciliary muscle contract -> trabecular mesh work opens -> allows aq. humour to flow out -> reduce intraocular pressure
- can lead to pulmonary edema as it increases pulmonary secretions
Cevimeline
I) Sialogogue to treat xerostomia due to cancer chemotherapy
- less toxic than pilocarpine hence it is used as an alternative
- benthanechol can also be used as a sialagogue alternative to pilocarpine
An example of a cholinomimetic drug which can cross BBB is …
Physostigmine
- a reversible anticholinesterase (natural alkaloid)
- Why? Because it is a tertiary ammonium alkaloid —others are quadternary , cannot cross BBB
List adverse effect of Oraganophosohate
DUMBBELS ( cholinergic overdose )
Diarrhoea , Urination , Miosis , Bradycardia , Bronchoconstriction , Lacrimation ,
The competitive antagonists of AcH & cholinomimetic drugs is ( ………….)
The competitive antagonists of AcH & cholinomimetic drugs is ( atropine )
Classification of antimuscarinic / anticholinergic drugs
1) Plant ( Atropa Belladonna )
I) Atropine
II) Scopolamine
2) Semisynthetics derivatives
I) Atropine methonitrate
II) Hyoscine butylbromide
3) Synthetics compounds
I) Glycopyrrolate
Explain the pharmacological action of atropine on CNS , CVS , EyE, respiratory system , GIT , urinary system , and body temperature.
On CNS
- excitatory effects
- restlessness , irritability , hallucinations , delirium
- uses : to treat Parkinson disease ( benztropine )
On CVS
- prevent the inhibitory effect of M2 receptor
- tachycardia , increase conduction velocity
- uses : Treat MI , abolish reflex vagal cardiac slowing
On eye
- cause mydriasis ( dilation of pupils) , dry eyes due to reduced lacrimation , cycloplegia ( loss of accommodation ) due to relaxation of ciliary muscle
- worsen glaucoma
- uses : fundoscopy
On respiratory system
- stimulate bronchodilator , acitivity of RS gland are inhibited -> drying and mucociliary clearance is inhibited
- uses : prevent reflex bronchioconstriction during intubation , COPD
On GIT
- decrease tone & motility of GIT — prolong gastric emptying time , contracts sphincters , decrease in peristalsis
- Relaxes the bile duct & gall bladder ( prevent release of bile )
- decrease in glandular secretions ( saliva -> dry mouth , gastric acid )
- uses : prevent biliary & intestinal colic , diarrhea , motion sickness treat peptic ulcer.
On genitourinary tract
- relaxation of bladder & ureter , contraction of urethral sphincter causing urinary retention
- uses : prevents involuntary micturition
On body temperature
- causes rise in body temperature due to hyperactivity , restlessness which is attenuated by abolishment of sweating
- uses : treat hyperhydrosis
Also treats :
I) Mushroom poisoning
II) Organphosphorus poisoning ***
Activation of alpha- adrenoreceptor will usually lead to ( …………… ) of all types of smooth muscle Except ( …………… )
Activation of beta p- adrenoreceptor will usually lead to ( ……………. ) of all types of smooth muscle
Activation of alpha- adrenoreceptor will usually lead to ( contraction ) of all types of smooth muscle Except ( GIT )
Activation of beta p- adrenoreceptor will usually lead to ( relaxation ) of all types of smooth muscle
Describe the therapeutic uses of adrenaline
Anaphylactic shock
- administer 0.3-0.5 mg IM in 1:1000 solution
Bronchial asthma
- in salbutamol longer acting in widen of airways
Cardiac arrest
Duration of LA
Epistaxis
Classify the Adrenergic drugs based on their usage ( PCBL NUMA)
Pressor agents - increase BP ( alpha 1 receptor )
: NE , dopamine
Cardiac agents: increase contraction ( beta 1 receptor )
:adrenaline , isoprenaline
Bronchodilators ( beta 2 receptor )
- salbutamol
Local vasoconstrictor effect - for homeostasis , prolong effect of LA ( alpha1 receptor ) Nasal decongestant ( alpha1 receptor ) \: phenylephrine
Uterine relaxant ( beta 2 receptor ) - salbutamol
Mydriatics -pupil dilation ( alpha 1 receptor ) - cause the constrictor of pupillary ciliary muscle
Anorexiants - suppress appetite
Describe the role of alpha agonists ( adrenaline ) in dental practice
Hemostasis
- used in 1:10000 or 1:20000 solution
- used following tooth extraction for homeostasis as it causes local vasoconstriction
Prolong duration of LA
- used in 1:100000 solution
- due to local vasoconstriction effect
- prevent systemic absorption & reduce toxicity of LA
Anaphylactic shock
- 1:1000 solution 0.3-0.5ml ,IM
- drugs like LA , penicillin can cause anaphylactic shock
Describe the role of adrenaline in anaphylactic shock
0.3-0.5mg in 1:1000 solution administered IM
- acting beta 1 receptor , it increases HR ( chronotropic ) and FOC ( inotropic )
- acting on beta 2 receptor , it increase bronchodilation and reduced release of mediator from mast cells
- acting on alpha 1 receptor , it causes vasoconstriction of blood vessels , increasing blood pressure .
- acting on alpha 1 receptor , it reduced mucosal / laryngeal edema
Give the classification of Adrenergic antagonists ( beta-blocker )
Non-selective ( acts on both beta 1 & beta 2 receptors ) (ptps)
- propranolol
- Timolol
- pindalol
- sotalol
Cardioselective / B1blocker (babem)
- bisoprolol
- atenolol
- betasolol
- esmolol ***shortest acting blocker
- metoprolol
Beta-blocker with additional vasodilatory effect ( alpha-1 blocking action )
- labetalol
- carvedilol
Describe the action of propranolol on CVS , RS , metabolism , eye and skeletal muscle
- it antagonists B1 and B2 receptor
On CVS
- blocks beta 1 receptor
- hence reduces conduction velocity , HR , FOC ,CO causing decreasing BP
- AV conduction decreases , increasing PR interval
- cardiac work decreases , decreasing O2 requirement of myocardium
- On kidney , decreases renin secretion causing decreased BP
On Respiratory system
- blocks B2 receptors , causing bronchoconstriction
- can lead to bronchospasm in asthmatic & COPD patients
- cardioselective beta- blockers ( metoprolol , bisoprolol ) less likely to cause bronco spasm in asthmatic patients
On eye
- acts on beta 2 receptors
- decreases secretion of aq . humour , reducing IOP, & glaucoma
- no effect on pupil size
- timolol is drug of choice
On metabolism
- acting beta2 receptors , decrease glycogenolysis and glucagon secretion
- contraindicated for diabetic patient
On skeletal muscle
- act on beta 2 receptor , causes decreased blood flow to skeletal muscle & lead to muscle fatigue due to decreased in CO
- inhibit tremors
On CNS
- decreases anxiety symptoms in short term
- causes behavioural changes , forgetfulness , nightmares in long term
(……………….) ( an opioid anatagonist ) can precipitate withdrawal symptoms in morphine & heroin addicts , hence it cannot be directly use to treat addicts
Instead , (……………………) should be given then only (………)
It is used in case of opoid overdose / poisoning in which it reverses the RS depressive effects
( IV naloxone , naltrexone , nalmefene ( an opioid anatagonist ) can precipitate withdrawal symptoms in morphine & heroin addicts , hence it cannot be directly use to treat addicts
Instead , ( methadone ) should be given then only ( naloxone )
It is used in case of opoid overdose / poisoning in which it reverses the RS depressive effects
Classify NSAID according to their selectivity to COX
Non COX selective inhibitors ( inhibits COX1 and COX 2)
- aspirin , ibuprofen , diclofenac
Preferential COX2 inhibitors
- diclofenac
- aceclofenac
Highly selective COX2 inhibitors ( coxibs )
I) Celecoxib
Analgesic and antipyretic but poor anti inflammatory effect
I) paracetamol
Describe the pharmacological actions of NSAIDS
1) Analgesic effects
- NSAIDS inhibits COX-2 enzymes , reducing synthesis of prostaglandins
- The role of these prostaglandins is to increase the sensitivity of central & peripheral pain receptors to inflammatory mediators eg , bradykinin
- hence , decrease PG synthesis -> decreased pain receptor sensitivity -> increased pain threshold
2) Antipyretic effect
- prostaglandins released due to the tissue damage , malignancy , graft injection etc set the hypothalamic heat regulating centre to a higher level cause hyperpyrexia
- hence NSAID which inhibits production of PG will reset the thermostat to normal body temperature.
3) Anti-inflammatory effect
- PG synthesis reduced -: less vasodilation , vascular permaebility decrease , edema decrease.
- NSAIDs also inhibit granulocyte adherence to the damaged vasculature
- NSAID also cause modulation of T cell function , stabilisation , of lysosomal membrane & inhibit chemotaxis
4) Antithrombotic effect ( blood thinning )
- aspirin inhibit TXA2 thus inhibit platelet aggregation , reducing risk of thrombi
State the function of TXA2 and PG
TXA2
-induce platelet aggregation
PG - vasodilation
- Inhibit platelet aggregation
Describe the adverse effect of NSAID
1) Gastric mucosal damage
- - due to inhibition of COX1 enzyme ( offers gut mucosa protection ) causing reduced PG ( PGE2 and PGI2) synthesis
- - PG acts as cytoprotectic agents by decreasing gastric acid production , stimulating mucous & HCO3 production and dilating mucosal blood vessels
- prevented by
I) Taking NSAID after food
II) Using Selective COX-2 inhibitors
III) Use proton pump inhibitors / H2 blockers / misrostol with NSAID
IV) paracetamol ( for cases of mild inflammation )
- hence contraindicated in patients with peptic ulcers
2) Renal dysfunction
- Prostalglandin cause vasodilation in kidney and help in salt and water excretion . In hypovolemia , the kidney blood flow is maintained Antihypertensives and diuretics produce some of their actions through prostaglandins .
- Inhibitor of PG mediated compensatory vasodilation and salt and water excretion
3) Hypersensitivity & asthma
4) Increase bleeding tendency ( anti platelet effect )
- due to inhibition of COX-1
- long term of aspirin decrease prothrombin levels by decreasing factor V ( proconvertin )
- hence non selective NSAID are contraindicated in Hemophilia and dengue & should be stopped 1 week before surgery
5) Reye’s syndrome
MOA of paracetamol
Produces analgesia centrally by inhibiting COX-3 enzyme and via activation of decreasing serotonergic pathways
Or it may produce effect by acting as cannabinols agonist and by antagonising NMDA and substance P in the spinal cord
Unlike other NSAID , paracetamol does not have ( …………. ) or ( …………….. ) effects
It is preferred in condition like :
- children < 12 yrs
- pt with history of peptic ulcer
- pt with bronchial asthma
- pt with bleeding disorder
- pt on anticoagulants
- pg with hypertension
- pregnancy
Unlike other NSAID , paracetamol does not have ( gastric side) or ( platelet ) effects
It is preferred in condition like :
- children < 12 yrs
- pt with history of peptic ulcer
- pt with bronchial asthma
- pt with bleeding disorder
- pt on anticoagulants
- pg with hypertension
- pregnancy
Mechanism of paracetamol toxicity
> 10 gum
- usually pcm is metablized by glucoronide & sulfate conjugation ( major pathway )
Phase 1 metabolism ( oxidation by CYP50 , minor pathway ) of PCM produces NAPQI , highly toxic minor metabolite which usually get detoxified by glutathione conjugation - with toxic doses PCM , glutathione stores plummet & large number of toxic metabolites accumulate form covalent bonds with hepatic renal ellualr proteins
- cause necrosis of the organs and eventual death.
Treantment - oral methionine or IV N-acetylcholine cysteine -> replenish glutathione stores in liver
Classify local anaesthetics based on their duration of action
1) Short acting , low potency
- procaine , chlorprocaine
2) Intermediate acting & potency
- lignocaine , prilocaine
3) Long acting , high potency
- tetracaine , bupivacaine , ropivacaine , dibucaine
What are advantages of amides LA over ester LA
1) Amide LA have long per duration of action -> greater efficacy
- as they are not hydrolysed by esterases ( which are found throughout the body )
- instead they are metabolised in the liver only
2) Hypersensitivity reactions are less with amides LAs
Describe the advantages and disadvantages of adding adrenaline to LA
Advantages
A) Increases the duration of action of LA
-Vasoconstriction reduces blood flow -> less absorption to systemic circulation -> drugs stays in tissue longer
B) Decreases systemic toxicity
- As drug is less absorbed into systemic circulation
C) Provide a bloodless field to surgery
D) Provides additional analgesic effect
- Due to alpha2 receptor stimulation -> decreased release of substance P
Disadvantages
A) Can make the injection more painful
B) Increased the chance of local tissue oedema
C) Delayed wound healing - due to vasoconstriction reducing blood flow
D) May raise BP & promote arrhythmias
E) If used on tissue with end arterial circulation may cause necrosis
- due to vasoconstriction and lack of collateral blood supply
- Lead to ischemia of the tissue
Describe the mechanism of action of local anaesthetics
LA in its unionised form crosses the nerve membrane
Then, it binds to the intracellular portion of Na+ voltage channnel in its ionised form
Inactive ( but open ) Na channels are most sensitive to LA — charged LA can only access to its binding site when the Na+ channels is open
Blocks Na+ voltage gated channels on neurons
Influx of Na during depolarisation is inhibited
Generation of AP& propagation of impulses is inhibited
Describe the adverse effect of local anaesthetics
- mainly involve CNS & CVS
I) CNS - mix of depressant & stimulant effects
- tremor , restlessness , convulsions , disorientation , twitching , dizziness , AV disturbance , respiratory depression
II) CVS
- depressant effect on heart
- decreased excitability , contractility & conduction due to inhibition of NA+voltage gated channels
- vasodilation of arterioles
- can lead to bradycardia , hypotension , arrhythmia , heart block
III) Hypersensitivity reactions
- more common in ester linked LAs
IV) Metheglobinemia
Describe surface anesthesia
- topical application of LA to mucus membrane / abraded skin
- LA used :
I) Eutectic mixture of lignocaine-prilocaine ( EMLA ) — the only preparation that can anaesthetise intact skin
Describe infiltration anaesthesia
- Subcutaneous injection of LA directly into tissue without taking into consideration the direction of cutaneous nerves
- only sensory nerve endings are blocked
- onset is immediate , duration is shorter than nerve block
- use : minor operation
- LA used : lignocaine
Describe the field block
- Subcutaneous injection of LA to anesthetiser the area distal to the site of injection
- All nerves coming to a particular field are blocked
- Lesser LA needed vs infiltration ananesthetia
Describe nerve block
- Injection LA closer to nerve trunks ( brachial plexus , intercostal , trunk of mandibular nerve , cervical plexus )
- leads to both sensory and motor paralysis
- drugs used : lignocaine ,mepivacaine , bupivacaine
